Endocrinology Flashcards

Question

what is humoral-stimulated hormone release?

Answer 1

hormone release caused by altered levels of certain critical ions or nutrients

Answer 2

hormone secreted in large quantities causes down regulation of its target receptors

Answer 3

combined effects of two hormones amplified

Answer 4

one hormone opposes other hormone

Answer 5

a product feeds back to decrease its own production

Answer 6

a product feeds back to increase its own production

Answer 7

supraoptic nucleus in the hypothalamus

Answer 8

- caffeine and alcohol inhibit its release - nausea, vomiting, stress, exercise stimulate its release - increased osmolality and decreased blood volume stimulate its release

Answer 9

- stimulates myoepithelial cells (mammary glands), leading to suckling and milk ejection - stimulates the uterus and cervical dilation, leading to labour and uterine contractions - produced by paraventricular nucleus in the hypothalamus

Answer 10

- thyroid stimulating hormone - growth hormone - adrenocorticotropic hormone - luteinising hormone - melanocyte stimulating hormone - prolactin - follicle stimulating horone

Answer 11

- metabolic, anti-insulin - fat metabolism -> increased fat breakdown and release - carbohydrate metabolism -> increased blood glucose and other anti-insulin effects

Answer 12

- growth promoting - production of insulin-like growth factors - increased cartilage formation and skeletal growth - increased protein synthesis and cell growth and proliferation

Answer 13

- accelerates food metabolism - increases protein synthesis - stimulation of carbohydrate metabolism - enhances fat metabolism - increase in ventilation rate - increase in cardiac output and heart rate - brain development during foetal life and postnatal development - growth rate accelerated

Answer 14

- increased HR - increased BP - bronchioles dilate - liver converts glycogen to glucose and releases glucose to blood - blood flow changes, reducing digestive system activity and urine output - metabolic rate increases

Answer 15

- kidneys retain sodium and water - blood volume and blood pressure rise - proteins and fats converted to glucose or broken down for energy - blood glucose increases - immune system suppressesd

Answer 16

- atrial natriuretic peptide - insulin-like growth factor I - erythropoietin - gastrin, secretin - prostanoids, nitric oxide, endothelin

Answer 17

body mass index = weight/(height)^2

Answer 18

underweight: <18.5 normal: 18.5-24.9 overweight: 25.0-29.9 obese: 30.0-39.9 morbidly obese: >40

Answer 19

usually abdominal (visceral) rather than subcutaneous fat - type 2 diabetes - hypertension - coronary artery disease - stroke - osteoarthritis - obstructive sleep apnoea - carcinoma of the breast, endometrium, prostate and colon

Answer 20

- lateral hypothalamus (hunger centre) | - ventromedial hypothalamic nucleus (satiety centre)

Answer 21

increase - NPY - MCH - AgRP - orexin - endocannabinoid decrease - alpha-MSH - CART - GLP-1 - serotonin

Answer 22

- psychological factors - neural afferents (vagal) - gut peptides: CCK, ghrelin, PYY - metabolites: glucose and ketones - hormones: leptin, insulin, cortisol - cultural factors

