Endo conditions

Question 1

Acromegaly

1. Definition
2. Aetiology/RF
3. Epidemiology
4. Presenting Syx
5. Presenting sx
6. Investigation
7. Management
8. Complicatiions
9. Prognosis

Answer 1

1. Constellation of s/syx caused by hypersecretion of GH in adutls, with excess before puberty leading to gigantism
2. Most caused by GH secreting pituitary adenoma; rarely caused by excess GHRH causing somatotroph hyperplasia from ganglioneuroma, bronchial carcinoid or pancreatic tumours
3. Rare, 5/million, age affected: 40-50yrs
4. very gradual progression over many years; rings and shoes becoming tight, increased sweating, headaches, carpal tunnel syndrome, hypopit syx: hypogonadism, hypothyroidism, hypoadrenalism; visual disturbances, hyperprolactinaemia leading to irreg periods, decreased libido, impotence
5. Examination:
   
   1. Hands: large spade like hands; thick greasy skin, carpal tunnel syndrome sx, premature osteoarthritis
   2. Face: prominent eyebrow rdge, prominent cheeks, broad nose bridge, prominent nasolabial folds, thick lips, increased gap between teeth, large tongue, prognathism, husky resonant voice (thickening of vocal cords)
   3. Visual field loss: bitemporal superior quadrantopia progressing to bitemporal hemianopia
   4. Neck: multinodular goitre
   5. Feet: enlarged
6. Serum IGF-1; Oral glucose tolernce test (+ve, failure of suppression of GH after 75g of oral glucose load); pit function tests: 9am cortisol, free T4 and TSH, LH/FSH, testosterone, prolactin; MRI of brain
7. x
   
   1. Surgical: transphenoidal hypophysectomy
   2. RT: adjunctive to surgery
   3. Medical if surgery refused:
      
      1. subcut Somatostatin analogues (e.g. octreotide/lanreotide) with side effects of abdo pain,steatorrhoea, glucose intolerance and gallstones;
      2. Oral DA agonists (bromocriptine and cabergoline), side effects: N/V, constipation, postural hypotension, psychosis (rare);
      3. GH antagonist = pegvisomant
      4. Monitor: GH and IGF1 levels can be used to monitor
8. x
   
   1. CVS: cardiomegaly, HTN
   2. Resp: obstructive sleep apnoea
   3. GI: colonic polyps
   4. Repro: hyperprolactinaemia (30%)
   5. Metabolic: hyperCa, hyperPO4, Renal stones, DM, hypertriglyceridaemia
   6. Psych: depression, psychosis
   7. Complications of surgery: nasoseptal perforation, hypopit, adenoma recurence, CSF leak, infection
9. Good with early dx and tx; physical changes irreversible

Question 2

Adrenal insufficiency

1. Definition
2. Aetiology/RF
3. Epidemiology
4. Presenting syx
5. Presenting sx
6. Investigations
7. Management
8. Complications
9. Prognosis

Answer 2

1. Deficiency of adrenal cortical hormones (mineralo/glucocorticoids and androgens)
2. x
   
   1. 1ry adrenal insufficiency = addison’s disease (AI)
   2. 2ry adrenal insufficiency = pit/hypothalamic disease
   3. Infections = TB, meningococcal septicaemia (waterhouse-friderichsen syndrome), CMV, histoplasmosis
   4. Infiltration = metastasis (lung, breast, melanoma), lymphomas, amyloidosis
   5. Infarction = 2ry to thrombophilia
   6. Inherited = adrenoleukodystrophy, ACTH receptor mutation
   7. Surgical = after bilateral adrenalectomy
   8. Iatrogenic = sudden cessation of long-term steroid therapy
3. Most common cause is iatrogenic; 1ry causes are rare
4. Chronic presentation tend to be non-specific = dizziness, anorexia, weight loss, D/V, abdo pain, lethargy, weakness, depression
   
   1. acute presentation: acute adrenal insufficiency, major haemodynamic collapse, precipitated by stress
5. Postural hypotension, increased pigmentation (more on buccal mucosa, scars, skin creases, nails and pressure points), loss of body hair in women (due to androgen deficiency), associated AI condition
   
