Old Endocrinology Flashcards

Question

Explain the synthesis of T3 and T4?

Answer 1

1. *Thyroglobulin* (T4 precursor) is synthesised in cells of thyroid gland and discharged into follicle lumen 2. *Iodide* is actively transported inside the follicular cell 3. Iodide is oxidised to *iodine*. 4. Iodine is attached to tyrosine in colloid, forming *Diiodotyrosine* (DIT) and *Monoiodotyrosine* (MIT). 5. DIT and MIT join together to form T3 and T4; - MIT + DIT = T3 - DIT + DIT = T4 6. T3 and T4 are stored in follicular cell 7. lysosomal enzymes cleave T4 and T3 from thyroglobulin and hormones diffuse into bloodstream

Answer 2

Iodothyronine deiodinase

Answer 3

Corticosteroids (Adrenocorticoids) sex steroids (Gonadal)

Answer 4

It is based upon the receptor that they bind to!

Answer 5

Corticosteroids

Answer 6

Sex steroids

Answer 7

Cholesterol

Answer 8

- Cholesterol is converted to Pregnenolone - Pregnenolone converted to **Progesterone** - In adrenal glands, progesterone changed to **Cortisol** - In ovaries or testes, progesterone converted to **Androstenedione** which is converted to **Testosterone** - Testosterone converted to **Estradiol** in the ovaries

Answer 9

Lipid soluble

Answer 10

Vitamin D binding protein

Answer 11

- 1️⃣ Diffuses through plasma membrane and binds to receptor (lipid soluble) - 2️⃣ Binds to receptor in cytoplasm producing receptor-hormone complex - 3️⃣ Receptor-hormone complex moves into nucleus - 4️⃣ Binding inside the nucleus initiates transcription of gene to mRNA - 5️⃣ mRNA directs protein synthesis.

Answer 12

Basal secretion that can be continuous or pulsatile

Answer 13

- Humoral stimulus; released as result of change in environment (e.g. low calcium causes release of PTH) - Neural stimulus; sympathetic nervous system stimulates adrenal gland to release adrenaline - Hormone stimulus; hypothalamus releases hormone which stimulates pituitary gland which releases further hormones to stimulate other glands.

Answer 14

Basal secretion - Continuous or Pulsatile Superadded Rhythms - Day night cycle Release inhibiting factors Release releasing factors

Answer 15

Hormone metabolism Hormone receptor induction Hormone receptor down regulation Synergism Antagonism

Answer 16

Pituitary gland Thyroid Gland Parathyroid Gland Adrenal Gland Pancreas Gonads - Ovary / Testes

Answer 17

Adrenal Cortex: Zona Glomerulosa - Mineralocorticoids - Aldosterone Zona Fasciculata - Glucocorticoids - Cortisol/cortisone Zona Reticularis - Androgens - Oestrogen / Testosterone Adrenal Medulla: Catecholamines - Adrenaline, Noradrenaline

Answer 18

The desire to eat food

Answer 19

The feeling of fullness Disappearance of appetite after a meal

Answer 20

Lack of Appetite

Answer 21

The need to eat

Answer 22

Weight (kg) / Height (m^2)

Answer 23

<18.5 underweight 18.5-24.9 normal 25-29.9 overweight 30-39.9 obese >40 morbidly obese

Answer 24

Internal Physiological drive - a feeling that prompts the thought of food and motivates food consumption External Psychological drive - Explains why we eat in the absence of hunger (eg. at a buffet)

Answer 25

The Hypothalamus Lateral Hypothalamus - Hunger centre Ventromedial Hypothalamic Nucleus - Satiety centre

Answer 26

Lateral Hypothalamus

Answer 27

Ventromedial Hypothalamic Nucleus

Answer 28

NPY - Neuropeptide Y MCH - Melanin concentrating Hormone AgRP - Agouti related peptide Orexin Endocannabinoid

Answer 29

- α-MSH: alpha melanocyte stimulating hormone from POMC - CART: cocaine and amphetamine regulated transcript - GLP-1: glucagon like peptide 1 - Serotonin - Peptide YY (PYY) - CCK

Answer 30

NPY POMC - α-MSH

Answer 31

Proopiomelanocortins Precursor polypeptides that are cleaved into 3 main hormones ATCH MSH Endorphins

Answer 32

Induces satiety by binding to the MCR3 and MCR4 receptors in the brain

Answer 33

Expressed in adipose tissue Switches off appetite and is immunostimulatory Leptin is sensed by the arcuate nucleus of the hypothalamus where it stimulates the release of anti-appetie factors (POMC; CART) and inhibits the release of pro-apeptite factors (NPY; AgRP).

Answer 34

In adipose tissue

Answer 35

Through leptin gene deficiency Through Leptin receptor mutation

Answer 36

Expressed in adipose tissue Switches off appetite and is immunostimulatory Leptin is sensed by the arcuate nucleus of the hypothalamus where it stimulates the release of anti-appetite factors (POMC; CART) and inhibits the release of pro-appetite factors (NPY; AgRP).

Answer 37

Ghrelin PYY GLP-1 CCK

Answer 38

Stimulates GH release Stimulates appetite (orexigenic)

Answer 39

The stomach

Answer 40

Peptide YY Structurally similar to NPY - binds to NPY receptors

Answer 41

Inhibits gastric motility Reduces appetite

Answer 42

Neuroendocrine cells in the ileum, pancreas, colon in response to food

Answer 43

Cholecystokinin Delays gastric emptying time gallbladder contraction Insulin release Acts on the vagus nerve to stimulate satiety

Answer 44

In a similar way to Leptin It inhibits NPY/AgRP release It stimulates POMC/CART release Acts to decrease appetite

Answer 45

Leptin and Insulin: Stimulate POMC/CART neurones - increase CART and alpha-MSH levels Inhibit NPY/AgRP neurones - Decrease NYP/AgRP Overall will increase satiety and decrease appetite. Ghrelin: Stimulates NPY/AgRP neurone - their levels increase Increase appetite PYY: Binds to an inhibitory receptor on NPY/AgRP neurones - decrease their levels Decrease appetite

Answer 46

Olfactory, visual gustatory stimuli stimulate appetite Oral receptors monitor food intake and begin to suppress feeding Food in stomach stimulates Ghrelin initially to increase appetite Stretch receptors in stomach begin to release satiety factors Release of CCK, GLP, Insulin and PYY all increase satiety to stop feeding

Answer 47

Liver - breakdown of glycogen -gluconeogenesis

Answer 48

Low - there is less glucose in the blood so insulin is low because it does not need to stimulate glucose storage

Answer 49

Free fatty acids

Answer 50

Inhibition of glucagon secretion Stimulation of insulin Glucose is taken up by the liver (40%) and peripheral tissues (60%)

Answer 51

Inhibition of lipolysis reduced levels of free fatty acids

Answer 52

Islets of langerhans of the pancrease Alpha cells - glucagon Beta cells - Insulin

Answer 53

The release of insulin from beta cells acts on the alpha cells of the pancreas to inhibit further glucagon release. In diabetes the insulin is lost and therefore you lose the alpha cell inhibition mechanism leading to excess glucagon and increased levels of glucose and free fatty acids in the blood.

Answer 54

Glucose is taken into the pancreas via GLUT2 transporters Once in the pancreas glucose is metabolised by glucokinase which forms ATP ATP then acts on the SUR1 potassium channels to close the K+ channels This leads to depolarisation of the cell membrane and thus the opening of Ca channels Calcium influx stimulates exocytosis of insulin secretory granules Insulin is released

Answer 55

Stimulates the metabolism of GLUT4 channels to the cell membrane Allows for the entry of glucose into the cell

Answer 56

Suppresses hepatic glucose output - Decrease glycogenolysis, Decrease gluconeogenesis. Increase glucose uptake into insulin sensitive tissues - fat and muscle. Suppresses lipolysis and muscle breakdown

Answer 57

Increases hepatic glucose output - increase glycogenolysis, increased gluconeogenesis Reduces peripheral glucose uptake stimulates peripheral release of gluconeogenic precursors - glycerol and amino acids, lipolysis, muscle glycogenolysis and breakdown.

Answer 58

A disorder of carbohydrate metabolism characterised by hyperglycaemia

Answer 59

Acute hyperglycaemia if untreated leads to diabetic ketoacidosis (DKA) and hyperosmolar hyperglycaemic states (HHS) Chronic hyperglycaemia leads to tissue complications (macro and microvascular) Side effects of treatment - hypoglycaemia

Answer 60

Diabetic retinopathy Diabetic neuropathy Stroke Cardiovascular disease Diabetic Nephropathy

Answer 61

Type 1 DM - Insulin dependent Type 2 DM - Insulin Independent - Maybe be gestational or medication induced) MODY Pancreatic diabetes Endocrine diabetes - Acromegaly, Cushing's Malnutrition related diabetes

Answer 62

Maturity onset diabetes of youth

Answer 63

Symptoms and random plasma glucose of >11mmol/L Fasting plasma glucose > 7mmol/L HbA1c of 48mmol/L (6.5%)

Answer 64

Autoimmune destruction of pancreatic Beta cells leading to an absolute insulin deficiency. T4 Hypersensitivity reaction.

Answer 65

Beta cells express HLA antigens ( HLA DR3 and HLA DR4) on MHC in response to an environmental event Activates chronic cell mediated immune response leading to chronic insulitis

Answer 66

Loss of beta cells - Loss of insulin secretion Leads to: Continued glycogenolysis in the liver Unrestricted lipolysis and skeletal muscle breakdown for gluconeogenesis Inappropriate increase in hepatic glucose output and suppression of peripheral glucose uptake. Glucose concentration rises lead to excretion of glucose in urine as renal reuptake routes are saturated (glycosuria)

Answer 67

Increased circulating glucagon - loss of paracrine function of beta cells - leads to increased glucose Perceived stress increases cortisol and adrenaline secretion Increases catabolic state and increases ketone production

Answer 68

Reduced insulin leads to increase lipolysis and the formation of glycerol and FFAs FFAs are transported to the liver and oxidised to ketone bodies Ketogenesis is highly sensitive to insulin Poor control of diabetes leads to DKA by uncontrolled ketone formation.

Answer 69

Glucose and ketones are excreted in the urine Causes osmotic diuresis Lower blood circulating volume Ketones cause anorexia and vomiting Vicious circle of dehydration, hyperglycaemia and increased acidosis leads to circulatory collapse and death

Answer 70

- Insulin resistance and impaired insulin release (though insulin is always detectable) - This leads to: - Reduced muscle and fat uptakes after eating - Failure to suppress lipolysis and high circulating free fatty acids - Abnormally high glucose output after a meal - Low levels of insulin enough to prevent muscle catabolism and ketogenesis so muscle breakdown and ketone production rarely excessive

Answer 71

Control glucose between meals and at night. Adjusted to maintain fasting blood glucose between 5-7mmol/L

Answer 72

Intesive basal bolus of insulin

Answer 73

Intensive basal bolus of insulin

Answer 74

Manage glucose according to carbohydrate intake and pre meal glucose

Answer 75

Progressive damage to pancreatic beta cells and or poor glucose control warrant insulin therapy

Answer 76

Basal insulin

Answer 77

Long acting basal insulin analogues

Answer 78

Their faster action means they can be adapted to the meal that is eaten

Answer 79

Once daily - basal insulin Twice daily - Mix insulin Basal Bolus therapy

Answer 80

- Simple for patient - adjust insulin themselves based on fasting glucose - Less risk of hypoglycaemia overnight - Carries on with oral therapy

Answer 81

- Doesn't cover meals - Best used with long-acting insulin analogues - expensive

Answer 82

- Both basal and prandial components in a single preparation per day - Can cover insulin requirements for the day

Answer 83

- Not physiological - Requires consistent meal and exercise pattern - Cannot separately titrate individual insulin components - Higher risk of nocturnal hypoglycaemia - Higher risk of hyperglycaemia is basal component not high enough - HbA1c is kept at a higher level

Answer 84

Low plasma glucose causing impaired brain function

Answer 85

Mild - self treated episodes Severe - Requires help from someone to recover

Answer 86

3.9 mmol/L

Answer 87

Level 1 - Alert value - Plasma glucose of under 3.9 mmol/l (70mg/dl) and no symptoms Level 2 - Serious biochemical - Plasma glucose of under 3.0 mmol/l (55mg/dl) Non-severe symptomatic - Mild hypoglycaemia Severe symptomatic - Level 3 - Severe hypoglycaemia