Answer 23

leptin and insulin

Answer 24

- ghrelin - PYY3-36 - glucagon like peptide 1 - CCK

Answer 25

``` NPY (arcuate nucleus) POMC - alpha MSH (acuate nucleus) agouti related peptide (arcuate nucleus) MC3 and MC4 receptors (paraventricular nucleus) serotonin ```

Answer 26

- leptin inhibits NPY/agouti related peptide (in arcuate nucleus) which affects PVN and LHA/PFA - leptin stimulates pro-opiomelanocortin/cocaine and amphetamine regulated transcript which affects LHA/PFA and PVN - decreased fat cell mass -> decreased leptin/insulin expression -> decreased leptin/insulin action in hypothalamus

Answer 27

- catabolic pathways activate nucleus tractus solitarius (NTS) - anabolic pathways inhibit nucleus tractus solitarius (NTS)

Answer 28

- Greek 'leptos' - thin - binds to leptin receptor - switches off appetite and is immunostimulatory - blood levels increase after meal and decrease after fasting

Answer 29

- activates NPY/AgRP neuron and increases NPY/AgRP expression, which blocks binding of alpha-MSH to melanocortin receptors leading to decreased activity of pathways, leading to increased food intake (obesity) - inhibits POMC neuron and decreases alpha-MSH expression and release

Answer 30

- 36 amino acids - structurally similar to NPY - binds NPY receptors - secreted by neuroendocrine cells in ileum, pancreas and colon in response to food - inhibits gastric motility - reduces appetite

Answer 31

- receptors in pyloric sphincter - delays gastric emptying, gall bladder contraction, insulin release - increases satiety

Answer 32

- 28 aa - expressed in stomach - stimulates growth hormone release and appetite - blood levels high when fasting, fall on re-feeding - levels lower after gastric bypass surgery - used in anorexia/cachexia

Answer 33

MCR1 - melanocytes; skin pigmentation MCR2 - adrenal; adrenal cortex, steroid production MCR3/4 - brain, signalling of satiety MCR5 - skin

Answer 34

no MCR1 - pale skin no MCR2 - adrenal insufficiency no MCR3/4 - hyperphagia and obesity

Answer 35

1. stimulate POMC/CART neurons -> increased CART and alpha-MSH levels 2. inhibits NPY/AgRP neurons -> decreased NPY and AgRP net effect: increased satiety and decreased appetite

Answer 36

stimulates NPY/AgRP -> increased NPY/AgRP secretion net effect: increased appetite

Answer 37

- homolog of NPY - binds to an inhibitory receptor on NPY/AgRP -> decreased secretion of NPY and AgRP net effect: decreased appetite

Answer 38

5' AMP activated protein kinase - plays a role in cellular energy homeostasis, to activate glucose and fatty acid uptake and oxidation when cellular energy is low

Answer 39

- decreased glucose (GLUT3) - decreased insulin (IR) - increased ghrelin (GR) - decreased leptin (LR) - decreased alpha-MSH (MCR) - increased AgRP (MCR)

Answer 40

- increased glucose (GLUT3) - increased insulin (IR) - decreased ghrelin (GR) - increased leptin (LR) - increased alpha-MSH (MCR) - decreased AgRP (MCR)

Answer 41

malonyl CoA - fasted state: decreased levels - fed state: increased levels

Answer 42

- hypercalcaemia is much more common than hypocalcaemia - mild asymptomatic hypercalcaemia occurs in 1 in 1000 of the population - incidence of 25-30 per 100000 population - occurs mainly in elderly females - usually due to primary hyperparathyroidism

Answer 43

- 84 amino acids - derived from a 115 residue preprohormone - secreted from the chief cells of the parathyroid glands

Answer 44

- PTH levels rise as serum ionised calcium falls - this is detected by specific G protein coupled calcium-sensing receptors on the plasma membrane of the parathyroid cells

Answer 45

all serve to increase plasma calcium by: - increasing osteoclastic resorption of bone (occurring rapidly) - increasing intestinal absorption of calcium (slow response) - increasing synthesis of 1,25-dihydroxy-cholecalciferol - increasing renal tubular reabsorption of calcium - increasing excretion of phosphate

Answer 46

- excessive PTH secretion - malignant disease; low PTH levels (myeloma, bone deposits, osteoclastic tumour factors, PTH secretion) - excess action of vitamin D - excessive calcium intake (milk-alkali syndrome) - other endocrine disease (thyrotoxicosis, Addison's) - drugs (thiazide diuretics, vitamin D analogues, lithium administration, vitamin A) - micellaneous (long-term immobility, familial hypocalciuric hypercalcaemia)

Answer 47

- primary hyperparathyroidism, adenoma, hyperplasia or carcinoma - tertiary hyperparathyroidism - ectopic PTH secretion (very rare)

Answer 48

- iatrogenic or self-administered excess - granulomatous diseases, e.g. sarcoidosis, TB - lymphoma

Answer 49

- unknown causes - monoclonal adenoma - multiple adenomas/hyperplasia - MENtype1 or familial hypocalciuric hypercalcaemia - inactivation of some tumour suppressor genes - cancer

Answer 50

occurs when the parathyroid glands become enlarged and release too much PTH - severe calcium deficiency - severe vitamin D deficiency - chronic kidney failure

Answer 51

- development of apparently autonomous parathyroid hyperplasia after long-standing secondary hyperparathyroidism, most often in renal failure - plasma calcium and phosphate are both raised - parathyroidectomy is necessary

Answer 52

- tiredness, malaise, dehydration and depression - renal colic from stones - polyuria or nocturia, haematuria and hypertension - polyuria due to the effect of hypercalcaemia on renal tubules, reducing their concentration ability - bone pain (affects mainly cortical bone) - bones cysts and locally destructive brown tumours - pain - chrondocalcinosis and ectopic calcification - corneal calcification

Answer 53

mild: adjusted calcium <3mmol/L severe: >3mmol/L

Answer 54

bronchus, breast, myeloma, oesophagus, thyroid, prostate, lymphoma, renal cell carcinoma

Answer 55

several fasting serum calcium and phosphate samples should be done - serum PTH - hyperchloraemic acidosis - renal function (usually normal, measured as baseline) - 24-hour urinary calcium or single calcium creatinine - elevated serum alkaline phosphatase - protein electrophoresis/immunofixation (to exclude myeloma) - serum TSH (to exclude hyperthyroidism) - 0900 hours cortisol and/or ACTH test (to exclude Addisons disease) - serum ACE (diagnosis of sarcoidosis) - hydrocortisone suppression test

Answer 56

kidney - increased Ca2+ reabsorption - decreased phosphate reabsorption - increased 1alpha-hydroxylation of 25-OH vitamin D bone - increased bone remodelling - bone resporption -> bone formation GI tract - no direct effect - increased Ca2+ absorption because of increased 1,25-dihydroxy-cholecalciferol

Answer 57

normal: equal low Ca2+: low Ca2+ and raised PTH high Ca2+: high Ca2+ and low PTH

Answer 58

corrected calcium = total serum calcium + 0.02*(40 - serum albumin)

Answer 59

- parasthesia - muscule spasm: hands and feet, larynx, premature labour - seizures - basal ganglia calcification - cataracts - ECG abnormalitites: long QT interval - Chvostek's sign - Trousseau's sign

Answer 60

- tap over the facial nerve - look for spasm of facial muscles - sign of neuromuscular irritability

Answer 61

- inflate the blood pressure cuff to 20mmHg above systolic for 5 minutes - in hypocalcaemia, there is flexion of the wrist and metacarpophalangeal joints, extension of DIP and PIP joints and adduction of fingers

Answer 62

- vitamin D deficiency (no gut absorption of Ca2+ and Pi) - undermineralised bone - hypoparathyroidism - renal disease - cancer - hungry bone syndrome - Fanconi syndrome - radiation exposure - metabolic disorder

Answer 63

- Di George - HDR - Kenney-Caffey - Sanjad-Sakati - Kearns-Sayre - blomstrand chondrodysplasia

Answer 64

developmental abnormality of third and fourth branchial pouches - hypoparathyroidism - thymic aplasia - immunodeficiency - cardiac defects - cleft palate - abnormal facies

Answer 65

- neck surgery - autoimmune disease - hereditary hypoparathyroidism - low magnesium - radiation to face/neck - haemochromatosis - Wilson's disease

Answer 66

- decreased renal calcium reabsorption -> increased relative calcium excretion -> decreased serum calcium - increased renal phosphate reabsorption -> increased serum phosphate -> decreased formation of 1,25(OH)2D - decreased bone resorption -> decreased serum calcium - decreased formation of 1,25(OH)2D -> decreased intestinal calcium absorption -> decreased serum calcium

Answer 67

- short stature - obesity - round facies - mild learning difficulties - subcutaneous ossification - short fourth metacarpals - other hormone resistance - resistance to PTH

Answer 68

- short stature - obesity - round facies - mild learning difficulties - subcutaneous ossification - short fourth metacarpals - other hormone resistance normal calcium metabolism

Answer 69

- all glucose comes from the liver (and some from the kidney) - glucose delivered to insulin independent tissues, brain and erythrocytes - insulin levels are low - muscle uses FFA for fuel - some processes are very sensitive to insulin, even low insulin levels prevent unrestrained breakdown of fat

Answer 70

after feeding (post prandial) - physiological need to dispose of a nutrient load - rising glucose (5-10 mins after eating) stimulates insulin secretion and suppresses glucagon - 40% of ingested glucose goes to liver and 60% to periphery, mostly muscle - ingested glucose helps to replenish glycogen stores both in liver and muscle - high insulin and glucose levels suppress lipolysis and levels of NEFA or FFA fall

Answer 71

- endocrine pancreas | - Islets of Langerhans

Answer 72

- duct and pancreatic acini on the periphery - red blood cells - islets of Langerhans: alpha cells, beta cells, delta cells, epsilon cells, PP cells - alpha cells: glucagon - beta cells: insulin and amylin - delta cells: somatostatin - epsilon cells: ghrelin - PP cells: pancreatic polypeptide

Answer 73

1. insulin binds to the insulin receptor on muscle and fat cells 2. intrasignalling cascade 3. intracellular GLUT4 vesicle mobilisation to plasma membrane 4. GLUT4 vesicle integration into plasma membrane 5. glucose entry into cell via GLUT4

Answer 74

- decreased glycogenolysis - decreased gluconeogenesis - increases glucose uptake into insulin sensitive tissues (muscle, fat) - supresses lipolysis and breakdown of muscle

Answer 75

- increased glycogenolysis - increased gluconeogenesis - reduces peripheral glucose uptake - stimulates peripheral release of gluconeogenic precursors (glycerol, AAs) by lipolysis and muscle glycogenolysis and breakdown

Answer 76

- type 1 - type 2: includes gestational and medication induced diabetes - maturity onset diabetes of youth (MODY), aka monozygotic diabetes - pancreatic diabetes - endocrine diabetes (acromegaly/Cushings) - malnutrition related diabetes

Answer 77

- symptoms and random plasma glucose > 11mmol/l - fasting plasma glucose > 7mmol/l - no symptoms - GTT (75g glucose) fasting >7 or 2h value > 11mmol/l (repeated on 2 occasions) - HbA1c of 48mmol/mol (6.5%)

Answer 78

- an insulin deficiency disease characterised by loss of beta cells due to autoimmune destruction - beta cells express antigens of HLA perhaps in response to an environmental event - activates a chronic cell mediated immune response leading to chronic 'insulitis'

Answer 79

- continued breakdown of liver glycogen - unrestrained lipolysis and skeletal muscle breakdown - inappropriate increase in hepatic glucose output and suppression of peripheral glucose uptake - rising glucose concentration leads to increased urinary glucose losses as renal threshold (10mM) is exceeded - reduced insulin leads to fat breakdown and formation of glycerol (a gluconeogenic precursor) and FFA - ketogenesis is exquistely sensitive to insulin

Answer 80

- increase in circulating glucagon (loss of local increases in insulin within the islets leads to removal of inhibition of glucagon release), further increasing glucose - perceived stress leads to increased cortisol and adrenaline - progressive catabolic state and increased levels of ketones

Answer 81

- impair glucose uptake - are transported to the liver, providing energy for gluconeogenesis - are oxidised to form ketone bodies (beta hydroxy butyrate, acetoacetate and acetone)

Answer 82

- absence of insulin and rising counterregulatory hormones leads to increasing hyperglycaemia and rising ketones - glucose and ketones escape in the urine but lead to an osmotic diuresis and falling circulating blood volume - ketones cause anorexia and vomiting - vicious circle of increasing dehydration, hyperglycaemia and increasing acidosis eventually lead to circulatory collapse and death

Answer 83

genes and environment -> impaired insulin secretion and insulin resistance -> impaired glucose tolerance -> type 2 diabetes -> progressive hyperglycaemia and high FFA progressive hyperglycaemia and high FFA -> insulin resistance and impaired insulin secretion

Answer 84

- reduced muscle and fat uptake after eating - failure to suppress lipolysis and high circulating FFAs - abnormally high glucose output after a meal

Answer 85

- even low levels of insulin prevent catabolism and ketogenesis - profound muscle breakdown and gluconeogenesis are restrained - ketone production is rarely excessive

Answer 86

one defect: absent insulin secretion - > no hepatic insulin effect - > no muscle/fat insulin effect - unrestrained glucose + ketone production, more glucose enters the blood - impaired glucose clearance + muscle/fat breakdown, less glucose enters peripheral tissues hyperglycaemia + raised plasma ketones -> glycosuria/ketonuria

Answer 87

two defects impaired insulin secretion -> hepatic insulin resistance -> muscle/fat insulin resistance - excessive glucose production, more glucose enters bloodstream - impaired glucose clearance, less glucose enters peripheral tissues hyperglycaemia -> glucosuria

Answer 88

insulin resistance and impaired insulin secretion due to a combination of genetic predisposition and environmental factors (obesity and lack of physical activity)

Answer 89

- it is rare because the low insulin levels are sufficient to suppress catabolism and prevent ketogenesis - can occur if hormones e.g. adrenaline rise to high levels (e.g. during an MI)

Answer 90

- genetic predisposition (i.e. abnormalities of insulin secretion in first degree relatives) - deposition of peptides within the beta cell (amilyn) - glucotoxicity hyperglycaemia inhibits insulin secretion - main factor is probably lipid deposition in the pancreatic islets which prevents normal function

Answer 91

- NPH insulin - insulin glargine (100 and 300 U/ml) - insulin detemir - insulin degludec - lente insulin series - pumped insulin

Answer 92

- insulin lispro - insulin glulisine - EDTA/citrate human insulin - faster acting insulin aspart

Answer 93

- separation of basal from bolus insulin to mimic physiology - pre-meal rapid acting boluses adjusted according to pre-meal glucose and carbohydrate content of food to cover meals - basal insulin should control blood glucose inbetween meals and during night - basal insulin is adjusted to maintain fasting blood glucose between 5-7 mmol/L

Answer 94

T1DM - autoimmune condition (beta-cell damage) with genetic component - profound insulin deficiency T2DM - insulin resistance - impaired insulin secretion and progressive beta-cell damage but initially continued insulin secretion - excessive hepatic glucose output - increased counter-regulatory hormones including glucagon

Answer 95

- many people with T2DM need insulin; esp. later or in individuals with poor glycaemic control on other medications - basal insulin is initiated followed by addition of a prandial insulin where necessary - premix insulins also available - long-acting basal insulin analogues associated with lower risk of symptomatic, overall and nocturnal hypoglycaemia - prandial insulins mimic meal-time insulin secretion and their faster action allows for greater flexibility at mealtimes

Answer 96

- human basal (intermediate-acting) - 90 minutes onset - 2-4 hours peak action - up to 24 hours duration

Answer 97

- basal analogue - steady state onset after 1-2 days - N/A peak action - up to 24 hours duration

Answer 98

- human short acting - 10-20 minutes onset - 30-90 minutes peak action - up to 2-5 hours duration

Answer 99

- human premixed 70/30 - 30 minutes onset - 2-8 hours peak action - up to 24 hours duration

Answer 100

NPH (neutral protamine hagedorn)

Answer 101

Detemir/Glargine U100

Answer 102

insulin aspart, insulin lispro, insulin glulisine

Answer 103

mixtard, humulin M3

Answer 104

- once daily basal insulin - twice daily mix-insulin - basal-bolus therapy

Answer 105

- simple for the patient, adjusts insulin themselves, based on fasting glucose measurements - carries on with oral therapy - less risk of hypoglycaemia at night

Answer 106

- doesn't cover meals | - best used with long acting insulin analogues which are considered expensive

Answer 107

- both basal and prandial components in a single insulin preparation - can cover insulin requirements through most of the day

Answer 108

- not physiological - requires consistent meal and exercise pattern - cannot separately titrate individual insulin components - risk for nocturnal hypoglycaemia - risk for fasting hyperglycaemia if basal component does not last long enough - often requires accepting higher HbA1c goal of <7.5% or <8%

Answer 109

with HbA1c levels of >9% | - earlier

Answer 110

low plasma glucose causing impaired brain function (neuroglycopenia) 3mmol/l - mild: self treated - severe: requiring help for recovery hypoglycaemia: 3.9mmol/L

Answer 111

alert value | - plasma glucose <3.9mmol/l (70mg/dl) and no symptoms

Answer 112

serious biochemical | - plasma glucose <3.0mmol/l (55mg/dl)

Answer 113

non-severe: patient has symptoms but can self-treat and cognitive function is mildly impaired severe: patient has impaired cognitive function sufficient to require external help to recover (level 3 of new classification)

Answer 114

- trembling - palpitations - sweating - anxiety - hunger - difficulty concentrating - confusion - weakness - drowsiness, dizziness - vision changes - difficulty speaking - nausea - headache

Answer 115

- inhibition of endogenous insulin secretion (4.6 mmol/l) - counter-regulatory hormones: glucagon and adrenaline - symptom onset (autonomic-neuroglycopenic) (3.2-3 mmol/L)

Answer 116

- widespread EEG changes (3.0 mmol/L) - neurophysiological dysfunction (2.6 mmol/L) - cognitive dysfunction; inability to perform complex tasks (3.0-2.4 mmol/L) - severe neuroglycopenia; reduced consciousness, convulsions, coma (<1.5mmol/L) - seizures, coma - cognitive dysfunction - accidents in employment - prevents desirable glucose targets - fear - quality of life

Answer 117

- history of severe episodes - HbA1c <6.5% (48 mmol/mol) - long duration of diabetes - renal impairment - impaired awareness of hypoglycaemia - extremes of age

Answer 118

- advancing age - cognitive impairment - depression - aggressive treatment of glycaemia - impaired awareness of hypoglycaemia - duration of multiple daily injection insulin therapy - renal impairment and other comorbidities

Answer 119

- low HbA1c; high pre-treatment HbA1c in T2DM - long duration of diabetes - a history of previous hypoglyaemia - impaired awareness of hypoglycaemia - recent episodes of severe hypoglycaemia - daily insulin dosage >0.85 U/kg/day - physically active - impaired renal function

Answer 120

- aim for lowest HbA1c not associated with frequent hypoglycaemia - HbA1c <7.0% (53 mmol/mol) is usually appropriate for recent-onset disease - may be appropriate to relax targets (severe complications, advanced co-morbidities, cognitive impairment, limited life expectancy, unacceptable hypoglycaemia from stringent control)

Answer 121

HbA1c <7.5%, <8% and <8.5%

Answer 122

- if on an SU (for T2DM), revise dose or consider changing to another drug class - if on basal-bolus insulin, check BG before each meal every day - ensure medication is dosed correctly - consider insulin adjustments: regular/soluble insulin -> rapid acting insulin NPH/isophane -> insulin analogues adjusting insulin in relation to exercise

Answer 123

1. recognise symptoms so they can be treated as soon as they occur 2. confirm the need for treatment if possible (BG <3.9 mmol/l is the alert value) 3. treat with 15g fast acting carbohydrate to relieve symptoms 4. retest in 15 minutes to ensure BG >4.0 mmol/l and retreat if needed 5. eat a long-acting carbohydrate to prevent recurrence of symptoms

Answer 124

- abdominal x-rays may show renal calculi or nephrocalcinosis - high definition hand x-rays can show subperiosteal erosions in the middle or terminal phalanges - DXA bone density scan is useful in detecting bone effects in asymptomatic people with hyperparathyroidism in whom conservative management is planned

Answer 125

- ultrasound, which, although insensitive for small tumours, is simple and safe - high resolution CT scan or MRI (more sensitive) - radioisotope scanning using 99Tc-sestamibi, which is 90% sensitive in detecting adenomas

Answer 126

- no effective medical therapies atm - high fluid intake should be maintained, a high calcium or vitamin D intake avoided and exercise encouraged - new therapeutic agents targeting calcium-sensing receptors (e.g. cinacalcet) are of proven value in parathyroid carcinoma and in dialysis patients and used in primary hyperparathyroidism where surgical intervention is contraindicated

Answer 127

- people with renal stones or impaired renal function - bone involvement or marked reduction in cortical bone density - unequivocal marked hyerglycaemia - uncommon younger patient, below 50 years - previous episode of severe acute hypercalcaemia

Answer 128

- dehydration - nausea and vomiting - nocturia and polyuria - drowsiness and altered consciousness - serum Ca2+ is over 3 mmol/L and sometimes as high as 5 mmol/L - immediate treatment is mandatory if the patient is seriously ill or if the Ca2+ is above 3.5 mmol/L

Answer 129

- rehydrate - IV bisphosphonates - prednisolone (30-60mg daily may be effective) - calcitonin (200 units IV 6hourly has short lived action and is little used) - oral phosphate (sodium cellulose phosphate 5g TDS; produces diarrhoea)

Answer 130

- at least 4-6L of 0.9% saline on day 1, and 3-4L for several days thereafter - central venous pressure (CVP) may need to be monitored to control the hydration rate

Answer 131

- used for hypercalcaemia of malignancy or of undiagnosed cause - pamidronate is preferred (60-90mg as an IV infusion in 0.9% saline or glucose over 2-4 hours, or if less urgent, over 2-4 days) - levels fall after 24-72 hours, lasting for about 2 weeks - zoledronate is an alternative

Answer 132

- postop hypocalcaemia - bleeding and recurrent laryngeal nerve palsies (<1%) - vocal cord function

Answer 133

treatment for hypocalcaemia (more common in patients who have significant bone disease and/or vitamin D deficiency) - pre-treating with alfacalcidol 2 um daily from 2 days postop for 10-14 days - routine vitamin D replacement (preferably without calcium) is indicated if deficiency is diagnosed - Chvostek and Trousseau signs monitored - biochemistry monitored - plasma calcium measurements are performed daily until stable - oral or IV calcium given temporarily

Answer 134

- uncommon - autosomal dominant - usually asymptomatic - demonstrates increased renal reabsorption of calcium despite hypercalcaemia - PTH levels are normal or slightly raised and urinary calcium is low - loss of function mutations in the gene on the long arm of chromosome 3 encoding for calcium-ion-sensing GPCR in the kidney and parathyroid gland

Answer 135

- detected by genetic analysis - parathyroid surgery is not indicated as course appears benign - diagnosis can be differentiated from hyperparathyroidism in an isolated case by the calcium creatinine ratio in blood and urine

Answer 136

- increased phosphate levels (CKD, phosphate therapy) - hypoparathyroidism (surgery, DiGeorge's, idiopathic, severe hypomagnesaemia) - vitamin D deficiency (osteomalacia/rickets, vitamin D resistance) - resistance to PTH (pseudohypoparathyroidism) - drugs (calcitonin and bisphosphonates) - miscellaneous (acute pancreatitis, citrated blood transfusion, low albumin, malabsorption)

Answer 137

- rare autoimmune disorder | - vitiligo, cutaneous candidiasis, other autoimmune disease

Answer 138

familial condition in which the hypoparathyroidism is associated with intellectual impairment, cataracts and calcified basal ganglia, and occasionally with specific autoimmune disease

Answer 139

- syndrome of end-organ resistance to PTH owing to a mutation in the Gsalpha-protein (GNAS1) which is coupled to the PTH receptor - variable degrees of resistance involving other G-protein linked hormone receptors may also be seen (TSH, LH, FSH)

Answer 140

- phenotypic defects of pseudohypoparathyroidism - without any abnormalities of calcium metabolism - may share same gene defect as individuals with pseudohypoparathyroidism and be in the same families

Answer 141

- neuromuscular irritability and neuropsychiatric manifestations - paraesthesiae, circumoral numbness, cramps, anxiety and tetany are followed by convulsions, laryngeal stridor, dystonia and psychosis - Chvostek's sign: gentle tapping over the facial nerve causes twitching of the ipsilateral facial muscles - Trousseau's sign: inflation of the sphygmomanometer cuff above systolic pressure for 3 min induces tetanic spasm of the fingers and wrist - severe hypocalcaemia may cause papilloedema and frequently a prolonged QT interval on the ECG

Answer 142

- low serum calcium (after correction for any albumin abnormality) - clinical history and picture - serum and urine creatinine (for renal disease) - PTH levels in serum (absent or inappropriately low in hypoparathyroidism, high in other causes of hypocalcaemia) - parathyroid antibodies (present in idiopathic hypoparathyroidism) - 25-hydroxy vitamin D serum level (low in vitamin D deficiency) - magnesium level (severe hypomagnasaemia results in functional hypoparathyroidism which is reversed by magnesium replacement) - x-rays of metacarpals showing short 4th metacarpals occurring in pseudohypoparathyroidism

Answer 143

- cholecalciferol in vitamin D deficiency - alpha-hydroxylated derivatives of vitamin D may be preferred for their shorter half life, especially in renal disease as the others require renal hydroxylation - daily maintenance doses are 0.25-2ug for allfacalcidol - plasma calcium must be monitored for hypercalcaemia - oral calcium supplements may be used in early stages of treatment - severe hypocalcaemia presenting as an emergency may require replacement with IV calcium gluconate

