Endocrinology Flashcards

Question

Define Cushing's Syndrome.

Answer 1

Syndrome associated with chronic inappropriate elevation of free circulating cortisol.

Answer 2

ACTH-dependent = 80% - Excess ACTH secreted from pituitary adenoma - Cushing's Disease (80%) - ATCH secreted from ectopic source - e.g. small-cell lung carcinoma, pulmonary carcinoid tumours (20%) ACTH-Independent (20%) - Excess cortisol secreted from benign adrenal adenoma (60%) - Excess cortisol secreted from adrenal carcinoma (40%) RARE: ACTH-Independent micro- or macro-nodular adrenal hyperplasia.

Answer 3

2-4 per 10 million per year May be more common Endogenous Cushing's Syndrome more common in females Peak incidence 20-40 years

Answer 4

- Weight gain - Fatigue - Muscle weakness - Myalgia - Thin skin - Easy bruising - Poor wound healing - Fractures - due to osteoporosis - Hirsutism - Acne - Frontal balding - Oligo or amenorrhoea - Depression - Psychosis

Answer 5

- Facial fullness - Facial plethora - Interscapular fat pad - Proximal muscle weakness - Thin skin - Bruises - Central obesity - Pink / purple striae on abdomen, breast and thighs - Kyphosis - due to vertebral fracture - Poorly healing wounds - Hirsutism - Acne - Frontal balding - Hypertension - Ankle oedema - salt and water retention as a result of mineralocorticoid effect of excess cortisol - Pigmentation in ACTH-dependent cases

Answer 6

1. Blood 2. High-Sensitivity Tests 3. Tests to Determine Underlying Cause Bloods - Non-specific changes - e.g. hypokalaemia (especially in ectopic), increased glucose Initial High-Sensitivity Test - Urinary free cortisol (2-3 24h urine collections) - Late-night salivary cortisol - Overnight dexamethasone suppression test - Low dose dexamethasone suppression test (LDDST) - give 0.5mg dexamethasone orally every 6h for 48h, Cushing's = fails to suppress serum cortisol below 50nmol/L 48h after 1st dose Tests to Detemine the Underlying Cause: - ACTH-independent (adrenal adenoma / carcinoma) - Low plasma ACTH, CT or MRI of adrenals - ACTH-independent (pituitary adenoma) - High plasma ACTH, pituitary MRI, high-dose dexamethasone suppression test, infeior petrosal sinus sampling - Cushings = central:peripheral ratio of venous ACTH >2:1 or >3:1 after CRH - ACTH-dependent (ectopic) - if suspect lung cancer then do CXR, sputum cytology, bronchoscopy, CT scan. ACTH-dependent (ectopic) - if suspect carcinoid tumours then do radiolabelled octreotide scans as express somatostatin receptors

Answer 7

Iatrogenic - Discontinue administration, lower steroid dose or use alternative steroid-sparing agent if possible Medical - Pre-operative or if unfit for surgery - Inhibition of cortisol synthesis with Metyrapone or Ketoconazole - Treat osteoporosis - Provide physiotherapy for muscle weakness Surgical - Pituitary adenoma - trans-sphenoidal adenoma resection (hydrocortisone replaced until pituitary recovery) - Adrenal adenoma/carcinoma - removel plus adjuvant therapy with Mitotane for adrenal carcinoma - Ectopic ACTH production - direct at tumour Radiotherapy - If not cured and have persistent hypercortisolaemia after transphenoidal resection of tumour - Stereotactic radiotherapy provides less irradiation to surrounding tissues Refractory Cases - Bilateral adrenalectomy

Answer 8

- DM - Osteoporosis - HTN - Pre-disposition to infections Surgical Complications: - CSF leakage - Meningitis - Sphenoid sinusitis - Hypopituitarism Radiotherapy Complications: - Hypopituitarism - Radionecrosis - Small increased risk of second intracranial tumours and stroke Bilateral Adrenalectomy Complications: - Nelson's Syndrome - locally aggressive pituitary tumour causing skin pigmentation due to excessive ACTH secretion

Answer 9

5-year survival rate - 50% | Depression persists for many years following successful treatment

Answer 10

A disorder of inadequate secretion of or insensitivity to vasopressin (ADH) leading to hypotonic polyruria.

Answer 11

Failure of ADH secretion by posterior pituitary = CENTRAL / CRANIAL Causes of CRANIAL: - Idiopathic - Tumours - e.g. pituitary tumour - Infiltrative - e.g. sarcoidosis - Infection - e.g. meningitis - Vascular - e.g. aneurysms, Sheehan Syndrome - Trauma - e.g. head injury, neurosurgery, DIDMOAD DIDMOAD (Wolfram's Syndrome) - DI, DM, optic atrophy, deafness (autosomal recessive with incomplete penetrance - WFS1, ZCD21 with products being a transmembrane protein expression in pancreatic B-cells & neurons) Insensitivity of collecting duct to ASDH = NEPHROGENIC - Aquaporins fail to activate - Luminal membrane of collecting duct remains impermeable to water - Large volume hypotonic urine - Polydipsia Causes of NEPHROGENIC: - Idiopathic - Drugs - e.g. lithium - Post-obstructive uropathy - Pyelonephritis - Pregnancy - Osmotic diuresis - e.g. DM

Answer 12

Depends on aetiology | Mean age of onset 24 yrs

Answer 13

- Polyruria - Nocturia - Polydipsia - Enuresis - Sleep disturbances - Other symptoms depend on aetiology

Answer 14

- Cranial diabetes insipidus has few signs if patients drink adequate fluids - Urine output >3L in 24h - Fluid intake < fluid output - Signs of dehydration - e.g. tachycardia, reduced tissue turgor, postural hypotension, dry mucous membranes - Signs of cause - e.g. visual field defect if pituitary tumour

Answer 15

- Blood - U&E, Ca2+, Na+ rise due to dehydration, increased plasma osmolality, reduced urine osmolality - Water deprivation test - restrict for 8h, plasma and urine osmolality measured every hour over 8h, weight patient every hour to monitor dehydration, stop test if fall in bodyweight is >3%, give desmopressin (2ug IM) after 8h and measure urine osmolality NORMAL - Water restriction causes rise in plasma osmolality - Increase ADH secretion - Increase water reabsorption in collecting ducts - Increase urine osmolality >600mosmol/kg Diabetes Insipidus - No ADH secretion - Urine unable to be concentrated by collecting ducts - Reduced urine osmolality <400mosmol/kg - Cranial - after desmopressin, increase in urine osmolality by 50% - Nephrogenic, after desmopressin, increase in urin osmolality by <45%

Answer 16

- Treat identified cause CRANIAL: - Desmopressin (vasopressin analogue) 10ug/day - Chlorpropamide or carbamazepine potentiate residual vasopressin in mild disease NEPHROGENIC: - Sodium and/or protein restriction helps polyuria - Thiazide diuretics

Answer 17

- Hypernatraemic dehydration | - Excess desmopressin therapy may cause hyponatraemia

Answer 18

Variable depending on cause Cranial - transient following head trauma Cure of cranial or nephrogenic may be possible if remove cause - e.g tumour resection, drug discontinuation

Answer 19

Elevation of one or more plasma lipid fractions.

Answer 20

LDL accummulates in the intima of systemic arteries. Taken up by LDLR on macrophage = foam cell. HDL is a shuttle in periphery for transport of cholesterol esters back to the liver --> cardioprotective Primary - molecular genetic basis, some unknown - Familial hypercholesterolaemia - reduced functional hepatic LDLR - Familial hypertriglyceridaemia - unknown, autosomal dominant - Hypertriglyceridaemia - lipoprotein lipase or apo-CII deficiency - Familial combined hyperlipidaemia - unknown - Remnant hyperlipidaemia - apo-E2 genotype inheritance, accumulation of LDL remnants Secondary - subdivided depending on abnormality - HIGH CHOLESTEROL - hypothyroidism, nephrotic syndrome, cholestatic liver disease, anorexia nervosa - HIGH TRIGLYCERIDES - diabetes, drugs (e.g. B-blockers, thiazides, oestrogens), alcohol, obesty, chronic renal disease, hepatocellular disease

Answer 21

50% of UK population have a cholesterol level high enough to be a risk for CHD.

Answer 22

- Asymptomatic - Symptoms of complications Ask about other CVS risk factors: - Diabetes - Smoking - Hypertension - Family history

Answer 23

Usually normal - examine for secondary causes. Lipid deposits: - Xanthelasmas - around eyes - Corneal arcus - Tendons xanthomas - e.g. extensor tendons of the hands, Achilles, patella - Tuberous xanthomas on knees and elbows - Xanthomas in palmar creases - in remnant hyperlipidaemia - Eruptive xanthomas and lipidaemia retinalis (pale retinal vessels) - severe hypertriglyceridaemia Signs of Complications: - Reduced peripheral pulses - Carotid bruits - CVD risks - High BP

Answer 24

1. Bloods 2. Cardiovascular Risk Assessment Bloods - Fasting lipid profile - Exclude secondary causes - e.g. glucose, TFT, LFT, U&E CVD Risk Assessment - Algorithms - E.g. Framingham risk equation, QRISK, ASSIGN`

Answer 25

Treat secondary causes. Advice - Exercise - Lose weight - Control BP - Control diabetes - Low alcohol - Dietary modification Lipid-lowering Drugs - Primary prevention - if multiple risk factors + no atherosclerosis + risk CHD >20% in 10 years - Secondary prevention - if established atherosclerosis (e.g. CHD, CAD, AA) - Target: total cholesterol <4mmol/L, LDL <2mmol/L Drugs for HIGH Total Cholesterol or HIGH LDL: - HMG-CoA Reductase Inhibitors - potently lowers mortality and CVS morbidity is demonstrated in numerous trials - high dose recommended as first line - e.g. 40mg simvastatin - Ezetimibe - inhibits cholesterol absorption in gut, used if statin not tolerated or as adjunctive agent Drugs for HIGH Triglycerides: - Fibrates - stimulates lipoprotein lipase activity via specific transcription factors - Fish oil - rich in omega-3 marine triglycerides, not recommended as can aggravate Others: - Anion-exchange resins - e.g. colestyramine, colestipol - binds bile acids and reduces reabsorption, increases hepatic cholesterol conversion to bile acids, increases LDLR on hepatocytes - Nicotinic acid - reduced hepatic VLDL release, reduces TG, reduces cholesterol, increases HDL, bad side effectes (PG-mediated vasodilation, flushing, dizziness, palpitations), increases glucose and urate.

Answer 26

- CAD - MI - PVD - Stroke - Hypertriglyceridaemia --> pancreatitis and retinal vein thrombosis - Complications of treatment - statins --> myositis

Answer 27

Depends on early diagnosis, treatment of hyperlipidaemia and control of other CVS risk factors. Lipid-lowering agents --> ?Reduce cerebrovascular accidents

Answer 28

An autoimmune thyroid condition associated with hyperthyroidism.