Answer 88

- Autonomic - Trembling - Palpitations - Sweating - Anxiety - Hunger - Neuroglycopenic - Difficulty concentrating - Confusion - Weakness - Drowsiness/Dizziness - Vision changes - Difficulty speaking - Non-specific - Nausea - Headache

Answer 89

The higher the HbA1c levels, the higher the glucose levels can be when the patient experiences a hypoglycaemic episode

Answer 90

- Type 1 DM - History of severe episodes - HbA1c > 48 mmol/l (6.5%) - Long duration of diabetes - Renal impairment - Impaired awareness of hypoglycaemia - Extremes of age - Type 2 DM - Advancing age - Cognitive impairment - Depression - Aggressive treatment of glycaemia - Impaired awareness of hypoglycaemia - Duration of multi dose insulin therapy - Renal impairment and other comorbidities

Answer 91

- Counter-regulatory hormones - Glucagon - Adrenaline

Answer 92

Threshold for secretion of counter-regulatory hormones can be altered, allowing for a lower value of glucose to be maintained and risking hypoglycaemia

Answer 93

- Reduced quality of life - Fear of hypoglycaemia - Mental illness comorbidity

Answer 94

- Accidents - Fear - Quality of life - Prevents desirable HbA1c targets - Cognitive dysfunction - Seizures/coma

Answer 95

- Low HbA1c (high pre-treatment HbA1c in Type 2 DM) - Long duration of diabetes - History of previous hypoglycaemia - Impaired awareness of hypoglycaemia - Recent episodes of severe hypoglycaemia - Daily insulin dose (>0.85 U/kg/day) - Physically active - Impaired renal function

Answer 96

Onset of symptoms below 0.3 mmol/l in blood glucose monitoring

Answer 97

- Lowest HbA1c not associated with frequent hypoglycaemia - May be appropriate to relax targets in patients with advanced disease, complications or limited life expectancy - In these patients, aim for low enough glucose levels to limit hyperglycaemia symptoms

Answer 98

- Lowest HbA1c not associated with frequent hypoglycaemia - HbA1c < 7% (53 mmol/l) usually appropriate for recent-onset of disease - May be appropriate to relax targets - Severe complications - Advanced co-morbidities - Cognitive impairment - Limited life expectancy - Unacceptable hypoglycaemia from stringent control

Answer 99

- If on insulin or sulphonylureas - How to identify and treat symptoms - Patients should report episodes of hypoglycaemia to doctor/educator

Answer 100

1. Recognise symptoms 2. Confirm the need for treatment with plasma glucose test 3. Treat with 15g fast-acting carbohydrate to relieve symptoms 4. Retest in 15 minutes to ensure blood glucose > 4 mmol/l and re-treat if needed 5. Eat a long-acting carb to prevent recurrence of symptoms

Answer 101

DCT - this is where PTH will act.

Answer 102

1. Absorbed from the intestine. 2. Resorbed from bone. 3. Reabsorbed at the kidney.

Answer 103

Duodenum and jejunum.

Answer 104

Ileum and colon.

Answer 105

At the PCT.

Answer 106

Low serum Ca2+ detected by receptors in the parathyroid.

Answer 107

1. It causes bone resorption: increased Ca2+ and phosphate. 2. It acts on the kidneys causing increased Ca2+ reabsorption and decreased phosphate reabsorption. 3. It stimulates 1-hydroxylase which increases formation of 1,25-(OH)2-vitD and so increases the absorption of Ca2+ and phosphate from the intestine.

Answer 108

It reduces bone resorption and so lowers Ca2. It is the antagonist to PTH.

Answer 109

Parafollicular C cells of the Thyroid release Calcitonin.

Answer 110

High Ca2+.

Answer 111

1. PTH. 2. 1,25-(OH)2-vitD. 3. FGF-23 = major regulator!

Answer 112

It increases phosphate absorption at the intestine and decreases phosphate reabsorption at the kidney.

Answer 113

Chief cells in the parathyroid gland - possess calcium sensing receptors on their cell surface

Answer 114

Stimulates osteoclasts to release ionic Ca2+ for reabsorption

Answer 115

- ↑ passive calcium reabsorption by the PCT - only 1% excreted - ↓ phosphate reabsorption - 20% excreted - ↑ 1 alpha hydroxylation of vitamin D to form 1,25-dihydroxyvitamin D - facilitates calcium absorption in the intestines

Answer 116

↑ calcium absorption via 1,25-dihydroxyvitamin D

Answer 117

Calcitonin!

Answer 118

- Reduces bone resorption by inhibiting osteoclast activity - Reduce renal reabsorption

Answer 119

Negative feedback! Increased serum PTH leads to reduced secretion.

Answer 120

Normal level of serum calcium: 2.2 - 2.6mmol/L Mild-moderate Hypocalcaemia: 1.9 - 2.2 mmol/L Severe Hypocalcaemia: <1.9 mmol/L

Answer 121

- Parasthesia - abnormal skin sensation (tingling, prickling, numbness) - Tetany - spasms of the hands, feet, larynx and premature labour - Seizures - Basal ganglia calcification - associated with neuropsychiatric and motor symptoms - Cataracts - Chvostek and Trousseau signs

Answer 122

Tap over the facial nerve - look for spasm of the facial muscles

Answer 123

Inflate blood pressure cuff to 20mmHg above systolic for 3-5 minutes - look for carpopedal spasm

Answer 124

Long QT interval - primarily the prolonging of the ST segment; slow ventricular repolarisation as a result of reduced calcium entering the cell through L-type channels.

Answer 125

- Hypoparathyroidism - Acute pancreatitis - Hyperphosphataemia - Hypomagnesaemia - Diuretics (frusemide) - Pseudohypoparathyroidism - Congenital disorders - Critical illness (e.g. sepsis)

Answer 126

Inactive Vitamin D is converted to 1,25-dihydroxyvitamin D), which facilitates Ca2+ absorption by the gut

Answer 127

Reduced secretion of PTH by Chief cells of the parathyroid. PTH acts in incidences of low serum to increase calcium absorption from bone, kidneys and intestines

Answer 128

- Surgery - parathyroid removal - Radiation - parathyroid damage - Autoimune diseases (e.g. Chronic Mucocutaneous Candidiasis) - Infiltration - caused by condition, such as Wilson's disease and Haemochromatosis - Magnesium deficiency - required for release of PTH - Syndromes - Genetic predisposition

Answer 129

Acute pancreatitis Di George Syndrome Pseudohypoparathyroidism

Answer 130

Precipitation of calcium stearate (carboxylated calcium) in the abdominal cavity; causes increased calcitonin release.

Answer 131

*A developmental abnormality of third and fourth branchial pouches of the pharyngeal arches - this causes;* - Hypoparathyroidism - Immunodeficiency - linked to thymic hypoplasia - Cardiac defects - Cleft palate

Answer 132

- Condition associated with the resistance of the body to PTH. - Causes Type 1 Albright hereditary osteodystrophy which presents with the following signs - Short stature - Obesity - Round facies - Mild learning difficulties - Subcutaneous ossification - Short fourth metacarpals

Answer 133

Normal level of serum calcium: 2.2 - 2.6 mmol/L Mild Hypercalcaemia: 2.7 - 2.9 mmol/L Moderate Hypercalcaemia: 3.0 - 3.4 mmol/L Severe Hypercalcaemia: >3.4 mmol/L

Answer 134

*Bones, stones groans and moans!* **BONES** - osteitis fibrosa cystica, osteoporosis Renal **STONES** - kidney stones Psychic **GROANS** - neurological symptoms (i.e. confusion, coma) Abdominal **MOANS** - constipation, nausea, acute pancreatitis *Also, thirst as polyuria

Answer 135

Short QT interval - primarily the shortening of the ST segment; faster ventricular repolarisation as a result of increased calcium entering the cell through L-type channels.

Answer 136

90% of the time caused; - Malignancies - Hyperparathyroidism - primary and teritiary

Answer 137

- Myeloma - causes overexpression of RANKL which activates osteoclastic bone resorption - Bone metastases - Lymphoma - PTH-Related Peptide (PTHrP) - produced in excess by a tumour; causes PTH secretion above physiological range

Answer 138

Increased secretion of PTH by Chief cells of the parathyroid. PTH acts to increase calcium absorption from bone, kidneys and intestines. Excessive PTH causes elevated serum calcium.

Answer 139

Hyperparathyroidism caused by; - 80% - sporadic single benign adenoma - 15-20% - parathyroid hyperplasia - <0.5% - parathyroid carcinoma

Answer 140

A result of chronic secondary hyperparathyroidism. High levels of PTH production over a long period of time results in parathyroid hyperplasia; this causes an extent PTH overproduction which increases serum calcium above physiological range.

Answer 141

Secondary hyperparathyroidism normally occurs as a a result of long term low serum calcium (e.g. due to kidney failure)

Answer 142

Diencephalon of the brain

Answer 143

- Hormones travelling to the APG (anterior Pituitary Gland) Travel down the median eminence, a prolongation of the hypothalamus, into the hypophyseal portal system, which carries them to the anterior pituitary where they exert their regulatory functions. - Hormones travelling to the PPG (Posterior Pituitary Gland) Hormones synthesised by neurones in the hypothalamus pass down the neuronal axons which travel into the posterior pituitary. Here, they are stored in the distended parts of the axon in the posterior pituitary.

Answer 144

- Gonadotropin Releasing Hormone (GnRH) - Growth Hormone Releasing Hormone (GHRH) - Somatostatin (SST); also known as - Growth Hormone Inhibiting Hormone (GHIH) - Tryrotropin Releasing Hormone (TRH) - Dopamine (DA) or Prolactin-Inhibiting Hormone (PIH) - Corticotrophin Releasing Hormone (CRH)

Answer 145

- System of blood vessels in the microcirculation at the base of the brain, connecting the hypothalamus to the anterior pituitary. - Function to rapidly transport hormones between the hypothalamus arcuate nucleus and anterior pituitary gland. - The capillaries in the portal system are fenestrated.

Answer 146

1️⃣ Neurones with cell bodies in the *medial hypothalamic nuclei* project to the median eminence 2️⃣ Here, the neurones secrete hormones into the pituitary portal veins 3️⃣ Hypothalmic hormones influence secretion of hormones from cells in the anterior lobe of the APG into the venous drainage of the gland.

Answer 147

1️⃣ Neurones with cell bodies in the supra and paraventricular nuclei of the hypothalamus have projections to the posterior pituitary 2️⃣ Neurones release their hormones directly into the venous drainage of the gland.