Answer 144

- hyperventilation - excess antacid therapy - persistent vomiting - hypochloraemic alkalosis e.g. primary hyperaldosteronism

Answer 145

a syndrome of chronic hyperglycaemia due to relative insulin deficiency, resistance or both - affects more than 220 million worldwide - will affect 440 million by the year - complications result in reduced life expectancy and major health costs (including coronary artery disease, peripheral vascular disease and stroke and microvascular damage causing diabetic retinopathy and nephropathy, and neuropathy)

Answer 146

- involved in storage and controlled release within the body of the chemical energy available from food - coded for on chromosome 11 - synthesised in beta cells of pancreatic iselts - enters portal circulation and is carried to the liver - about 50% is extracted and degraded in the liver and kidneys - C peptide is only partially extracted by the liver and is mainly degraded by the kidneys

Answer 147

- blood glucose levels are closely regulated in health - around 3.5-8.0 mmol/L (63-144 mg/dL) - stay similar despite food, fasting and exercise

Answer 148

- liver absorbs and stores glucose (as glycogen) in the post-absorptive state and releases it into circulation between meals to match the rate of glucose utilization by peripheral tissues - combines 3-carbon molecules derived from breakdown of fat (glycerol), muscle glycogen (lactate) and protein (e.g. alanine) into the 6-carbon glucose molecule by gluconeogenesis

Answer 149

- about 200g of glucose is produced and utilised each day | - more than 90% is derived from liver glycogen and hepatic gluconeogenesis, and the remainder from renal gluconeogenesis

Answer 150

1 mg/kg bodyweight per minute, or 100g daily in a 70kg man

Answer 151

stored as glycogen or metabolised to lactate or CO2 and water

Answer 152

- source of energy - substrate for TG synthesis - lipolysis releases fatty acids from triglyceride together with glycerol, a substrate for hepatic gluconeogenesis

Answer 153

- ribosomes manufacture pre-proinsulin from insulin mRNA - hydrophobic pre portion of the pre-proinsulin allows it to transfer to the Golgi apparatus, and is enzymatically cleaved off - proinsulin is parcelled into secretory granules in the Golgi - pass towards membrane and are stored before release - proinsulin molecule folds back onto itself and is stabilised by disulphide bonds - biochemically inert peptide, connecting (C) peptide splits off from proinsulin, leaving insulin as two linked peptide chains

Answer 154

regulated pathway: releases equimolar quantities of insulin and C-peptide constitutive pathway: small amount of insulin is secreted by the beta cell directly. bypasses the secretory granules

Answer 155

1. glucose enters the beta cell via the GLUT-2 transporter protein 2. metabolism of glucose within the beta cell generates ATP 3. ADP/ATP binds to SUR1 (regulatory subunit) 4. ATP closes potassium channels in the cell membrane 5. closure of potassium channels predisposes to membrane depolarisation, allowing calcium ions to enter the cell; if a sulfonylurea binds to its receptor this also closes potassium channels 6. rise in intracellular calcium triggers activation of calcium-dependent phospholipid protein kinase, which leads to fusion of the granules and exocytosis 7. this secretes insulin

Answer 156

enables basal non-insulin-stimulated glucose uptake into many cells

Answer 157

transports glucose into beta cell, a prerequisite for glucose sensing, and is also present in renal tubules and hepatocytes

Answer 158

enables non-insulin-mediated glucose uptake into brain neurones and placenta

Answer 159

enables much of the peripheral action of insulin. glucose is taken up into muscle and adipose tissue cells following stimulation of the insulin receptor

Answer 160

- glycoprotein (400 kDa) - coded for on the short arm of chromosome 19 - on cell membrane - dimer with two alpha subunits which include the binding sites for insulin, and two beta subunits, which traverse the cell membrane - when insulin binds to the alpha subunits it induces a conformational change in the beta subunits, which activates tyrosine kinase and initiation of a cascade response - leads to migration of GLUT-4 to cell surface and increased transport of glucose into the cell - insulin receptor complex is internalised, insulin is degraded and the receptor is recycled - insulin signal pathway leads to effects on protein metabolism, effects on growth, effects on lipid metabolism and translocation of GLUT-4 vesicle to cell membrane

Answer 161

- pancreatitis - trauma/pancreatectomy - neoplasia - CF - haematochromatosis - fibrocalculous pancreatopathy

Answer 162

- acromegaly - Cushing's syndrome - glucagonoma - phaeochromocytoma - hyperthyroidism - somatostatinoma - aldosteronoma

Answer 163

- vacor (pyrinuron) - pentamidine - nicotinic acid - beta blockers - thyroid hormone - diazoxide - beta adrenergic agonists - thiazides - phenytoin - alpha interferon - protease inhibitors

Answer 164

- glucocorticoids - ciclosporin - tacrolimus - sirolimus

Answer 165

- clozapine | - olanzapine

Answer 166

- congenital rubella | - cytomegalovirus

Answer 167

- stiff person syndrome | - anti-insulin receptor antibodies

Answer 168

- Down's - Friedreich's ataxia - Huntington's chorea - Klinefelter's syndrome - Laurence-Moon-Biedl syndrome - myotonic dystrophy - porphyria - Prader-Willi syndrome - Turner's syndrome - Wolfram's syndrome

Answer 169

- younger age (<30) - lean weight - symptom duration of weeks - northern/European people have higher risk - seasonal onset - HLA-DR3 or DR4 in >90% - autoimmune disease - ketonuria - clinical: insulin deficiency, ketoacidosis, always need insulin - C-peptide disappears

Answer 170

- older (>30) - overweight - symptom duration of months/years - Asian, African, Polynesian and American-Indian have higher risk - no seasonal onset - no HLA links - no immune disturbance - no ketonuria - clinical: partial insulin deficiency initially, hyperosmolar state, need insulin when beta cells fail over time - C-peptide persists

Answer 171

- chromosome 6 - 90% of patients carry HLA-DR3-DQ2, HLA-DR4-DQ8 or both, compared to 35% of the background population - all DQB1 alleles with an aspartic acid at residue 57 confers neutral to protective effects with the strongest effect from DQB1*0602 (DQ6), while DQB1 alleles with an alanine at the same position (DQ2 and DQ8) confer strong susceptibility - HLA DR3-DQ2/HLA DR4-DQ8 heterozygotes have an increased risk of disease - some HLA class I alleles modify the risk conferred by class II susceptibility genes

Answer 172

- more than 50 non-HLA genes or gene regions influence risk - gene encoding insulin (INS) on chromosome 11 - cytotoxic T-lymphocyte-associated protein-4 (CTLA4) gene - lymphoid-specific protein tyrosine phosphatase (PTPN22) gene - IL-2R alpha-subunit of the IL-2 receptor complex locus (IL2RA)

Answer 173

- GAD65 (glutamic acid decarboxylase) - IA-2/ICA512 (protein tyrosine phosphatase) - insulin - cation transporter ZnT8

Answer 174

infiltration of pancreatic islets by mononuclear cells | - resembles that in other autoimmune diseases e.g. thyroiditis

Answer 175

- incidence of childhood diabetes is rising across Europe by 2-3% each year - islet autoantibodies appear in the first few years of life - exposure to dietary constituents, enteroviruses e.g. Coxsackie B4 and relative deficiency of vitamin D may play a role - cleaner environment with less early stimulation of the immune system may increase susceptibility - atopic/allergic conditions and more rapid weight gain leading to insulin resistance may accelerate clinical onset

Answer 176

- children who test positive for 2+ autoantibodies have a >80% risk of progression to diabetes, and the risk approaches 100% in those who lose their first phase insulin response to IV glucose and/or develop glucose intolerance - intervention before clinical onset of diabetes has been unsuccessful

Answer 177

- increasing age - ethnicity - family history - in poor countries, it's a disease of the rich, and in rich countries, a disease of the poor - stress of pregnancy, drug treatment or intercurrent illness may accelerate onset - more prevalent in South Asian, African, Caribbean people - those of Middle Eastern and Hispanic American origin living western lifestyles have risk - obesity increases the risk of type 2 80-100 fold - sedentary/western lifestyle - insulin resistance - metabolic syndrome

Answer 178

- type 2 diabetes is associated with central obesity, hypertension, hypertriglyceridaemia, decreased HDL-cholesterol, disturbed haemostatic variables and modest increases in pro-inflammatory markers - insulin resistance and increased cardiovascular risk is associated with these variables - criteria: increased waist circumference (or BMI >30) plus two of the following: diabetes (or fasting glucose >6.0 mmol/L), hypertension, raised TGs or low HDL cholesterol

Answer 179

- transcription factor-7-like (TCF7-L2) most common variant in Europeans; increased risk of 35%; modulates pancreatic islet cell function - KCNQ1 (potassium voltage gated channel) in Asians; increased risk of 10-20%

Answer 180

- low weight at birth and at 12 months is linked to glucose intolerance later in life, esp. in overweight/obese - poor nutrition early in life impairs beta-cell development and function, predisposing to diabetes - low birthweight also predisposes to heart disease and hypertension

Answer 181

- subclinical inflammatory changes are characteristic of both type 2 diabetes and obesity - in diabetes, high sensitivity C-reactive protein levels are modestly elevated in association with raised fibrinogen and increased plasminogen activator inhibitor-1 (PAI-1) - CRP levels contribute to cardiovascular risk - circulating levels of pro-inflammatory cytokines TNF-alpha and IL-6 are elevated in diabetes and obesity

Answer 182

- some degree of beta-cell dysfunction is necessary - insulin binds normally to its receptor - insulin resistance is associated with central obesity and accumulation of intracellular TG in muscle and liver, and many have NAFLD - patients retain up to 50% of their beta cell mass at time of diagnosis - show islet amyloid deposition at autopsy, derived from amylin or islet amyloid polypeptide, which is cosecreted with insulin

Answer 183

- circulating insulin levels are higher than healthy people following diagnosis - tend to rise further - decline after months or years due to secretory failure insulin deficiency relative to increased demand leads to hypersecretion of insulin by a depleted beta-cell mass and progression towards absolute insulin deficiency requiring insulin therapy

Answer 184

glucotoxicity: hyperglycaemia and lipid excess are toxic to beta cells; this results in further beta-cell loss and further deterioration of glucose homeostasis

Answer 185

- insulin receptor mutations (obesity, insulin resistance, hyperandrogenism, acanthosis nigricans) - maternally inherited diabetes and deafness - Wolfram's syndrome - severe obesity and diabetes (Alstroems, Bardet-Biedl, Prader-Willi, reinitis pigmentosa, mental insufficiency, neurological disorders) - disorders of intracellular insulin signalling (Leprechaunism, Rabson-Mendenhall, pseudoacromegaly, lipodistrophy) - genetic defects of beta cell function

Answer 186

- mutation in mitochondrial DNA - diabetes onset before age 40 - variable deafness - neuromuscular and cardiac problems - pigmented retinopathy

Answer 187

DIDMOAD - diabetes insipidus, diabetes mellitus, optic atrophy and deafness - recessively inherited - mutation in the transmembrane gene, WFS1 - insulin-requiring diabetes and optic atrophy in the first decade - diabetes insipidus and sensorineural deafness in teh second decade progressing to multiple neurological problems - few live beyond middle age

Answer 188

- 20q - 5% of all cases - teens/30s onset - progressive hyperglycaemia - frequent microvascular complication

Answer 189

- 7p - 15% of all cases - present from birth - little deterioration with age - rare microvascular complications - reduced birthweight

Answer 190

- 12q - 70% of all cases - teens/20s onset - progressive hyperglycaemia - frequent microvascular complications - sensitivity to sulfonylureas

Answer 191

- 13q - <1% of all cases - teens/30s onset - progression unclear - pancreatic agenesis in homozygotes

Answer 192

- 17q - 2% of all cases - teens/20s onset - progression unclear - renal cysts, proteinuria, CKD

Answer 193

transient neonatal diabetes mellitus - occurs soon after birth - resolves at a median of 12 weeks - 50% of cases relapse later in life - most have an abnormal imprinting of the ZAC and HYMAI genes on chromosome 6q

Answer 194

permanent neonatal diabetes mellitus | - mutations in the KCNJ11 gene encoding the Kir6.2 subunit of the beta-cell potassium-ATP channel

Answer 195

young people often present with a 2-6 week history and report: - polyuria: due to osmotic diuresis that results when blood glucose levels exceed the renal threshold - thirst: due to loss of fluid and electrolytes - weight loss: due to fluid depletion and the accelerated breakdown of fat and muscle secondary insulin deficiency ketonuria is often present in young people and may progress to ketoacidosis

Answer 196

- clinical onset may be over several months or years, esp. in older patients - thirst, polyuria and weight loss are present - lack of energy, visual blurring (glucose-induced changes in refraction) or pruitus vulvae or balanitis due to Candida

Answer 197

- staphylococcal skin infections - retinopathy noted during a visit to the optician - polyneuropathy causing tingling and numbness in the feet - erectile dysfunction - arterial disease, resulting in MI or peripheral gangrene

Answer 198

- glycosuria or raised BP on routine examination - glycosuria indicates need for further investigations - 1% of the population have renal glycosuria

Answer 199

- evidence of weight loss and dehydration - breath smells of ketones - older patients may have complications - retinopathy is diagnostic of diabetes - physical signs of an illness causing secondary diabetes - may have acanthosis nigricans

Answer 200

- fasting plasma glucose >7.0 mmol/L (126 mg/dL) - random plasma glucose >11.1 mmol/L (200 mg/dL) - one abnormal lab value is diagnostic in symptomatic individuals; two values for asymptomatic people - HbA1c >6.5 (48 mmol/mol)

Answer 201

normal f: <7.0 mmol/L 2hrs: <7.8 mmol/L impaired glucose tolerance f: <7.0 mmol/L 2hrs: 7.8-11.0 mmol/L diabetes mellitus f: >7.0 mmol/L 2hrs: >11.1 mmol/L

Answer 202

haemoglobin A1c - integrated measure of prevailing blood glucose over several weeks >6.5% (48 mmol/mol) is diagnostic of diabetes 5.7-6.4% (39-46 mmol/mol) is increased risk of diabetes

Answer 203

- low in sugar (not sugar free) - high in starchy carbohydrate (esp. foods with low glycaemic index) i.e. slower absorption - high in fibre - low in fat (esp. saturated fat)

Answer 204

- used in diabetes - activates AMP-kinase, which is involved in regulation of cellular energy metabolism - reduces the rate of gluconeogenesis, and hence hepatic glucose output, to increase insulin sensitivity - doesn't induce hypoglycaemia, doesn't affect weight gain and doesn't affect insulin secretion

Answer 205

- anorexia - epigastric discomfort - diarrhoea - prohibits its use in 5-10% of patients

Answer 206

- diabetes - act on beta cell to promote insulin secretion in response to glucose and other secretagogues - ineffective in patients without a functional beta-cell mass, and are usually avoided in pregnancy - bind to sulfonylurea receptor which closes ATP-sensitive potassium channels and leads to depolarisation

Answer 207

- cheap - more effective than other agents in achieving short term (1-3 years) glucose control - effect wears off as the beta cell mass declines - may hasten beta cell apoptosis and promote weight gain - best avoided in the overweight - can cause potentially fatal hypoglycaemia - long half lives - avoided in liver disease and renal impairment

Answer 208

- tolbutamide - glibenclamide - glipizide and glimepiride - gliclazide - chlorpropamide

Answer 209

- lower maximal efficacy than other sulfonylureas - short half life; preferable in elderly - largely metabolised by liver; can use in renal impairment

Answer 210

- long biological half-life - severe hypoglycaemia - do not use in elderly

Answer 211

- active metabolites | - renal excretion; avoid in renal impairment

Answer 212

- very long biological half-life - renal excretion - avoid in renal impairment - 1-2% develop inappropriate ADH-like syndrome - facial flush with alcohol - very inexpensive - major issue for developing countries - can produce fatal hypoglycaemia - not recommended in the elderly

Answer 213

- e.g. repaglinide and nateglinide - insulin secretagogues - the non-sulfonylurea moiety of glibenclamide - act via closure of K+-ATP channel in beta cells - short acting agents that promote insulin secretion in response to meals

Answer 214

- known as the glitazones - reduce insulin resistance by interaction with peroxisome proliferator-activated receptor-gamma (PPAR-gamma); this regulates large numbers of genes including those in lipid metabolism and insulin action - potentiate the effect of endogenous or injected insulin - binds to nuclear receptors mainly found in fat cells - act indirectly via the glucose-fatty acid cycle, lowering free fatty acid levels and thus promoting glucose consumption by muscle - reduce hepatic glucose production (synergistic with metformin) and enhance peripheral glucose uptake

Answer 215

- troglitazone and rosiglitazone have been withdrawn for safety reasons (liver failure and increased CV risk) - pioglitazone is only remaining agent unwanted effects of pioglitazone - weight gain of 5-6kg - fluid retention and heart failure - mild anaemia and osteoporosis resulting in peripheral bone fractures - increased risk of bladder cancer

Answer 216

- enhance the incretin effect - enzyme dipeptidyl peptidase 4 rapidly inactivates GLP-1 as this is released into circulation - potentiates the effect of endogenous GLP-1 secretion - lower blood glucose and are weight neutral

Answer 217

- linagliptin - saxagliptin - sitagliptin - vildagliptin most effective in early stages of type 2 diabetes when insulin secretion is relatively preserved. currently recommended for second-line use in combination with metformin or a sulfonylurea

Answer 218

adverse effects are uncommon - nausea - acute pancreatitis - short term safety record is good - it's widely distributed in the body - long-term consequences of inhibition of this enzyme in other tissues is not known

Answer 219

the insulin response to oral glucose is greater than the response to IV glucose

Answer 220

two intestinal peptide hormones, glucose-dependent insulinotropic peptide (GIP) and glucagon-like peptide-1 (GLP-1) have a potentiating effect on pancreatic secretion of insulin - GIP causes 30% and GLP-1 70% of the incretin effect - both hormones have short half-lives in the circulation, being degraded by DPP4 - diminished in T2DM

Answer 221

- GIP is secreted from the K cells in the duodenum | - GLP-1 is secreted from the L cells of the ileum in response to food

Answer 222

- exenatide and liraglutide are long-acting analogues of GLP-1, which enhance the incretin effect - promote insulin release, inhibit glucagon release, reduce appetite and delay gastric emptying - blunt the post-prandial rise in plasma glucose and promote weight loss

Answer 223

- main disadvantage is the need for subcutaneous injection (twice daily for exenatide and once daily for liraglutide) - main advantage is improving glucose control while inducing useful weight reduction - work well in 70% but have little benefit in 30%

Answer 224

nausea, acute pancreatitis and acute kidney injury

Answer 225

- insulin derived from beef or pig pancreas have been replaced by biosynthetic human insulin - short-acting insulins are used for pre-meal injection in multiple dose regimens, for continuous IV infusion in labour or in medical emergencies, and in patients using insulin pumps

Answer 226

- slowly, reaching a peak 60-90 min after subcutaneous injection and its action tends to persist after meals, predisposing to hypoglycaemia - absorption is delayed because soluble insulin is in the form of stable hexamers (six insulin molecules around a zinc core) and needs to dissociate to monomers and dimers before it can enter circulation

Answer 227

- soluble insulin is in the form of stable hexamers (six insulin molecules around a zinc core) - needs to dissociate to monomers or dimers before it can enter the circulation

Answer 228

- short acting insulin analogues have been engineered to dissociate more rapidly following injection without altering the biological effect - insulin analogues e.g. rapid acting insulins (insulin lispro, insulin aspart and insulin glulisine) enter the circulation more rapidly than human soluble insulin and disappear more rapidly - short-acting analogues have little effect upon overall glucose control

Answer 229

insulin lispro, insulin aspart and insulin glulisine

Answer 230

by addition of zinc or protamine derived from fish sperm

Answer 231

- NPH (isophane insulin) - insulin glargine - insulin detemir

Answer 232

- can be premixed with soluble insulin to form stable mixtures (biphasic insulins) - combination of 30% soluble with 70% NPH is most widely used

Answer 233

- long acting insulin soluble in the vial as a slightly acidic (pH 4) solution, but precipitates at subcutaneous pH, thus prolonging its duration of action

Answer 234

- long acting insulin has a fatty acid tail, which allows it to bind to serum albumin, and its slow dissociation from the bound state prolongs its duration of action

Answer 235

A chain and B chain connected by disulphide bridges

Answer 236

a genetically engineered rapidly acting insulin analogue created by reversing the order of the amino acids proline and lysine in positions 28 and 29 of the B chain

Answer 237

similar analogue to lispro created by replacing proline at position 28 of the B chain with an aspartic acid residue

Answer 238

a genetically engineered long-acting insulin created by replacing asparagine in position 21 of the A chain with a glycine residue and adding two arginines to the end of the the B chain

Answer 239

discards threonine in position 30 of the B chain and adds a fatty acyl chain to lysine in position B29

Answer 240

stage 1: lifestyle changes and metformin stage 2: add sulphonylurea, basal insulin, consider adding DPP4 inhibitor or glitazone stage 3: change from SU to basal insulin or add DPP4 inhibitor, add mealtime short-acting SU or intensity insulin to basal insulin, change to basal insulin from DPP4 inhibitor or glitazone or add remaining DPP4 inhibitor or glitazone stage 4: further intensify treatment or switch to insulin *progress to further step if HbA1c >53mmol/mol*

Answer 241

- an intermediate insulin given at night with metformin during the day - multidose insulin regimens - metformin is a useful adjunct - addition of a morning dose of insulin may be needed to control postprandial hyperglycaemia - twice daily injections of pre-mixed soluble and isophane insulins - more aggressive treatment e.g. multiple injections or continuous infusion pumps

Answer 242

- low first-pass metabolism in subcutaneous injection compared to secreted insulin - subcutaneous soluble insulin takes 60-90 min to achieve peak plasma levels, so the onset and offset of action are too slow - absorption of subcutaneous insulin insulin into the circulation is variable - basal insulin levels are constant in normal people, but injected insulin peaks and declines in diabetics, with swings in metabolic control

Answer 243

- hypoglycaemia between meals and particularly at night is the limiting factor for patients on multiple injection regimens - more expensive rapid-acting insulin analogues are a substitute for soluble insulin - analogues reduce frequency of nocturnal hypoglycaemia - used on convenience, as patients can inject before meals - analogues can reduce high or erratic morning blood sugar readings

Answer 244

persistently too high: increase evening long-acting insulin persistently too low: reduce evening long-acting insulin

Answer 245

persistently too high: increase morning short-acting insulin persistently too low: reduce morning short-acting insulin or increase mid-morning snack

Answer 246

persistently too high: increase morning long-acting insulin or lunch short-acting insulin persistently too low: reduce morning long-acting insulin or lunch short-acting insulin or increase mid-afternoon snack

Answer 247

persistently too high: increase evening short-acting insulin persistently too low: reduce evening short-acting insulin

Answer 248

- before meals - during the night - during exercise - irregular eating habits, unusual exertion and alcohol excess may precipitate episodes - other cases are just due to variation in insulin absorption

Answer 249

- develop when blood glucose level falls below 3 mmol/L - develop over a few minutes - adrenergic features of sweating, tremor and a pounding heartbeat - all patients with type 1 have intermittent hypoglycaemia - one in three go into a coma at some point - pallor and a cold sweat - hypoglycaemic unawareness: lose warning symptoms; risk of central nervous dysfunction - pale, drowsy, detached - clumsy, inappropriate, irritable or aggressive behaviour - hypoglycaemic coma

Answer 250

- basal insulin requirements fall during the night but increase from 4am, when injected insulin levels are falling - patients may wake with high glucose levels, but find that injecting more insulin at night increases the risk of hypoglycaemia in the morning

Answer 251

- regular bedtime snack - patients taking twice-daily mixed insulin can separate their evening dose and take the intermediate insulin at bedtime rather than dinner - reducing dose of soluble insulin before dinner, as this will persist into the night - changing to a rapid-acting insulin analogue, with long-lasting analogue at night - changing to an infusion pump programmed to deliver lower doses at night

Answer 252

- rapidly absorbed carbohydrate relieves the early symptoms - glucose or sweets - liquid form

Answer 253

- unconscious patients should be given IM glucagon or IV glucose followed by a flush of 0.9% saline to preserve the vein - glucagon mobilises hepatic glycogen; works almost as rapidly as glucose - glucagon doesn't work when liver glycogen levels are low, e.g. after a prolonged fast - oral glucose given to replenish glycogen once patient revives

Answer 254