   1. Addisonian crisis: hypotensive shock, tachycardia, pale, cold, clammy, oliguria
6. Dx: 9am serum cortisol (<100nmol/L and >550 makes it unlikely) or short Synacthen test (IM 250 ug tetrocosactrin - synth ACTH, serum cortisol <550nmol/L at 30 min = adrenal failure)
   
   1. ID level of defect -> High in 1ry disease, Low in 2ry and Long synacthen test (1mg synth ACTH admin, measure serum cortisol at 0, 30, 60, 90 and 120 min and then measure again at 4, 6, 8, 12 and 24hrs; pts with 1ry show no increase after 6hrs)
   2. ID the cause = AutoAb (against 21-OHase), abdoCT/MRI, other tests (adrenal biopsy, culture, PCR)
   3. Check TFTs
   4. In addisonian crisis = FBC, U+E (high urea, low Na, high K), CRP/ESR, Ca, glucose (low), blood cultures, urinalysis, culture and sensitivity
7. x
   
   1. Addisonian crisis = rapid IV fluid rehydration; 50mL of 50% dextrose to correct hypoglycaemia; IV 200mg hydrocortisone bolus, followed by 100mg 6hrly hydrocortisone until BP is stable, treat precipitating cause (Abx for infection), monitor
   2. Chronic: replacement of glucocorticoids with hydrocortisone (3/d), mineralocorticoids with fludrocortisone; hydrocortisone dosage increased during times of acute illness or stress. NB: hydrocortisone before thyroxine if hypothyroidism
   3. Advice: have a steroid warning card, wear a medic alert bracelet, emergency hydrocortisone on hand
8. Hyperkalaemia; death during addisonian crisis
9. Adrenal function rarely recovers, nomal life expectancy if treated; Autoimmune polyendocrine syndrome
   
   1. type 1 - autosomal recessive disorder caused by mutations in the AIRE gene -> addison’s disease, chronic mucocutaneous candidiasis, hypoparathyroidism
   2. Type 2 - schmidt’s syndrome; addison’s disease, T1DM, hypothyrooidism, hypogonadism

Question 3

Carcinoid syndrome

1. Definition
2. Aetiology/RF
3. Epidemiology
4. Presenting syx
5. Presenting sx
6. Investigations

Answer 3

1. Constellation of syx caused by systematic release of humoral factors from carcinoid tumours
2. Carcinoid tumours are slow growing neuroendocrine tumours, mostly derived from serotonin-producing enterochromaffin cells -> produce serotonin, histamine, tachykinins, kallikrein and prostaglandins
   
   • NB: hormones released into the portal circulation will be metabolised by the liver so syx don’t tend to appear until hepatic mets/release into systemic circulation from bronchial or extensive retroperitoneal
3. Rare, UK incidence 1/million; asyx carcinoid tumours more common; 10% of pts with MEN-1 have carcinoid tumours
4. Paroxysmal flushing, diarrhoea, crampy abdo pain, wheeze, sweating, palpitations
5. Facial flushing, telangiectasia, wheeze, right-sided murmurs (tricuspid stenosis/regurg or pulm stenosis), nodular hepatomegaly in cases of mets disease
   
   1. Carcinoid crisis sx: profound flushing, bronchospasm, tachycardia, fluctuating BP
6. 24 hr urine collection (check 5-HIAA levels), bloods (plasma chromogranin A/B and fasting gut hormones), CT/MRI scan (localise tumour), radioisotope scan (radiolabelled somatostatin analogue helps localise the tumour), investigations for MEN-1

Question 4

Cushing’s syndrome

1. Definition
2. Aetiology/RF
3. Epidemiology
4. Presenting syx
5. Presenting sx
6. Investigations
7. Management
8. Complications
9. Prognosis

Answer 4

1. Syndrome associated with chronic inapproriate elevation of free circulating cortisol
2. ACTH dependent (80% - excess from pit adenoma ‘disease’ - ectopic from lung cancer ‘syndrome’) and ACTH independent (20% - benign adrenal adenoma, adrenal carcinoma)
3. incidence 2-4/million per year; peak 20-40yrs
4. Increasing weight, fatigue, muscle weakness, myalgia, thin skin, easy bruising, poor wound healing, fractures, hirsuitism, acne, frontal balding, oligo/amenorrhoea, depression/psychosis
5. Moon face, facial plethora, interscapular fat pad, proximal muscle weakness, thin skin, bruises, central obesity, pink/purple striae on abdo/breasts/thighs, kyphosis, poorly healing wounds, hirsuitism, acne, frontal balding, HTN, ankle oedema, pigmentation in ACTH dependent cases
6. Must be performed on pts with high pretest probability;
   