Answer 148

- ollicle Stimulating Hormone (FSH) → Gonads - Luteinizing Hormone (LH) → Gonads - Growth hormone (GH) → Liver (IGF-1) and other tissue (growth) - Thyroid Stimulating Hormone (TSH) → Thyroid - Prolactin (PL) → Breasts - Adrenocorticotropic Hormone (ACTH) → Adrenal Cortex

Answer 149

- Vasopressin/ ADH - acts to upregulate water retention in the kidneys (aquaporins) - Oxytocin - induces contractions of the uterus during labour

Answer 150

1️⃣ TRH from hypothalamus acts on anterior pituitary 2️⃣ Anterior pituitary produces TSH (thyrotroph cells in anterior pituitary has receptors that TRH acts on) 3️⃣ TSH acts on thyroid which produces T4 and T3; these acts as negative feedback on both hypothalamus and pituitary 4️⃣ Deiodinases act to convert T4 to T3 by removal of iodine

Answer 151

- 1️⃣ Hypothalamus produces GnRH which acts on pituitary - 2️⃣ Pituitary produces LH and FSH - 3️⃣ LH travels to the gonads and causes; - Men - LH stimulates interstitial cells of the testes to produce testosterone - FSH stimulates spermatogenesis - Women FSH and LH act to activate the ovaries to produce oestrogen and inhibin; regulate the menstrual and ovarian cycle - 4️⃣ Negative feedback for hypothalamus and pituitary - Men - Testosterone acts on the hypothalamus to inhibit the production of GnRH - Women - Oestrogen acts on the hypothalamus directly to inhibit the production of GnRH - Inhibin acts to inhibit *activin*, a peripherally produced hormone that positively stimulates GnRH-producing cells

Answer 152

1️⃣ Hypothalamus produces CRH which acts on the pituitary 2️⃣ Pituitary produces ACTH 3️⃣ ACTH acts on the adrenal glands to produce *cortisol* 4️⃣ Cortisol acts as negative feedback for pituitary and hypothalamus

Answer 153

1️⃣ Hypothalamus produces GHRH and Somatostatin which acts on pituitary 2️⃣ Pituitary produces GH which acts on liver 3️⃣ Liver produces Insulin-like Growth Factor 1; this acts as negative feedback for hypothalamic secretions There are pulsatile secretions of GH and SMS that enable growth during sleep

Answer 154

1️⃣ Hypothalamus produces LHRH which acts on the pituitary 2️⃣ Pituitary produces Prolactin 3️⃣ Hypothalamus also produces dopamine; this acts on the pituitary gland to reduce prolactin secretion 4️⃣ Cortisol acts as negative feedback for pituitary and hypothalamus

Answer 155

- Benign pituitary adenoma - Craniopharyngioma - Trauma - Apoplexy - Sarcoid/TB

Answer 156

- Exerts pressure on local structures (e.g. optic nerves) - Exert pressure on the normal pituitary - Behaves as a functioning tumour

Answer 157

- Bitemporal hemianopia (Loss of lateral fields of vision in both eye) Caused by compression of the nasal retinal fibres; responsible for carrying the information along the optic nerve. Specifically, compression of the optic chiasma; the area where optic nerves from the right and left eyes cross near the pituitary gland. - Compression of Nasal Retinal Fibres - Inferior nasal fibres cause reduction in upper outfield - Superior nasal fibres cause reduction in lower outfield

Answer 158

Expansive tumour causes stretching of the dura mater; layer of connective tissue associated with the meninges

Answer 159

Accumulation of CSF within the brain caused by compression of the brain

Answer 160

Hypopituitarism - lack of pituitary function! Symptoms relate to deficiency of specific hormone secretions

Answer 161

- Central obesity - Decreased muscle mass - Impaired memory

Answer 162

*Associated with low testosterone/ oestrogen and progesterone* - Men → loss of body hair, decreased muscle mass, anaemia, loss of sexual function - Women → infertility, oligo-/amenorrhea (infrequent/light or absent periods), loss of sexual function - Children → delayed puberty

Answer 163

*Associated with low cortisol!* - Pallor - Fatigue - Weight loss - Failure to thrive

Answer 164

*Associated with hyperthyroidism!* - Tiredness - Constipation - Weight gain - Hair loss - Low BP and HR.

Answer 165

Inability to breastfeed

Answer 166

*Diabetes insipidus!* - Inability to concentrate the urine, leading to polyuria - Dehydration and, in compensation, extreme thirst (polydipsia) - Hypernatremia (high serum sodium).

Answer 167

Rare - issues arise during breastfeeding and childbirth

Answer 168

Tumour causing the pituitary to make too much prolactin

Answer 169

- Galactorrhoea - abnormal white breast discharge - Reduced ability to breast feed - Amenorrhoea/ infertility - Loss of libido - Visual field defect - see above

Answer 170

Dopamine agonist (e.g. Cabergoline or Bromocriptine) - produces prolactin-reducing feedback Surgery possibly

Answer 171

Growth hormone

Answer 172

Acromegaly occurs in adults - after growth plates are closed Gigantism occurs in children caused by a pituitary tumour causing increased GH release however the tumour also presses on the pituitary so you get hypopituitarism which means the other hormones do not work and therefore they don't go through puberty as no testosterone is being produced

Answer 173

Chronic, excessive and inappropriate elevated levels of circulating cortisol. (not necessarily tumour related) **Cushing's syndrome occurring as a result of a pituitary tumour is known specifically as Cushing's Disease.*

Answer 174

ACTH - causes the overproduction of cortisol by the adrenal cortex

Answer 175

- Carbohydrate metabolism - diabetes, glucose intolerance - Electrolyte disturbance - hypertension; sodium retention and potassium loss - Immune suppression - Central effects - malaise, depression, psychosis - Suppressed gonadal function - oligo/ amenorrhoea, infertility, loss of libido

Answer 176

- Obesity - Muscle wasting (protein catabolism) - Redistribution of fat around abdomen and top of back - Hirsutism - excessive growth of coarse hair facial, chest and back hair in women - Repeated bruising, thin skin, thin hair and stretch marks - Acne

Answer 177

- ACTH-dependent → caused by a pituitary adenoma (or ectopic, ACTH producing tumour) - ACTH-independent → caused directly by the adrenal glands

Answer 178

- Urinary free cortisol - Low dose dexamethasone suppression test - synthetic steroid feedback at pituitary and hypothalamus which leads to reduced CRH and ACTH. Therefore, low levels of cortisol found in blood. - Late night/midnight serum or salivary cortisol.

Answer 179

- Urinary free cortisol - Low dose dexamethasone suppression test - synthetic steroid feedback at pituitary and hypothalamus which leads to reduced CRH and ACTH. Therefore, low levels of cortisol found in blood. - Late night/midnight serum or salivary cortisol.

Answer 180

Chronic, excessive and inappropriate elevated levels of circulating cortisol that is specifically caused by a pituitary tumour

Answer 181

Describes the physiological, morphological, and behavioural changes as the gonads switch from infantile to adult forms

Answer 182

- Girls - menarche - First menstrual bleed - Boys - first ejaculation - Often nocturnal

Answer 183

- Girls - Ovarian oestrogens - Growth of breasts and female genitalia - Ovarian and adrenal androgens - Control pubic and axillary hair - Boys - Testicular androgens - External genitalia and pubic hair growth - Enlargement of larynx and laryngeal muscles - Deepening of the voice

Answer 184

Scale of physical development through puberty

Answer 185

>3ml (>2.5cm in longest diameter)

Answer 186

Orchidometer

Answer 187

- Breast development - Oestrogen

Answer 188

- Ductal proliferation - Site specific adipose deposition - Enlargement of the areola and nipple

Answer 189

- Prolactin - Glucocorticoids - Insulin

Answer 190

- Corpus:cervix ratio flips from 1:2 to 2:1 - Changes from tubular shape to pear shape - Increases in length and volume - Endometrium thickens

Answer 191

- Volume increases - Change from non-functional to multicystic

Answer 192

- Are the Mullerian structures present? - Fallopian tubes - Uterus - Uterine cervix - Superior aspects of the vagina - Morphology of the uterus - Morphology of the ovaries - Requires an experienced examiner so careful when reporting absence of structures

Answer 193

- Becomes a duller red - Epithelium thickens - Cornification of the superficial layer of stratified squamous epithelium - pH changes from neutral to acidic - Secretion of clear whitish discharge in the months prior to menarche - Increase in length

Answer 194

- Oestrogens - Labia majora and minora increase in size and thickness - Rugation and change in colour of labia majora - Hymen thickens - Clitoris enlarges - Vestibular glands begin secretion - Adrenal and ovarian androgens - Growth of pubic hair

Answer 195

- Maturation process of the adrenal gland - Specialised subset of cells arises forming the androgen producing zona reticularis

Answer 196

- Peri-puberty - Premature or exaggerated adrenarche can occur up to 2 years prior to puberty, especially in obese children

Answer 197

- DHEA - DHEA-S - Both precursors of androgens

Answer 198

- Mild advance in bone age - Axillary hair growth - Mild acne - Body odor

Answer 199

Early puberty

Answer 200

- Up to 80% female - If male patients present with precocious puberty, differentials should be ruled out before a diagnosis of idiopathic puberty is given - Brain tumour may be highly likely or some other significant pathology

Answer 201

Resembles puberty, but not from normal hypothalamus activation

Answer 202

- Adrenal sex hormones excess - Congenital adrenal hyperplasia - hCG Secreting Tumours - Gonads - Brain - Liver - Retroperiteneum - Mediastinum

Answer 203

- Use of gonadotrophin releasing hormone (or luteinising hormone-releasing hormone) test - Measure LH and FSH before and 30 and 60 minutes after injection of GnRH (or LHRH) - If GnRH or LHRH stimulates an increase of LH and FSH, then true puberty - If there is not a rise of LH:FSH the likely pseudopuberty - Stimulated LH:FSH ratio > 1 to be true precocious puberty

Answer 204

- Use of GnRH super-agonist suppresses pulsatility of normal physiology - Stops the process

Answer 205

Idiopathic precocious puberty CNS Tumours CNS Disorders Secondary central precocious puberty Psychosocial - adoption from abroad

Answer 206

Increased androgen secretion Gonadotrophin secreting tumours McCune Albright syndrome Ovarian Cyst Oestrogen secreting neoplasm Hypothyroidism Iatrogenic or exogenous sex hormones

Answer 207

- Idiopathic Hypogonadotropic Or hypergonadotropic hypogonadism

Answer 208

Delayed activation of the hypothalamic pulse generator

Answer 209

Diagnosis of exclusion

Answer 210

- Late menarche in mother or sister - Delayed growth spurt in father

Answer 211

- Hypogonadotropic hypogonadism - Sexual infantilism related to gonadotrophin deficiency - Hypergonadotrophic hypogonadism - Primary gonad problems

Answer 212

- Delay in acquisition of secondary sex characteristics - Psychological problems - Defects in reproduction - Reduced peak bone mass

Answer 213

Girls: Lack of breast development by 13yrs More than 5yrs between breast development and menarche Lack of pubic hair by age 14yrs Absent menarche by 15-16yrs Boys: Lack of testicular enlargement by age 14yrs Lack of pubic hair by age 15yrs More than 5 years to complete genital enlargement

Answer 214

Totally absent or started and then arrested Family Hx Review of Symptoms Perinatal Hx Prior Medical Illnesses Medication Psychosocial deprivation Nutrition, exercise and health Neurological symptoms Hypoglycaemia Cancer Hx Testicular injury

Answer 215

- FBC - U&Es - Renal function test - LFTs - Coeliac abs - Testosterone/oestrodiol - Thyroid function - Prolactin - DHEA-S - ACTH - Cortisol - Karyotyping/CGH array - Where physical examination/biochemistry suggestive of genetic syndrome - in all girls with short stature

Answer 216

- Bone age (skeletal maturity) - Delayed bone age in growth hormone - Advanced bone age in precocious puberty

Answer 217

Chronic Renal disease Chronic GI disease/malnutrition Sickle cell disease Chronic lung disease Anorexia nervosa Bulimia Psychosocial stress Extreme exercise Drugs AIDs Poorly controlled T1DM Hypothyroidism Cushing's Syndrome Hyperprolactinaemia

Answer 218

- Issue with the gonads - Also known as hypergonadotropic hypogonadism - Gonads not responding to stimulus so hypothalamus and pituitary more stimulated - FHS/LH will both be high - Sex hormones will be low

Answer 219

Issue with the pituitary

Answer 220

Issue with the hypothalamus

Answer 221

Secondary and tertiary hypogonadism

Answer 222

CNS disorders - tumours Kallmanns' Syndrome - Gonadotrophin deficiency Prader willi syndrome sickle cell CF AIDS

Answer 223

- Issues with: - GnRH neurone migration - GnRH synthesis and release - GnRH action - Gonadotropin synthesis

Answer 224

- No gold-standard diagnostic test available - Inhibin B marker of Sertoli cell number correlates with testicular volume - In men with central hypogonadotropic hypogonadism and severe GnRH deficiency serum levels of inhibin B are typically very low - For partial forms of central hypogonadotropic hypogonadism, inhibin B levels overlap with those in patients with constitutional delay in growth and puberty and in healthy controls

Answer 225

Mainly Males 4:1 M:F

Answer 226

- Failure of migration of GNRH neurones from hypothalamus to pituitary - X-linked, autosomal recessive or dominant

Answer 227

Klinefelters - Males Turners Syndrome - Females

Answer 228

45 XO Loss of an X chromosome

Answer 229

- At birth - Oedema of dorsa of hands and feet - Loose skinfolds at the nape of the neck - Webbing of neck - Low posterior hairline - Small mandible - Prominent ears - Epicanthal folds in high arched pallet - Broad chest - Cubitus valgus - Hyperconvex fingernails - Cardiovascular malformations - Renal malformations (horseshoe kidney) - Recurrent otitis media - Middle ear infections - Short stature - Primary hypogonadism