``` HbA1c: <7% (53 mmol/mol) BP: 130/80 total cholesterol: <4 mmol/L LDL: <2 HDL: >1.1 TGs: <1.7 ```

Answer 255

``` HbA1c: <8% (64 mmol/mol) BP: 140/80 total cholesterol: <5 mmol/L LDL: <3 HDL: >0.8 TGs: <2 ```

Answer 256

- biochemical assessment of metabolic control - measure bodyweight - measure BP - measure plasma lipids - measure visual acuity - examine state of retina - test urine for proteinuria/microalbuminuria - test blood for renal function (creatinine, eGFR) - check condition of feet, pulses and neurology - review CV risk factors - review self-monitoring and injection techniques - review eating habits

Answer 257

- detectable ketone levels in the urine | - occurs in fasted non-diabetics and may be found in well-controlled patients

Answer 258

elevated plasma ketone levels in the absence of acidosis

Answer 259

a metabolic emergency where hyperglycaemia is associated with a metabolic acidosis due to greatly raised (>5 mmol/L) ketone levels

Answer 260

a metabolic emergency where uncontrolled hyperglycaemia induces a hyperosmolar state in the absence of significant ketosis

Answer 261

a metabolic emergency where elevated lactic acid levels induce a metabolic acidosis - rare in diabetic patients - associated with biguanide therapy

Answer 262

hallmark of type 1 diabetes - previously undiagnosed diabetes (10%) - interruption of insulin therapy (15%) - stress of intercurrent illness (30%)

Answer 263

increased glucose -> hyperglycaemia and glycosuria > osmotic diuresis -> fluid and electrolyte depletion -> renal hypoperfusion -> impaired excretion of ketones and hydrogen ions increased ketones -> acidosis -> vomiting -> fluid and electrolyte depletion -> renal hypoperfusion -> impaired excretion of ketones and hydrogen ions kidney becomes less able to compensate for the acidosis

Answer 264

triglycerides from adipose tissue -> FFA(plasma) -> FFA(hepatocyte) -> fatty acyl carnitine -> acetyl CoA(in mitochondrion) -> acetoacetate -> acetone and beta-hydroxybutyrate

Answer 265

- acetoacetate - acetone - beta-hydroxybutyrate

Answer 266

- state of uncontrolled catabolism associated with insulin deficiency - counter regulatory hormone excess and fluid depletion - absence of insulin -> hepatic glucose production increased -> reduced peripheral uptake -> osmotic diuresis, loss of fluid and electrolytes and dehydration - rapid lipolysis -> increased FFA levels - accumulation of ketone bodies produces a metabolic acidosis - respiratory compensation for acidosis -> hyperventilation - impaired renal excretion of hydrogen ions and ketones due to dehydration - as pH falls below 7 (H+ conc > 100 nmol/L), enzyme systems may fail

Answer 267

- prostration - hyperventilation - nausea - vomiting - abdominal pain - confusion and stupor - coma (5%) - dehydration, eyeball lax to pressure - smell of ketones on breath - dry skin - subnormal body temp

Answer 268

- hyperglycaemia: measure blood glucose - ketonaemia: test plasm with Ketostix. finger prick sample for beta-hydroxybutyrate - ketonuria: measure urine ketone levels where plasma ketone measurements are unavailable - metabolic acidosis - blood and urine culture - cardiac enzymes - CXR - ECG - catheterisation if no urine passed after 3 hours of hydration - if conscious, nasogastric tube - antibiotics if infection

Answer 269

- pulse >100 bpm or <60 - systolic BP <90mmHg - Glasgow Coma Score <12 or abnormal AVPU - sats <92% on air

Answer 270

- blood ketones >6 mmol/L - bicarbonate <12 mmol/L - venous/arterial pH <7.1 - hypokalaemia on admission <3.5 mmol/L

Answer 271

1. assess 2. send bloods to lab 3. set up IV infusion blood glucose - measure baseline and hourly initially - aim for fall of 3-6 mmol/L per hour urea and electrolytes - do baseline and hourly until 6 hours, then at 12 hours and at 24 hours - add potassium when K+ <3.5 mmol/L. give 20 mmol/h in infusion. 10 mmol/h when K+ = 3.5-5 mmol FBC blood gases: 0, 2, 6 hours creatinine: at 0, 6, 12, 24 hours bicarbonate: at 0, 1, 2, 3, 6, 12, 24 hours

Answer 272

- admit to level 2 HDU - insulin: soluble insulin by infusion or IM - fluid and electrolyte replacement: IV 0.9% NaCl with 20 mmol KCL/L - adjust KCl conc depending on results of regular blood K+ measurement - if BP below 80, give 500 mL 0.9% NaCl over 15min if pH below 7 give 500ml of sodium bicarb 1.26% plus 10 mmol KCl

Answer 273

insulin and glucose - when blood glucose falls to 10-12 mmol/L, change infusion fluid to 1L 5% glucose and 20 mmol KCl 6 hourly - continue insulin with dose adjusted according to hourly glucose test results

Answer 274

when stable and able to eat and drink normally, transfer to QDS subcutaneous insulin

Answer 275

- broad-spectrum antibiotic if infection likely - bladder catheter if no urine passed in 2 hrs - nasogastric tube if drowsy - consider CVP pressure monitoring if shocked or if previous cardiac or renal impairment - give SC prophylactic LMW heparin

Answer 276

- monitor glucose hourly for 8 hrs - monitor electrolytes 2 hourly for 8 hours - adjust K+ replacement according to results

Answer 277

- replace fluid losses (with 0.9% saline) - replace electrolyte losses (with K+) - restore acid-base balance - replace the deficient insulin - monitor blood glucose closely - seek the underlying cause

Answer 278

- consumption of glucose rich fluids - concurrent medication e.g. thiazide diuretics or steroids - intercurrent illness

Answer 279

- plasma osmolality is usually extremely high - extremely sensitive to insulin - glucose conc may plummet - can cause cerebral damage - infuse insulin at 3 U/hour for first 2-3 hours, increasing to 6 U/hour if falling too slowly - 0.9% saline - low molecular weight heparin to counter increased risk of thromboembolic complications

Answer 280

- biguanide therapy - low risk in patients on metformin - large anion gap (<17 mmol/L) - usually without significant hyperglycaemia or ketosis - treatment is rehydration and infusion of isotonic 1.26% bicarbonate - mortality 50%

Answer 281

- stoke - MI - coronary artery disease - atherosclerosis - amputation of limbs for gangrene

Answer 282

affected sites: retina, renal glomerulus, nerve sheaths - diabetic retinopathy, nephropathy and neuropathy - cataracts - peripheral retina - macular oedema/damage

Answer 283

- gustatory sweating - cardiac denervation - postural hypotension - gastroparesis - diarrhoea - atonic bladder/erectile dysfunction - arteriovenous shunting

Answer 284

- ocular palsies - carpal tunnel syndrome - small muscle wasting - amyotrophy - painful neuropathy - neuropathic foot

Answer 285

- claudication and rest pain - dependent rubor and trophic changes - cold and pulseless - painful ulceration in heels and toes

Answer 286

- usually painless, sometimes painful neuropathy - high arch, clawing of toes, no trophic changes palpation: warm, bounding pulses - painless, plantar ulceration

Answer 287

- has vital centres for appetite, thirst, thermal regulation and sleeping/waking - integrates neural and endocrine inputs to control release of pituitary hormones - role in circadian rhythm, menstrual cyclicity and responses to stress, exercise and mood

Answer 288

- most hormones secreted by it are under positive control by the hypothalamic releasing hormones apart from prolactin - prolactin is under tonic inhibition by dopamine - conditions interrupt the flow of hormones between the hypothalamus and pituitary gland and cause deficiency of most hormones but oversecretion of prolactin

Answer 289

- connected to specific hypothalamic nuclei - acts as a storage organ - ADH and oxytocin are synthesised in the supraoptic and paraventricular nuclei in the anterior hypothalamus - stored in the posterior pituitary

Answer 290

``` source: hypothalamus site of action: pituitary hormone structure: 44 AA receptor: membrane; 7TM post-receptor activity: Gproteins and cAMP ```

Answer 291

source: hypothalamus site of action: pituitary hormone structure: cyclic peptide, 14 or 28 AA receptor: membrane; 7TM, SST2 + SST5 post-receptor activity: G proteins, inhibit cAMP

Answer 292

``` source: pituitary site of action: liver and other tissues hormone structure: 191 AA receptor: transmembrane, dimerised, GHR post-receptor activity: JAK2, STAT ```

Answer 293

source: liver and locally elsewhere site of action: many tissues hormone structure: peptide; 70 AA, 3 disulphide bridges receptor: transmembrane, IGFR, 2alpha and 2beta subunits post-receptor activity: receptor tyrosine kinase

Answer 294

``` source: hypothalamus site of action: pituitary hormone structure: peptide; 3 AA receptor: membrane; 7TM, TRHR post-receptor activity: G proteins, PLC/IP3 ```

Answer 295

source: pituitary site of action: thyroid hormone structure: glycoprotein; alpha and beta subunits receptor: membrane; 7TM, TSHR post-receptor activity: G proteins, cAMP/PLC/IP3

Answer 296

source: thyroid site of action: all tissues hormone structure: thyronines - 4/3 iodine atoms receptor: nuclear; TR-alpha and beta post-receptor activity: transcription, TRE/RXR

Answer 297

``` source: hypothalamus site of action: pituitary hormone structure: peptide; 10 AA receptor: membrane, 7TM, GnRH-R1 post-receptor activity: G proteins, PLC/IP3 ```

Answer 298

``` source: pituitary site of action: gonad hormone structure: glycoprotein; alpha and beta subunits receptor: membrane, 7TM, LHhCGR post-receptor activity: G proteins, cAMP ```

Answer 299

``` source: pituitary site of action: gonad hormone structure: glycoprotein; alpha adn beta subunits receptor: membrane, 7TM FSHR post-receptor activity: G proteins, cAMP ```

Answer 300

source: ovary site of action: uterus, breast, bone, vascular hormone structure: steroid ring receptor: nuclear, ER alpha and beta (ESR1/ESR2) post-receptor activity: homo/hetero dimer, ERE, transcription

Answer 301

``` source: testis site of action: many tissue hormone structure: steroid ring receptor: nuclear, AR (NR3C4) post-receptor activity: dimer, ARE, transcription ```

Answer 302

source: gonad site of action: pituitary - hypothalamus hormone structure: peptide dimers, alpha and beta subunits receptor: transmembrane, dimerised post-receptor activity: phosphorylation by receptor

Answer 303

``` source: hypothalamus site of action: pituitary hormone structure: amine receptor: membrane, 7TM, D2 receptor post-receptor activity: G proteins, inhibit cAMP ```

Answer 304

source: pituitary site of action: breast, other tissues hormone structure: peptide, 199AA receptor: transmembrane, PRLR, class 1 cytokine post-receptor activity: JAK2 and other pathways

Answer 305

``` source: hypothalamus site of action: pituitary hormone structure: peptide, 41AA receptor: membrane, 7TM, CRF1 post-receptor activity: G proteins, cAMP ```

Answer 306

``` source: pituitary site of action: adrenal hormone structure: peptide, 39 AA receptor: membrane, 7TM ACTHR (MCR2) post-receptor activity: G proteins, cAMP ```

Answer 307

``` source: adrenal site of action: all tissues hormone structure: steroid ring receptor: nuclear, GRalpha post-receptor activity: transcription, GRE ```

Answer 308

``` source: hypothalamus -> pituitary site of action: kidney hormone structure: peptide, 9AA receptor: membrane, 7TM, AVPR2 post-receptor activity: G proteins, cAMP, aquaporin 2 ```

Answer 309

``` source: hypothalamus -> pituitary site of action: vascular hormone structure: peptide 9AA receptor: membrane, 7TM, AVPR1A post-receptor activity: G proteins, PLC/IP3 ```

Answer 310

source: hypothalamus -> portal veins site of action: pituitary (ACTH secretion) hormone structure: peptide, 9AA receptor: membrane, AVPR1B post-receptor activity: G proteins, PLC/IP3