Answer 29

Circulating IgG autoantibodies bind to and activate G-protein-couples thyrotropin receptors. Causes smooth thyroid enlargement and increased T3 production and react with orbital autoangitens. Risk Factors: - Family history autoimmune thyroid disease - Female sex - Tobacco use - High iodine intake Triggers: - Stress - Infection - Childbirth

Answer 30

F:M 9:1 0.5% prevalence - 2/3rd cases of hyperthyroidism. 40-60yrs - younger if maternal family history

Answer 31

- Heat intolerance - Sweating - Weight loss - Palpitations - Tremor - Irritability - Diarrhoea - Increased appetite - Labile emotions - Oligomenorrhoea - Infertility - Psychosis - Chorea - Panic - Itch - Alopecia - Urticaria

Answer 32

- Diffuse goitre - Orbitopathy - exophthalmos - Tremor - Pretibial myxoedema - oedematous swellings above lateral malleoli - Thyroid acropachy - extreme manifestation, with clubbing, painful finger, toe swelling and periosteal reaction in limb bones - Tachycardia - Pulse fast / irregular - AF, SVT, VT rare - Warm moist skin - Palmar erythema - Thin hair - Lid lag - Lid retraction - exposure of sclera above iris - Causing stare - Thyroid nodules - Bruit

Answer 33

- Serum TSH - Serum free or total T4 - Serum free or total T3 - Calculation of total T3/T4 or FT3/FT4 ratio - T3 resin uptake (T3RU) - Free T4 index - Radioactive iodine (I-131, I-123) or technetium-99 (Tc-99) uptake - Thyroid isotope scan - TSH receptor natibodies (TRAb) - Thyroid ultrasound - CT or MRI scan of orbit - Skin biopsy

Answer 34

Primary - Increased secretion of parathyroid hormone (PTH) unrelated to plasma calcium concentration Secondary - Increased secretion of PTH secondary to hypocalcaemia. Tertiary - Autonomous PTH secretion following chronic secondary hyperparathyroidism.

Answer 35

Primary - Parathyroid gland adenoma or hyperplasia - Rarely parathyroid carcinoma (2%) - may be associated with multiple endocrine neoplasias (MEN) (80% single adenoma, 18% multiple adenomas / hyperplasia) Secondary - Chronic renal failure - Vitamin D deficiency

Answer 36

Primary - 5 in 100,000 - Twice as common in females - 40-60 yrs peak incidence

Answer 37

Primary - Mild hypercalcaemia - Asymptomatic Hypercalcaemia - Polyuria - Polydipsia - Renal calculi - Bone pain - Abdominal pain - Nausea - Constipation - Psychological depression - Lethargy Secondary - Symptoms and signs of hypocalcaemia and underlying cause - e.g. osteomalacia, chronic renal failure, Vitamin D deficiency

Answer 38

Primary - Mild hypercalcaemia - Asymptomatic Hypercalcaemia - Polyuria - Polydipsia - Renal calculi - Bone pain - Abdominal pain - Nausea - Constipation - Psychological depression - Lethargy Secondary - Symptoms and signs of hypocalcaemia and underlying cause - e.g. osteomalacia, chronic renal failure, Vitamin D deficiency

Answer 39

1. Bloods 2. Urine 3. Renal Ultrasound 4. Radiographs 5. Preoperative localization Bloods - U&E - increased in primary and tertiary, reduced or normal in secondary - Serum calcium - increased in primary and tertiary, reduced or normal in secondary - Phosphate - reduced in primary and tertiary, increased in secondary - Albumin - calculate corrected calcium - High AlkPhos - Vit D (low in secondary) - PTH levels - patients with parathyroid carcinomas more likely to have marked hypercalcaemia with high serum PTH levels Primary - Hypercholraemic acidosis - normal anion gap - Caused by PTH inhibition of renal tubular reabsorption of bicarbonate Urine - Differential - familial hypocalciuric hypercalcaemia (FHH) - In patients with high or inappropriately normal PTH levels, measure Ca2+: creatinine ratio to differentiate - Primary hyperparathyroidism = ratio > 0.01 - FHH (familial hypocalciuric hypercalcaemia) = ratio < 0.01 Ca2+:Creatinine - Urine calcium mmol/L x Plasma creatinine umol/L / 1000 - Plasma calcium mmol x Urine creatinine mmol/L - 24h urine collection sent for creatinine clearance and calcium measurement Renal Ultrasound - At baseline - Look for renal calculi Radiographs - Subperiosteal erosions of phalanges - Brown tumours - osteolucent bone defects - Diffuse porotic mottling of skull caused by demineralization - pepper pot skull - Sclerosis of superior and inferior vertebral margins with central demineralization - rugger jersey spine - Renal calculi / nephrocalcinosis Preoperative Localization - Ultrasound of neck and technetium sestamibi scan

Answer 40

PRIMARY Acute Hypercalcaemia: - IV fluids - 4-6 in first 24h Conservative Management: - If patients don't meet surgical criteria - Avoid factors that exacerbate hypercalcaemia - e.g. thiazide diuretics - Maintain adequate hydration - 6-8 glasses of water per day - Moderate calcium and vitamin D intake Surgical: - Subtotal parathyroidectomy - Total parathyroidectomy in MEN1 Surgical Indications: - Symptomatic patients or asymptomatics with ABCDE - A = Age <50 yrs - B = Bone mineral density T-score <2.5 - C = Calculi (renal stones), Creatinine clearance reduced by 30% - D = Difficult to do follow up periodically - E = Elevated serum calcium >0.25mmol/L above upper limit of normal or 24h urinary calcium >10mmol SECONDARY - Treat underlying renal failure - Calcium and Vitamin D supplements

Answer 41

Primary - Surgery curative for benign disease Secondary or Tertiary - As for chronic renal failure

Answer 42

Characterised by impairment of ovarian function.

Answer 43

PRIMARY HYPOGONADISM - hypergonadotrophic. Gonadal dysgenesis - Chromosomal abnormalities - e.g. Turner's Syndrome - FMR1 gene pre-mutation carriers (CGG repeats of between 55 and 200) Gonadal Damage - Autoimmune - Iatrogenic - e.g. chemotherapy, radiotherapy, surgery SECONDARY HYPOGONADISM - hypogonadotrophic Functional - Stress - Weight loss - Excessive exercise - Eating disorders - e.g. anorexia nervosa, bulimia Pituitary / Hypothalamic Tumours and Infiltrative Lesions - Pituitary adenomas - Craniopharyngiomas - Haemochromatosis Hyperprolactinaemia - Prolactinomas - Tumours causing pituitary stalk compression Congenital GnRH Deficiency - Kallmann's Syndrome - Idiopathic

Answer 44

Secondary hypogonadism - due to ovulation and amenorrhoea, than primary hypogonadism Turners - 1.5% conceptions, 10% spontaneous abortions, 1 in 2000-2500 live births.

Answer 45

- Night sweats - Hot flush - Vaginal dryness - Dyspareunia - Reduced libido - Infertility - Symptoms of underlying cause

Answer 46

PRE-PUBERTAL HYPOGONADISM - Delayed puberty - primary amenorrhoea, absent breast development, no secondary sexual characteristics - Eunuchoid proportions - e.g. long legs, increased arm span for height POST-PUBERTAL HYPOGONADISM - Regression of secondary sexual characteristics - e.g. loss of secondary sexual hair, breast atrophy - Perioral and periorbital fine facial wrinkles SIGNS OF UNDERLYING CAUSE / ASSOCIATED CONDITIONS - Hypothalamic / Pituitary Disease - visual field defects - Kallmann's Syndrome - anosmia - Turner's Syndrome- short stature, low posterior hairline, high arched palate, widely spaced nipples, wide carrying angle, short fourth and fifth metacarpals, congenital lymphoedema - Patients with Autoimmune Primary Ovarian Failure - signs of other autoimmune diseases - e.g. hyperpigmentation in Addison's Disease or vitiligo

Answer 47

- Low serum oestradiol - Serum FSH and LH - high in primary (due to -ve feedback), low or inappropriately normal in secondary - Investigations to determine aetiology PRIMARY - Karyotype - chromosomal abnormalities, complete or partial deletion of X Chromosome in Turner's, presence of Y chromosome - Pelvic imaging - US or MRI, if primary amenorrhoea to determine presence / absence of uterus, vagina, vaginal or cervical outlet obstruction (Mullerian agenesis, androgen insensitivity, transverse vaginal septum, imperforate hymen) - Unexplained premature ovarian failure - screen for pre-mutation in FMR1 gene after counseling & consent SECONDARY - Pituitary function tests - 9am cortisol, TFTs, prolactin - Visual field testing - Hypothalamic-pituitary MRI - Smell tests for anosmia - Serum transferrin saturation if hereditary haemochromatosis INVESTIGATION OF ASSOCIATED CONDITIONS - Turner's - periodic echocardiography and cardiology follow up, renal US - Autoimmune oophoritis - evaluate for autoimmune adrenal insufficiency (measure 21-hydroxylase antibodies, ACTH stimulation test if positive)

Answer 48

A syndrome of reduced testosterone production, sperm production or both.

Answer 49

PRIMARY HYPOGONADISM - hypergonadotrophic Gonadal Dysgenesis - Klinefelter's Syndrome (XXY) - Undescended testes - cryptochidism Gonadal Damage - Infection - e.g mumps - Torsion - Trauma - Autoimmune - Iatrogenic - e.g. chemotherapy, surgery, radiation Rare Causes - Defects in enzymes involved in testosterone synthesis - Myotonic dystrophy SECONDARY HYPOGONADISM - hypogonadotrophic Pituitary / Hypothalamic Lesions GnRH Deficiency - Kallmann's Syndrome - Idiopathic Hyperprolactinaemia Systemic / Chronic Diseases Rare Causes - Genetic mutations - Prader-Willi Syndrome - loss of critical region on Chr15 causing obesity, short stature, small hands, almond-shaped eyes, learning difficulties / postnatal hypotonia - Laurence-Moon-Biedl Syndrome - obesity, polydactyly, retinitis pigmentosa, learning difficulty

Answer 50

- 30-40% male infertility cases = Primary Hypogonadism - 1-2% male infertility = Secondary Hypogonadism - 10-20% male infertility = disorders of sperm transprot - 40-50% male infertility = non-classifiable - Klinefelter's Syndrome - 1 in 500-1000 live births

Answer 51

- Delayed puberty - Reduced libido - Impotence - Infertility - Symptoms of underlying cause Klinefelter's Syndrome - Intellectual dysfunction - Behavioural abnormalities that cause difficulty in social interactions

Answer 52

- Measure testicular volume using Prader's orchidometer - ellipsoids of different sizes (normal = 15-25ml) PRE-PUBERTAL HYPOGONADISM - Signs of delayed puberty - e.g. high-pitched voice, reduced pubic/axillary/facial hair, small or undescended testes, small phallus - Gynaecomastia - Eunuchoid proportions - arm span > height, lower segment > upper segment - due to delayed fusion of the epiphyses and continued growth of long bones - Features of underlying cause - e.g. cryptorchidism, anosmia in Kallmann's Syndrome POST-PUBERTAL HYPOGONADISM - Reduced pubic / axillary / facial hair - Soft and small testes - Gynaecomastia - Fine perioral wrinkles - Features of underlying cause - e.g. visual field defects due to a pituitary tumour, signs of chronic / systemic illness

Answer 53

- Calculate serum free testosterone - serum total testosterone, SHBG and albumin - LH, FSH PRIMARY - Low testosterone - High LH & FSH (due to -ve feedback) SECONDARY - Low testosterone - Low or inappropriately normal LH & FSH Determine level of defect: PRIMARY - Karyotype - to exclude Klinefelter's Syndrome SECONDARY - Pituitary function tests - 9am cortisol, TFTs, prolactin - MRI hypothalamic-pituitary area - Visual field testing - Smell tests for anosmia - Iron studies - ferritin, transferrin saturation (if hereditary hemochromatosis)

Answer 54

Deficiency of one or more of the hormones secreted by the anterior pituitary. PAN-hypopituitarism - deficiency of ALL pituitary hormones.

