Endocrinology Flashcards

Question

Pseudohypoparathyroidism

Answer 1

Hereditary end-organ resistance to PTH Can have low Ca2+ and high PO4 or be biochemically normal - kidneys favour maternal gene with imprinting so retain PTH sensitivity Features: - Short stature + rounded face + short 4th/5th metacarpals - High PTH - Mental retardation - Calcified choroid plexus

Answer 2

The main human glucocorticoid Follows a circadian pattern - highest in morning and declines over the day Additionally secreted as an acute stress response to consolidate SNS responses - Amygdala triggers SNS signalling into HPA Antagonises insulin effects and secretion of TSH, GHRH, ADH. Stimulates glucagon secretion Effects: - Catabolic state - mobilises glucose, suppresses glucose uptake into the tissue - later causes protein degradation and wasting - Fat redistribution - Immunomodulatory - promotes a TH2 response to prevent excessive and harmful inflammation - Bone resorption - Water and fluid retention - via mineralocorticoid secretion - helps to increase BP - Gastric acid secretion

Answer 3

Diagnose excess - 24hr urine cortisol collection - Morning cortisol following overnight low-dose dexamethasone suppression test Localise cause - High-dose dexamethasone suppression test - If suppresses = pituitary - ACTH measuring - Low = ectopic, high = adrenal

Answer 4

A deficiency in cortisol +/- aldosterone Aetiology: - Primary (adrenal) - Autoimmune - CAH - Adenomas - Secondary (pituiary) - Adenoma - Tertiary (hypothalamic) - Tumour, stroke - Exogenous steroids Features: - Hypotension and postural hypotension - Nausea/vomiting - Dehydration - Tanning of skin creases + buccal mucosa (primary only) - Hypoglycaemia Investigations: - Bloods: - Metabolic acidosis - Hyponatraemia, hyperkalaemia, hypercalcaemia - Special: - 9am cortisol - Short synachthen test Management: - Acute - IV hydrocortisone + fluids - Chronic - Prednisolone +/- fludrocortisone

Answer 5

Aetiology: - Primary: - Adrenal adenoma - 33% single, rest bilateral - Adrenal adenocarcinoma - Familial - Secondary: - Renal, heart, or liver disease - Renal artery stenosis Features: - Resistant HTN - Hypokalaemia - Elevated aldosterone:renin ratio Investigation: - Bloods - Renin:Aldosterone ratio - Imaging - Renal USS - CT/MRI adrenals Management: - Spironolactone - BP control

Answer 6

Production: - Combination of iodine + tyrosine (on thyroglobulin) in the thyroid glands to make T4 - T4 then deiodinised to T3 (active and inactive forms) - T3/4 attached to colloid molecules and stored in the thyroid gland Secretion: - TRH -> TSH -> T4/3 Activation: - T3 > T4 in activity, but production requires deiodinase enzymes and also produces inhibitory T3r - Deiodinisation possible in the thyroid and pituitary glands, but also in target tissues - Type 1 deiodinase = T3 + T3r - Type 2 deiodinase = T3 to T3r - Type 3 deiodinase = T3r to T3 - Circulates in the blood bound to thyroid binding globulin Actions: - Generally permissive for the actions of catecholamines (aka energy mobilisation, hypertension, hyperthermia) - Also promotes protein anabolism - so useful in childhood for growth - Supports brain maturation and myelination

Answer 7

Aetiology: - Iodine deficiency - Most common cause worldwide - Autoimmune e.g. Hashimoto's - Painless goitre, other AI illness - Anti-TPO and anti-thyroglobulin - Infectious thyroiditis (De Quervain's) - Painful swollen neck, fever, dysphagia - Medications - Lithium, amiodarone - Iatrogenic - Post-radio-iodine or thyroidectomy - Congenital - Post-partum - Brief hyper- then prolonged self-resolving hypo- Features: - Fatigue - Cold sensitivity - Weight gain - Cool peripheries - Heavy/irregular periods, reduced libido - Suppression of LH/FSH, increased PRL - Hair thinning - Myxoedema and carpal tunnel syndrome - Decreased clearance of glycoasminoglycan Management: - Thyroid hormone replacement