Answer 311

``` source: hypothalamus -> pituitary site of action: uterus and breast hormone structure: peptide, 9AA receptor: membrene, 7TM, OXTR post-receptor activity: G proteins ```

Answer 312

- local effects of a tumour - excess hormone secretion - result of inadequate production of hormone by the remaining normal pituitary, i.e. hypopituitarism

Answer 313

- pressure on the visual pathways, with field defects and visual loss (most common) - pressure of the cavernous sinus, with II, IV and VI cranial nerve lesions - bony structures and the meninges surrounding the fossa, causing headache - hypothalamic centres: altered appetite, obesity, thirst, somnolence/wakefulness or precocious puberty - infiltration of the ventricles, causing interruption of CSF flow leading to hydrocephalus - infiltration of the sphenoid sinus with invasion causing CSF rhinorrhoea

Answer 314

MRI and visual field testing

Answer 315

temporal quadrantanopia and bitemporal hemianopia

Answer 316

- prolactin excess (prolacinoma or hyperprolactinaemia): histologically, they are chromophobe adenomas - GH excess (acromegaly or gigantism): somatotroph adenomas, usually acidophil, sometimes due to specific G protein mutations - excess ACTH secretion (Cushing's disease of Nelson's syndrome): corticotroph adenomas, usually basophil

Answer 317

most <10 mm (microprolactinoma) - galactorrhoea, amenorrhoea, hypogonadism, erectile dysfunction some >10 mm (macroprolactinoma) - as above plus headaches, visual field defects and hypopituitarism

Answer 318

surgery - trans-sphenoidal route is usually treatment of choice - very large tumours are sometimes removed via open transcranial (usually transfrontal) route radiotherapy - by conventional linear accelerator or newer stereotactic techniques - usually employed when surgery is impracticable or incomplete - controls but rarely abolishes tumour mass - conventional regimen is a dose of 45 Gy, given as 20-25 fractions via three fields medical therapy - somatostatin analogues and/or dopamine agonists may cause shrinkage of tumour - growth hormone receptor antagonist

Answer 319

pituitary adenomas are the most common mass lesion of the pituitary (90%) - craniopharyngioma - uncommon tumours - hypophysitis and other inflammatory masses - other lesions

Answer 320

- 1-2% - cystic hypothalamic tumour, often calcified - arises from Rathke's pouch - often mimics an intrinsic pituitary lesion - most common pituitary tumour in children

Answer 321

- meningiomas - gliomas - chondromas - germinomas - pinealomas - primary pituitary carcinomas are very rare - prolactin and ACTH secreting tumours may require chemotherapy - secondary deposits

Answer 322

- deficiency of hypothalamic releasing hormones or of pituitary trophic hormones - can be selective or multiple - isolated deficiencies of all pituitary hormones are seen

Answer 323

- multiple deficiencies of hormones result from tumour growth or other destructive lesions - progressive loss of anterior pituitary function - GH and gonadotropins are first affected - hyperprolactinaemia occurs early due to loss of tonic inhibitory control by dopamine - TSH and ACTH are last to be affected

Answer 324

- deficiency of all anterior pituitary hormones - caused by pituitary tumours, surgery or radiotherapy - vasopressin and oxytocin secretion will be affected only if the hypothalamus is involved in a tumour or a suprasellar extension of a pituitary lesion, or an infiltrative/infalmmatory process - posterior pituitary deficiency is rare in uncomplicated pituitary adenoma

Answer 325

- congenital (isolated deficiency of pituitary hormones e.g. Kallmann's syndrome, POUF1 (PIT-1), PROP1, HESX1 mutations) - infective (basal meningitis, encephalitis, syphilis) - vascular (pituitary apoplexy, Sheehan's syndrome, carotid artery aneurysms) - immunological (hypophysitis, antibodies) - neoplastic (pituitary tumours, brain tumours, lymphoma, metastases) - trauma (skull fracture, surgery, perinatal) - infiltrative (sarcoidosis, Langerhans', hereditary haemochromatosis) - miscellaneous (radiation, fibrosis, chemo, empty sella, anorexia) - genetic (PROP1 and POU1F1 mutations prevent differentiation of anterior pituitary cells)

Answer 326

- secondary hypothyroidism and adrenal failure both lead to tiredness and general malaise - hypothyroidism causes weight gain, slowness of thought and action, dry skin and cold intolerance - hypoadrenalism causes mild hypotension, hyponatraemia and ultimately cardiovascular collapse during severe intercurrent stressful illness - gonadotrophin leads to loss of libido, loss of secondary sexual hair, amenorrhoea and erectile dysfunction - hyperprolactinaemia may cause galactorrhoea and hypogonadism - weight may increase or decrease - longstanding panhypopituitarism gives the classic picture of pallor with hairlessness

Answer 327

- Kallman's syndrome - septo-optic dysplasia - Sheehan's syndrome - pituitary apoplexy - empty sella syndrome

Answer 328

- isolated gonadotrophin deficiency - arises due to mutations in the KAL1 gene located on the short arm of the X chromosome - characterised by anosmia, which has a role in development of the olfactory system and migration of GnRH secreting neurones

Answer 329

- rare congenital syndrome - associated with mutations in the HESX1 gene - presents in childhood with a clinical triad of midline forebrain abnormalities, optic nerve hypoplasia and hypopituitarism

Answer 330

- due to pituitary infarction following postpartum haemorrhage - rare in developed countries

Answer 331

- pituitary tumour enlarged rapidly due to infarction or haemorrhage - severe headache, double vision and sudden severe visual loss, sometimes followed by acute life-threatening hypopituitarism - can be managed with hormone replacement and close monitoring of vision

Answer 332

- empty sella is sometimes reported on pituitary imaging - may be due to a defect in the diaphragma and extension of the subarachnoid space (cisternal herniation) or may follow spontaneous infarction or regression of a pituitary tumour - all or most of the sella turcica is devoid of apparent pituitary tissue - pituitary function is usually normal

Answer 333

pituitary hormones: LH and FSH end-organ product/function: oestradiol, progesterone (day 21 of cycle) other tests: ovarian ultrasound, LHRH test

Answer 334

pituitary hormone: LH, FSH end-organ product/function: testosterone other tests: sperm count, LHRH test

Answer 335

pituitary hormone: GH end-organ product/functionL IGF-1, IGF-BP3 common dynamic tests: insulin tolerance test, glucagon test other tests: GH response to sleep, exercise or arginine infusion, GHRH test

Answer 336

pituitary hormone: prolactin | end-organ product/function: prolactin

Answer 337

pituitary hormone: TSH end-organ product/function: free T4, T3 other tests: TRH test

Answer 338

pituitary/hormone: ACTH end-organ product/function: cortisol common dynamic tests: insulin tolerance tests, short ACTH (tetracosactide) stimulation test other tests: glucagon test, CRH test, metyrapone test

Answer 339

end-organ product/function: plasma/urine osmolality common dynamic tests: water deprivation test other tests: hypertonic saline infusion

Answer 340

- exclude cardiovascular disease (ECG), epilepsy or unexplained blackouts; exclude severe untreated hypopituitarism - IV hydrocortisone and glucose available for emergency - overnight fast, begin at 8/9 - soluble insulin, 0.15 U/kg, IV at time 0 - glucose, cortisol and GH levels at 0, 30, 45, 60, 90, 120 min

Answer 341

- cortisol rises above 550 nmol/L - GH rises above 7 ng/L (severe deficiency = <3 ng/L) - glucose must be <2.2 mmol/L to achieve adequate stress response

Answer 342

- hydrocotisone 15-40 mg daily (starting dose 10mg on rising/5mg lunchtime/5mg evening) - normally no need for mineralocorticoid replacement

Answer 343

levothyroxine 100-150 um daily

Answer 344

male: testosterone IM, orally, transdermally or implant female: cyclical oestrogen/proestrogen orally or as patch fertility: HCG plus FSH (purified or recombinant) or pulsatile GnRH to produce testicular development, spermatogenesis or ovulation - prevents long term problems related to deficiency (e.g. osteoporosis)

Answer 345

- recombinant human GH used routinely to achieve normal growth in children - also advocated for replacement therapy in adults where GH has effects on muscle mass and wellbeing

Answer 346

- desmopressin 10-20 um one to three times daily by nasal spray or orally 100-200 um three times daily - carbamazepine, thiazides and chlorproamide are sometimes used in mild diabetes insipidus

Answer 347

dopamine agonist (e.g. cabergoline, 500um)

Answer 348

- growth hormone stimulates skeletal and soft tissue growth - excess produces gigantism in children and acromedaly in adults - due to a GH secreting pituitary tumour (somatotroph adenoma) - hyperplasia due to ectopic GHRH excess is very rare

Answer 349

- 3-4 million per year | - 50-80 million world wide

Answer 350

- change in appearance - increased size of hands/feet - headaches - excessive sweating - visual detioration - tiredness - weight gain - amenorrhoea or oligomenorrhoea - galactorrhoea - impotence or poor libido - deep voice - goitre - breathlessness - pain/tingling in hand - polyuria/polydipsia - muscular weakness - joint pains - arthralgias - hypogonadal symptoms

Answer 351

- prominent supraorbital ridge - prognathism - interdental separation - large tongue - hirsutism - thick greasy skin - spade-like hands and feet - tight rings - carpal tunnel syndrome - colonic polyps - visual field defects - galactorrhoea - hypertension - oedema - heart failure - arthropathy - proximal myopathy - glycosuria - arthralgias - maxillofacial changes - acral englargement

Answer 352

- GH levels (normal levels <0.5ug/L) - glucose tolerance test (acromegalics fail to suppress GH below 0.3 ug/L) - IGF-1 levels (almost always raised in acromegaly) - visual field examination - MRI scan (reveals pituitary adenoma) - pituitary function (partial or complete anterior hypopituitarism is common) - prolactin (mild to moderate hyperprolactinaemia in 30% of patients; adenoma may secrete both GH and prolactin)

Answer 353

- heart failure - coronary artery disease - hypertension-related causes - neoplasia (esp. large bowel tumours)

Answer 354

- to achieve a mean growth hormone level below 2.5 ug/L - normal IGF1 - may be discordance between GH and IFG1 levels - hypopituitarism should be corrected when present - concurrent diabetes and hypertension should be treated conventionally

Answer 355

- surgery - pituitary radiotherapy - medical therapy (somatostatin receptor agonists, dopamine agonists, growth hormone antagonists)

Answer 356

trans-sphenoidal surgery is appropriate first-line therapy - results in remission in 60-90% of cases with pituitary microadenoma, and 50% for macroadenoma - high preop GH and IGF1 levels are poor prognostic markers of surgical care - surgical success rates are variable and dependent on experience transfrontal surgery rarely required except for massive macroadenomas - 10% recurrence rate

Answer 357

- external radiotherapy usually used after surgery fails to normal GH levels rather than as primary therapy - combined with medium-term treatment with somatostatin analogue, dopamine agonist or GH antagonist due to slow biochemical response to radiotherapy - stereotactic radiotherapy sometimes used

Answer 358

three receptor targets - pituitary somatostatin receptors - dopamine (D2) receptors - growth hormone receptors in the periphery

Answer 359

- octretide and lanreotide are synthetic analogues of somatostatin that selectively act on receptor subtypes SST2 and SST5 - receptor subtypes are highly expressed in GH-secreting tumours - reduce GH and IGF levels in most patients

Answer 360

- administered as monthly depot injections - generally well tolerated - increased incidence of gallstones - expensive

Answer 361

- act on D2 receptors - given to shrink tumours prior to therapy or to control symptoms and persisting GH secretion - most effective in mixed GH producing (somatotroph) and prolactin producing (mammotroph) tumours

Answer 362

- bromocriptine 10-60 mg daily - cabergoline 0.5 mg daily - given alone they reduce GH to safe levels in a minority of cases - useful for mild residual disease or in combination with somatostatin analogues

Answer 363

- pegvisomant is a genetically modified analogue of GH - GH receptor antagonist which binds to and prevents dimerisation of the GH receptor - does not lower GH levels or reduce tumour size - does normalise IGF1 levels in 90% of patients

Answer 364

- given by daily injection - main role is treatment of patients in whom GH and IGF levels cannot be reduced to safe levels with somatostatin analogues alone, surgery or radiotherapy

Answer 365

- prolactin is mainly controlled by tonic inhibition by hypothalamic dopamine - prolactin stimulates lactation and inhibits hypothalamic GnRH secretion and gonadal actions of LH

Answer 366

- large peptide secreted in the pituitary - acts via a transmembrane receptor stimulating JAK2 and other pathways - stimulates milk secretion but not breast tissue development - inhibits gonadal activity - decreases GnRH pulsatility at the hypothalamic level - blocks the action of LH on the ovary or testis, producing hypogonadism even when the pituitary gonadal axis itself is intact

Answer 367

- tonic dopamine inhibition | - factors, e.g. TRH that increase prolactin secretion, are probably of less relevance

Answer 368

- pregnancy - lactation - severe stress - sleep - coitus

Answer 369

400-600 mU/L

Answer 370

above 5000 mU/L

Answer 371

- prolactinoma - co secretion of prolactin in tumours causing acromegaly - stalk compression due to pituitary adenomas and other pituitary masses - PCOS - primary hypothyroidism - idiopathic hyperprolactinaemia - rarer causes: oestrogen therapy, renal failure, liver failure, post-ictal state, chest wall injury - dopamine agonist drugs - other antiemetics and opiates

Answer 372

stimulates milk production in breast and inhibits GnRH and gonadotropin secretion - galactorrhoea, spontaneous or expressible (60% of cases) - oligomenorrhoea or amenorrhoea - decreased libido - decreased potency in men - subfertility - oestrogen/androgen deficiency - delayed or arrested puberty - mild gynaecomastia in men - headaches and visual field defects if pituitary tumour present - infertility

Answer 373

- confirmed by repeated measurement | - if no clinical features, macroprolactinaemia should be considered

Answer 374

- higher molecular weight complex of prolactin bound to IgG - physiologically inactive but occurs in small proportion of normal people - can lead to unneccessary treatment

Answer 375

in laboratory by precipitation of IgG with polyethylene glycol, after which prolactin levels will be normal on testing

Answer 376

- visual fields should be checked - primary hypothyroidism must be excluded as this can cause it - anterior pituitary function should be assessed if any evidence of hypopituitarism or radiological evidence of a pituitary tumour - MRI of the pituitary if any clinical features, or when prolactin is above 1000 mU/L

Answer 377

prolactin helps determine whether the mass is a prolactinoma or a non-functioning pituitary tumour causing stalk-disconnection hyperprolactinaemia - above 5000 mU/L in presence of macroadenoma - above 2000 mU/L in presence of a microadenoma

Answer 378

a pituitary tumour above 10mm diameter

Answer 379

smaller pituitary tumours (less than 10mm diameter)

Answer 380

very large prolactinomas can be associated with such high serum prolactin levels that some assays give an artefactual falsely low results - can be excluded by serial dilutions of the serum sample

Answer 381

usually treated to avoid the long-term effects of oestrogen or testosterone deficiency exceptions: minor elevations (400-1000 mU/L) with preservation of normal menstruation and post menopausal people with microprolactinomas who are not taking oestrogen replacement

Answer 382

dopamine agonist - cabergoline - bromocriptine - quinagolide

Answer 383

- 500ug once or twice a week judged on clinical response and prolactin levels - best tolerated and longest-acting drug and is the first drug of choice

Answer 384

- longest established therapy - preferred if pregnancy is planned - initial dose should be small (1mg), taken with food and increased to 2.5mg two or three times daily - side effects include nausea and vomiting, dizziness and syncope, constipation and cold peripheries

Answer 385

75-150ug once daily

Answer 386

- may restore normoprolactinaemia in people with microadenoma - rarely completely successful with macroadenomas and risks damage to normal pituitary function - prolactin should be measured before surgery on any mass in the pituitary region

Answer 387

- usually controls adenoma growth - slowly effective in lowering prolactin - causes progressive hypopituitarism - may be used after medical tumour shrinkage or after surgery in larger tumours

Answer 388

hypothalamus releases TRH -> pituitary releases TSH which acts on the thyroid -> thyroid releases T4 and T3 which has negative feedback on the hypothalamus and pituitary

Answer 389

- GnRH released from the hypothalamus - GnRH travels down anterior pituitary via the hypophyseal portal system and binds to receptors on adenohypophysis -> LH and FSH produced - FSH has positive effect on Sertoli cells/ovaries; Sertoli cell produces inhibin which has negative feedback on FSH - LH stimulates Leydig cell, which produces testosterone, which negatively affects GnRH

Answer 390

- hypothalamus releases CRH - CRH stimulates anterior pituitary to produce ACTH - ACTH stimulates the adrenal cortex to produce cortisol - cortisol has negative feedback effect on the anterior pituitary and hypothalamus

Answer 391

- hypothalamus releases GHRH and somatostatin - GHRH positively stimulates the pituitary to produce GH - somatostatin negatively inhibits the pituitary from producing GH - GH causes the liver to release IGF-1 - IGF-1 has an inhibitory effect on the hypothalamus

Answer 392

inhibitory

Answer 393

- GHRH and somatostatin (growth hormone) - GnRH (LH and FSH) - CRH (ACTH) - TRH (TSH) - dopamine (prolactin

Answer 394

- benign pituitary adenoma - craniopharyngioma - trauma - apoplexy/Sheehans - sarcoid/TB

Answer 395

pressure on local structure e.g. optic nerves - bitemporal hemianopia pressure on normal pituitary - hypopituitarism functioning tumour - prolactinoma - acromegaly - Cushing's disease

Answer 396

prolactinomas, acromegaly and Cushing's disease

Answer 397

headaches - stretching of dura by tumour - hydrocephalus (rare) visual field defects - nasal retinal fibres compressed by tumour visual

Answer 398

cranial nerve palsies and temporal lobe epilepsy | - lateral extension of tumour

Answer 399

CSF rhinorrhoea | - downward extension of tumour

Answer 400

pale, no body hair, central obesity

Answer 401

chronic, excessive and inappropriate elevated levels of circulating plasma glucocorticoids (cortisol)

Answer 402

- ACTH produced by pituitary, pituitary tumour, ectopic tumour or synthetic ACTH stimulates the adrenal gland to secrete cortisol - cortisol is produced by the stimulated adrenal gland and an adrenal tumour - cortisol has a negative feedback on the pituitary and the hypothalamus (CRH) - exogenous steroid has a negative feedback on the pituitary and hypothalamus (CRH)

Answer 403

negative feedback effect on the pituitary gland and the hypothalamus (CRH)

Answer 404

- increased ACTH production (Cushing's disease) - ectopic ACTH secretion - primary adrenal disease

Answer 405

- Cushing's disease (pituitary-dependent) - ectopic ACTH syndrome/producing tumours - unknown source of ACTH - ACTH administration

Answer 406

- adrenal adenoma - adrenal carcinoma - macronodular hyperplasia (AIMAH) - primary pigmented nodular adrenal disease (PPNAD) - McCune Albright syndrome - glucocorticoid administration - alcohol-induced pseudo-Cushing's syndrome

Answer 407

- moon face - hirsutism - facial plethora - acne - thinned scalp hair

Answer 408

- carbohydrate metabolism (IGT, diabetes) - electrolyte disturbance (sodium retention, hypertension, hypokalaemia) - immune suppression (susceptibility to infection) - central effects (malaise, depression, psychoses) - suppressed gonadal function (oligo/amenorrhoea, impotence, loss of libido) - obesity - facial plethora - rounded face - thin skin - decreased linear growth - hirsutism - easy bruising - weakness - osteopaenia - nephrolithiasis - pigmentation (only with ACTH-dependent causes) - cushingoid appearance

Answer 409

those associated with protein wasting - thin skin - decreased linear growth - easy bruising - weakness

Answer 410

1. confirmation | 2. differential diagnosis of the cause; investigation of cause, in major referral centre

Answer 411

- 24-hour urinary free cortisol measurements - 48-hour low dose dexamethasone suppression tests - circadian rhythm; late night/midnight serum or salivary cortisol no single test is perfect repeated tests may be needed to avoid missing mild or periodic/cyclical disease

Answer 412

- elevated urinary free cortisol (three 24 hour collections) - serum cortisol >50nM (1.8ug/dl) on dexamethasone-suppression testing - plasma midnight cortisol; sleeping >50nM (1.8ug/dl); awake > 207nmol/l (7.5ug/dl) - elevated late night salivary cortisol - circadian rhythm: high midnight cortisol levels >100 nmol/L; 0900 values may be normal

Answer 413

measure plasma ACTH | - <5pg/ml on more than 2 occasions

Answer 414

measure plasma ACTH | - >15pg/ml

Answer 415

adrenal imaging with CT - > adrenal lesion - > no adrenal lesion adrenal lesion - adenoma - carcinoma - AIMAH no adrenal lesion - PPNAD - exogenous glucocorticoid

Answer 416

pituitary MRI and CRH test: - adenoma >6mm AND - positive CRH response AND - suppression on dexamethasone small or no adenoma on MRI and CRH test/inconclusive -> BIPSS positive ACTH gradient or all three of above -> Cushing's disease no ACTH gradient -> CT/MRI thorax and abdomen; somatostatin scintigraphy -> ectopic ACTH?

Answer 417

adrenal blockage | - preparation for surgery, not usually a long-term solution

Answer 418

Cushing's syndrome - transsphenoidal surgery - bilateral adrenalectomy; risk of Nelson's ectopic - remove source adrenal adenoma/carcinoma - adrenalectomy PPNAD - adrenalectomy AIMAH - adrenalectomy/block aberrant receptors

Answer 419

Cushing's disease | - adjuvant (primary) therapy

Answer 420

- incidence of 3.3 per million - prevalence of 58 per million - mean age at diagnosis is 44 years - mean duration of symptoms is 8 years

Answer 421

- hypertension and heart disease - sleep apnea - insulin-resistant diabetes - arthritis - cerebrovascular events and headache

Answer 422

life expectancy decreased by average of 10 years - lowest decrease in all acromegaly - medium decrease in acromegaly and diabetes - highest decrease in acromegaly and cardiac disease

Answer 423

excluded if: random GH <0.4 ng/ml and normal IGF-1 if either abnormal proceed to: 75gm glucose tolerance test acromegaly excluded if: IGF1 normal and GTT nadir GH <1ng/ml

Answer 424

- restoration of basal GH and IGF1 to normal levels - relief of symptoms - reversal of visual and soft tissue changes - prevention of further skeletal deformity - normalisation of pituitary function

Answer 425

microadenoma <1cm; surgical cure rate ~90% macroadenoma >1cm; surgical cure rate <50% determinants - size of tumour - the surgeon

Answer 426