Answer 55

Pituitary Masses - Pituitary adenomas - Parapituitary tumours - e.g. craniopharyngioma, meningioma, glioma, metastases - Cysts - e.g. arachnoid cyst, Rathke's cleft cyst Pituitary Trama - Radiation - Surgery - Skull base fracture Hypothalamus (Functional) - Anorexia - Starvation - Over-exercise Infiltration - TB - Sarcoidosis - Haemochromatosis - Histiocytosis X Vascular - Pituitary apoplexy - Sheehan's Syndrome Infection - Meningitis - Encephalitis - Syphilis - Fungal abscess Genetic Mutations - Pit-1 gene - Prop-1 gene

Answer 56

Pituitary Adenoma - Annual incidence - 1 in 100,000 - Prevalence - 9 in 100,000

Answer 57

- Symptoms or signs depending on aetioogy - e.g. bitermporal hemianopia is due to pituitary mass - Symptoms and signs according to type of hormone deficiency Hormones & Features GH - Children - short stature (<3rd centile or not in keeping with parental height) - Adults - low mood, fatigue, reduced exercise capacity/muscle strength, increased abdominal fat mass LH / FSH - Delayed puberty - Female - loss of secondary sexual hair, breast atrophy, menstrual irregularities, dyspareunia, reduced libido, infertility - Males - loss of secondary sexual hair, gynecomastia, small or soft testes, reduced libido, impotence ACTH - See adrenal insufficiency TSH - See hypothyroidism Prolactin - Absence of lactation - in Sheehan's Syndrome Pituitary Apoplexy - life-threatening hypopituitarism with headache, visual loss, cranial nerve palsies = haemorrhage or infarction of pituitary tumour Sheehan's Syndrome - pituitary infarction, haemorrhage and necrosis following post-partum haemorrhage

Answer 58

- Symptoms or signs depending on aetioogy - e.g. bitermporal hemianopia is due to pituitary mass - Symptoms and signs according to type of hormone deficiency Hormones & Features GH - Children - short stature (<3rd centile or not in keeping with parental height) - Adults - low mood, fatigue, reduced exercise capacity/muscle strength, increased abdominal fat mass LH / FSH - Delayed puberty - Female - loss of secondary sexual hair, breast atrophy, menstrual irregularities, dyspareunia, reduced libido, infertility - Males - loss of secondary sexual hair, gynecomastia, small or soft testes, reduced libido, impotence ACTH - See adrenal insufficiency TSH - See hypothyroidism Prolactin - Absence of lactation - in Sheehan's Syndrome Pituitary Apoplexy - life-threatening hypopituitarism with headache, visual loss, cranial nerve palsies = haemorrhage or infarction of pituitary tumour Sheehan's Syndrome - pituitary infarction, haemorrhage and necrosis following post-partum haemorrhage

Answer 59

Pituitary Function Tests: Basal Tests - 9am Cortisol - LH - FSH - Testosterone - Oestradiol - IGF-1 - Prolactin - Free T4 - TSH Dynamic Tests - Insulin-induced hypoglycaemia (give IV 0.15U/kg insulin) - contraindicated in epilepsy, IHD, hypoadrenalism - Peak GH and cortisol response to insulin-induced hypoglycaemia = <20mU/L GH, <550nmol/L Cortisol - Short Synacthen Test - MRI or CT of brain - Visual field testing

Answer 60

Hormone Replacement Hydrocortisone - 20mg in morning - 10mg in evening - Double oral dose for febrile illness - IM hydrocortisone at times of surgery - MedicAlert bracelet and steroid card L-Thyroxine - Approx 100ug daily - Take after hydrocortisone to avoid Addisonian crisis Sex Hormones - Male - testosterone - Female - oestrogen with/without progesterone Growth Hormone - SC 1.2unit / day in adults - Children require specialist supervision Posterior Pituitary Deficiency - Due to damage to pituitary stalk - Desmopressin - vasopressin analogue 10-20ug / day intranasally

Answer 61

- Adrenal crisis - Hypoglycaemia - Myxoedema coma - Infertility - Osteoporosis - Dwarfism - children Complications of Pituitary Mass - Optic chiasm compression - Hydrocephalus - 3rd ventricular compression - Temporal lobe epilepsy

Answer 62

Good with lifelong hormone replacement

Answer 63

The clinical syndrome resulting from insufficient secretion of thyroid hormones.

Answer 64

PRIMARY - reduced thyroid hormone production Acquired - Autoimmune - Hashimoto's Thyroiditis (cellular and antibody-mediated) - Iatrogenic - e.g. post-surgery, radioiodine, medication for hyperthyroidism - Severe iodine deficiency or iodine excess (Wolff-Chaikoff Effect) - Thyroiditis Congenital - Thyroid dysgenesis - Inherited defects in thyroid hormone biosynthesis SECONDARY - Pituitary or hypothalamic disease - e.g. tumours - Results in low TSH or TRH and reduced stimulation of thyroid hormone production

Answer 65

Frequency 0.1-2% of adults F:M 6:1 Age onset - >40 years, but can occur at any age Iodine deficiency see in mountainous areas

Answer 66

Insidious onset - Cold intolerance - Lethargy - Weight gain - Constipation - Dry skin - Hair loss - Hoarse voice - Mental slowness - Depression - Dementia - Cramps - Ataxia - Paraesthesia - Menstrual disturbances - irregular cycles, menorrhagia - History of surgery or radioiodine therapy for hyperthyroidism - Family or personal history of other autoimmune conditions - e.g. Addison's disease, T1DM, pernicious anaemia, premature ovarian failure - Myxoedema coma - severe hypothyroidism in elderly --> hypothermia, hypoventilation, hyponatremia, heart failure, confusion, coma

Answer 67

Hands - Bradycardia - Cold hands Head/Neck/Skin - Pale puffy face - Goitre - Oedema - Hair loss - Dry skin - Vitiligo Chest - Pericardial effusion - Pleural effusion Abdomen - Ascites Neurological - Slow relaxation of reflexes - Signs of carpal tunnel syndrome

Answer 68

Bloods: - TFT - PRIMARY - low T4/T3, high TSH (due to reduced -ve feedback), SECONDARY - low T4/T3, low or inappropriately normal TSH Subclinical hypothyroidism - normal serum free T4/T3, high TSH FBC - Normocytic anaemia U&E - Low Na+ Cholesterol - Raised Secondary cases: - Pituitary function tests - Pituitary MRI - Visual field testing

Answer 69

Chronic - Levothyroxine (25-200ug/day) - Rule out underlying adrenal insufficiency - Treat before starting thyroid hormone replacement to avoid Addisonian crisis - Adjust dosage dependent on TFT and clinical picture - monitor at 6 weeks - If IHD, start at low dose (25ug/day) and gradually increase at 6 week intervals if IHD symptoms do not deteriorate Myxoedema Coma - Oxygen - Rewarming - Rehydration - IV T4/T3 - IV hydrocortisone - in case hypothyroidism is secondary to hypopituitarism - Treat underlying disorder - e.g. infection

Answer 70

- Myxoedema coma - Myxoedema madness - psychosis with delusions, hallucinations, dementia (seen after starting levothyroxine treatment in elderly)

Answer 71

Lifelong levothyroxine replacement therapy required Mortality of up to 80% if myxoedema coma

Answer 72

Hereditary tumour syndromes of variable neoplastic patterns and characterised by the development of multple endocrine tumours. - Parathyroid adenomas - Pituitary adenomas - can be non-secretory or affect profiles of ACTH, GH, TSH, prolactin - Enteropancreatic neuroendocrine tumours - affects profiles of gastrin, insulin, glucagon, vasoactive intestinal protein - Facial lipomas - Facial angiofibroma - Medullary thyroid cancers - Phaeochromocytoomas

Answer 73

Mutations - MEN1 gene cause Type 1 multiple endocrine neoplasia (MEN) - RET proto-oncogene cause Type 2 multiple endocrine neoplasia (MEN) Risk Factors: - Familial cases of MEN - RET proto-oncogene mutation - MEN1 (menin) mutation

Answer 74

The prevalence of all MEN 2 cases is ∼1 in 35,000 [2]. The prevalence of MEN 2B is estimated as between 1 in 600,000 [10] to 1 in 4 million [11], but no figures exist. The annual incidence has been estimated at 4 per 100 million per year [12].