Answer 8

Abnormal levels of TSH, T3, T4 in the context of non-thyroid systemic illness Due to: - Increased type 3 deiodinase -> increased T3 production - Displacement from thyroid binding globulins as albumin decreases in illness Management: - Thyroid hormone treatment not required - Monitor and should resolve with illness

Answer 9

The consequence of prolonged undiagnosed/under-treated hypothyroidism Triggers include infection, medications, surgery Features: - Hypotension - Hypothermia - Bradycardia - Reduced GCS or confusion - Hypoventilation with T2RF Management: - IV hydrocortisone (e.g. 100mg) then IV levothyroxine (200-400mcg) or liothyronine - Supportive care - Treat underlying cause

Answer 10

Pre-hypothyroidism - TSH high - T4 normal Hypothyroidism - TSH high - T4/T3 low Sick euthyroid - TSH normal/low - T4/T3 low - T3r high Non-thyroid gland hypothyroidism - TSH + T4 + T3 low

Answer 11

Most commonly due to failure to form a functional thyroid gland Features: - Dry skin, coarse hair, macroglossia - Prolonged jaundice - Bradycardia, hypothermia - Hypotonia Investigations: - Screening levels of TSH at 7 days - Screen for hypopituitarism if signs of abnormal genitalia, midline defects, or hypoglycaemia Management: - Thyroid hormone replacement - Inadequate treatment leads to irreversible mental retardation

Answer 12

Aetiology: - NB can be a transient phase in many conditions which progress to hypothyroidism, progressive damage from hyperthyroid processes can cause the same - Grave's disease - Anti-TSH-receptor - Toxic mulltinodular goitre - Thyroid adenoma or cancer - Medications - amiodarone Features: - Tachycardia + hypertension - Heat sensitivity - Anxiety and agitation - Weight loss + hair loss - Fatigue - Light/absent periods - Atrial fibrillation - Osteoporosis - Grave's specific - exophthalmos, acropachy, pretibial myxoedema Investigations: - TFTs - Low TSH, high T4 - Thyroid US - Smoothly enlarged = Grave's - Multifocal = TMG Management: - Symptom relief - beta-blockers - Thyroid suppression - carbimazole - 1st line - radioiodide - must not become pregnant within 6/12, limit contact with others - thyroidectomy - risk of RLN palsy, hypocalcaemia, haematoma - Thyroid replacement

Answer 13

Usually result of a stressor e.g. infection, surgery, DKA, MI, contrast (iodinated) Can also be due to sudden cessation of anti-thyroid medications Features: - Hyperthermia (>40) - Tachycardia + heart failure - Nausea/vomiting + diarrhoea - Agitation - Confusion Management: - Supportive care - Beta-blockers - Thyroid suppression with carbimazole or propylthiouracil + steroids

Answer 14

Aetiology: - Pituitary adenoma (98%) - Ectopic GH production e.g. pancreatic or lung tumours Features: - Enlarged facial features and hands - Spade-like hands - Frontal bossing - Macroglossia - Deepening voice - Swollen vocal cords - Headaches - Hyperhidrosis - Bilateral carpal tunnel syndrome - Hyperglycaemia Investigations: - Screening - IGF-1 levels - Confirmation - glucose tolerance test (GH remains high) - Imaging - MRI pituitary Management: - Trans-sphenoidal surgery +/- RT - Medical therapy incl. octreotide Complications: - Diabetes mellitus - Cardiomyopathy + heart failure - screening echo + ECG - Increased risk of thyroid and colorectal cancers - screening colonoscopies - Arthropathy