Answer 230

- Primary hypogonadism - Azoospermia - Gynaecomastia - Reduced secondary sexual hair - Osteoporisis - Tall stature - Reduced IQ

Answer 231

20-fold increased risk of breast cancer

Answer 232

Ethinyloestradiole Oestrogen - Start low, gradually increase doses to provide time for pubertal growth and gradual breast development - Over 2 years - Progesterone added when full replacement dose achieved

Answer 233

Testosterone Enanthate (most common) Testosterone Transdermal - Several incremental steps - Over 2-4 years

Answer 234

- GnRH therapy - Pituitary must be intact - Parenteral combination of gonadotropin therapy - LH/hCG and FSH

Answer 235

- Weight gain - Tiredness - Constipation - Cold intolerance - Poor concentration - Poor sleep pattern - Dry skin

Answer 236

Autoimmune Hashimotos Atrophic Thyroiditis Prior surgery Radio-ablation Drugs - Lithium, Amiodarone Iodine deficiency Congenital

Answer 237

Post partum Thyroiditis Subacute thyroiditis

Answer 238

Hypopituitarism

Answer 239

Primary Transient Secondary

Answer 240

- Iodine, inorganic or organic iodide - Iodinated contrast agents - **Amiodarone** - Lithium - Thionamides - Interferon alpha

Answer 241

- Thyroid agenesis - lack of thyroid - Thyroid ectopia - embryological aberration of thyroid - Thyroid dyshormonogenesis - genetic defects in the synthesis of thyroid hormones

Answer 242

- Gestational hypertension and pre-eclampsia - Placental abruption - Post partum haemorrhage

Answer 243

- Low birth weight - Preterm delivery - Neonatal goitre - Neonatal respiratory distress

Answer 244

Synthetic L-thyroxine (T4) - 1.6 mg/kg

Answer 245

- **Primary - monitor TSH** - L-thyroxine (T4) is titrated until TSH is within normal range - **Secondary/ tertiary - monitor serum T4** - TSH will always be low

Answer 246

- Preconception counselling - ideal preconception TSH <2.5 mIU /L - Increase thyroxine dose by 30% - Arrange thyroid function tests in early pregnancy

Answer 247

*Aim to normalise ASAP!* Start thyroxine 50-100mcg and measure thyroid function every 4-6 weeks

Answer 248

Early mild form of hypothyroidism characterised by high TSH levels but free T4 and free T3 are normal.

Answer 249

- Age > 30 - BMI > 40 - Miscarriage preterm labour - Personal or family history - Goitre - Type 1 Diabetes - Head and neck irradiation - Amiodarone, Lithium or contrast use

Answer 250

High serum thyroid hormones caused by; - Overproduction of thyroid hormone - Leakage of preformed hormone from thyroid - Ingestion of excess thyroid hormone

Answer 251

- Weight loss - Heat Intolerance - Sweating - Diarrhoea - Tachycardia - Anxiety - Tremor - Menstrual disturbance

Answer 252

- Primary hyperthyroidism - Increased (free) T4 - Increased (free) T3 - Reduced TSH - Secondary hyperthyroidism - Increased (free) T4 - Increased (free) T3 - Excessively high TSH

Answer 253

- 85-90% due to Graves disease - Less commonly cause by; - Toxic adenoma or multi nodular goitre - Gestational thyrotoxicosis, - Trophoblastic neoplasia - TSHoma

Answer 254

An autoimmune disease characterised by the development of TSH-receptor activating antibodies. This leads to hyperthyroidism.

Answer 255

- Diffuse goitre - enlargement of the entire thyroid - Thyroid eye disease (inflitrative) - Pretibial myxoedema - excess of glycosaminoglycans in the dermis and subcutis of the skin resulting in waxy, orange appearance of skin - Acropachy - soft tissue swelling of hands and clubbing of the fingers

Answer 256

- Iodine, inorganic or organic iodide - Radiocontrast agents - Amiodarone - Lithium

Answer 257

- Intrauterine growth resistance (IUGR) - Low birth weight - Pre ecclampsia - Preterm delivery - Risk of stillbirth - Risk of miscarriage

Answer 258

- β-blockers (e.g. propranolol) - symptomatic treatment - Anti-thyroid medication; Thionamides → Propylthiouracil (PTU) or Carbimazole - Prevent thyroid peroxidase enzyme coupling and iodinating tyrosine residues on thyroglobulin → reduce T3 and T4 - PTU also inhibits the conversion of T4 to T3

Answer 259

- Rash (Most Common) - Arthralgia - Neuritis - inflammation of optic nerve - Thrombocytopenia - Hepatitis - Vasculitis - inflammation of small and large blood vessels - Agranulocytosis (most serious) - bone marrow stops production of WBC resulting in sore throat, fever, mouth ulcers

Answer 260

Individuals with current Graves', past Graves' and mothers who have previously had a child with Graves' Measured at 22-26 weeks - if raised there is a risk of foetal/neonatal thyrotoxicosis

Answer 261

Transplacental transfer of thyroid stimulating autoantibodies from mother to fetus. These autoantibodies bind to the fetal thyroid stimulating hormone (TSH) receptors and increase the secretion of the thyroid hormones. Begins around 20th week of pregnancy and reaches its maximum by 30th week. Managed using anti-thyroid medication.

Answer 262

- IUGR - Foetal goitre - Foetal tachycardia - Foetal hydrops - Preterm delivery - Foetal demise

Answer 263

Transient form of thyrotoxicosis caused by excessive stimulation of thyroid gland by hCG. This leads to raise free T4 but low TSH. Usually limited to the first 12-16 weeks of pregnancy

Answer 264

- Multiple gestation - Hydatidaform mole - Hyperplacentosis - Choriocarcinoma

Answer 265

Graves Disease symptoms predate pregnancy (and are more prominent during pregnancy) N&V is greater in Gestational Thyrotoxicosis Graves disease will present with Goitres Graves disease ill have TSH-R antibodies

Answer 266

- ↑ erythropoetin, cortisol, noradrenaline - ↑ cardiac output - ↑ plasma volume - High cholesterol triglycerides - Pro-thrombotic and inflammatory state - Insulin resistance

Answer 267

- Pre-eclampsia; hypertension in pregnancy associated with seizures - Obestetric cholestasis; abnormal liver function - Gestational hyperthyroidism; excessive stimulation of thyroid gland by hCG - Postpartum thyroiditis; results in either excessive or deficient secretion of thyroid hormones - Gestational diabetes - Transient diabetes insipidus - Post-natal depression - Postnatal autoimmune disease

Answer 268

- Fetal thyroid follicles and thyroxine synthesis occurs at 10 weeks - Fetal thyroid axis matures at 15-20 weeks - For the first trimester (0-12 weeks) the foetus is reliant on maternal T4 to regulates neurogenesis, migration and differentiation then foetal T4

Answer 269

- ↑ in Thyroid Binding Globulin (TBG) - ↑ HCG - stimulates TSH receptor - ↑ free T4 - in response to TSH receptor stimulus by hCG - ↑ in total T4 - ↓ TSH - ↑ Iodine clearance

Answer 270

- First trimester: initial increase ↑ in TBG, total T4, TSH, and free T4 which continues throughout development - Second trimester: ↑ total T3 - Third trimester: ↑ free T3

Answer 271

Glycoprotein hormones! Same α-subunit but a different β-subunit

Answer 272

First Trimester - 0.1-2.5 mlU/L Second Trimester - 0.2-3.0 mlU/L Third Trimester - 0.3-3.0 mlU/L

Answer 273

Potent anti-arrhythmic used in individuals with atrial fibrillation, nodal fibrillation and ventricular tachycardia Blocks Potassium channels to inhibit repolarisation

Answer 274

- High in iodine (37% by weight) - Lipid soluble (stored in adipose tissue) - Long elimination half life

Answer 275

- Amiodarone Induced Hypothyroidism (AIH) - Amiodarone Induced Thyrotoxicosis (AIT)

Answer 276

Amiodarone has an inhibitory effect on thyroid hormone synthesis, leading to downregulation of peripheral receptors and hypothyroidism

Answer 277

Type 1 - Increased synthesis and release of thyroid hormone induced by drug-related iodine excess. Usually associated with pre-existing thyroid disease. Type 2 - Destruction of the thyroid caused by direct toxicity of amiodarone. Characterised by excessive release of thyroid hormones without excessive production

Answer 278

Both conditions caused by an excess of growth hormone (GH) - Acromegaly Occurs in adulthood; following epiphyseal fusion - Gigantism Occurs in childhood; prior to epiphyseal fusion Defined a height >2SD for the patients age and sex

Answer 279

44 years old; mean duration of symptoms is 8 years

Answer 280

- GHRH From: arcuate nucleus of hypothalamus → ant. pituitary - GH From: somatotropic cells of the ant. pituitary Exhibits pulsatile secretion; levels vary wildly throughout the day - ILG-1 From: liver Negative feedback: IGF-1 and GH inhibit GHRH secretion BUT promote somatostatin release (GHIH or SRIF).

Answer 281

Pituitary adenomas account for >90% of cases

Answer 282

excess secretion of GH from an ectopic source e.g. lung/adrenal tumours that produce GHRH or GH Hypothalamic dysfunction e.g. hypothalamic tumours

Answer 283

Insidious onset Often diagnosed late Headaches and visual changes Large lips and nose wide spaced Teeth Deep skin creases Large Hands and Feet Hyperpigmentation Acanthosis Nigricans

Answer 284

Headache and Visual Changes Coarse Facial Features Frontal Bossing Tall stature Large Hands and Feet Obestity

Answer 285

- Wide spaced teeth - Prognathism: protrusion of lower jaw - Frontal bossing: prominent, protruding forehead associated with a heavy brow ridge - Males; deeping of their voice - Males; carpel tunnel syndrom

Answer 286

Serum IGF-1 - Raised indicates periods of GH excess Pituitary MRI Glucose tolerance test: patient is given 100g of glucose orally. Serum glucose is measured before and after glucose stimulation. - In a healthy individual: GH release is suppressed following the administration of exogenous glucose (i.e. < 0.6 mcg/L). Now - as assays have improved - we are looking a suppression down to <0.2mcg/L - In a patient with acromegaly: In patients with acromegaly, GH levels are increased above the testing threshold i.e. GH levels wouldn't decrease in response to glucose stimulation.

Answer 287

Acormegaly excluded if: random GH <0.4ng/ml and normal IGF-1 If either are abnormal, progress to: 75mg glucose tolerance test (GTT) Acromegaly excluded if: IGF-1 normal AND GTT lowers GH <1ng/ml

Answer 288

Hypertension and heart disease Cerebrovascular events and headache Arthritis Insulin resistant Diabetes Sleep Apnoea

Answer 289

- Surgery (first-line) Surgery to remove the pituitary adenoma Microadenomas tend to have better results than macroadenomas as macroadenomas can be too big and dangerous to remove. Recurrence is common, ~ >10% - Radiotherapy Generally reserved for cases in which surgery fails (rarely a primary therapy). The biochemical response to radiotherapy can be slow at > 10 years.

Answer 290

1. Conventional; aka fractionated, therapy delivers a part of the complete radiation dose over several sessions i.e any radiation damage to normal cells can be repaired between treatments. 2. Stereotactic; gives radiotherapy from many different angles around the body. The beams meet at the tumour. This means the tumour receives a high dose of radiation and the tissues around it receive a much lower dose. 3. Gamma knife; type of stereotactic therapy - focused array of intersecting beams that concentrate at a target 4. LINAC; combines two technologies - an MRI scanner and linear accelerator – to precisely locate tumours, tailor the shape of X-ray beams in real time and accurately deliver doses of radiation to moving tumours. 5. Proton beam; treatment delivered by accelerated proton beams rather than X-rays

Answer 291

The development hypopituitarism; therefore, it is generally avoided in those of reproductive age.