Answer 75

- Weight changes (MEN1/2) - Abdominal pain (MEN1/2) - Headache (MEN1/2) - Episodic triad of sweating, palpitations, headache (MEN2) - Clinical features of kidney stones (MEN1/2)

Answer 76

- Hypertension (MEN1/2) - Young age (MEN1/2) - Positive family history (MEN1/2)

Answer 77

1st Line Investigations: - Serum calcitonin (MEN2) - Serum carcinoembryonic antigen (MEN2) - Plasma metanephrines (MEN2) - Serum parathyroid hormone and calcium (MEN1/2) Others to Consider - Fasting serum glucose / insulin (MEN1) - Serum C peptide (MEN1) - Calcium-stimulated gastrin (MEN1) - Serum proinsulin (MEN1)

Answer 78

A chronic adverse condition due to an excess amount of body fat. BMI = weight (kg) divided by height squared (m) Obesity = BMI > 30kg/m^2

Answer 79

BMI 30.0 to 39.9 kg/m²; class III obesity: BMI ≥40.0 kg/m² Risk Factors - Hypothyroidism - Hypercortisolism - Corticosteroid therapy - Age > 40 years - Peri- and post-menopause - Prior pregnancy - Married - Sleep deprivation - History of tobacco smoking - Less formal education - Poor in utero nutrition - Low socioeconomic status - Sedentary lifestyle - Television watching and video games >2-3 hours daily - Diet high in sugar, cholesterol, fat and fast food - Heavy alcohol intake (>2 drinks per day) - Binge-eating disorder - Night eating syndrome - Leptin deficiency - Antidepressant therapy - Antipsychotic therapy - Beta-blocker therapy - Adjuvant breast cancer therapy - Psychiatric diagnosis

Answer 80

Central or abdominal obesity has a stronger association with obesity-related comorbidity than peripheral (i.e., subcutaneous) obesity, so waist circumference may be a better indicator of the risk for obesity-related comorbidity than BMI. <1/3 world's population 2030 estimated 38% world adult population overweight, 20% obese

Answer 81

- Asymptomatic | - Multiple co-morbidity complications - e.g. cancer, CAD, DM, HTN, gout, obstructive sleep apnoea, osteoarthritis

Answer 82

Diagnostic Factors - Height - Weight - Waist circumference - >94cm in men, >80cm in women

Answer 83

- BMI - weight divided by height squared Not accurate in pregnancy or in people with large amounts of muscle mass. Does not account for sex, age or bone structure. Bloods - FBC - normal, may show anaemia - Serum transaminases - may be elevated if liver dysfunction - TFTs - may be low T4, high TSH if primary hypothyroidism, or normal/ inappropriately low TSH with secondary hypothyroidism - ECG - may show IHD - Abdominal US - fatty liver screen (steatohepatitis) - Polysomnography (sleep study) - may show obstructive sleep apnoea

Answer 84

Osteomalacia - a disorder of mineralization of bone matrix (osteoid) Rickets - a disorder of defective mineralization of cartilage in the epiphyseal growth plates of children

Answer 85

VITAMIN D DEFICIENCY - Lack of sunlight exposure - Dietary deficiency - Malabsorption in small bowel disease (coeliac disease, IBD), extensive bowel surgery, gastrectomy, pancreatic insufficiency - Reduced 25-hydroxylation of Vitamin D - e.g. liver disease, anticonvulsants - Reduced 1-alpha-hydroxylation - e.g CKD, hypoparathyroidism mutations in the gene encoding 1-alpha-hydroxylase - Vitamin D resistance - mutations in the VitD Receptor gene RENAL PHOSPHATE WASTING - Fanconi's Syndrome - phosphaturia, glycosuria, aminoaciduria - Renal tubular acidosis Type 2 - Hereditary hypophosphataemic rickets - X linked or autosomal dominant - Tumour-induced osteomalacia

Answer 86

Uncommon in industrialized countries | More common in females

Answer 87

Osteomalacia - Bone pain - especially axial skeleton - Weakness - Malaise Rickets - Hypotonia - Growth retardation - Skeletal deformities

Answer 88

Osteomalacia - Bone tenderness - Proximal muscle weakness - Waddling gait - Signs of hypocalcaemia may be present - e.g. Trosseau's Sign, Chvostek's Sign Trosseau's Sign - inflation of the sphygmomanometer cuff to above the systolic pressure for >3 mins causes tetanic spasm of the wrist and fingers Chvostek's Sign - tapping over the facial nerve causes twitching of the ipsilateral facial muscles Rickets - Bossing of frontal and parietal bones - Swelling of costochondral junctions (rickety rosary) - Bowed legs in early childhood - Knock-knees in later childhood - Short stature

Answer 89

1. Bloods 2. Radiographs 3. Bone Biopsy after Double Tetracycline Labelling Bloods - Low or normal Ca2+ - Low phosphate - High AlkPhos - Low 25(OH)Vitamin D - High PTH - secondary hyperparathyroidism - Check U&E, ABG - patients with renal tubular acidosis have normal anion gap hyperchloremic metabolic acidosis - Increased phosphate excretion - if renal phosphate wasting is not cause of hypophosphataemia, the fractional excretion of phosphate should be below 5% Radiographs - Appear normal - Show osteopenia - Looser's Zones - Pseudofractures - radiolucent bands - Seen on ribs, scapula, pubic rami, upper femur Bone Biopsy - After double tetracycline labelling - Tetracycline is deposited at mineralization front as band - x2 courses - separated by period of days - Distance between bands of deposited tetracycline is reduced in osteomalacia - Not usually performed as osteomalacia can be diagnosed from history, examination, laboratory and radiologic studies

Answer 90

- Vitamin D and Ca2+ replacement - Monitor 24h urinary calcium, serum calcium, phosphate, AlkPhos, PTH, Vit D - Treat underlying cause - e.g. advice on diet and sunlight exposure - X-linked hypophosphataemia: Oral phosphate, 1,25 (OH)2 Vitamin D

Answer 91

- Bone deformities | - Hypocalcaemia may cause epileptic seizures, cardiac arrhythmias, hypocalcemic tetany, depression

Answer 92

Symptoms and radiological appearances improve with Vitamin D treatment. Bone deformities in children tend to be permanent.

Answer 93

Reduced bone density (defined as <2.5 SD below peak bone mass achieved by healthy adults - T-score < - 2.5) resulting in bone fragility and increased fracture risk.

Answer 94

PRIMARY - Idiopathic - <50 years - Post-menopausal SECONDARY - Malignancy - myeloma, metastatic carcinoma - Endocrine - Cushing's disease, thyrotoxicosis, primary hyperparathyroidism, hypogonadism - Drugs - corticosteroids, heparin - Rheumatological - rheumatoid arthritis, ankylosing spondylitis - Gastrointestinal - malabsorption syndromes (e.g. coeliac disease, partial gastrectomy), liver diseases (PBC), anorexia Risk Factors: - Age - Family history - Low BMI - Low calcium intake - Smoking - Lack of physical exercise - Low exposure to sunlight - Alcohol abuse - Late menarche - Early menopause - Hypogonadism

Answer 95

Common >50 years - 1/3 women, 1/12 men Causes >200,000 fractures annually in UK - especially hip fractures More common in Caucasians than Afro-Carribeans

Answer 96

- Asymptomatic until characteristic fractures occur - Femoral neck fractures commonly occur after minimal trauma - Vertebral fractures - loss of height or stooped posture or acute back pain after listing - Colles' fractures of the distal radius after fall onto outstretched hand

Answer 97

No signs till complications develop: - Tenderness on percussion over vertebral fractures - Thoracic kyphosis - if multiple vertebral fractures - Severe pain with leg shortened and externally rotated - in femoral neck fracture

Answer 98

1. Bloods 2. X-Ray / Radiography 3. Isotope Bone Scan 4. Bone Densitometry (Dual-Energy X-Ray Absorptiometry DEXA Scan) Bloods - Ca2+ normal (if primary) - Phosphate normal (if primary) - AlkPhos normal (if primary) X-Rays - Diagnose fractures when symptomatic - Normal - >30% loss in density before showing radiolucency, abnormal trabeculae or cortical thinning evident - Biconcave vertebrae - Crush fractures Isotope Bone Scans - Highlight stress or microfractures - Not commonly used DEXA Scan - For obtaining T and Z scores of bone density - T-Score - the number of SD the bone mineral density measurement is above or below the young normal mean bone mineral density (defines osteoporosis) - Z-Score - the number of SD the measurement is above or below the age-matched mean bone mineral density (helpful in identifying patients who may need a work-up for secondary causes of osteoporosis)

Answer 99

Characterized by excessive bone remodelling at one (monostotic) or more (polyostotic) sites resulting in bone that is structurally disorganized.

Answer 100

Unknown. Genetic factors, viral infection. - Abnormally large osteoclasts - Excessive bone resorption - Increased bone formation by osteoblasts in a disorganized fashion - Abnormal mosaic pattern of lamellar bone - Marrow spaces filled by excess of fibrous tissue - Increased blood vessels

Answer 101

Older age 3% of all >50-year-olds 10% of all >80-year-olds M = W

Answer 102

- Asymptomatic - Present with insidious onset pain - Aggravated by weight-bearing and movement - May be caused by Pagetic process, associated degenerative joint disease or stress fractures - Headaches - Deafness - Increasing skull size

Answer 103

- Bitemporal skull enlargement - Frontal bossing - Spinal kyphosis - Anterolateral bowing of femur, tibia or forearm - Skin over the involved bone may be warm - due to increased vascularity - Sensorineural deafness - due to compression of the vestibulocochlear nerve

Answer 104

1. Bloods 2. Bone Radiographs 3. Bone Scan (99mTC MDP) 4. Resorption Markers Bloods - Increased AlkPhos - Ca and Phosphate normal - except if immobilized Bone Radiographs - Enlarged, deformed bones - Mixed lytic/sclerotic appearance - Lack of distinction between cortex and medulla - Osteoporosis circumscripta - Enlargement of frontal and occipital skull areas - Associated with 'cotton wool' appearance Bone Scan - To assess the extent of skeletal involvement - Not specific for the diagnosis - Pagetic bone lesions are focal areas of markedly increased uptake = hot spots Resorption Markers - For monitoring of disease activity - Urinary hydroxyproline

Answer 105

Catecholamine-producing tumours that usually arise from chromaffin cells of the adrenal medulla but are extra-adrenal in about 10% of cases. 10% bilateral, 10% malignant. Extra-adrenal phaeochromocytoma referred to as paragangliomas.

Answer 106

Cause of sporadic cases unknown. Familial - 30% patients - Multiple endocrine neoplasia Type 2A (MEN2A) - Von Hippel-Lindaeu (VHL) Syndrome - Neurofibromatosis Type 1 (NF1) - Mutations in genes encoding subunits of mitochondrial enzyme succinate dehydrogenase (SDHB, SDHD, SDHC) Mutations in VHL, SDHB, SDHD may contribute to pathogenesis of tumours via dysregulation of HIF-1 (hypoxia-inducible factor 1) and HIF-2 transcription factors.