Answer 15

Aetiology: - Cranial - impaired ADH synthesis/release - Congenital - Head trauma - SAH - Tumours e.g. craniopharyngoma - Infiltrative - Nephrogenic - impaired response to ADH - Hereditary - Drugs - lithium, mannitol - Infiltrative e.g. amyloidosis - Primary polydipsia - Psychogenic - Dry mouth e.g. Sjogren's, anticholingergics Features: - Polyuria - Polydipsia - Dehydration - Postural hypotension - Nocturia (incl. enuresis in paeds) Investigations: - Bloods - Hypernatraemia - Low urine osmolality + high serum osmolality - Water deprivation test - Deprive of water + later administer desmopressin Management: - Cranial - Desmopressin - Nephrogenic - Thiazide diuretics, high-dose desmopressin, NSAIDs - Primary - Counselling, water restriction

Answer 16

Sudden pituitary haemorrhage with subsequent dysfunction - Usually into a pituitary adenoma Features: - Sudden headache +/- visual changes - Followed by acute hypopituitarism + adrenal crisis - Nausea/vomiting - Meningism Management: - Supportive - Manage adrenal crisis

Answer 17

Decreased secretion of at least one of the 8 pituitary hormones Aetiology: - Pituitary tumours with compression - Pituitary apoplexy - Meningitis - SAH etc. Features: - LH/FSH - Oligo-/amenorrhoea + poor libido - Infertility - Hair loss + bone loss - GH - Muscle wasting + central obesity - Poor concentration - Delayed growth in paeds - ACTH - Adrenal insufficiency - TSH - Hypothyroidism - PRL - Inability to breastfeed - ADH - Central diabetes insipidus - Oxytocin - ?impaired social awareness

Answer 18

The most common form of secretory pituitary adenoma Features: - Heavy, irregular periods - Decreased libido - Erectile dysfunction - Galactorrhoea and gynaecomastia - Osteoporosis - Infertility Management: - Bromocriptine - Dopamine agonist - If fails, surgery

Answer 19

Usually a benign beta-cell tumour Symptoms caused by insulin secretion and hypoglycaemia (Whipple's triad) - Fasting hypoglycaemia - Symptomatic hypoglycaemia - Symptoms relieved by glucose administration Management: - Surgery

Answer 20

MEN1 - Parathyroid - Pituitary - Pancreas (secretory tumours) MEN2a - Medullary thyroid cancer - Parathyroid - Phaeochromocytoma (ret mutation) MEN2b - Medullary thyroid cancer - Phaeochromocytoma - Marfanoid habitus - Neuromas

Answer 21

Neoplasm of the chromaffin cells of the adrenal medulla Features: - Episodic symptoms (15-45 min) - Diaphoresis - Palpitations - Headaches - Hypertension Investigations: - Serum and urinary metanephrines - CT/MRI adrenals - Biospy - staining for chromogranin A Management: - Alpha- then beta-blockade - Adrenalectomy

Answer 22

21-hydroxylase - 95% of cases - Failure to produce cortisol and aldosterone, overproduction of testosterone - Salt-wasting crisis from 3 days + hypoglycaemia - Virilised female genitalia +/- pigmentation 11-beta - Failure to produce cortisol and aldosterone, overproduction of testosterone - However, able to produce a precursor with mild gluco- and mineralocorticoid activity - Lack salt-wasting crisis - Virilised female genitalia +/- pigmentation

Answer 23

Papillary - BRAF mutations - Most common, rarely metastasises - May produce thyroglobulin Follicular - 2nd most common, rarely metastasises - May produce thyroglobulin Medullary - MEN2 complex - AD, RET mutations - C-cells - calcitonin production Anaplastic - Poorly differentiated and aggressive - Often present with signs of local invasion or compression Thyroid lymphoma - Associated with an underlying Hashimoto's or pre-existing goitre - Majority NHL type, occur in older age - Large and quick-growing