Answer 292

Somatostatin receptor agonists (somatostatin analogues) - Octreotide/Lanreotide - inhibits GH secretion Dopamine agonists - Cabergoline Bromocriptine GH antagonists - Pegvisomant - lowers IGF-1 levels

Answer 293

Negative regulator of GH Can achieve control of GH and IGF-1

Answer 294

Lactotroph

Answer 295

Hyperprolactinemia: excess levels of prolactin in the blood

Answer 296

- Hypothalamic-pituitary stalk damage - Drug induced e.g. anti-psychotics which block dopamine - Pregnancy and lactation - Systemic disorders e.g. CKD or cirrhosis

Answer 297

Local effects of tumour (particularly if macroadenoma) - Headache - Visual field defect (bitemporal hemianopia) - CSF leak (rare) - Systemic effect of prolactin - Mensuration irregularity/amenorrhoea - Infertility - Galactorrhoea - Low libio - Low testosterone in males - Erectile dysfunction in males - Gynaecomastia in males - Hypogonadism

Answer 298

- MRI scan - Prolactin levels in the blood

Answer 299

- Unexplained milk secretion (galactorrhea) - Irregular menses or infertility in females - Males with impaired sexual function and/or milk secretion

Answer 300

- Medical therapy > Surgery *Recall: endogenous DA secretion from the hypothalamus is normally suppressing the secretion of prolactin from the ant. pituitary* **Dopamine agonists** (e.g. Cabergoline) = drastic shrinkage with macroadenomas; reduced pressure on optic chiasm → sight saving

Answer 301

HLA DR3 HLA DR4

Answer 302

Related to Metabolic Syndrome It has a high environmental factor Potentially a genetic component - increased risk with first degree relative Dx

Answer 303

3 or More of: Fasting Glucose > 100mg/dl Triglycerides > 150mg/dl HDL < 50mg/dl (female) <40mg/dl (male) Blood pressure >130/85 BMI >35 (female) >40 (male)

Answer 304

T4 hypersensitivity Rxn Auto immune destruction of pancreatic beta cells Causes absolute insulin deficiency

Answer 305

Triggered by environmental event (eg. virus) Leads to autoimmune antibodies against beta cells (HLA DR3 and HLA DR4)

Answer 306

Autoimmune Beta cell islet destruction - leads to absolute decrease in insulin Therefore causes Hyperglycaemia Low cellular glucose - Increased lipolysis and gluconeogenesis Hyperkalaemia

Answer 307

Lean Young Px Polydipsia Polyuria Polyphagia Weight loss Glycosuria Signs of DKA (ketoacidosis)

Answer 308

Increase glucose in blood Increase glucose filtered in the kidney Glucose in the kidney draws water into the kidney Causes increased urination - polyuria Causes Glycosuria - glucose in urine Due to increased urination, the blood is hyperosmolar (high glucose) detected by the hypothalamus and so stimulates thirst centres (causes polydipsia)

Answer 309

Decreased glucose in the cells (no GLUT4) Therefore cells need energy from Lipolysis and Gluconeogenesis Increased Lipolysis and Increase proteolysis leads to weight loss Leads to increased hunger - causes Polyphagia

Answer 310

Random Plasma Glucose (RPG) = > 11.1 mmol/L Fasting Plasma Glucose (FPG) = > 7.0 mmol/L HbA1C = 48mmol/mol (6.5%)

Answer 311

No - lifestyle modification will not prevent T1DM

Answer 312

Basal Bolus Insulin Basal - longer acting to maintain stable insulin levels through out the day Bolus - Faster acting - 30mins preprandial

Answer 313

Diabetic Ketoacidosis (DKA) From poorly managed T1DM Absolute insulin deficiency - unrestricted lipolysis and gluconeogenesis Not all glucose is usable so some is converted to ketone bodies There are acid and their increased concentration leads to ketoacidosis

Answer 314

T1DM Sx +: Kussmaul Breathing - Deep laboured breaths to blow off CO2 as compensation Pear drop breath - ketones have a pear drop smell Reduced tissue turgor - hypotension and tachycardia

Answer 315

Ketones (blood) >3mmol/L Hyperglycaemia > 11.1mmol/L - RPG Acidosis (metabolic) - <7.3pH or <15mmol HCO3 + Ketonuria, Glycosuria and Hyperkalaemia

Answer 316

ABCDE emergency 1st line is ALWAYS FLUID - Px die from dehydration Then insulin + glucose + K+

Answer 317

Peripheral insulin resistance With partial insulin deficiency that tends to present later in life (30+)

Answer 318

Genetic link - FHx very strong Smoking Obesity HTN Sedentary lifestyle

Answer 319

HTN Silent MI Nephrotic Syndrome CKD

Answer 320

Peripheral insulin resistance (malfunctioned insulin intracellular activation pathway) Decreased GLUT4 expression due to lower insulin Some destruction of pancreatic beta cells Causes hyperglycaemia with an increased insulin demand from a depleted Beta cell population

Answer 321

Obese Hypertensive Older Px Polydipsia Polyuria Nocturia Glycosuria Acanthosis Nigracans - dark pigmented skin folds

Answer 322

Same as T1DM: Random Plasma Glucose (RPG) = > 11.1 mmol/L Fasting Plasma Glucose (FPG) = > 7.0 mmol/L HbA1C = 48mmol/mol (6.5%)

Answer 323

Prediabetes is a condition in which your blood sugar or A1C levels are higher than normal but not high enough for a diagnosis of type 2 diabetes.

Answer 324

OGTT (oral glucose tolerance test) = 7.8-11 FPG = 6-6.9mmol/L

Answer 325

Lifestyle advice: Diet exercise modify RFs

Answer 326

Metformin - Increase peripheral sensitivity to Insulin If HbA1c >58mmol/mol then add sulfonylurea If persistently high then consider 3rd drug - DPP4-i/ SGLT2 inhibitor Then as a last resort give insulin.

Answer 327

Hyperosmolar - Hyperglycaemic State (HHS) Excessive hepatic gluconeogenesis (when not completely insulin deficient) leads to increased glucose in the blood therefore become hyperosmolar and hyperglycaemic. (don't get ketogenesis so no DKA)

Answer 328

Severe T2DM Decreased Consciousness - related to plasma osmolarity

Answer 329

High Glycosuria High plasma osmolarity (>300mol/L) Hyperglycaemia No ketonuria/hyperketonaemia

Answer 330

First give Insulin Then give IV fluid LWMH (Low molecular weight heparin) - anticoagulant as patients have thicker blood due to the glucose.

Answer 331

Macrovascular - Cardiovascular, cerebrovascular, peripheral vascular Disease Microvascular - retinopathy, neuropathy, nephropathy

Answer 332

Hyperglycaemia can lead to glucose conjugating with proteins and lipids to create proinflammatory molecules. These can lead to inflammation and LDL deposition leading to atherosclerosis This will lead to Macrovascular complications

Answer 333

Abnormally low blood glucose levels

Answer 334

T1DM T2DM MODY (Maturity Onset Diabetes of Youth) Pancreatic Diabetes Endocrine Diabetes Malnutrition related Diabetes

Answer 335

Diabetes drugs: Sulfonylureas - Stimulate insulin Insulin

Answer 336

Reduced consciousness Dizziness Sometimes may faint

Answer 337

IV glucose (if no IV access then IM Glucagon)

Answer 338

Between C5-T1 2 lobes connected via an isthmus

Answer 339

Inferior thyroid artery - branch of thyrocervical trunk (subclavian) Superior Thyroid artery - branch of external carotid

Answer 340

Iodine is trapped and diffuses into the colloid It binds to tyrosine residues on Thyroglobulin molecules using Thyroid peroxidase enzyme to produce T1/T2 TSH bind to TSH-R to stimulate the production of T3/T4 from T1/T2. T3/T4 are released into the circulation.

Answer 341

Graves disease (75-80%) Toxic multinodular Goitre (TMG) - nodules secrete thyroid hormone Toxic Adenoma

Answer 342

The 6 I Decreased insulin supply: low insulin Increased insulin demand (via stress): Infections Inflammation Intoxication Infarction Iatrogenic

Answer 343

T1DM - DKA T2DM - HHS (may also get DKA in severe chronic T2DM)

Answer 344

Excess of thyroid hormones in the blood Overproduction of thyroid hormone Leakage of preformed hormone from thyroid Ingestion of excess thyroid hormone

Answer 345

Increase glycogenolysis Increase glycolysis Increase lipolysis

Answer 346

Ophthalmopathy Pretibial Myxoedema Acropachy (characteristic rash) Also diffuse goitre and thyroid eye disease

Answer 347

Autoimmune disease characterised by the presence of TSH receptor autoantibodies. These stimulate the TSH-R Leading to the over production of T3/T4

Answer 348

Symptoms: Heat intolerance Diarrhoea Weight loss + Hyperphagia Anxiety Oligomenorrhoea Signs (everything FAST): Goitre Tachycardia exophthalmos - Protruding eyeball (graves specific) Pretibial Myxoedema Muscle wasting Fine Tremor

Answer 349

TSH-R Abs - In graves disease Clinical Hx Thyroid Function Tests (TFTs)

Answer 350

1' Hyperthyroidism - Decrease TSH, Increase T4 2' Hyperthyroidism - Increase TSH, Increased T4 Subclinical Hypothyroid - Increased TSH, = T4 Subclinical Hyperthyroid - Decreased TSH, = T4

Answer 351

Amiodarone Iodine Lithium

Answer 352

Thyroid Ultrasound or RAIU (Radioiodine uptake test) Presence of multinodular goitres in TMG

Answer 353

1st Line = Carbimazole - inhibits T3 to T4 conversion (if contraindicated such as in pregnancy = use Propylthiouracil + Propranolol alongside - targets symptomatic effects Can also use radioactive iodine - destroys thyroid tissue Last resort is surgery

Answer 354

Thyroid storm - where large amounts of Thyroid hormone is released very quickly (A MEDICAL EMERGENCY) Rapid deterioration of thyrotoxicosis leads to systemic compensation causing AF, HTN and coma

Answer 355

Propylthiouracil + KI

Answer 356

Diffuse goitre Thyroid Eye disease Pretibial Myxoedema Acropachy

Answer 357

Diffuse goitre Thyroid Eye disease Pretibial Myxoedema Acropachy

Answer 358

Low birth Weight Pre eclampsia Preterm delivery Risk of still birth Risk of Miscarriage

Answer 359

Where the thyroid overproduces thyroid hormone for a short period of time before then it may lead to hypothyroidism. This usually occurs due to destruction of the thyroid gland and therefore T3/T4 hormones are leaked/released but then greater destruction leads to less T3/T4 being produced causing hypothyroidism

Answer 360

Agranulocytosis Presents as a sore throat

Answer 361

Where there is too little thyroid hormone

Answer 362

Hashimoto's Thyroiditis - more common in developed world Iodine Deficiency - more common in developing world Post partum Thyroiditis

Answer 363

Hypothyroidism due to aggressive destruction of thyroid cells. Autoimmune condition where there are Anti-TPO (thyroid peroxidase) Abs that leads to less production of T3 and T4.