Answer 107

<0.2% of hypertensive patients

Answer 108

- Paroxysmal episodes of headache - Sweating - Palpitations - Chest pain - Dyspnoea - Epigastric pain - Nausea - Constipation - Weakness - Tremor - Anxiety

Answer 109

- Hypertension (50-70%) - 2/3 sustained hypertension, 1/3 paroxysmal - Postural hypertension - due to reduced plasma volume - Pallor - Tachycardia - Fever - Weight loss

Answer 110

1. 24h Urine Collections 2. Plasma Free Metanephrines 3. Tumour Localization 4. 123I-MIBG Scintigraphy 5. Screen for Associated Conditions 6. Genetic Testing and Counselling 24h Urine Collections - In acid-containing bottle - Catecholamines - e.g. adrenaline, noradrenaline, dopamine - Fractionated metanephrines - Creatinine - verify adequate collection - Blood glucose - Ca2+ - may be high - K+ - may be low NB: Certain drugs may increase measured catecholamines - e.g. tricyclic antidepressants, levodopa Plasma-Free Metanephrines - In high-risk patients - 99% sensitivity Tumour Localization - CT or MRI 123I-MIBG Scintigraphy - For large phaeochromocytomas - increased risk of malignancy - For paraganglioma (extra-adrenal) - increased risk of multiple tumours and malignancy - If CT or MRI is negative, but diagnosis considered likely due to clinical and biochemical evidence Screen - MEN2A - serum calcium, calcitonin - VHL - opthalmoscopy, MRI posterior fossa, renal USS - NF1 - clinical examination for neurofibromas, cafe-au-lait spots, axillary freckling Genetic Testing and Counselling - For mutations in VHL, SDHB, SDHD, RET genes in patients with onset at a young age (<20yrs) - Family history - Evidence of one of the familial disorders mentioned or bilateral tumours

Answer 111

Characterized by oligomenorrhoea/amenorrhoea and hyperandrogenism (clinical or biochemical). Frequently associated with obesity, insulin resistance, T2DM, dyslipidaemia.

Answer 112

- Environmental factors - e.g. diet, obesity - Genetic variants - genes regulation gonadotrophin, insulin, androgens (synthesis, secretion, action), weight and energy regulation - Hyperinsulinaemia - increased ovarian androgen synthesis, reduced hepatic SHBG synthesis (increased free androgens)

Answer 113

Most common cause of infertility in women | 6-8% of women

Answer 114

- Menstrual irregularities - oligomenorrhoea / amenorrhoea - Dysfunctional uterine bleeding - Infertility - Symptoms of hyperandrogenism - e.g. hirsutism, male-pattern hair loss, acne

Answer 115

- Hirsutism - Male-pattern hair loss - Acne - Acanthosis nigricans - sign of severe insulin resistance, involving velvety thickening and hyperpigmentation of skin of axillae or neck

Answer 116

1. Bloods 2. Tests to Excluse 3. Looking for Impaired Glucose Tolerance / T2DM 4. Transvaginal USS Bloods - High LH - High LH: FSH ratio (>3) - High testosterone - High androstenedione - High DHEA-S - Low SHBG Tests to Exclude - Hyperprolactinaemia - do serum prolactin - Hypo/ hyperthyroidism - do TFTs - Congenital adrenal hyperplasia - do 17-OH-progesterone - Cushing's Syndrome - if clinically suspected T2DM - Fasting glucose - HbA1C - Oral glucose tolerance test - Fasting lipid profile Transvaginal USS - 12 or more folicles in each ovary - Measuring 2-9mm - Increased ovarian volume >10mL

Answer 117

Pituitary adenomas that do not cause a characteristic hormone hypersecretion syndrome (null cell and the majority of gonadotroph adenomas).

Answer 118

Classified into micro-adenomas (<1cm diameter) or macro-adenomas (>1cm diameter). May have suprasellar extension towards optic chiasm, lateral extension into cavernous sinuses or downward extension into sphenoid. Modest elevation of prolactin may occur due to compression of pituitary stalk and interruption of intrinsic dopaminergic tone. Risk Factors: - Multiple endocrine neoplasia Type 1 (MEN-1) - Familial isolated pituitary adenomas (FIPA) - Carney complex (CNC)

Answer 119

Small pituitary tumours (<4mm) common - up to 10% of MRIs in general population A small fraction of such tumours are associated with clinical features suggestive of pituitary disorder. 3rd most common intra-cranial neoplasm in adults, 10% of all intra-cranial tumours.

Answer 120

- Headaches - Visual field deficits - Erectile dysfunction - Long-standing and progressive symptoms - Constipation - Cold intolerance

Answer 121

- Increased central adiposity - Reduced muscle mass - Cranial nerve palsies (rare)

Answer 122

1st Line - Prolactin - Insulin-like Growth Factor (IGF) 1 - LH & FSG - Alpha-subunit of human pituitary glycoprotein hormones To consider: - Growth hormone stimulation test - Lipid panel - Humphrey or Goldmann formal visual fields test - Immunohistochemical staining

Answer 123

Aldosteronism production exceeds the body's requirements and is relatively autonomous with regard to its normal chronic regulator, the renin-angiotensin II system.

Answer 124

Results in excessive Na+ reabsorption via amiloride-sensitive epithelial Na+ channels within the distal nephron, leading to hypertension and suppression of renin-angiotensin II. Urinary loss of K+ and H+, exchanged for sodium at the distal nephron, may result in hypokalaemia and metabolic alkalosis if severe and prolonged. Risk Factors - Family history of primary aldosteronism - Family history of early onset of hypertension and / or stroke

Answer 125

5% of hypertensive patients - with most patients being normokalaemic. 30% unilateral forms correctable by unilateral laparoscopic adrenalectomy. 70% bilateral forms that respond to aldosterone antagonist medicines.

Answer 126

- Nocturia - Polyuria - Lethargy - Mood disturbance - irritability, anxiety, depression - Difficulty concentrating - Muscle cramps - Muscle weakness - Palpitations

Answer 127

- Hypertension - Hypokalaemia - Metabolic alkalosis

Answer 128

- Plasma potassium - low in 20% of patients - Aldosterone / renin ratio - A grey zone exists in ratios between 20 and 35. Some regard a ratio of >20 in combination with a plasma aldosterone concentration of >15 nanograms/dL as a positive screen.[27][29] This approach, however, will miss some patients with PA (more than one third in one series),[23] including those with aldosterone-producing adenoma (one-fifth) who have lower plasma aldosterone levels. - Fludrocortisone suppression test - failure of upright (10 a.m.) plasma aldosterone to suppress to <166 picomol/L (<6 nanogram/100 mL or <6 nanogram/dL) - Saline infusion testing - plasma aldosterone (measured at the end of the infusion) regarded as diagnostic, but the required level has varied from >139 to >277 picomol/L (>5 to >10 nanogram/100 mL or >5 to >10 nanogram/dL) - Oral salt loading - 24-hour urinary aldosterone level >12 microgram/day - Genetic testing for hybrid gene - positive in patients with familial hyperaldosteronism type I Others: - Adrenal CT, venous sampling, MRI, selenocholesterol scanning - Posture stimulation testing - Angiotensin II infusion testing - 24-hour urinary hybrid steroids (18-hydroxy and 18-oxo-cortisol) - Dexamethasone suppression testing

Answer 129

1) Unilateral PA - Surgical Patients - unilateral laparoscopic adrenalectomy, with pre/post-op aldosterone antagonists (spironolactone, amiloride or eplerenone) - Non-surgical Candidates - aldosterone antagonists (amiloride, spironolactone or eplerenone) 2) Bilateral PA - No adrenal lesion >2.5cm - aldosterone antagonists (amiloride, spironolactone, eplerenone) and lapasroscopic adrenalectomy, plus pre/post-op aldosterone antagonists (amiloride, spironolactone or eplerenone) - Adrenal lesion >2.5cm - unilateral laparoscopic adrenalectomy plus pre/post-op aldosterone antagonists (amiloride, spironolactone, eplerenone) 3) Familial Hyperaldosteronism Type I - Adults - glucocorticoids (dexamethasone or prednisolone) and aldosterone antagonists (amiloride, spironolactone or eplerenone) - Children - amiloride and eplerenone (2nd line)

Answer 130

- Heart attack - Heart failure - Stroke - Renal disease - Renal failure - Hypertension - Hypokalaemia

Answer 131

More likely to have or develop left ventricular hypertrophy, stroke, acute coronary syndromes than other patients with similar degrees of HTN from other causes.

Answer 132

Benign lactotroph adenomas expressing and secreting prolactin.

Answer 133

Risk Factors: - Genetic predisposition - e.g. presence of mutation resulting in multiple endocrine neoplasia-1 (MEN-1), familial isolated pituitary adenoma (FIPA) - Oestrogen therapy - Female gender, 20-50 years of age - Male gender - 30-60 years of age

Answer 134

40% of all pituitary adneomas. Female preponderance 0 present earlier due to menstrual irregularity and usually have microprolactinomas. Men and post-menopausal women often present later with macro-adenomas, which may be invasive or giant tumours.

Answer 135

Female: - Amenorrhoea - Galactorrhoea - Infertility - Oligomenorrhoea Male: - Sexual dysfunction - Hypogonadism - Gynaecomastia All: - Osteoporosis - Ophthalmoplegia - Headaches - Visual deterioration - e.g. temporal hemianopia - Loss of sexual desire - libido

Answer 136

Female: - Amenorrhoea - Galactorrhoea - Infertility - Oligomenorrhoea Male: - Sexual dysfunction - Hypogonadism - Gynaecomastia All: - Osteoporosis - Ophthalmoplegia - Headaches - Visual deterioration - e.g. temporal hemianopia - Loss of sexual desire - libido

Answer 137

- Serum prolactin - elevated - Macroprolactin (if high serum prolactin and asymptomatic) - Pituitary MRI - characteristic features of pituitary adenoma - Computerised visual-field examination - unilateral or bi-temporal hemianopia

Answer 138

1) Pre-menopausal Women - If asymptomatic microprolactinomas, normal menstrual cycle and do not desire pregnancy - observe! - If symptomatic microprolactinomas who do not desire pregnancy - give dopamine agonist (cabergoline, bromocriptine), combined oral contraceptive, trans-sphenoidal surgery, sellar radiotherapy - If symptomatic microprolactinomas who desire pregnancy or macroprolactinomas - give dopamine agonist (cabergoline, bromocriptine), trans-sphenoidal surgery, sellar radiotherapy 2) Post-menopausal Women - Microadenomas - observation - Macroadenomas - give dopamine agonsit (cabergoline, bromocriptine), trans-sphenoidal surgery, sellar radiotherapy 3) Men (both micro- or macro- adenomas) - Dopamine agonist - cabergoline, bromocriptine - Transphenoidal surgery - Sellar radiotherapy

Answer 139

- Bone loss - osteoporosis - Pregnancy complications - Vision disturbances - Low levels of other pituitary hormones

Answer 140

95% of cases the tumour will not show any signs of growth after a 4-6 year period. Macroprolactinomas often require more aggressive treatment otherwise they may continue to grow.

Answer 141

Characterized by continued secretion of ADH, despite the absence of normal stimuli for secretion - e.g. high serum osmolality or low blood volume.

Answer 142

Brain - Haemorrhage / thrombosis - Meningitis - Abscess - Trauma - Tumour - Guillain-Barre Syndrome Lung - Pneumonia - TB - Abscess - Aspergillosis - Small cell carcinoma Tumours - Small cell lung cancer - Lymphoma - Leukaemia - Pancreas - Prostate - Mesothelioma - Sarcoma - Thymoma - Ecoptic ADH secretion Drugs - Vincristine - Opiates - Carbamazepine - Chlorpropamide Metabolic - Porphyria - Alcohol withdrawal

Answer 143

Hyponatremia is the most common electrolyte imbalance seen in hospitals. <50% severe hyponatremia due to SIADH.