Answer 24

Occurs alongside, or several years either side of, Grave's disease - 30% of Grave's - Can occur in euthyroid patients - 5x more common in smokers Pathophysiology: - Inflammation in the orbit - swelling - Early disease (3-12 months) - Later fibrosis of the orbital adipose tissue + extra-ocular muscles Features: - Lid retraction - Earliest + commonest sign - Lid lag - Blepharitis - Proptosis - Periorbital + lid oedema - Extra-ocular muscle involvement - Most commonly MR + IR - Painful eye movement - Diplopia - Visual loss Management: - Refer to TED clinic - Smoking cessation - Thyroid disease control - In acute sight-threatening disease, IV methylpred +/- mycophenolate AVOID radioiodine as worsens TED

Answer 25

Uses 99mTc or radioiodine to measure uptake into the thyroid gland Thyroiditis - reduced uptake Other causes of hyperthyroidism - increased uptake

Answer 26

NET arising from the alpha-cells found in the tail of the pancreas Features: - 4D's - Dermatitis - Necrolytic migratory erythema - Widespread but markedly perioral, perigenital, and extremities - Diabetes - DVTs - Depression - Weight loss - Chronic diarrhoea Investigations: - Fasting glucagon levels - CT abdomen Management: - Only surgical excision is curative - However, 50% metastatic at diagnosis - Medications e.g. somatostatin, streptozocin

Answer 27

Digestion + absorption - Digested (e.g. by lipase) and emulsified in the intestines with assistance from bile acids - Absorbed through into the intestinal cells - Reconstituted into chylomicrons for transport Transport - Chylomicrons - Least dense - Transport from intestines to liver and transport of triglycerides around the body - VLDL - Transports lipids from the liver and transport of triglycerides around the body - LDL - Delivers cholesterol to cells - HDL - Picks up cholesterol from cells and transports to the liver for disposal

Answer 28

Hypercholesterolaemia - Hypothyroidism - Diabetes mellitus - Cholestasis Hypertriglyceridaemia - Obesity - Renal failure - Alcohol excess Mixed lipidaemia (both) - Diet - Nephrotic syndrome - Glycogen storage disease type 1 - Medications - COCP, beta-blockers, thiazide diuretics

Answer 29

Lifestyle advice - Diet + exercise aiming for a calorie deficit of 500kcal/day - c. 30 mins of intermediate exercise 5 days a week Medication: - Orlistat or liraglutide - For BMI > 30, or in run-up to bariatric surgery - Aim for weight loss > 5% after 12 weeks Bariatric surgery: - The above failed and: - BMI > 40 - BMI > 35 and recent-onset T2DM or other sequelae of weight and metabolic syndrome - First-line if BMI > 50

Answer 30

Features: - Bradycardia + hypotension + hypothermia - Loss of heart muscle with reduced cardiac output - Low Na+, Mg2+, PO4, K+ - Low urea and urine output - Reduced bone mineral density - Low insulin, glucagon, TSH, LH/FSH - High cortisol Quantification: - Low serum albumin is poor marker - BMI more useful but caution at extremes High risk if BMI < 18.5 or > 10% weight loss over the last 6 months Complications: - Refeeding syndrome - Extreme shifts in electrolytes -> life- threatening arrythmias - Heart failure - Fluid retention during refeeding + loss of cardiac muscle - Wernicke-Korsakoff's - Low thiamine - should be replaced prior to any glucose - Osteoporosis - Urinary retention or incontinence - Wasting of the detrusor muscle

Answer 31

Types of error: - Disorders of carbohydrate metabolism e.g. glycogen storage disease, G6PD deficiency - Disorders of amino acid metabolism - Organic acidaemias - Urea cycle defects - Disorders of fatty acid oxidation e.g. MCADD - Disorders of porphyrin metabolism e.g. AIP - Disorders of purine/pyramidine synthesis e.g. Lesch-Nyhan syndrome - Peroxisome disorders e.g. Zellweger syndrome - Mitochondrial disorders - Lysosomal disorders e.g. Fabry, Gaucher, Niemann-Pick Heelprick screening - phenylketonuria (PKU) - medium-chain acyl-CoA dehydrogenase deficiency (MCADD) - maple syrup urine disease (MSUD) - isovaleric acidaemia (IVA) - glutaric aciduria type 1 (GA1) - homocystinuria