Answer 364

(everything slow) Symptoms: Cold intolerance Constipation Weight gain lethargy menorrhagia Signs: Bradycardia Slow reflexes Cold hands Goitre - in hashimoto's and I2 deficiency Pretibial Myxoedema

Answer 365

Primary: Hashimoto's Thyroiditis Drugs - Lithium, Amiodarone Iodine Deficiency Transient: Post Partum Thyroiditis Secondary: Hypopituitarism

Answer 366

Women Elderly Post partum

Answer 367

Younger onset (<30yrs) Usually lean North European

Answer 368

Older onset (>30yrs) Usually overweight More common in african/asian

Answer 369

TFTs: 1' Hypothyroidism = High TSH, Low T4 2' Hypothyroidism = Low TSH, Low T4 Subclinical Hypothyroidism = High TSH, = T4 Anti TPO Antibdoies increased in titres Typically anaemic

Answer 370

Levothyroxine (T4 analogue) - must be careful with the dose to prevent iatrogenic hyperthyroidism

Answer 371

Myxoedema coma - usually infection precipitated Rapid loss of T4 Hypothermia, loss of consciousness, heart failure

Answer 372

Levothyroxine, Abx Hydrocortisone until adrenal insufficiency has been ruled out

Answer 373

Papillary - (70%) Follicular (25%) Anaplastic - worst prognosis

Answer 374

Presents as Thyroid Nodules - hard and irregular May have local compression on the recurrent laryngeal nerve - hoarse voice

Answer 375

Fine needle aspriation biopsy TFTs Thyroid ultrasound

Answer 376

Lung Bone Liver Brain

Answer 377

Papillary / Follicular - Thyroidectomy / radioiodine Anaplastic - palliative care

Answer 378

Ingestion of water Decrease plasma osmolality Increase cellular hydration Decrease thirst - decrease water intake Decrease ADH secretion - Increase urine excretion of water Decrease total body water

Answer 379

GPCR: V1a - in vasculature (similar to adrenoceptors) V2 - in collecting tubules of nephron - water reabsorption V1b - In pituitary in the brain

Answer 380

- Osmoreceptors in hypothalamus - Routine - Baroreceptors in brain stem and great vessels - Emergency

Answer 381

Concentration of a solute per KG of solution mOsmol/Kg

Answer 382

The number of molecules (concentration)

Answer 383

- Size is irrelevant - a molecule of sodium has the same effect as a molecule of albumin It is the number of particles (concentration) that makes a difference to the osmolality

Answer 384

- Sodium - Potassium - Chloride - Bicarbonate - Urea - Glucose

Answer 385

- Alcohol - Methanol - Polyethylene glycol - Manitol

Answer 386

282-295 mOsmol/kg

Answer 387

2x[Na] mmol/L + [Glucose] mmol/L + [urea] mmol/L

Answer 388

To account for the anion gap

Answer 389

- Acts on V2 receptors - Stimulates an intracellular cascade - Aquaporin-2 proteins are synthesised and inserted into the apical membrane - Permeability to water is increased - Increased reabsorption of water - Concentration of Urine

Answer 390

Arginine Vasopressin Deficiency - Central diabetes insipidus Arginine Vasopressin Resistance - Nephrogenic diabetes insipidus

Answer 391

Polyuria Polydipsia No glycosuria

Answer 392

- >3L urine per day - Check renal function - Check serum calcium

Answer 393

- Inappropriately dilute urine for plasma osmolality - Serum osmolality >300 and urine osmolality >200 - Normonatraemia or hypernatraemia - Water deprivation test

Answer 394

(formerly cranial diabetes insipidus) Lack of vasopressin (ADH)

Answer 395

Genetic - mutations in ADH gene Idiopathic Tumours - Craniopharyngioma, germinoma, metastases Trauma Infections - TB, meningitis Vascular Inflammatory

Answer 396

(formerly Nephrogenic Diabetes insipidus) Resistance to vasopressin (ADH) action - reduced kidney response to ADH

Answer 397

Osmotic Diuresis - DM Renal tubular acidosis Drugs Metabolic ADH-R mutation - V2 receptor defect

Answer 398

Polyuria Polydipsia Hypernatraemia Lethargy confusion Severe dehydration

Answer 399

Decreased ADH secretion/response to ADH Cannot reabsorb water Water lost through urine dilute high volumes of water dehydration

Answer 400

3+ L of urine daily (24 hrs) Water deprivation test (no fluid for 8 hrs) -Normally serum Osm stays normal and urine Osm increases -AVP Def/Rest - Serum Osm rises and urine Osm does not change Inject IM desmopressin - differentiates between Deficiency and Resistance AVP Deficiency - will provide adequate ADH to have an effect and therefore concentrate urine AVP resistance - Similar mechanism to ADH and therefore will have no effect on the kidney. Urine stays dilute

Answer 401

Treat underlying condition AVP Deficiency - Desmopressin AVP Resistance - Thiazides (hydrochlorothiazide)

Answer 402

Block Na+/Cl- transporter in DCT Increases Na+ in filtrate in CD. encourages Na uptake and H2O follows in CD will concentrate urine and increase water reabsorption Loss of K+ ions

Answer 403

- Mild130-135mmol/l - Moderate 125-129mmol/L - Severe <125mmol/l

Answer 404

134-144mmol/l

Answer 405

- Excess water - SIADH - Drip arm - Sodium deficiency - Renal failure - Malignancy - Liver failure - Addison's

Answer 406

- Water moves into the brain as a result of reduced osmolality - Producing brain oedema - Swelling in the brain leads to expulsion of electrolytes and osmalytes - Water loss accompanies loss of solutes, reduces brain swelling - If hypoosmolality is sustained, brain volume normalises and brain becomes adapted to hyponatraemia

Answer 407

- Acute - 48 hours - Rapid correction safer and may be necessary - Chronic - CNS adapts - Correction must be slow - <8mmol/24hr

Answer 408

Biochemically - Mild, Moderate, Severe Na decrease Syptomatically - Mild, Moderate, Severe Aetiology - Hypovolaemic, Euvolemic, Hypervolemic Acuity of Onset - Actue (<48hrs), Chronic (>48hrs)

Answer 409

Vomiting Headache Decreased GCS Muscle Weakness coma Severe Hyponatraemia Seizures Neurological complications Brainstem herniation

Answer 410

Low Na means increased compensatory H2O Enters skull and raises ICP Causes Hyponatraemic encephalopathy Risk of brainstem herniating through foramen magnum

Answer 411

Decreased serum Na Normal Serum K+ High urine Osm as concentrated urine and dilute serum

Answer 412

Na depletion: Give 0.9 saline Na depletion - serum Na will normalise SIADH - Serum fails to normalise

Answer 413

Syndrome of Inappropriate ADH: Too much ADH is released when it should not be

Answer 414

SIADH will release more ADH Will increase water retention but have compensatory Na excretion to maintain euvolemia Therefore SIADH presents as Euvolemia and Hyponatraemia Other Hyponatraemia causes can be fluid overload (Liver failure) or dehydration

Answer 415

Tumours (SCLC, prostate, pancreatic) Trauma Infection - TB, Meningitis SIADH: SCLC Infection/immunosuppressed Abscesses Drugs - SSRI Head trauma

Answer 416

Low osmolality Urine inappropriately concentrated Normal thyroid and adrenal function

Answer 417

Normal circulating volume No oedema

Answer 418

Need to know cause to determine Tx: If Fluid overload - Restrict fluids If SIADH - Restrict fluid + hypertonic saline + treat underlying cause If dehydration - Saline replacement

Answer 419

Treat underlying cause Fluid restrict <1L/24hrs Sometimes Demeclocycline - decreases responsivity of ADH Sometimes Vaptan - V2 receptor antagonist

Answer 420

- Glandular tissue - Accounts for 75% of total weight - Develops from the roof of the mouth (Rathke's pouch); loses stalk of rathke's pouch

Answer 421

- Nerve tissue - Contains axons that originate in hypothalamus. - Nerves from the floor of the 3rd ventricle

Answer 422

- Pituitary gland (anterior + posterior) - Hypothalamus - Optic chiasm - compression by pituitary tumour can lead to visual defects - Pituitary stalk

Answer 423

- Non-functioning pituitary adenomas (silent) - Endocrine active pituitary adenomas - Malignant pituitary tumours: - Functional and - Non-functional pituitary carcinoma - Metastases in pituitary (breast, lung, stomach, kidney) - Pituitary cysts: Rathke's cleft cyst, Mucocoeles.

Answer 424

Non functioning pituitary adenoma A benign growth in the pituitary gland that does not produce excessive hormones into the blood

Answer 425

Rare type of brain tumour derived from pituitary gland embryonic tissue.

Answer 426

Squamous epithelial remnants of Rathke's pouch

Answer 427

- Adamantinous (classical) - Papillary

Answer 428

- Headaches and raised intracranial pressure - Visual defects (20% of children and 80% of adults) - Hormonal imbalances, leading to; - Short stature and delayed puberty in children - Decreased libido - Amenorrhea - Diabetes insipidus Behavioural change; due to frontal or temporal extension

Answer 429

Tumour forming from the three membranous layers of the meninges

Answer 430

- Commonest tumour of region after pituitary adenoma - Slow growing - 90% benign - Often a complication of radiotherapy

Answer 431

Tumour Mass Effects - Headaches, CSF Rhinorrhoea, Visual field defects, CN palsy Hormone excess - Hormone tests Hormone deficiency

Answer 432

> Measure free T4 and TSH in plamsa - Primary Hypothyroidism - Raised TSH, low free T4 - Hypopituitary - Low free T4 with normal/ low TSH - Graves' disease - Suppressed TSH and high free T4 - Thyrotropinoma (TSHoma) - High free T4 with normal/ high TSH - Hormone resistance - High free T4 with normal or high TSH

Answer 433

> Measure Testosterone and FH/ FSH in plasma - Primary hypogonadism - Low testosterone, raised LH/FSH - Hypopituitary - Low testosterone, low/ normal LH/FSH - Anabolic steroid use - Supressed LH, low testosterone

Answer 434

> Measure Oestradiol and FH/ FSH in plasma - Before puberty - Oestradiol very low/ undetectable - Low LH and FSH; FSH slightly higher than LH - At puberty - Pulsatile LH increases - Oestadiol increases - During monthly menstrual cycle - Mid-cycle surge in LH and FSH - Oestradiol increases throughout the cycle - Primary ovarian failure (including menopause) - High LH and FSH; FSH higher than LH - Low oestradiol - Hypopituitary - Low oestradiol - Normal or low LH and FSH - Incidence of oligo- or amenorrhoea

Answer 435

> Measure Cortisol and ACTH and Short Synacthen Test (SST); response to injection of synthetic ACTH - Primary Adrenal Insufficiency - Low cortisol, high ACTH - Poor response to synacthen - Hypopituitarism - Low cortisol, low/ normal ACTH - Poor response to synacthen

Answer 436

> Measure of Growth Hormone (GH) and Insulin-like Growth Factor 1 (IGF1) - GH is secreted in pulses; greatest pulse at night, low or undetectable levels between pulses - GH levels fall with age and are low in obesity - Measure IGF-1 and GH stimulation test - Insulin stress test - Glucagon test - Other

Answer 437

> Measure Prolactin - Negative feedback control of dopamine - Measure prolactin or cannulated prolactin; three samples over an hour to exclude stress or venepuncture - Prolactin maybe raised because - Stress - Drugs: antipsychotics - Stalk pressure - Prolactinoma

Answer 438

GH - Replacement GH LH/FSH - Testosterone in men, Oestradiol +/- Progesterone in women TSH - Levothyroxine ACTH - Hydrocortisone ADH - DDAVP

Answer 439

- Hypothalamus - Pituitary - Adrenals

Answer 440

- Cortisol - Released from adrenal glands - Act on pituitary and hypothalamus - Corticotrophin releasing hormone - Released from hypothalamus - Acts on pituitary - Adrenocorticotropic hormone - Released from pituitary - Acts on adrenal glands

Answer 441

- On waking up - Lunchtime - Dinnertime

Answer 442

Glucocorticoids

Answer 443

Addison's disease

Answer 444

Autoimmune

Answer 445

Hypopituitarism

Answer 446

Suppression of HPA axis from steroids

Answer 447

- Steroids - Oral - Inhaler - Creams

Answer 448

- Symptoms - Fatigue - Weight loss - Poor recovery from illness - Adrenal crisis - Headache - Past history - TB - Post partum bleed - Cancer - Family history - Autoimmunity - Congenital disease - Drug history - Any steroid use - Etomidate - Ketoconazole

Answer 449

- Pigmentation and pallor - Hypotension

Answer 450

- 09:00 Cortisol and ACTH - If cortisol > 450-500 nmol/l, adrenal insufficiency unlikely - Cortisol < 100nmol/l high likelihood of adrenal insufficiency - ACTH > 22pmol/l primary adrenal insufficiency - ACTH < 5pmol/l secondary adrenal insufficiency Renin/Aldosterone - Elevated in primary adrenal insufficiency Synacthen Test

Answer 451

- Stimulation test - Synacthen is synthetic ACTH - 250µg IV measure at 0 and 30 mins - Cortisol >450-550nmol/l, adrenal insufficiency unlikely

Answer 452

- Take bloods to test for ACTH and cortisol - Confirmation of adrenal crisis when patient is stable - Immediate hydrocortisone (100mg IV, IM) - Fluid resuscitation (1L N/saline 1 hour) - Hydrocortisone 50-100mg IV/IM 6 hourly or 200mg/24 hour - Continue until patient has stabilised - When stable, wean to normal replacement over 24-72 hours - If the patient has primary adrenal insufficiency, give fludocortisone (100-200µg)