- anaesthetic complications - carotid artery injury - CNS injury - haemorrhage - loss of vision - opthalmoplegia - meningitis - nasal septum perforation - post op epistaxis/sinusitis - hypopituitarism - DI - death

Answer 427

- conventional (multi-fractional) - sterotactic (single fraction; less radiation to surrounding tissues; proton beam) - gamma knife - LINAC - proton beam

Answer 428

- GH level | - tumour extension

Answer 429

- delayed response - hypopituitarism - rare secondary tumours - rare visual defects

Answer 430

- control GH - control IGF1 - improve well being

Answer 431

advantages - no hypopituitarism - oral administration - rapid onset disadvantages - relatively ineffective - side effects

Answer 432

- human somatostatins - ocreotide - lanreotide

Answer 433

- amino acids essential for receptor binding - inhibit multitude of hormones - half life of 3 minutes - rebound - binds all 5 receptor subtypes

Answer 434

- more specific - half life of 100 minutes - no rebound

Answer 435

- control GH - control IGF1 - clinical improvement

Answer 436

- IGF1 controlled 65% - GH controlled 60% - tumour shrinkage

Answer 437

- GH level - tumour size - SMS receptor expression

Answer 438

- injectable | - side effects

Answer 439

- GH analogue - 191 amino acids - 9 amino acid substitutions - 4-5 PEG moieties - molecular weight 42-46000 D - half life >70 hours - subcutaneous administration - > serum GH cannot be used as a disease marker - > cross-reacts in GH assays

Answer 440

- incidence 10 per 100000 - women > men - prevalence 90 per 100000

Answer 441

benign lactrotroph cell tumour (adenoma) of the pituitary gland that produces prolactin

Answer 442

- headache - visual field defect (bitemporal hemianopia) - CSF leak (rare)

Answer 443

- weight gain (central) - change of appearance - depression - insomnia - amenorrhoea/oligomenorrhoea - poor libido - thin skin/easy bruising - hair growth/acne - muscular weakness - growth arrest in children - back pain - polyuria/polydipsia - psychosis old photos may be useful

Answer 444

- moon face - plethora - depression/psychosis - acne - hirsutism - frontal balding (female) - thin skin - bruising - poor wound healing - pigmentation - skin infections - hypertension - osteoporosis - pathological features (esp. vertebrae and ribs) - kyphosis - buffalo hump (dorsal fat pad) - central obesity - striae (purple or red) - rib fractures - oedema - proximal myopathy - proximal muscle wasting - glycosuria

Answer 445

increased circulating ACTH from the pituitary | - causes 65% of cases of Cushing's syndrome

Answer 446

ectopic, non-pituitary ACTH producing tumour elsewhere in the body - causes 10% of Cushing's syndrome cases - causes consequent glucocorticoid excess

Answer 447

primary excess of endogenous cortisol secretion (25% of cases) by an adrenal tumour or nodular hyperplasia - subsequent physiological suppression of ACTH - rare cases are due to aberrant expression of receptors for other hormones in adrenal cortical cells

Answer 448

insulin stress test, desmopressin stimulation test and CRH test

Answer 449

- plasma ACTH levels (low or undetectable ACTH levels, <10ng/L, on two or more occasions indicates non-ACTH-dependent disease) - adrenal CT or MRI scan - pituitary MRI - plasma potassium levels (hypokalaemia is common with ectopic ACTH secretion) - high-dose dexamethasone test - CRH test - chest xray

Answer 450

hypertension, MI, infection, heart failure

Answer 451

successful treatment with a normal biochemical profile should lead to reversal of clinical features - cortisol hypersecretion should be controlled before surgery or radiotherapy - metyrapone (11beta-hydroxylase blocker), given in doses of 750mg to 4g daily in 3-4 divided doses - ketoconazole given 200mg TDS - plasma cortisol should be reduced during the day to 150-300nmol/L - aminoglutethimide and trilostane (reversibly inhibits 3-hydroxysteroid dehydrogenase/5-5,4 isomers) are sometimes used

Answer 452

pituitary-dependent hyperadrenalism - transphenoidial removal of the tumour (remission in 75-80% of cases) - external pituitary irradiation (slow acting, 50-60% effective, stereotactic radiotherapy may be useful) - medical therapy (e.g. bromocriptine, cabergoline, cyproheptadine, STS analogues are rarely effective) - bilateral adrenalectomy (effective last resort; can be performed laparoscopically)

Answer 453

- should be resected after achievement of clinical remission with metyrapone or ketoconazole - contralaeral adrenal suppression may last for a year or more

Answer 454

- highly aggressive with a poor prognosis - if no widespread metastases, tumour bulk should be reduced surgically - mitotane (adrenolytic drug) may inhibit growth of tumour and prolong survival, though it can cause nausea and ataxia

Answer 455

- should be removed if possible | - chemotherapy/radiotherapy may be used

Answer 456

increased pigmentation (because of high levels of ACTH) associated with an enlarging pituitary tumour - occurs in 20% of cases after bilateral adrenalectomy for Cushing's disease - rare now that adrenalectomy is an uncommon primary treatment - incidence may be reduced by pituitary radiotherapy soon after adrenalectomy - may be treated by pituitary surgery/radiotherapy

Answer 457

- may rarely secrete TSH (and cause thyrotoxicosis); TSHomas - > leads to the unusual biochemical pattern of elevated fT4 levels with normal or high circulating TSH levels - FSH and LH secreting pituitary tumours may cause elevated sex steroids; extremely rare

Answer 458

overnight: take 1mg when going to bed at 2300hrs - measure: plasma cortisol at 0900hrs next morning - normal test result/positive suppression: plasma cortisol <100nmol/L - use and explanation: outpatient screening test; some false positives

Answer 459

- test and protocol: 0.5mg 6-hourly; 8 doses from 0900 on day 0 - measure: plasma cortisol at 0900hrs on days 0 and +2 - normal test result/positive suppression: plasma cortisol <50nmol/L on second sample - use and explanation: for diagnosis of Cushing's

Answer 460

- test and protocol: 2mg 6-hourly; 8 doses from 0900hrs on day 0 - measure: plasma cortisol at 0900hrs on days 0 and +2 - normal test result/positive suppression: plasma cortisol on day +2 less than 50% of that on day 0 suggests pituitary-dependent disease - use and explanation: differential diagnosis

Answer 461

- two lateral lobes connected by an isthmus - closely attached to the thyroid cartilage and the upper end of the trachea - embryologically, it originates from the base of the tongue and descends to the middle of the neck - rich blood supply from superior and inferior thyroid arteries

Answer 462

- follicles lined by cuboidal epithelial cells - inside the follicles is colloid (iodinated glycoprotein thyroglobulin) which is synthesised by follicular cells - each follicle is surrounded by basement membrane - parafollicular cells are between follicular cells - parafollicular cells contain calcitonin-secreting C cells

Answer 463

- is inside thyroid follicles - iodinated glycoprotein thyroglobulin - synthesised by follicular cells

Answer 464

calcitonin-secreting C cells

Answer 465

- triiodothyronin (T3) which acts at the cellular level | - L-thyroxine (T4) which is a prohormone

Answer 466

T3: triiodothyronin; acts at the cellular level T4: L-thyroxine; prohomone

Answer 467

inorganic iodide is trapped by the thyroid by an enzyme-dependent system, oxidised and incorporated into the glycoprotein thyroglobulin to from mono- and diiodotyrosine and then T4 and T3

Answer 468

- more T4 than T3 is produced - T4 is converted in some peripheral tissues (liver, kidney and muscles) to T3 by 5'-monodeiodination - alternative 3'-monodeiodination yields the inactive reverse T3 (rT3)

Answer 469

3'-monodeiodination | - occurs particularly in severe non-thyroidal illness

Answer 470

by 5'-monodeiodination | - T3 is more active

Answer 471

- in plasma, more than 99% of all T4 and T3 is bound to hormone binding proteins (thyroxine-binding globulin, TBG; thyroid-binding prealbumin, TBPA; albumin) - only free hormone can act in the target tissues - T3 binds to specific nuclear receptors

Answer 472

- thyrotropin releasing hormone (TRH) from the hypothalamus stimulates the pituitary to secrete TSH - TSH stimulates growth and activity of thyroid follicular cells via the G-protein coupled TSH membrane receptor - T3 and T4 exert negative feedback on the hypothalamus

Answer 473

binds to the thyroid hormone nuclear receptor (TR) on target organ cells to cause modified gene transcription - TRalpha and TRbeta - TRalpha knock out mice show poor growth, bradycardia and hypothermia - TR beta knock out mice show thyroid hyperplasia and high T4 levels in presence of inappropriately normal circulating TSH; thyroid hormone resistance?

Answer 474

- TRalpha knock out mice show poor growth, bradycardia and hypothermia - TR beta knock out mice show thyroid hyperplasia and high T4 levels in presence of inappropriately normal circulating TSH; thyroid hormone resistance?

Answer 475

- at least 140ug per day - supplementation of salt and bread has reduced number of areas where endemic goitre still occurs - dietary iodine deficiency is a major cause of thyroid disease, as it's an essential requirement for thyroid disease

Answer 476

CVS: increases heart rate and cardiac output bone: increases bone turnover and resorption respiratory system: maintains normal hypoxic and hypercapnic drive in respiratory centre GI system: increases gut motility blood: increases red blood cell 2,3-BPG, facilitating oxygen release to tissues neuromuscular function: increases speed of muscle contraction and relaxation and muscle protein turnover carbohydrate metabolism: increases hepatic gluconeogenesis/glycolysis and intestinal glucose absorption lipid metabolism: increases lipolysis and cholesterol synthesis and degradation SNS: increases catecholamine sensitivity and beta-adrenergic receptors in heart, skeletal muscle, adipose cells and lymphocytes; decreases cardiac alpha-adrenergic receptors

Answer 477

inorganic iodide

Answer 478

1. inorganic iodide is transferred from the blood into the follicular cell by Na+/I- symporter 2. iodide is transferred from the follicular cell to the colloid by the iodide transporter, pendrin 3. thyroperoxidase oxidises two I- to form I2 4. thyroperoxidase iodinates the tyrosyl residues of the thyroglobulin within the colloid 5. iodinated thyroglobulin binds megalin for endocytosis back into the cell 6. TSH binding stimulates endocytosis of the colloid 7. endocytosed vesicles fuse with lysosomes of follicular cell

Answer 479

by the Na+/I- symporter - transports two sodium ions across the BM with one iodide ion - secondary active transporter - utilises the concentration gradient of Na+ to move I- against its gradient

Answer 480

pendrin; an anion exchange protein

Answer 481

- thyroperoxidase oxidises two I- to form I2 - iodide is non-reactive - only the more reactive iodine is needed for the next step

Answer 482

- oxidises two I- to form I2 (iodine) | - iodinates tyrosyl residues of the thyroglobulin within the colloid (synthesised in the ER of the follicular cell)

Answer 483

binds megalin

Answer 484

- a 660kDa, dimeric protein produced by the follicular thyroid cells - accounts for half of the protein content of the thyroid gland - contains 100-120 tyrosine residues; <20 are iodinated by thyroperoxidase

Answer 485

- monoiodotyrosine is produced by tyrosine residues in thyroglobulin being iodinated on their phenol rings at one position ortho to the phenolic hydroxyl group by thyroperoxidase - DIT is produced by the same process above except at both positions ortho to the phenolic hydroxyl group

Answer 486

peptidic MIT + peptidic DIT | - catalysed by thyroperoxidase

Answer 487

2 peptidic DIT2 -> peptidic thyroxine | - catalysed by thyroperoxidase

Answer 488

peptidic DIT + peptidic MIT -> reverse peptidic triiodothyronine - catalysed by thyroperoxidase - paired in reverse order

Answer 489

- unknown mechanism | - may be monocarboxylate transporter (MCT) 8 and 10 play major roles

Answer 490

>99% protein bound | <1% free

Answer 491

- TSH measurements | - TRH test

Answer 492

- TSH levels can discriminate between hyperthyroidism, hypothyroidism and euthyroidism (normal thyroid gland function) - except hypopituitarism and the sick euthyroid syndrome where low levels occur with low or normal T4 and T3 levels - most sensitive - accurate diagnosis requires at least 2 tests

Answer 493

- rendered almost obsolete by modern sensitive TSH assays except for investigation of hypothalamic-pituitary dysfunction - TRH (protirelin) may be used to differentiate between thyroid hormone resistance and TSHoma in context of fT4 and TSH levels - after TRH administration there is a rise in TSH in thyroid hormone resistance - in TSHoma there is a flat response due to continued autonomous TSH secretion which doesn't respond to TRH

Answer 494

normal values: 0.3-3.5mU/L - thyrotoxicosis: suppressed (<0.05mU/L) - primary hypothyroidism: increased (>10mU/L) - TSH deficiency: low-normal or subnormal - T3 toxicosis: suppressed (<0.05mU/L) - compensated euthyroidism: slightly increased (5-10mU/L)

Answer 495

normal values: 10-25pmol/L - thyrotoxicosis: increased - primary hypothyroidism: low/low-normal - TSH deficiency: low/low-normal - T3 toxicosis: normal - compensated euthyroidism: normal

Answer 496

normal levels 3.5-7.5pmol/L - thyrotoxicosis: increased - primary hypothyroidism: normal or low - TSH deficiency: normal or low - T3 toxicosis: increased - compensated euthyroidism: normal

Answer 497

- primary disease of thyroid - secondary (to hypothalamic-pituitary disease) - peripheral resistance to thyroid hormone

Answer 498

congenital - agenesis - ectopic thyroid remnants defects of hormone synthesis - iodine deficiency - dyshormonogenesis - antithyroid drugs - other drugs (e.g. lithium, amiodarone, interferon) autoimmune - atrophic thyroiditis - Hashimoto's thyroiditis - postpartum thyroiditis infective - post-subacute thyroiditis post surgery/irradiation - radioactive iodine therapy - external neck irradiation infiltration - tumour

Answer 499

- iodine deficiency - dyshormonogenesis - antithyroid drugs - other drugs (e.g. lithium, amiodarone, interferon)

Answer 500

- serious acute or chronic illness - pregnancy and oral contraceptives - drugs

Answer 501

- reduced concentration and affinity of binding proteins - decreased peripheral conversion of T4 to T3 with more rT3 - reduced hypothalamic-pituitary TSH production - systemically ill patients can have a low total and free T4 and T3 with a normal or low basal TSH (sick euthyroid syndrome) - levels are mildly below normal and may be mediated by interleukins IL-1 and IL-6

Answer 502

IL-1 and IL-6

Answer 503

- greatly increased TBG levels - thus high-normal total T4 - free T4 is usually normal - normal ranges for free T4 and TSH alter with normal physiological changes during pregnancy - TSH is often slightly suppressed in the first trimester

Answer 504

- amiodarone decreases T4 to T3 conversion and free T4 levels may be above normal in a euthyroid patient - amiodarone may induce both hyper- and hypothyroidism - many drugs affect thyroid function by interfering with protein binding

Answer 505

serum antibodies to the thyroid are common and may be either destructive or stimulating; they may co-exist in the same patient

Answer 506

- directed against the microsomes or against thyroglobulin - antigen for the thyroid microsomal antibodies is the thyroid peroxidase (TPO) enzyme - TPO antibodies are found in up to 20% of the normal population - only 10-20% of these develop overt hypothyroidism

Answer 507

thyroid peroxidase (TPO) enzyme

Answer 508

TSH receptor IgG antibodies (TRAb) typically stimulate, but may block, the receptor

Answer 509

- by inhibition of binding of TSH to its receptors (TSH-binding inhibitory immunoglobin, TBII) - by demonstrating that they stimulate the release of cAMP (thyroid-stimulating immunoglobulin/antibody TSI, TSAb)

Answer 510

- primary hypothyroidism is one of the most common endocrine conditions with an overall UK prevalence of over 2% in women, under 0.1% in men - lifetime prevalence for an individual is higher: 9% for women and 1% for men with a mean age at diagnosis of about 60 years - world prevalence of subclinical hypothyroidism varies from 1% to 10%

Answer 511

- atrophic (autoimmune) hypothyroidism - Hashimoto's thyroiditis - postpartum thyroiditis - focal thyroiditis and positive TPO and thyroglobulin antibodies - Graves' disease

Answer 512

- most common cause of hypothyroidism - associated with antithyroid autoantibodies leading to lymphoid infiltration of the gland and eventually atrophy and fibrosis - 6x more common in females; incidence increases with age - associated with other autoimmune disease, e.g. pernicious anaemia, vitiligo and other deficiencies

Answer 513

- more common in women and in late middle age - produces atrophic changes with regeneration, leading to goitre formation - gland is usually firm and rubbery but may range from soft to hard - TPO antibodies are present, often in high titres (>100IU/L_ - patients may be hypothyroid or euthyroid, and go through an initial toxic phase, Hashi-toxicity - levothyroxine therapy may shrink the goitre

Answer 514

- transient after pregnancy - may cause hyper/hypothyroidism or the two sequentially - results from modifications to immune system in pregnancy - histologically is a lymphocytic thyroiditis - self-limiting, but may proceed to permanent hypothyroidism - may be diagnosed as postnatal depression

Answer 515

- still exists in some areas as endemic goitre - iodine is required for thyroid hormone synthesis - patients may be euthyroid or hypothyroid depending on severity of deficiency - borderline hypothyroidism -> TSH stimulation and thyroid enlargement in the face of continuing iodine deficiency

Answer 516

Netherlands, Western Pacific, India, South East Asia, Russia and parts of Africa

Answer 517

providing iodine in salt

Answer 518

- rare - due to genetic defects in the synthesis of thyroid hormones - patients develop hypothyroidism with a goitre - a particular familial form is associated with sensorineural deafness due to a deletion mutation in chromosome 7, causing a defect in pendrin (Pendred's syndrome)

Answer 519

- genetic condition - associated with sensorineural deafness - deletion mutation in chromosome 7 - causes a defect in transporter pendrin, which has a role in thyroid hormone synthesis

Answer 520

- tiredness/malaise - weight gain - anorexia - cold intolerance - poor memory - change in appearance - depression - poor libido - goitre - puffy eyes - dry, brittle unmanageable hair - dry coarse skin - arthralgia - myalgia - muscle weakness/stiffness - constipation - menorrhagia or oligomenorrhoea - psychosis - coma - deafness

Answer 521

- mental slowness - psychosis/dementia - ataxia - poverty of movement - deafness - periorbital oedema - deep voice - peaches and cream complexion - dry thin hair - loss of eyebrows - dry skin - mild obesity - hypertension - hypothermia - heart failure - bradycardia - pericardial effusion - myotonia - muscular hypertrophy - proximal myopathy - slow-raising reflexes - cold peripheries - carpal tunnel syndrome - oedema - anaemia

Answer 522

accumulation of mucopolysaccharide in subcutaneous tissues; occurs in hypothyroidism

Answer 523

slow, dry-haired, thick-skinned, deep-voiced patient with weight gain, cold intolerance, bradycardia and constipation

Answer 524

- children with hypothyroidism may not show classic features but often have slow growth velocity, poor school performance and sometimes arrest of pubertal development - young women with hypothyroidism may not show obvious signs; should be excluded in oligomenorrhoea/amenorrhoea, menorrhagia, infertility or hyperprolactinaemia - the elderly show clinical features that are difficult to differentiate from normal ageing

Answer 525

- serum TSH - anaemia - increased serum aspartate transferase levels (from muscle/liver) - increased serum creatine kinase levels - hypercholesterolaemia and hypertrigliceridaemia - hyponatraemia due to increased ADH and impaired free water clearance

Answer 526

- high TSH confirms it | - low free T4 confirms hypothyroid state

Answer 527

levothyroxine (thyroxine/T4) - given for life - starting dose depends on severity of deficiency, age and fitness of patient - 100ug daily for young and fit - 50ug for small, old or frail

Answer 528

- low normal serum T4 levels and slightly raised TSH levels | - if after surgery or radioactive iodine therapy, it is compensatory

Answer 529

- treatment with levothyroxine when TSH is consistently above 10mU/L, or when symptoms, antibodies or lipid abnormalities are present - where TSH is only marginally raised, tests should be repeated 3-6 months later

Answer 530

- severe hypothyroidism may present with confusion/coma - hypothermia often present, cardiac failure, pericardial effusions, hypoventilation, hypoglycaemia and hyponatraemia - mortality was 50%

Answer 531

- T3 orally and IV in doses of 2.5-5ug every 8hrs - large IV doses shouldn't be used - oxygen - monitoring of CO and pressures - gradual rewarming - hydrocortisone 100mg IV 8hrly - glucose infusion to prevent hypoglycaemia

Answer 532

- depression is commmon in hypothyroidism - may become demented or psychotic, with delusions - may occur shortly after starting T4 replacement

Answer 533

- incidence is 1 in 3500 births - untreated it produces permanent neurological and intellectual damage (cretinism) - blood spot, as in the Guthrie test, detecting a high TSH level is efficient and cost-effective - cretinism prevented if T4 started within first few months

Answer 534

- low pick-up rate - controversial, not currently recommended - patients who have had thyroid surgery or received radioiodine should have regular tests, and those receiving lithium or amidarone therapy

Answer 535

- Graves' disease (autoimmune) - toxic multinodular goitre - solitary toxic nodule/adenoma

Answer 536

- acute thyroiditis (viral e.g. de Quervain's, autoimmune, post-irradiation, postpartum) - gestational thyrotoxicosis (HCG stimulated) - neonatal thyrotoxicosis (maternal thyroid antibodies) - exogenous iodine - drugs; amiodarone - thyrotoxicosis factitia (secret T4 consumption)

Answer 537

- TSH-secreting pituitary tumours - metastatic differentiated thyroid carcinoma - HCG producing tumours - hyperfunctioning ovarian teratoma (struma ovarii)

Answer 538

- most common cause - serum IgG antibodies bind to TSH receptors in the thyroid, stimulating thyroid hormone production - TSHR-Ab are specific for Graves'

Answer 539

- HLA-B8, DR3 and DR2 - 40% concordance rate in MZ twins and 5% DZ - weak association with cytotoxic T lymphocyte-associated antigen 4, HLA-DRB*08 and DRB3*0202 on chromosome 6

Answer 540

- Yersinia enterocolitica, E. coli and other Gram-negatives contain TSH binding sites - may be an infection in a genetically susceptible indivisuals

Answer 541

- thyroid eye disease - Graves' dermopathy is rare - lymphadenopathy and splenomegaly - other autoimmune disorders

Answer 542

- transient hyperthyroidism from an acute inflammatory process, probably viral in origin - toxicosis, fever, malaise, pain in neck, tachycardia and local thyroid tenderness - thyroid function test show initital hyperthyroidism, erythrocyte sedimentation rate and plasma viscosity are raised - thyroid uptake scans show suppression in acute phase - hypothyroidism may follow after few weeks - treatment of acute phase is aspirin, and short-term prednisolone in symptomatic cases

Answer 543