Answer 144

Mild Hyponatraemia (Na+ 125-135mmol/L) - may be asymptomatic Severe Hyponatraemia: - Headache - Nausea - Vomiting - Muscle cramps - Muscle weakness - Irritability - Confusion - Drowsiness - Convulsions - Coma - Symptoms of underlying cause

Answer 145

Mild Hyponatraemia - No signs Severe Hyponatraemia - Reduced reflexes - Extensor plantar reflexes - Signs of the underlying cause The hyponatremia in SIADH is dilutional from high body water and not total body low Na+ .

Answer 146

- Low Na+, creatinine, glucose, serum protein and lipids - to exclude psuedohyponatraemia seen with high proteins and lipids - Free T4 & TSH - to exclude hypothyroidism - Short ACTH stimulation test - to exclude adrenal insufficiency SIADH Diagnosis: - Low plasma osmolality - Low plasma Na+ concentration - High urine osmolality - >100mosmol/kg - High urine Na+ - >20mmol/L Presence of the above and absence of hypovolaemia/hypotension, oedema, renal failure, adrenal insufficiency, hypothyroidism are required. Investigations for Identification of Cause: - CXR - CT chest / abdomen / pelvis - MRI / CT head

Answer 147

- Treat the underlying cause - Water restriction - 0.5-1L / day - Demeclocycline if insufficient water restriction - reduce the responsiveness of the collecting tubule cells to ADH - Vasopressin (V2) Receptor Antagonists (e.g. tolvaptan) - useful in moderate chronic hyponatremia if water restriction insufficient - Severe cases (seizures, LOS) - give slow IV hypertonic 3% saline and furosemide with close monitoring - Change in Na+ concentration must not exceed 10mmol/L in first 24h and 18mmol/L in the first 48h - may result in central pontine myelinolysis

Answer 148

- Convulsions - Coma - Death - Central pontine myelinolysis = quadriparesis, respiratory arrest, fits with rapid correction

Answer 149

Depends on the underlying cause High morbidity and mortality with Na+ concentration <110mmol/L Up to 50% mortality with central pontine myelinolysis

Answer 150

5 Types: 1) Papillary - 60% - Younger patients - Spread - lymph nodes, lung (jugulodigastric node) - Treatment - total thyroidectomy to remove non-obvious tumour +/- node excision +/- radioiodine - Give levothyroixine to suppress TSH - Prognosis - better if young and female 2) Follicular - <25% - Middle-age - Spread - via blood to bone and lungs early - Well-differentiated - Treatment - total thyroidectoomy + T4 suppression + radioiodine ablation 3) Medullary - 5% - Sporadic (80%) or part of MEN Syndrome - Produce calcitonin which can be used as a tumour marker - Do not concentrate iodine - Perform a phaeochromocytoma screen pre-operatively - Treatment - thyroidectomy + node clearance - External beam radiotherapy may prevent regional reoccurrence 4) Lymphoma - 5% - F:M 3:1 - Present with stridor or dysphagia - Do full staging pre-treatment - chemoradiotherapy - Assess histology for mucosa-associated lymphoid tissue (MALT) origin - associated with good prognosis 5) Anaplastic - Rare - F:M 3:1 - Elderly, poor response to any treatment - In absence of unresectable disease, excision and radiotherapy may be tried

Answer 151

Risk Factors: - Head and neck irradiation - Female sex - Family history of thyroid cancer

Answer 152

4 types account for 98% of thyroid malignancies.

Answer 153

- Asymptomatic thyroid nodule - Detected by palpation or US in women in 30s or 40s - Hoarseness - Dyspnoea - Rapid neck enlargement

Answer 154

- Palpable thyroid nodule - Vocal hoarseness - Tracheal deviation - Cervical lymphadenopathy

Answer 155

1st Line - TSH - normal - US neck - nodule number, characteristics, cervical lymph nodes - Fine needle biopsy - Laryngoscopy - may show ipsilateral paralyzed vocal cord - Free T4, T3 - I-123 thyroid scan and uptake - Core biopsy - US elastography - Molecular analysis of cytology specimens - Sentinel node biopsy

Answer 156

Lumps or bumps in the thyroid gland. Types: - Diffuse goitre - Nodular goitre

Answer 157

DIFFUSE GOITRE Causes: - Endemic (iodine deficiency) - Congenital - Secondary to goitrogens - substances that reduce iodine uptake - Acute thyroiditis - de Quervain's - Physiological - e.g. pregnancy, puberty - Autoimmune - e.g. Graves' disease, Hashimoto's thyroiditis NODULAR GOITRE A) Multinodular Goitre (MNG) - Most common - 50% who present with a single nodule have MNG - Euthyroid - May become hyperthyroid - May be retro- or sub- sternal - Hypothyroidism or malignancy with MNG is rare - Plummer's Disease = hyperthyroidism + single toxic nodule (uncommon) B) FIBROTIC GOITRE - E.g. Reidel's thyroiditis C) SOLITARY THYROID NODULE - Cyst - Adenoma - Discrete nodule - In MNG or malignancy (10%)

Answer 158

Most are benign, but 2-3 in 20 are cancerous.

Answer 159

- Palpable - Observable - swelling at base of the neck - Press on windpipe or oesophagus and may cause SOB or dysphagia If hyperthyroid: - Unexplained weight loss - Increased sweating - Tremor - Nervousness - Rapid or irregular heartbeat If hypothyroid: - Feeling cold - Feeling tired more easily - Dry skin - Memory problems - Depression - Constipation

Answer 160

If the thyroid is enlarged upon palpation (= goitre) - ask yourself: 1) If the thyroid diffusely enlarged or nodular? 2) Is the patient euthyroid, thyrotoxic or hypothyroid?

Answer 161

- Check TSH - USS - solid, cystic, complex or part of a group of lumps - T4 - Autoantibodies - if Hashimoto's Thyroiditis or Graves' Disease - CXR with thoracic inlet view - tracheal goitres and metastases - Radionuclide scans may show malignant lesions as hypofunctioning or cold - Hyperfunctioning 'hot' lesion = adenoma - FNA (fine-needle aspiration) - characterize lesion with cytology FNA finding - Follicular neoplasm can be challenged = 15-30% malignant - Discuss with cytologist and perform molecular diagnostics where avaliable, if any doubt, refer for surgery

Answer 162

Inflammatory disease of the thyroid gland: 1) Acute Suppurative Thyroiditis - due to bacterial infection 2) Subacute Thyroiditis - due to viral infection 3) Chronic Thyroiditis - autoimmune Secondary Thyroiditis - may be due to administration of amiodarone to treat cardiac arrhythmias or interferon-alpha for viral diseases

Answer 163

Inflammatory disease of the thyroid gland: 1) Acute Suppurative Thyroiditis - due to bacterial infection - E.g. S. aureus, S. hemolyticus, S. pneuococcus - Left lobe of the thyroid - Associated with a developmental abnormality of thyroid migration & persistence of pyriform sinus from the pharynx to thyroid capsule 2) Subacute Thyroiditis - due to viral infection - E.g. mumps, measles, influenza, infectious mononucleosis, adenoviral or Coxsackievirus infections, myocarditis, common cold - E.g. catscratch fever, sarcoidosis, Q fever, malaria, emotional crisis, dental work - More common if HLA-Bw35 3) Chronic Thyroiditis - autoimmune - Chidren usually - HLA-associated - Lymphocytic thyroid infiltration obliterates normal thyroid tissue - Small or hyperplastic follicular thyroid cells - Fibrosis too (varies) - Blood contains autoantibodies to thyroid peroxidase and thyroglobulin Secondary Thyroiditis - may be due to the administration of amiodarone to treat cardiac arrhythmias or interferon-alpha for viral diseases

Answer 164

Studies in the United States and Western Europe report a prevalence of 1.2% in individuals aged 11-18 years. Approximately 25% of adults with type 1 diabetes have thyroiditis, about one half of whom have hypothyroidism. Approximately 10% of children with type 1 diabetes have antithyroid antibodies. Thirteen of 121 children with vitiligo were also found to have subsequent evidence of autoimmune thyroiditis. [1] Similarly, a Korean study, by Bae et al, indicated that persons with vitiligo have an odds ratio for the autoimmune disease Hashimoto thyroiditis of 1.609. [2] The disease is also more common in children with Down syndrome or Turner syndrome.

Answer 165

Acute Thyroiditis: - Fever - 38-40 degrees - Neck tenderness - Swollen thyroid gland - may be unilateral - Erythema over the thyroid gland - Regional lymphadenopathy as the disease progresses - Abscess formation Subacute Thyroiditis: - Systemic illness - e.g. low-grade fever, weakness - Hyperthyroidism - tachycardia, widened pulse pressure, fidgeting, tremor, nervousness, tongue fasciculations, brisk reflexes, weight loss, warm & moist skin - Enlarged & tender thyroid gland - exacerbated by neck extension Chronic Autoimmune Thyroiditis: - Enlarged, lumpy, bumpy, non-tender thyroid (not necessarily enlarged) - Hypothyroidism - slow growth rate, weight gain, bradycardia, cold, dry skin, coarse hair and facial features, oedema, delayed relaxation of deep tendon reflexes - Signs of hyperthyroidism present early in disease occasionally

Answer 166

Acute Thyroiditis: - Leukocytosis with left shift (increased young cells) - Increase ESR - Thyroid function test within normal Subacute Thyroiditis: - TSH low - Free T4 high - As the disorder progresses, transient or permanent hypothyroidism Chronic Autoimmune Thyroiditis: - TSH high, T4 levels normal / low = subclinical, hypothyroidism - TSH low = hyperthyroidism - TSH & TFTs normal often - Anti-thyroid peroxidase (anti-thyrocellular, antimicrosomal) antibodies high Radioactive iodine thyroid scanning helpful in hyperthyroidism (particularly subacute thyroiditis) - low uptake consistent with thyrocellular destructionin progress. Thyroid ultrasonography - reveals abscess formation if acute thyroiditis. Fine-needle Aspiration - obtain material for culture, for appropriate antibiotic therapy.