Answer 453

10x 10mg Tablets Hydrocortisone

Answer 454

Cannot harm the patient and can be life saving

Answer 455

Hydrocortisone 15-25mg in 2-3 divided doses

Answer 456

- First on waking - Second midday - Third 17:00

Answer 457

- 3-5mg/d orally once or twice a day - Patients with reduced compliance to hydrocortisone

Answer 458

Women with low libido and low energy levels

Answer 459

Provides normal body hair in young women with adrenal insufficiency

Answer 460

- If symptomatic: - fasting glucose greater than or equal to 7.0 mmol/l - random glucose greater than or equal to 11.1 mmol/l (or after 75g oral glucose tolerance test- OGTT, at 2hrs post ingestion) - If asymptomatic: the above criteria apply but must be demonstrated on **TWO** separate occasions

Answer 461

- Commonest age at diagnosis is 5-15 years but can occur at any age - Relatively rare: prevalence of 3/1000 among children and adolescents - ~300,000 patients in the UK

Answer 462

1. Thirst: osmotic activation of hypothalamus 2. Polyuria: osmotic diuresis 3. Weight loss: lipid and muscle loss due to unrestrained gluconeogenesis 4. Hunger: lack of useable energy resources 5. Pruritus vulvae and balanitis (swelling of the foreskin or head of the penis): vaginal candidiasis; chest infections 6. Blurred vision: altered acuity due to uptake of glucose/water into lens

Answer 463

1. Weight loss 2. SHORT history of of severe symptoms (weeks) 3. Moderate or large urinary ketones Any 2/3 of these features indicates T1DM and are indication for immediate insulin therapy at ANY age

Answer 464

1. Usually present > 30 years old 2. Onset is gradual 3. FH is often positive; familial hypercholesterolemia 4. Almost 100% concordance in identical twins

Answer 465

Because of increased levels of obesity, T2DM is being diagnosed in younger patients including children. Uncontrolled T2DM can present with weight loss and ketonuria

Answer 466

- Early onset in childhood/adolescence - Lean body habitus; BMI normal or below normal range - Acute onset of osmotic symptoms; symptoms come on fast - Prone to ketoacidosis - High levels of islet autoantibodies

Answer 467

- Anti GAD - Pancreatic islet cell Ab - Islet antigen-2 Ab - ZnT8

Answer 468

- Relieve symptoms - Prevent DKA - Prevent microvascular and macrovascular complications i.e. CVD

Answer 469

- ~30% in the UK will develop diabetic nephropathy - Those with nephropathy tend to develop proliferative retinopathy and severe neuropathy (e.g. patients may lose sensation in feet → ulcers → amputations) with major effect on quality of life

Answer 470

Insulin treatment: "Basal-bolus" regime - once/twice daily medium acting insulin plus pre-meal quick acting insulin. Patient need to: - Have the ability to judge CHO intake - Be aware of blood glucose lowering effect of exercise

Answer 471

- Risk of hypoglycaemia - Too arduous a treatment - Risk of weight gain - Interference with lifestyle - Lack of sufficient training from diabetes teams

Answer 472

DKA: Fat metabolism and the formation of ketones Reduced insulin → fat breakdown and formation of glycerol (a gluconeogenic precursor) and FFA FFAs: - Impair glucose uptake - Are transported to the liver → provide energy for gluconeogenesis - Are oxidised to from ketone bodies (β-hydroxy butyrate; acetoacetate; acetone) ****which the body can use as a form of energy

Answer 473

1. Absence of insulin and rising counterregulatory hormones = increased hyperglycaemia and rising ketones 2. Glucose and ketones escape in the urine but lead to an osmotic diuresis and falling circulating blood volume 3. Ketones (which are weak acids) also cause anorexia and vomiting 4. = vicious cycle of increasing dehydration; hyperglycaemia and increasing acidosis eventually lead to circulatory collapse and death

Answer 474

- abdominal pain - drowsiness/confusion - polyuria; polydipsia - dehydration (av fluid loss of 5-6L) - hypotension and tachycardia - Kussmaul respiration (deep hyperventilation) - Acetone-smelling breath ('pear drops' smell)

Answer 475

- Blood ketones are ≥3.0 mmol/L OR there is ketonuria (more than 2+ on standard urine sticks) *AND* - Blood glucose is >11.1 mmol/L OR known diabetes *AND* - Bicarbonate (HCO3) is <15.0 mmol/L AND/OR venous pH is <7.3.

Answer 476

fluid replacement: most patients with DKA are deplete around 5-8 litres. Isotonic saline is used initially. - insulin: an intravenous infusion should be started at 0.1 unit/kg/hour. Once blood glucose is < 15 mmol/l an infusion of 5% dextrose should be started - correction of hypokalaemia (NB: K+ may be high on presentation despite total body K+ deficit - due to acute shift of K+ out of cells with acidosis - levels will subsequently fall with insulin and rehydration therapy, i.e. anticipate this fall! - long-acting insulin should be continued, short-acting insulin should be stopped - treat the underlying cause e.g. infection or MI

Answer 477

- gastric stasis - thromboembolism: venous and arterial as blood is made thicker by hyperglycaemia - arrhythmias secondary to hyperkalaemia/iatrogenic hypokalaemia - iatrogenic due to incorrect fluid therapy: cerebral oedema*, hypokalaemia, hypoglycaemia - acute respiratory distress syndrome - acute kidney injury - aspiration pneumonia in drowsy/comatose patient

Answer 478

1. Loss of concentration; confusion and coma Caused by acute deprivation of glucose within the brain leading to cerebral dysfunction 2. Sweating; tremor; palpitations (autonomic activation); hunger Caused by release of glucagon and adrenaline

Answer 479

- Hormonal response The first response of the body is decreased insulin secretion. This is followed by increased glucagon secretion. Growth hormone and cortisol are also released but later. - Sympathoadrenal response Increased catecholamine-mediated (adrenergic) and acetylcholine-mediated (cholinergic) neurotransmission in the peripheral autonomic nervous system and in the central nervous system

Answer 480

**Maturity-Onset Diabetes of the Young** It is the commonest type of monogenic diabetes (~1% diabetes) and is usually diagnosed < 25 years old. It is: - Autosomal dominant - Non-insulin dependent - A single gene defect alters beta cell function - Tends to be non-obese Because patients are young and not obese, they are often diagnosed as T1DM. But the big difference here is that they are not insulin dependent and therefore wouldn't need to be taking insulin as opposed to a T1DM patient.

Answer 481

HNF1A mutation (MODY 3) HNF4A mutation (MODY 1) Glucokinase (GCK) gene mutation (MODY 2)

Answer 482

- Parent affected with MODY - Absence of islet autoantibodies - Evidence of non-insulin dependence - Good control on low-dose insulin - No ketosis - Measurable C-peptide: in T1DM C-peptide test is negative within 5 years due to compete autoimmune beta cell destruction but in T2DM and MODY, C-peptide persists

Answer 483

< 6 months (usually *de novo;* from birth) Neonates may also present with: - small size - epilepsy - muscle weakness

Answer 484

Mutations in genes that encode Kir6.2 and SUR1 subunits of the beta cell ATP sensitive K+ channel.

Answer 485

A mutation in mitochondrial DNA

Answer 486

- Loss of beta cell mass - Overweight - Sensorineural hearing loss Overall, a similar presentation as T2DM

Answer 487

An abnormal distribution of fat in the body, usually due to a selective loss of adipose tissue. Associated with severe insulin resistance; dyslipidemia; hepatic stenosis; hyperandrogenism; PCOS

Answer 488

Due to inflammation; transient hyperglycaemia due to increased glucagon secretion

Answer 489

Chronic use of alcohol: it alters secretions; forms proteinaceous plugs that block ducts and act as a foci for calculi formation Treat by stopping alcohol intake and starting insulin

Answer 490

an accumulation of iron in various organs of the body such as the liver, hear, pituitary and pancreas?

Answer 491

Autosomal recessive: a triad of cirrhosis, diabetes and bronzed hyperpigmentation Treatment: most patients need insulin

Answer 492

- Amyloidosis - Cystinosis

Answer 493

The CFTR gene regulates Cl- secretion. In patients with defective CFTR, they have thick mucus secretions which can block ducts and lead to pancreatic fibrosis. CF survival rates are better than in the past, but this means people are living longer with the disease and microvascular complications are increasing 25-50% of CF patients will have diabetes. Insulin treatment will be needed.

Answer 494

Acromegaly

Answer 495

Presents similar to T2DM; Increased GH insulin resistance rises impairs insulin action in the liver and peripheral tissue

Answer 496

Cushing's syndrome

Answer 497

This leads to increased insulin resistance and reduced glucose uptake into peripheral tissues. Hepatic glucose production is increased through stimulation of gluconeogenesis via increased substrates (proteolysis and lipolysis)

Answer 498

Rare tumour of adrenal gland tissue → excess epinephrine and norepinephrine This leads to increased gluconeogenesis and decreased glucose uptake .

Answer 499

- Steroids - Tacrolimus - Thiazides - Protease inhibitors (HIV) - Antipsychotics

Answer 500

- Acute hyperglycaemia which can lead to hyperglycaemic hyperosmotic state or diabetic ketoacidosis - Chronic hyperglycaemia can cause tissue damage and complications (micro and macrovascular) - Side effects of treatment (namely hypoglycaemia)

Answer 501

- Stroke - CVD - Leading cause of mortality - Peripheral vascular disease

Answer 502

Pain: Allodynia Paraesthesia Burning Hyperaethesia Autonomic: Gastroparesis Diarrhoea/Constipation Incontinence Orthostatic Hypotension - Postural hypotension Insensitvity: Foot ulceration Infection amputation Charcot foot

Answer 503

Abnormal sensation (normally tingling or pins and needles) due to peripheral nerve damage

Answer 504

pain response to normally non-painful stimulus

Answer 505

Weakening of the bones of the foot, they are more prone to fractures and the stress of walking leads to deformity of the foot

Answer 506

What is the treatment of diabetic neuropathy?

Answer 507

- gloves and stocking sensory loss - Starts in tips of fingers and toes and works its way up

Answer 508

- Hypertension - Smoking - Poor glycaemic control - Diabetic duration - BMI - Triglycerides - Total cholesterol

Answer 509

- Good glycaemic control - Tricyclic antidepressants/SSRIs - Anticonvulsants (carbamazepine, Gabapentin) - Opioids (tramadol, oxycodone) - IV lignocaine - Capsaicin

Answer 510

- Test sensation - Vibration perception - Ankle Reflexes

Answer 511

Amputation

Answer 512

1. Neuropathy 2. Trauma 3. Ulcer 4. Failure to heal 5. Infection 6. Amputation

Answer 513

- Peripheral neuropathy - Painless foot - Lack of sweating in the skin can cause skin to become cracked and dry - Suggest moisturising - Peripheral vascular disease - Deformity - Increases pressure on the foot that can lead to ulceration - Hyperextended toes due to extensor muscles of the feet become more dominant

Answer 514

Distal sites

Answer 515

- Intermittent claudication - Rest pain - Diminished or absent pedal pulses - Coolness of feet and toes - Poor skin and nails - Absence of hair on feet and legs

Answer 516

Quit smoking Walk through the pain Surgical Intervention

Answer 517

- Long duration of diabetes - Poor glycaemic control - Hypertension - Insulin treatment - Pregnancy

Answer 518

Patients with diabetes over the age of 11

Answer 519

- Hyperglycaemia induces apoptosis of perictyes (which causes micro-aneurysms) and endothelial cells (which increases permeability of capillaries, proteins leak into retina) - It does this by increasing blood flow to the retinal capillaries and inducing abnormal metabolism - Loss of pericytes cause endothelial cells to respond by increasing turnover, which cause thickening of the capillary wall and cause ischaemia - Vascular growth factors are released in response to ischaemia, which cause the growth of new, fragile blood vessels which are prone to bursting

Answer 520

- R0 - None detected - R1 - Background changes; screened once a year - R2 - Pre-proliferative; early changes screened 6-monthly - R3 - Proliferative; called into eye clinic to look at interventions to protect vision - M - Maculopathy; changes that happen close to the fovea - P - Photocoagulation; laser treatment has been done - U - Unclassifiable