``` class III antiarrythmic drug - causes type I and type II AIT ```

Answer 544

- caused by amiodarone - associated with pre-existing Graves' disease or multinodular goitre - hyperthyroidism is probably triggered by high iodine content of amiodarone - may be higher T4;T3 ratios than usual - low iodine areas - iodine induced excess - thyroid hormone release - Jode-Basedow phenomenon

Answer 545

- not associated with previous thyroid disease - may be due to direct effect of drug on follicular cells leading to a destructive thyroiditis with release of T4 and T3 - may be associated with a hypothyroid phase months after presentation - amiodarone inhibits deiodination fo T4 to T3; may be higher T4;T3 ratios than usual - normal thyroid - destructive

Answer 546

infiltration of the skin on the shin

Answer 547

- rare | - clubbing, swollen fingers and periosteal new bone formation

Answer 548

- weight loss - increased appetite - irritability/behaviour change - restlessness - malaise - stiffness - muscle weakness - tremor - choreoathetosis - breathlessness - palpitation - heat intolerance - itching - thirst - vomiting - diarrhoea - eye complaints - goitre - oligomenorrhoea - loss of libido - gynaecomastia - onycholysis - tall stature - sweating

Answer 549

- tremor - hyperkinesis - psychosis - proximal myopathy - proximal muscle wasting - onchyolysis - palmar erythema - tachycardia or AF - full pulse - warm vasodilated peripheries - systolic hypertension - cardiac failure - exophthalmos - lid lag and stare - conjunctival oedema - opthalmoplegia - periorbital oedema - goitre, bruit - weight loss

Answer 550

primary hyperthyroidism - serum TSH suppressed (<0.05mU/L) - raised free T4 and T3 secondary hypothyroidism - raised free T4 and T3 - inappropriately high TSH - thyroid peroxidase and thyroglobulin, TRAb antibodies are present in Graves' - isotope uptake scan

Answer 551

- antithyroid drugs (course or long-term) - radioiodine 131I - surgery (partial, subtotal thyroidectomy)

Answer 552

- carbimazole and propylthiouracil (UK) - thiamazole/methimazole (USA) - inhibit formation of thyroid hormones and suppress immune function - decrease synthesis of new thyroid hormone - PTU inhibits conversion T4 -> T3 - do not treat underlying cause of hyperthyroidism but immune modifying effects are seen (decrease IL-6) and reduction in antibody titres

Answer 553

- 20-40mg daily, 8hrly or single dose - rash, nausea, vomiting, arthralgia, agranulocytosis, jaundice - active metabolite is thiamazole (methimazole) - mild immunosuppressive activity

Answer 554

- 100-200mg, 8hrly - rash, nausea, vomiting, agranulocytosis - blocks conversion of T4 to T3

Answer 555

- 40-80mg every 6-8hrs - avoid in asthma - use agents without intrinsic sympathomimetic activity as receptors highly sensitive

Answer 556

1. start carbimazole 2-40mg daily 2. review after 4-6 weeks and reduce dose of carbimazole, depending on clinical state and fT4/fT3 levels. TSH levels may be suppressed for months 3. when clinically and biochemically euthyroid, stop beta-blockers 4. review thyroid function regularly during treatment course 5. reduce carbimaozle if fT4 falls below or TSH rises above normal 6. increase carbimazole if fT4 or fT3 are above normal 7. stop treatment at end of course if patient is euthyroid on 5mg daily carbimazole

Answer 557

- full doses of antithyroid drugs are given to suppress thyroid completely - thyroid activity is replaced with 100ug of levothyroxine daily once euthyroid - continued for 18 months - avoids over- or undertreatment - contraindicated in pregnancy

Answer 558

- iodine given in empirical dose (200-550MBq) due to variable uptake and radiosensitivity of the gland - accumulates in the gland and destroys it by local radiation - takes months - should be euthyroid before - stop drugs 4 days before, not recommence until 3 days after - long term surveillance - eye problems and neck pain

Answer 559

- only in patients who have previously been euthyroid - stop drug 10-14 days before - give potassium iodide 60mg TDS to reduce vascularity of the gland - experienced surgeons

Answer 560

- early postop bleeding causing tracheal compression and asphyxia - laryngeal nerve palsy (1%) - transient hypocalcaemia (10%) - reduced thyroid function

Answer 561

- rare - mortality 10% - rapid deterioration of hyperthyroidism - hyperpyrexia, severe tachycardia, extreme restlessness, cardiac failure, liver dysfunction - precipitated by stress, infection, surgery in unprepared patient, radioiodine therapy

Answer 562

- propranolol in full doses - potassium iodide - antithyroid drugs - corticosteroids - supportive measures - control of cardiac failure and tachycardia