Answer 167

Acute Thyroiditis - Parenteral antibiotic therapy before abscess formation - Penicillin or ampicillin - cover gram-positive cocci and anaerobes - May need surgery to drain abscess and correct developmental abnormality responsible Subacute Thyroiditis - Self-limiting disease - Relieve discomfort - Control abnormal thyroid function Chronic Autoimmune Thyroiditis: - Depends on TFTs - Hypothyroidism - levothyroxine

Answer 168

Acute Thyroiditis: - Usually complete recovery - Normal thyroid function returns Subacute Thyroiditis: - Self-limiting - 2-7 months Chronic Autoimmune Thyroiditis: - Permanent hypothyroidism - main complication - Enter remission and become euthyroidism - 20% of children with subclinical hypothyroidism

Answer 169

Acute Thyroiditis: - Usually complete recovery - Normal thyroid function returns Subacute Thyroiditis: - Self-limiting - 2-7 months Chronic Autoimmune Thyroiditis: - Permanent hypothyroidism - main complication - Enter remission and become euthyroidism - 20% of children with subclinical hypothyroidism

Answer 170

An acute metabolic complications of diabetes that is potentially fatal and requires prompt medical attention for successful treatment. Characterised by absolute insulin deficiency and is the most common acute hyperglycaemic complications of T1DM.

Answer 171

Triad - hyperglycaemia, ketonaemia and metabolic acidosis. Risk factors: - Inadequate or inappropriate insulin therapy - Infection - Myocardial infarction - Pancreatitis - Stroke - Acromegaly - Hyperthyroidism - Drugs - e.g. corticosteroids, thiazides, pentamidide, sympathomimetics, second-generation antipsychotics, cocaine, immune checkpoint inhibitors, SGLT2 inhibitors - Cushing's syndrome - Hispanic or black ancestry - Bariatric surgery

Answer 172

While the exact incidence is not known, it is estimated to be 1 out of 2000. DKA occurs primarily in patients with type 1 diabetes. The incidence is roughly 2 episodes per 100 patient years of diabetes, with about 3% of patients with type 1 diabetes initially presenting with DKA.

Answer 173

- Thirst - Polyuria - Weight loss - Excessive tiredness - Nausea and vomiting - Dehydration - Abdominal pain - Hyperventilation - Reduced consciousness

Answer 174

- Acetone smell on breath | - Hypothermia

Answer 175

- VBG - pH>7 mild, pH <7 severe, hyperkalaemia, plasma osmolality = metabolic acidosis with raised anion gap (>16) - Serum ketones - >3.0 mmol/L ketonaemia - Blood glucose - hyperglycaemia >11.1 mmol/L - U&E - hyponatraemia, hyperkalaemia (hypokalaemia = severe), hypermagnesaemia, hypophosphataemia - FBC - leukocytosis To consider: - Urinalysis - ketonuria, glycosuria, leukocytes & nitrites in presence of infection, myoglobinuria or haemoglobinuria in rhabdomyolysis - ECG - abnormal T or Q waves or ST segment changes in MI, hypokalaemia (U waves), hyperkalaemia (peaked tall T waves) - Pregnancy - Amylase & lipase - Cardiac enzymes - Creatinine kinase - high with rhabdomyolysis - Chest X Ray - signs of pulmonry oedema, consolidation in pneumonia - Liver function tests - Blood, urine, sputum cultures

Answer 176

SBP <90 mmHg 1) Serum K+ <3.5mmol/L - IV fluids - 500ml bolus 0.9% saline over 10-15mins (repeat if needed), 1L 0.9% saline over 1 hour once SBP >90mmHg - K+ replacement - add to 2nd litre of IV fluids, give 10% glucose if level <14.0mmol/L - Supportive care and referral to critical care - Insulin - dose per kg per hour, start at fixed-rate IV insulin infusion 0.1 units / kg /hour - Identify and treat any precipitating acute illness - e.g. MI, sepsis, pancreatitis - Monitor biochemical markers - ketones, glucose, bicarbonate, K+, pH - Monitor and treat complications - Sodium bicarbonate - if pH <6.9 - Thromboprophylaxis - LMWH 2) Serum K+ 3.5-5.5mmol/L - IV fluids - 500ml bolus 0.9% saline over 10-15mins (repeat if needed), 1L 0.9% saline over 1 hour once SBP >90mmHg - K+ replacement - add to 2nd litre of IV fluids, give 10% glucose if level <14.0mmol/L - Supportive care and referral to critical care - Insulin - dose per kg per hour, start at fixed-rate IV insulin infusion 0.1 units / kg /hour - Identify and treat any precipitating acute illness - e.g. MI, sepsis, pancreatitis - Monitor biochemical markers - ketones, glucose, bicarbonate, K+, pH - Monitor and treat complications - Sodium bicarbonate - if pH <6.9 - Thromboprophylaxis - LMWH 3) Serum K+ >5.5 mmol/L - IV fluids - 500ml bolus 0.9% saline over 10-15mins (repeat if needed), 1L 0.9% saline over 1 hour once SBP >90mmHg - Supportive care and referral to critical care - Insulin - dose per kg per hour, start at fixed-rate IV insulin infusion 0.1 units / kg /hour - Identify and treat any precipitating acute illness - e.g. MI, sepsis, pancreatitis - Monitor biochemical markers - ketones, glucose, bicarbonate, K+, pH - Monitor and treat complications - Potassium replacement (once <5.5 mmol/L) - Sodium bicarbonate - if pH <6.9 - Thromboprophylaxis - LMWH SBP >90mmHg 1) Serum K+ <3.5mmol/L - IV fluids - 1L 0.9% saline over 1 hour - K+ replacement - add to 2nd litre of IV fluids, give 10% glucose if level <14.0mmol/L - Supportive care and referral to critical care - Insulin - dose per kg per hour, start at fixed-rate IV insulin infusion 0.1 units / kg /hour - Identify and treat any precipitating acute illness - e.g. MI, sepsis, pancreatitis - Monitor biochemical markers - ketones, glucose, bicarbonate, K+, pH - Monitor and treat complications - Sodium bicarbonate - if pH <6.9 - Thromboprophylaxis - LMWH 2) Serum K+ 3.5-5.5mmol/L - IV fluids - 1L 0.9% saline over 1 hour - K+ replacement - add to 2nd litre of IV fluids, give 10% glucose if level <14.0mmol/L - Supportive care and referral to critical care - Insulin - dose per kg per hour, start at fixed-rate IV insulin infusion 0.1 units / kg /hour - Identify and treat any precipitating acute illness - e.g. MI, sepsis, pancreatitis - Monitor biochemical markers - ketones, glucose, bicarbonate, K+, pH - Monitor and treat complications - Sodium bicarbonate - if pH <6.9 - Thromboprophylaxis - LMWH 3) Serum K+ >5.5 mmol/L - IV fluids - 1L 0.9% saline over 1 hour - Supportive care and referral to critical care - Insulin - dose per kg per hour, start at fixed-rate IV insulin infusion 0.1 units / kg /hour - Identify and treat any precipitating acute illness - e.g. MI, sepsis, pancreatitis - Monitor biochemical markers - ketones, glucose, bicarbonate, K+, pH - Monitor and treat complications - Potassium replacement (once <5.5 mmol/L) - Sodium bicarbonate - if pH <6.9 - Thromboprophylaxis - LMWH Resolution of DKA defined as: - pH >7.3 - blood ketone level <0.6 mmol/L - bicarbonate >15mmol/L

Answer 177

- Hypokalaemia - Cerebral oedema - Pulmonary oedema - AKI - Hypoglycaemia - ARDS (acute respiratory distress syndrome)

Answer 178

2-10% mortality rate.

Answer 179

Metabolic, hyperglycaemic condition caused by absolute insufficiency of pancreatic insulin production. Absolute insulin deficiency.

Answer 180

Caused by destruction of pancreatic insulin-producing B-cells, resulting in absolute insulin deficiency. B-cell destruction caused by autoimmune process in 90% of patients. Genetic susceptibility + environmental agent. Gene encoding pre-proinsulin, HLA-DQ-beta, HLA-DR, PTPN22, CTLA-4. Pancreatic B-cell autoantigens role in initiation and progression - glutamic acid decarboxylase (GAD), insulin, insulinoma-associated protein 2 (IA-2) and cation efflux zinc transporter (ZnT8).

Answer 181

One of the most common chronic diseases in childhood. Prevalence 0.25% in UK. US & Northern Europe 8-17 / 100,000 per year.

Answer 182

Juvenile onset - <30 years. - Polyuria - Nocturia - Polydipsia - Tiredness - Weight loss DKA - N&V - Abdominal pain - Polyuria - Polydipsia - Drowsiness - Confusion - Coma - Kussmaul breathing - deep and rapid - Ketotic breath - Signs of dehydration - e.g. dry mucous membrane, low tissue turgor

Answer 183

Signs of Complications: - Fundoscopy - look for diabetic retinopathy - Examination of the feet - neuropathy - 10g monofilament testing and vibration sensation, palpate dorsalis pedis and posterior tibial pulses - Measure BP Signs of Associated Autoimmune Disease - Vitiligo - Addison's disease - Autoimmune thyroid disease

Answer 184

1st line: - Plasma glucose - >11 mmol/L - Fasting plasma glucose - >6.9 mmol/L - 2 hour plasma glucose - >11 mmol/L - Plasma or urine ketones - medium or high quantity - HbA1c - >48 mmol/mol (>6.5%) Consider - Fasting C-peptide - low or undetectable - Autoimmune markers - positive

Answer 185

NON PRGENANT - Basal bolus insulin - insulin glargine [OR insulin isophane human (NPH) OR insulin detemir OR insulin degludec] AND insulin neutral [OR insulin lispro or insulin aspart or insulin glulisine] (or pump can be used) - Pre-meal insulin correction dose - Amylin analogue - Pramlintide before each meal - Fixed-dose insulin combinations with different proportions of each - insulin isophane human/ insulin neutral OR insulin aspart protamine / insulin aspart OR insulin lispro protamine / insulin lispro OR insulin degludec / insulin aspart PRE-MEAL CORRECTION DOSE Example of correction dosing based on pre-meal glucose and above calculation: 2. 2 to 4.9 mmol/L (45-90 mg/dL): subtract 1 unit from mealtime insulin 5. 0 to 7.4 mmol/L (91-135 mg/dL): add 0 units of correction insulin 7. 5 to 9.9 mmol/L (136-180 mg/dL): add 1 unit of correction insulin 9. 9 to 12.4 mmol/L (181-225 mg/dL): add 2 units of correction insulin 12. 4 to 14.5 mmol/L (226-270 mg/dL): add 3 units of correction insulin 14. 5 to 17.3 mmol/L (271-315 mg/dL): add 4 units of correction insulin 17. 4 to 19.8 mmol/L (316-360 mg/dL): add 5 units of correction insulin 19. 8 to 22.3 mmol/L (361-405 mg/dL): add 6 units of correction insulin >22.3 mmol/L (>405 mg/dL): add 7 units of correction insulin; seek medical assistance. PREGNANT - Basal-bolus insulin - insulin isophane human (NPH) [OR insulin determir] AND insulin neutral [OR insulin lispro or insulin aspart] (OR insulin glargine AND either insulin neutral, insulin lispro or insulin aspart, OR pump) - Low-dose aspirin - Aspirin to reduce risk of pre-eclampsia

Answer 186

DIABETIC KETOACIDOSIS - Low insulin and high counter-regulatory hormones - Results in increased hepatic gluconeogenesis and low peripheral glucose utilisation - Renal absorptive capacity of glucose is exceeded causing glycosuria, osmotic diuresis and dehydration - Increased lipolysis leads to ketogenesis and metabolic acidosis - DKA precipitated by infection, errors in management, newly diagnosed diabetes, other medical disease or no cause MICROVASCULAR - Retinopathy - Nephropathy - Neuropathy MACROVASCULAR - PVD - IHD - Stroke / TIA Susceptible to infections, especially on feet. COMPLICATIONS OF INSULIN TREATMENT - Weight gain - Fat hypertrophy at insulin injection sites - Hypoglycaemia caused by missing a meal or overdosage of insulin - present with neuroglycopenic and adrenergic signs (personality change, fits, confusion, coma, pallor, sweating, tremor, tachycardia, palpitations, dizziness, hunger, focal neurological symptoms) - Hypoglycaemic symptoms can be masked by autonomic neuropathy, B-blockers and brain adapting to recurrent episodes

Answer 187

Depends on early diagnosis, good glycaemic control and compliance with screening and treatment. Vascular disease and renal failure are major causes of increased morbidity and mortality.