Answer 32

- Congenital - Acute or chronic liver failure - SIBO - Glycine toxicity (e.g. post-TURP) - Sodium valproate overdose

Answer 33

Risk factors - Intake < 500 kcal/day for > 5 days - Little or no intake for > 10 days - Weight loss > 5-10% in the last 1-2 months - Weight-for-height < 70% - Morbid obesity with weight loss > 10% over last 2 months - History of substance abuse - Chronic disease states e.g. IBD, cancer, anorexia - Abnormal electrolytes (esp. low phosphate) prior to refeeding Monitoring: - Prior to feeding - FBC, U&Es, LFTs, bone profile, magnesium, clotting - Blood tests at 6-12hr after refeeding then daily for days 2-5 - Can reduce to every 5 days once stable for 48hr Management: - Administer thiamine/Pabrinex and multivitamins prior to beginning refeeding - Carefully manage feeding speeds - Start 30-35kcal/kg/day (or less) - Increase by 200-330 kcal/day every 2-3 days - If hypophosphataemia occurs, keep intake static and consider oral replacement

Answer 34

Cardiovascular: - Bradycardia - If unstable (< 35bpm) manage as per ALS - If stable, rx is nutrition + monitoring - Prolonged QTc - Bed rest + nutrition + monitoring - Hypotension - Nutrition + bed rest - Attempt oral fluid bolus (10ml/kg over 1hr) - If need IV, give 10 ml/kg only Electrolytes - Hypokalaemia - Oral replacement or IV if < 2.5 - Hyponatraemia - Prevent water overloading - Hypoglycaemia - Aim oral replacement but IV if symptomatic - Eliminate other causes e.g. insulin misuse, Addisons disease

Answer 35

Aka a ketoacidosis in a diabetic with BMs < 11 Important to rule-out an alcoholic ketoacidosis or a starvation ketoacidosis Aetiology - SGLT2 inhibitors - Pregnancy - Prolonged fasting Management: - As per DKA - IV fluids + IV insulin

Answer 36

Aetiology: - GIT inflammation Uses: - Regeneration of retinal membranes - Maintenance of mucous membranes - Immune function Presentation: - Gradual onset night blindness - Frequent GI, pulmonary, urinary tract infections - Xeroderma

Answer 37

Aetiology: - Poor intake - Reduced activation - renal failure, limited sunlight exposure - Medications Uses: - Bone and calcium homeostasis - promoted calcium mobilisation and uptake from the gut Features: - Rickets - Osteoporosis - Hypocalcaemia

Answer 38

Aetiology: - Fat malabsorption Uses: - Reduces oxidative damage to lipid membranes including immune cells, platelets, and neurones Features: - Ataxia - Hyporeflexia - Blindness - Dementia

Answer 39

Aetiology: - Poor intake - Malabsorption - Medications (warfarin) Uses: - Binds factors II, VII, IX, X and proteins C/S/Z to enable coagulation - Bone metabolism - Improves cardiovascular health Features: - Excessive bleeding (prolonged PT)

Answer 40

Aetiology - Poor intake - Malnutrition (rice-heavy diet), ETOH - Reduced absorption - IBD, diarrhoea/vomiting Uses - Cofactor for glycolysis and the Kreb's cycle Features - Neurological - Wernicke's and Korsakoff's - Impaired reflexes - Symmetrical sensory and motor neuropathies - Cardiovascular - RHF with peripheral oedema - Dilated cardiomyopathy

Answer 41

Uses: - Integral part of NAD and NADPH so used in cellular metabolism Features: - Pellagra - Dermatitis - brown/erythematous sore patches on sun-exposed skin - Diarrhoea - Dementia or milder memory loss/confusion