Answer 563

- patient choice - persistent drug side effects - poor compliance with drug therapy - recurrent hyperthyroidism after drugs

Answer 564

large goitre, unlikely to remit after antithyroid drugs

Answer 565

a swelling of the neck resulting from enlargement of the thyroid gland

Answer 566

- high level of HCG is a weak stimulator of the TSH receptor | - causes suppressed TSH with elevated fT4/fT3 in first trimester, associated with hyperemesis gravidarum

Answer 567

- TSI crosses placenta to stimulate fetal thyroid - carbimazole and PTU cross placenta - T4 crosses poorly - smallest does of PTU is used - fetal heart rate above 16/minute suggest hyperthyroidism

Answer 568

- inherited condition caused by an abnormality of the thyroid hormone receptor - mutations to TRbeta lead to higher levels being needed - normal feedback control mechanisms lead to high levels of T4 with normal TSH to maintain euthyroid state

Answer 569

1. tests appear abnormal even when euthyroid and not needing treatment 2. different tissues contain different receptors, thus different levels of hormones to maintain euthyroidism may be needed in different places

Answer 570

- due to specific immune response causing retro-orbital inflammation - swelling and oedema of extraocular muscles leads to limited movement and proptosis - increased pressure on optic nerve may cause optic atrophy - histology shows focal oedema and GAG deposition, then fibrosis - TSH receptor antibodies are seen in the serum - more common and severe in smokers

Answer 571

1. thyrotrophin receptor internalised and degraded by APC that present thyrotophin-receptor peptides, in association with MHCII, to T helper cells 2. helper cells become activated, interact with autoreactive B cells through CD154-CD40 bridges, and secrete IL-1 and INF-gamma 3. these cytokines induce differentiation of B cells into plasma cells that secrete anti-thyrotrophin-receptor antibodies 4. antibodies recognise thyrotrophin receptor on orbital fibroblasts and initiate tissue changes, with IFN-gamma and TNF 5. antibodies stimulate thyrotrophin receptor on thyroid follicular cells, leading to hyperplasia and increased production of T3 and T4

Answer 572

APC that present thyrotropin-receptor peptides, in association with MHCII antigens, to helper T cells

Answer 573

- become activated - interact with autoreactive B cells through CD154-CD40 bridges - secrete IL-2 and IFN-gamma

Answer 574

- induce the differentiation of B cells into plasma cells | - plasma cells secrete anti-thyrotrophin-receptor antibodies

Answer 575

- anti-thyrotrophin-receptor antibodies recognise the thyrotrophin receptor on orbital fibroblasts - these antibodies, with the secreted type 1 helper T cytokines IFN-gamma and TNF, initiate tissue changes - stimulate thyrotropin receptor on thyroid follicular epithelial cells, leading to hyperplasia and increased production of T3 and T4

Answer 576

- high proportion of people with Graves' disease notice soreness, painful watering or prominence of the eyes - more severe proptosis occurs in some cases - limitation, discomfort of eye movement and visual impairment due to optic nerve compression are uncommen - corneal damage may occur - periorbital oedema and conjunctival oedema and inflammation

Answer 577

- stopping smoking - treatment may be local or systemic, and always requires liason between specialist endocrinologist and ophthalmologists - methylcellulose or hypromellose eyedrops (aid lubrication and improve comfort) - sleeping upright - eyelids taped to ensure closure at night - systemic steroids (prednisolone 30-120mg daily; reduce inflammation) - surgical decompression of the orbit - lid surgery (protects cornea if lids cannot be closed) - corrective eye muscle surgery - irradiation of the orbits (20Gy in divided doses; improves inflammation and ocular motility but not proptosis) - immunomodulatory agents

Answer 578

- 9% of population - noticed as cosmetic defect by family/friends - painless - pain and discomfort in acute varieties - large goitres can produce dysphagia and difficulty in breathing; oesophageal or tracheal compression - puberty/pregnancy may cause diffuse increase in size

Answer 579

- size, shape, consistency and mobility of gland - if the lower margin can be demarcated (implying absence of retrosternal extension) - bruit may be present - associated lymph nodes should be found - tracheal position determined - medications/exposure to radiation

Answer 580

thyroiditis, bleeding into a cyst, thyroid tumour

Answer 581

- physiological (puberty, pregnancy) - Graves' disease - Hashimoto's disease - acute thyroiditis (de Quervain's) - iodine deficiency (endemic goitre) - dyshormonogenesis - goitrogens (e.g. sulfonylureas)

Answer 582

- multinodular goitre - solitary nodular - fibrotic (Reidal's thyroiditis) - cysts

Answer 583

- adenomas - carcinomas - lymphomas

Answer 584

- sarcoidosis | - tuberculosis

Answer 585

- simple - autoimmune - thyroiditis - iodine deficiency - dyshormonogenesis - goitrogens

Answer 586

- smooth and soft - no clear cause found for enlargement - associated with thyroid growth-stimulating antibodies

Answer 587

- firm diffuse goitre of variable size - bruit often present in thyrotoxicosis - Hashimoto's thyroiditis and thyrotoxicosis

Answer 588

- acute tenderness in diffuse swelling, with severe pain | - may produce transient clinical hyperthyroidism with an increase in serum T4

Answer 589

- most common - patient usually euthyroid but may be hyperthyroid or borderline with suppressed TSH levels but normal free T4 and T3 - most common cause of tracheal/oesophageal compression and can cause laryngeal nerve palsy - readily apparent clinically - small nodules in glands which are clinically diffusely enlarged and associated with autoimmune thyroid disease

Answer 590

- difficult problem of diagnosis - malignancy should be concern - often cystic or benign - challenge is to identify small minority of malignant nodules, which require surgery, from the majority of benign nodules - history of rapid enlargement, associated lymph nodes or pain may suggest aggressive malignancy - risk factors for malignancy are previous irradiation, iodine deficiency and familial cases

Answer 591

- rare - woody gland - associated with other midline fibrosis - hard to distinguish from carcinoma, being irregular and hard - systemic symptoms of inflammation and elevation in inflammatory markers - IgG4 related disease

Answer 592

- possibility of malignancy - pressure symptoms on trachea or oesophagus - cosmetic reasons

Answer 593

- papillary (70%) - follicular (20%) - anaplasic (<5%) - lymphoma (2%) - medullary cell (5%)

Answer 594

- young people - local, sometimes lung/bone secondaries - good prognosis, esp. in young

Answer 595

- most common in women - metastases to lung/bone - good prognosis if resectible

Answer 596

- aggressive - locally invasive - very poor prognosis

Answer 597

- variable behaviour | - sometimes responsive to radiotherapy

Answer 598

- often familial - local and metastases - poor prognosis, but indolent course

Answer 599

neuroendocrine tumour of the calcitonin-producing C cells of the thyroid - prophylactic thyroidectomy - total thyroidectomy and wide lymph node clearance - local invasion/metastasis is frequent - responds poorly to treatment

Answer 600

- often associated with multiple endocrine neoplasia type 2 - 25% have a mutation of the RET proto-oncogene - people with MEN2 mutations are advised to have a prophylactic thyroidectomy as early as 5 to prevent development of MTC

Answer 601

- first autoimmune diseases to be described - 2% of women will get Graves' disease or autoimmune hypothyroidism (5-10 times the frequency in men) - 5% will have postpartum thyroiditis and up to 20% have positive thyroid antibodies - associated with other serious autoimmune disorders

Answer 602

- thyroglobulin and thyroid peroxidase (TPO) antibodies found in almost all patients with autoimmune hypothyroidism - present in 75% of Graves' patients - low levels present in healthy individuals at risk of thyroid or other autoimmune disease

Answer 603

- cytotoxic (CD8+) T cell mediated - thyroglobulin and TPO antibodies may cause secondary damage, but alone have no effect - uncommonly, antibodies against the TSH-receptor may block the effects of TSH

Answer 604

TSH receptor antibodies - originally called long acting thyroid stimulators (LATS) - now called thyroid stimulating antibodies - cause of Graves' disease - some TSH-R antibodies don't stimulate the receptor; may block the effects of TSH - these (rarely) can cause hypothyroidism

Answer 605

TSH receptor antibodies (thyroid stimulating antibodies)

Answer 606

stimulating TSAb (stimulating) -> hyperthyroidism (Graves' disease) blocking TSBAb (blocking) -> hypothyroidism (myxoedema)

Answer 607

- genetic and environmental factors in varying proportion - being female is a bigger risk factor, and onset of disease is common postpartum - HLA-DR3 and other immunoregulatory genes contribute (25% MZ concordant) - environmental factors including stress, high iodine intake, smoking

Answer 608

``` HLA target organ T cell response immunoglobin cytokine ```

Answer 609

diet, infection, drugs, toxins, stress

Answer 610

sex hormones, glucocorticoids, prolactin, birthweight, pregnancy

Answer 611

decreases in pregnancy and increases in the postpartum period (autoimmune thyroiditis and Graves' thyrotoxicosis)

Answer 612

- T1DM - Addison's disease - pernicious anaemia - vitiligo - alopecia areata - coeliac disease/dermatitis herpetiformis - chronic active hepatitis - rheumatoid arthritis/SLE/Sjorgren's syndrome - mysathenia gravis (Graves')

Answer 613

- present in most Graves' and some autoimmune hypothyroidism patients - swelling in extraocular muscles - most likely due to an autoantigen in the extraocular muscle that cross reacts with, or is identical to, a thyroid autoantigen - current favourite candidate is the TSH receptor

Answer 614

- TSH-R specific T cells bind to TSH-R cells on preadipocyte fibroblast - TSH-R stimulating antibody binds to TSH-R - leads to adipogenesis -> muscle swelling -> proptosis, peiorbital edema, diplopia, optic neuropathy

Answer 615

- cytokines (IFN-gamma, TNF, IL-1) act on preadipocyte fibroblast - preadipocyte fibroblast releases GAG -> water trapping -> edema and muscle swelling -> proptosis, peiorbital edema, diplopia, optic neuropathy

Answer 616

- commonest endocrine disorder - 8.6% prevalence thyroid enlargement - euthyroid - goitre: diffuse, multinodular, solitary nodule, dominant nodule - differentiate benign from malignant

Answer 617

1. overproduction of thyroid hormone 2. leakage of preformed hormone from thyroid 3. ingestion of excess thyroid hormone

Answer 618

excess of thyroid hormones in the blood

Answer 619

- congenital (neonatal) hyperthyroidism - non autoimmune hereditary hyperthyroidism - subacute thyroiditis - silent thyroiditis - postpartum thyroiditis - iodine induced hyperthyroidism - hyperemesis gravidarum - molar pregnancy (hCG) - thyrotoxicosis factitia - metastatic differentiated thyroid Ca2+ - struma ovarii - pituitary resistance to thyroid hormone - pituitary adenoma (TSHoma)

Answer 620

iodine, amiodarone, lithium, radiocontrast agents

Answer 621

- diffuse goitre - thyroid eye disease (infiltrative) - pretibial myxoedema - acropachy

Answer 622

- thyroid function tests to confirm biochemical hyperthyroidism - diagnosis of underlying cause is important because treatment varies - clinical history, physical signs usually sufficient for diagnosis - supporting investigations

Answer 623

- remission rates 30-50% - no definite way to predict remission/relapse for an individual patient poor prognostic factors: - severe biochemical hyperthyroidism - large goitre - TRAb +ve at end of course of ATD - male sex - young age of disease onset

Answer 624

common: rash less common: - arthralgia - hepatitis - neuritis - thrombocytopenia - vasculitis usually occur within first few months and resolve after stopping drug

Answer 625

- most serious side effect - occurs in 0.1 to 0.2% - manifests as sore throat, fever, mouth ulcers - must warn patients before starting ATD - stop if patient develops symptoms and check FBC

Answer 626

- one of 2 isotopes of I (127I stable) - ideal for ablation - emits large beta particles of moderate energy - beta particles non-penetrating and deliver 90% of energy within a 1-2mm zone to follicular cells - some gamma ray emission - half life 8.1 days

Answer 627

- emission of beta particles results in ionization of thyroid cells - direct damage to DNA and enzymes - indirect damage via free radicals

Answer 628

- necrosis of follicular cells - vascular occlusion - occur over weeks to months

Answer 629

- shorter cell survival - impaired replication of cells - atrophy and fibrosis - chronic inflammation resembling Hashimoto's - late hypothyroidism

Answer 630

- near total thyroidectomy for Graves' disease and multi nodular goitre - near total thyroidectomy/lobectomy for toxic adenoma

Answer 631

primary (>99%) - absence/dysfunction of thyroid gland - most cases due to Hashimoto's thyroidits secondary/tertiary - pituitary/hypothalamic dysfunction

Answer 632

- Hashimoto's thyroiditis - 131I therapy - thyroidectomy - postpartum thyroiditis - drugs - thyroiditides - iodine deficiency - thyroid hormone resistance

Answer 633

pituitary disease, hypothalamic disease

Answer 634

- iodine, inorganic or organic (iodide, iodinated contrast agents, amiodarone) - lithium - thionamides - interferon-alpha

Answer 635

thyroid agenesis, thyroid ectopia, thyroid dyshormonogenesis

Answer 636

resistance to thyroid hormone, isolated TSH deficiency

Answer 637

- increased TSH (most sensitive marker) - usually decreased free T4 and T3 - T4/T3 may be low normal in mild hypothyroidism - positive tire of TPO antibodies in Hashimoto's

Answer 638

TSH inappropriately low for reduced T4/T3 levels

Answer 639

- synthetic L-thyroxine (T4) | - older treatments: dessicated thyroid (pig and beef extracts)

Answer 640

- dose titrated until TSH normalises | - T4 half-life is long; check levels 6-8 weeks after dose adjustment

Answer 641

- TSH will always be low | - T4 is monitored

Answer 642

iodide, amiodarone, lithium

Answer 643

dopamine and dopaminergic agonists, glucocorticoids, cytokines, octreotide

Answer 644

rifampin, phenytoin, carbamazepine, barbituates

Answer 645

carbimazole, propylthiouracil, lithium

Answer 646

beta-blockers, glucocorticoids, amiodarone, propylthiouracil, radiocontrast dyes

Answer 647

furosemide, NSAIDs, mefenamic acid, carbamazepine, beta-blockers

Answer 648

estrogens, tamoxifen, heroin, methadone, raloxifene

Answer 649

cholestyramine, aluminum hydroxide, ferrous sulfate, sucralfate, calcium carbonate, protein pump inhibitors

Answer 650

interleukin-1, interferon-alpha, interferon-beta, TNF-alpha

Answer 651

amiodarone

Answer 652

- increase or decrease thyroid hormone secretion - decrease TSH secretion - increase hepatic metabolism of T4 - decrease thyroidal synthesis - impair T4 to T3 conversion - displacement of T4/T3 from plasma proteins - increase TBG and total T3/T4 - impair absorption of thyroxine - autoimmunity altered - modify thyroid hormone action

Answer 653

- dirty drug - potent anti-arrhythmic (AF) - 37% iodine by weight - 200mg tablet; 75mg iodide - lipid soluble - long elimination and half-life - 14-18% get abnormalities - AIT or AIH

Answer 654

- susceptibility - inhibitory effect on thyroid hormone synthesis - inability of gland to escape Wolf-Chaikoff effect - accelerate Hashimoto's trend - reduction in thyroid hormone synthesis - downregulation of peripheral receptors

Answer 655

- recently recommended by NICE for advanced melanoma - mode of action: monoclonal antibody, activates immune system by inhibiting CTLA-4 which normally downregulates immune system - target CTLA-4; keeps T cell active to destroy cancer cells

Answer 656

inflammation of the pituitary gland induced by ipilimumab - can occur as early as 4 weeks after - median 11 weeks - most remain on glucocorticoids - males>females - more frequent with increased usage given overall survival benefit - strategies for early detection

Answer 657

- tingling/burning in fingertips, toes, lips - muscle aches/cramps - twitching of muscles - fatigue - painful menstrual periods - patchy hair loss - dry, coarse skin - brittle nails - depression/anxiety

Answer 658

- osteoporosis - kidney stones - excess urination - abdominal pain - tiring easily - depression/forgetfulness - bone and joint pain - nausea, vomiting, loss of appetite

Answer 659

- calcium increased - PTH increased - phosphate decreased

Answer 660

- calcium decreased - PTH decreased - phosphate increased

Answer 661

- calcium decreased - PTH increased - phosphate increased

Answer 662

- calcium normal or decreased - PTH normal - phosphate normal or increased

Endocrinology Flashcards

(686 cards)