Answer 188

Characterised by increased peripheral resistance to insulin action, impaired insulin secretion and increased hepatic glucose output.

Answer 189

GENETIC - Monozygotic twins have 90% concordance rate - Lifetime risk for 1st degree relative of patient with T2DM is 5-10x higher than those without - Monogenic causes (small fraction) - Inherited polymorphisms - e.g. TF7-like 2 Obesity, increased plasma free fatty acid levels and adipokines secreted by ADIPOCYTES - e.g. leptin, adiponectin, TNF-alpha, resistin. Chronic hyperglycaemia - toxic effect on B-cells = GLUCOTOXICITY. Increased plasma free fatty acid levels worsens pancreatic B-cell function = LIPOTOXICITY SECONDARY DIABETES - Pancreatic diseases - e.g. chronic pancreatitis, hereditary haemochromatosis, pancreatic cancer, surgical removal of pancreas - Endocrinopathies - e.g. Cushing's, acromegaly, phaemochromocytoma, glucagonoma - Drugs - e.g. corticosteroids, atypical antipsychotics, protease inhibitors

Answer 190

5-10% prevalence in UK. Asian, African and Hispanic descent at greater risk. Increased over last 20 years, in parallel with increased prevalence of obesity worldwide.

Answer 191

- Incidental finding - Polyuria - Polydypsia - Tiredness - Hyperosmolar hyperglycaemia state (HHS) presentation - non-ketotic state - Infections - infected foot ulcers, candidiasis, balanitis, pruritus vulvae - Assess for other cardiovascular risk factors - HTN, HLD, smoking

Answer 192

- Measure weight and height - calculate BMI = weight / height, waist circumference, BP - Look for signs of complications DIABETIC FOOT - Both ischaemic and neuropathic signs - Dry skin - Reduced subcutaneous tissue - Corns and calluses - Ulceration - Gangrene - Charcot's arthropathy and signs of peripheral neuropathy, weak foot pulses = ischaemic foot SKIN CHANGES (RARE) - Necrobiosis lipoidica diabeticorum - well-demarcated plaques on shins or arms with shiny atrophic surface and red-brown edges - Granuloma annulare - flesh-coloured papules coalescing in rings on back of hands and fingers - Diabetic dermopathy - depressed pigmented scars on shins

Answer 193

1st line: - HbA1c - 48mmol/mol (6.5%) or greater - Fasting plasma glucose - >6.9 mmol/L - Random plasma glucose - >11.1 mmol/L - 2-hour post-load glucose after 75g oral glucose - >11.1 mmol/L Consider: - Fasting lipid profile - may show high LDL, low HDL and high TG - Urine ketones - positive in DKA - Random C-peptide - >1 nanomol/L - Urinary albumin excretion - may be increased - Serum creatinine and eGFR - renal insufficiency - ECG - may indicate prior ischaemia - ABPI - <0.9 is ABNORMAL - Dilated retinal examination - may show retinopathy

Answer 194

AT INITIAL DIAGNOSIS - Lifestyle changes - Glycemic management with individualised HbA1c goals - BP management - hydrochlorothiazide/chlortalidone / indapamide AND/OR lisinopril / analapril / captopril /candesartan / irbesartan / losartan /valsartan AND/OR amlodipine / felodipine/nifedipine/diltiazem Make sure to learn previous algorithm for BP! - Lipid management - atorvastatin, rosuvastatin, simvastatin, pravastatin, lovastatin, fluvastatin, pitavastatin (+ ezetimibe + evolocumab, alirocumab) - Anti-platelet therapy - aspirin, clopidogrel or combined MARKED HYPERGLYCAEMIA NON PREGNANT - Basal-bolus insulin + CVS risk reduction - PRIM: NPH + insulin neutral, OR insulin glargine/detemir/degludec + lispro, aspart, glulisine, OR insulin isophane/neutral, OR insulin aspart protamine/aspart, OR insulin ispro protamine/lispro OR insulin degludec/aspart - Metformin WITHOUT MARKED HYPERGLYCAEMIA NON-PREGNANT ASYMPTOMATIC If HbA1c above goal at diagnosis - Metformin - Cardiovascular risk reduction / lifestyle measures If HbA1c above goal on metformin - SGLT2 inhibitor OR GLP-1 Agonist OR DDP-4 inhibtor OR sulfonyluria / meglitinide OR basal insulin OR alpha-glucosidase inhibitor OR thiazolidinedione - Metformin - Cardiovascular risk reduction / lifestyle measures SGLT2 inhibitor - empaglifozin, canagliflozin, dapagliflozin, ertugliflozin GLP-1 Agonist - liraglutide, dulaglutide, semaglutide, exenatide, lixisenatide DPP-4 Inhibitor - sitagliptin, linagliptin, alogliptin, saxagliptin Sulphonylurea - glimepiride, glipizide, gliclazide, repaglinide, nateglinide Basal Insulin - NPH, glargine, detemir, degludec Alpha-Glucosidase Inhibitor - acarbose, migllitol Thiazolidinedione - pioglitazone If HbA1c above goal on metformin + basal insulin or second non-insulin agent - Individualised augmented regimen or switch to basal-bolus insulin - do not combine DPP-4 inhibtor + GLP-1 agonist in same regimen - Metformin - Cardiovascular risk reduction / lifestyle measures - Bariatric surgery - if BMI > 40kg/m^2, >37.5 kg/M^2 for Asian-family origin with any level of glycaemic control and complexity of glucose-lowering regimen PREGNANT - Diet - Basal-bolus insulin - NPH + neutral / lispro / aspart INFORM: - Information - diabetic nurses, websites, explaining diabetes control, complications - Nutrition - optimizing meal plans, diet (complex carbohydrates as opposed to simple sugars, low fat intake) - Foot care - regular inspection, appropriate footwear, role of chiropodist - Organizations - local and national support groups - Recognition and treatment of hypoglycaemia - Monitoring capillary blood glucose and charting it, monitoring for ketones during intercurrent illness HHS - Management similar to diabetic ketoacidosis - Except use 0.45% saline if serum Na+ > 170mmol/L and a lower rate of insulin infusion (1-3 U/h) - DVT prophylaxis with SC heprain

Answer 195

HHS - Due to insulin deficiency - Patient is usually old - Presenting for first time - history is longer - Marked dehydration, high sodium, high glucose, high osmolality, no acidosis NEUROPATHY - Distal symmetrical sensory neuropathy - Painful neuropathy - Carpal tunnel syndrome - Diabetic amyotrophic - asymmetrical wasting of proximal msucle - Mononeuritis - 3rd nerve palsy with preservation of pupillary response, VI nerve - Autonomic neuropathy - e.g. postural hypotension - Gastroparesis - abdominal pain, N&V - Impotence - Urinary retention NEPHROPATHY - Microalbuminuria - Proteinuria - Renal failure - Prone to UTI and renal papillary necrosis BACKGROUND RETINOPATHY - Dot and blot haemorrhages - Hard exudates PRE-PROLIFERATIVE RETINOPATHY - Cotton wool spots - Venous beading PROLIFERATIVE - New vessels on the disc and elsewhere MACULOPATHY - Macular oedema - Exudates within 1 disc diameter of the centre of fovea - Haemorrhage within 1 disc diameter of centre of the fovea - Low visual acuity - Prone to glaucoma, cataracts, transient visual loss MACROVASCULAR - IHD - Stroke - PVD

Answer 196

Intensive therapy to achieve lower levels of glycaemia reduce the risk of development and progression of microvascular complications. Intensive early glucose control reduces risk for MI and all-cause mortality.

Answer 197

Can be diagnosed based upon a fasting blood glucose test or an oral glucose tolerance test. Impaired fasting glucose (IFG) - fasting plasma glucose between 5.6-6.9 mmol/L Impaired glucose tolerance (IGT) - plasma glucose level for 7.8-11.0 mmol/L measured 2h after 75g oral glucose tolerance test. Individuals are at considerable risk for developing T2DM - 40% risk over next 5 years.

Answer 198

A rare cause of T2DM due to mutations transmitted in an autosomal dominant manner. MODY1, MODY3 and MODY5 are due to mutations in genes encoding hepatocyte nuclear transcription factors 4-alpha, 1-alpha and 1-beta respectively. MODY2 is caused by mutations in glucokinase gene. MODY4 is caused by mutations in the insulin promoter factor-1, a transcription factor that regulates pancratic development and insulin gene transcription. MODY6 is caused by mutations of the gene for neurogenic differentiation 1 (NeuroD1).

Answer 199

- Block ATP-sensitive K+ channels in B-cells - Stimulates insulin release SE: Hypoglycaemia, weight gain.

Answer 200

Inhibits hepatic gluconeogenesis. SE: GI disturbance, lactic acidosis (stop in unwell patients).

Answer 201

E.g. Pioglitazone. - Activates PPAR gamma - Reduces peripherla insulin resistance Rosiglitazone not recommended as risk of MI and incidence of fractures.

Answer 202

E.g. Exenatide GLP-1 produced by L-cells in gut. - Increases glucose-stimulated insulin secretion - Reduces glucagon release - Reduces gastric emptying - Reduces appetite

Answer 203

- Enzyme that degrades GLP-1 is inhibited - Considered in patients who have contraindications or intolerance to metformin, sulfonylureas or pioglitazone (e.g. CKD) NB: Acarbose inhibits intestinal glucosidases and reduces carbohydrate digestion, less used due to bloating and flatulence.

Endocrinology Flashcards

(227 cards)