Answer 521

- Laser therapy - Aim is to stabilise the changes - Target abnormal blood vessels to stop them bleeding - Does not improve sight

Answer 522

- Difficulty with night vision - Loss of peripheral vision - Temporary drop in acuity (if intensive, reversible) - Vitreous haemorrhage (very rare) - Benefits far outweigh risks

Answer 523

- Very effective - 90% of severe eye sight loss prevented by early treatment

Answer 524

Proteinuria

Answer 525

Progressive decline in renal function

Answer 526

Poor blood pressure and blood glucose control

Answer 527

- Glomerulus changes - Increased injury of glomerulus - Filtration of proteins - Diabetic nephropathy

Answer 528

Monitor levels of albumin excreted in urine

Answer 529

- Spot collection (mg/mmol) (albumin/creatine ratio) - Male - <2.5 - Female - <3.5 - 24-hour collection (mg/24hr) - <30 - Timed collection (µg/min) - <20

Answer 530

- Spot collection (mg/mmol) (albumin/creatine ratio) - Male - 2.5-25 - Female 3.5-35 - 24-hour collection (mg/24hr) - 30-300 - Timed collection (µg/min) - 20-200

Answer 531

- Spot collection (mg/mmol) (albumin/creatine ratio) - Male - >25 - Female - >35 - 24-hour collection (mg/24hr) - >300 - Timed collection (µg/min) - >200

Answer 532

- Repeat the test within 3-6 months - Preferably first morning midstream void

Answer 533

Chronic kidney disease classification

Answer 534

T1DM - Around 10 years after diagnosis T2DM - Can be present at diagnosis

Answer 535

- Blood pressure control - Glycaemic control - ARB/ACEi - Proteinuria control - Cholesterol control

Answer 536

Hypercortisolaemia of any cause - excess cortisol production leading to excess cortisol in the blood

Answer 537

Hypercortisolaemia caused by a pituitary adenoma secreting excess ACTH that acts on the adrenals to increase cortisol.

Answer 538

ACTH dependent - Cushings diseae - Pituitary adenoma (80%) or ectopic ACTH production (5-10%) ACTH independent - Iatrogenic cause - Steroid use, adrenal carcinoma/adenoma

Answer 539

Mimics cushings syndrome Due to alcohol excess or severe depression. Resolves in 1-3 weeks

Answer 540

Constantly high cortisol levels Therefore CRH and ACTH are inhibited (unless ACTH dependent) Therefore there is loss of the circadian rhythm release of cortisol

Answer 541

Moon face Central obesity abdominal striae Osteoporosis Thin easy bruising Muscle wasting Hyperglycaemia - leading to DM, HTN and CVD plethoric complexion

Answer 542

Rule out oral steroids - if on steroids then stop these) Random serum cortisol measured at 12 am Dexamethasone suppression test: - Measure Cortisol levels at midnight. Give dexamethasone - in Normal person it should supress cortisol production by activating negative feedback loop. - Measure cortisol 8hrs later - Non cushings - suppression of cortisol - cortisol levels >50nmol/L - Cushings - little/no suppression

Answer 543

Rule out oral steroids - if on steroids then stop these) Random serum cortisol measured at 12 am Dexamethasone suppression test if positive - Measure Plasma ACTH Low ACTH - adrenal adenomas/carcinomas High ACTH - Cushings disease

Answer 544

Measure Cortisol levels Give low dose dexamethasone This inhibits CRH and ACTH release Should decrease cortisol if cushings is caused by endogenous cortisol then levels would remain unchanged.

Answer 545

Cushings disease - Transsphenoidal resection or bilateral adrenalectomy Cushings syndrome - Drug cause - drug is reduced/withdrawn adrenal steroid inhibitors.

Answer 546

Osteoporosis T2DM

Answer 547

Where the adrenal glands cannot make enough adrenal hormones such as cortisol.

Answer 548

Developed - Addisons disease Developing - TB (+Sarcoidosis)

Answer 549

Addison's Disease

Answer 550

Iatrogenic - Steroids - suppression of HPA axis Adrenal mets (lung liver and breast) Adrenal Haemorrhage (meningococcal septicaemia)

Answer 551

Autoimmune destruction of the adrenal glands. Auto Abs against 21-alpha-Hydroxylase reduced cortisol and aldosterone produced.

Answer 552

Destruction of adrenal cortex Increase ACTH - no feedback (therefore high ACTH, Low adrenal hormones)

Answer 553

Addison's disease - High ACTH, Low Adrenal hormones 2' Cause - HPA suppression - Low ACTH, Low adrenal hormones (no hyperpigmentation)

Answer 554

Hyperpigmentation due to excess ACTH activating melanocytes

Answer 555

Lethargy Weight loss Postural hypotension (due to reduced aldosterone) Vitiligo Hyperpigmentation (in 1') Hypoglycaemia Abdo pain and vomiting

Answer 556

Short Synacthen Test: - measure basal cortisol at 9am (normally highest here) - administer Synacthen - Sample cortisol again after 30 mins. If plasma cortisol > 580nmol/L after 30 min - not Addisons Auto 21-alpha-hydroxylase Abs ACTH (high in 1') (low in 2') at 9am.

Answer 557

Hydrocortisone Fludrocortisone

Answer 558

Severe adrenal insufficiency - Hypocortisolaemia Leads to N + V+, renal failure Tx is immediate Hydrocortisone, IV saline and dextrose (if hypoglycaemic)

Answer 559

Hyperaldosteronism Excess aldosterone independent of RAAS

Answer 560

Secondary HTN

Answer 561

2/3 - Adrenal adenoma 1/3/ Bilateral Hyperplasia

Answer 562

Increase aldosterone Increase Na and H2O and decrease K+ Causes Hypertension and Hypokalaemia

Answer 563

Resistant HTN (unfixable with ACEi / Bb) Hypokalaemia Muscle weakness Paraesthesia Polydipsia Polyuria

Answer 564

Aldosterone Renin ratio Serum aldosterone not suppressed with 0.9 IV saline or Fludrocortisone Hypokalaemic ECG

Answer 565

Surgery (Laparoscopic Adrenalectomy) Spironolactone (aldosterone antagonist)

Answer 566

Adrenal medullary tumour that secretes excess catecholamines (NAdr and Adr)

Answer 567

Usually inherited disorder associated with Men - multiple endocrine neoplasia Nerurofibromatosis

Answer 568

Hypertension Pallor Very sweaty Tachycardic

Answer 569

Plasma Metanephrines + Normetanephrine Urinary catecholamines CT image of tumour

Answer 570

Alpha blocker first ( phenoxybenzamine) Beta blocker second (atenolol) Surgery if possible.

Answer 571

Hypertension crisis (180/120+ BP) Tx Phentolamine

Answer 572

Hyperparathyroidism Bone malignancy drugs - Thiazides Excess Ca intake

Answer 573

BONES STONES GROANS MOANS

Answer 574

PTH decreases Except in hyperparathyroidism

Answer 575

CKD (decreased Vit D activation) Severe Vit D deficiency Hypoparathyroidism Drugs - Bisphosphates, Calcitonin Acute Pancreatitis

Answer 576

Chvostek sign Trousseau sign

Answer 577

PTH always increases Except in hypothyroidism

Answer 578

AKI Drugs - NSAIDS, Spironolactone, ACEi Addison's Disease DKA (+DM)

Answer 579

Increase K+ decreases threshold for AP Easier depolarisation Arrhythmias

Answer 580

Fast irregular pulse VF risk Myalgia

Answer 581

ECG: Go - Absent P wave Go long - Prolonged PR interval Go tall - Tall T waves Go wide - Wide QRS Increased K+ on U&Es

Answer 582

If urgent - Calcium Gluconate If non urgent - Insulin (+dextrose)

Answer 583

Thiazides = loop diuretics Conn's Renal tubular acidosis GI losses Reduced Intake

Answer 584

Hypotonia Hyporeflexia Arrhythmias (AF)

Answer 585

ECG: Small inverted T waves Prominent U waves ST Depression Pr Prolongation

Answer 586

K+ replacement Aldosterone antagonist - Spironolactone

Answer 587

Hypothyroidism Addison's Disease Coeliac Disease

Answer 588

Hyperglycaemia Ketones - Urine ketones >2+ Metabolic Acidosis - plasma HCO3 <15mmol/l

Answer 589

- What should patients carry with them? - 10x 10mg tables hydrocortisone - When ill, what should the patients do to their steroid dose - If unwell with fever or flu like symptoms, double dose of steroids - If in doubt, double dose of steroids - What should the patient do if they're vomiting and can't take their medication? - Emergency injection of hydrocortisone 100mg IM - If they are unable to inject themselves but are vomiting, what should the patient do? - 20mg hydrocortisone 6 hourly and repeat if vomited - Call an ambulance/go to ED - Why should hydrocortisone be administered without prejudice? - Cannot harm the patient and can be life saving

Answer 590

Diabetic retinopathy Nephropathy Neuropathy Microalbuminaemia

Answer 591

Reducing blood glucose Reduce the risk of CDV, CKD, Macro/microvascular complications Weight reduction, increase physical activity, decrease dietary fat.

Answer 592

Metformin Then dietary advice

Answer 593

1. ↑ insulin sensitivity by enhancing peripheral glucose uptake through inducing phosphorylation of GLUT-4 enhancer factor 2. ↓ hepatic gluconeogenesis (via a complex cell signalling pathway!)

Answer 594

Slight decrease in weight; more likely weight neutral

Answer 595

1. Gastrointestinal upset 2. Lactic acidosis

Answer 596

Increased weight gain patients experienced whilst taking them

Answer 597

Stimulate the release of insulin by pancreatic β-cells. Initiates cellular depolarisation to cause an influx of Ca2+ into the cell → increased fusion of insulin granulae w/ cell membrane = release of insulin

Answer 598

1. Hypoglycaemia 2. Weight gain 3. Hyponatraemia

Answer 599

Gliclazide Glimepiride

Answer 600

SGLT2 inhibitors

Answer 601

Inhibit Na/Glu cotransporters (SGLT-2) to inhibit reabsorption of glucose by the kidney (PCT)

Answer 602

Typically result in weight loss

Answer 603

1. Increased risk of UTI 2. Increased risk of candidiasis (thrush)

Answer 604

1. canagliflozin 2. dapagliflozin 3. empagliflozin

Answer 605

1. GLP-1 is excreted by L-cells of the intestine upon ingestion of food. GLP-1 → binds to the GLP-1 receptor → inhibits glucagon release → stimulation of insulin release → decrease of blood sugar (GLP-1 is has a very short half-life - they are broken down by DPP-4 very quickly - so a GLP-1 analogue can be administered to mimic its action) 2. Induces a delay in gastric emptying

Answer 606

Typically result in weight loss (a major advantage in T2DM)

Answer 607

Injectable on: Subcutaneous

Answer 608

1. Induces nausea and vomiting 2. Increased risk of pancreatitis

Answer 609

Liraglutide

Answer 610

1. Dipeptidyl-peptidase 4 (DPP-4) is an enzyme present in vascular endothelial lining which inactivates the incretin hormones GIP and GLP-1 DPP-4 Inhibitors are competitive antagonists of the DPP-4 enzyme, enhancing the effects of GIP and GLP-1. 2. Little effect on gastric emptying

Answer 611

Very little effect, "weight neutral"

Answer 612

Generally well tolerated: less likely to cause nausea and vomiting 1. Increased risk of pancreatitis

Answer 613

1. Vildagliptin 2. Sitagliptin

Answer 614

1. Vildagliptin 2. Sitagliptin

Answer 615

1. ↑ adipogenesis and fatty acid uptake by activating PPAR-γ (its endogenous ligand is FFA) 2. This leads to altered gene expression = ↑ storage of FFA so there are less FFA in the circulation. 3. Other cells become more dependent on glucose for respiration and so increase their uptake of glucose → reduced blood glucose levels

Answer 616

Induce weight gain

Answer 617

1. Weight gain 2. Fluid retention 3. Contraindicated in: CCF; high risk of fractures; macula oedema 4. Increased CV risk; lipid abnormalities (apart from Pioglitazone)

Answer 618

Pioglitazone

Answer 619

Bariatric surgery: Bypass surgery Sleeve Gastrectomy

Old Endocrinology Flashcards

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