   1. bloods (U+Es hypoK due to mineralocorticoid effect, BM high glucose)
   2. Initial high sensitivity tests = urinary free cortisol, late night salivary cortisol, overnight/low dose dexamethasone suppression test (give 0.5mg DXM orally every 6hrs for 48hrs; failure to suppress below 50 nmol/L)
   3. Test to determine underlying cause:
      
      1. ACTH independent -> low plasma ACTH, CT/MRI of adrenals
      2. ACTH dependent -> high plasma ACTH, pit MRI, high-dose DXM suppression test, inferior petrosal sinus sampling (superior to HDDST)
      3. ACTH dependent ectopic -> lung cancer = CXR, sputum cytology, bronchoscopy, CT scan; radiolabelled octreotide scans can detect carcinoid tumours because they express somatostatin receotirs
7. Iatrogenic = discontinue steroids, use lower dose or steroid-sparing agents
   
   1. Medical = used pre-op or if unfit for surgery, inhibit cortisol synth with metyrapone or ketoconazole, treat osteoporosis, physio for muscle weakness
   2. Surgical = pit adenomas (trans-sphenoidal resection), adrenal adenoma/carcinoma (surgical removal), ectopic ACTH (tx directed at the tumour)
   3. RT = performed in those not cured and have persistent high cortisol after resection of tumour; bilat adrenalectomy may be performed in refractory cushing’s disease
8. DM, OP, HTN, pre-dispositions to infections
   
   1. Surgery = CSF leakage, meningitis, sphenoid sinusitis, hypopit
   2. RT = hypopit, radionecrosis, increased risk of 2nd intracranial tumours and stroke
   3. Bilat adrenalectomy = complicated by development of Nelson’s syndrome
9. Untreated 5yr survival = 50%; depression persists for many years following treatment

Question 5

Diabetes insipidus

1. Definition
2. Aetiology/RF
3. Epidemiology
4. Presenting syx
5. Presenting sx
6. Investigations
7. Management
8. Complications
9. Prognosis

Answer 5

1. Disorder of inadequate secretion or of insensitivity to ADH leadig to hypotonic polyuria
2. Central DI: failure of ADH secretion by the post pit; nephrogenic DI: insensitivity of the Collecting duct to ADH; results in large volumes of hypotonic urine and polydipsia.​Causes:
   
   1. Central: idiopathic, tumours (pit), infiltrative (sarcoidosis), infection (meningitis), vascular (aneurysms), trauma (head injury, neurosurgery)
   2. Nephrogenic: Idiopathic, drugs, post-obstructive uropathy, pyelonephritis, pregnancy, osmotic diuresis
3. Median onset is 24yrs; depends on cause
4. Polyuria, nocturia, polydipsia; children = enuresis, sleep disturbance; other syx depend on aetiology
5. Central DI has few sx if pt drinks sufficiently to maintain levels; urine output >3L/d; fluid intake<output>
   </output><li>Bloods: U+Es, Ca, increased plasma osm, decreased urine osm
   <ol>
   <li>Water deprivation test = restricted for 8hrs; plasma and urine osm measured every hour for 8hrs; weigh the pt hourly to monitor level of dehydration; STOP the test body weight fall &gt;3%. <u>Desmopressin</u> given after 8hrs and urine osm measured</li>
   <li>Results = normal (water restriction causes): increased plasma osm, ADH secretion, water reabsorption, urine osm (&gt;600mosmol/kg); DI: Lack of ADH so urine osm LOW (&lt;400), cranial means urine osm rises &gt;50% after Desmopressin, nephrogenic means urine osm rises &lt;45% after desmo</li>
   </ol>
   </li><li>Treat the cause;
   <ol>
   <li>cranial DI: give DP and if mild chlorpropamide/carbamazepine to potentiate the residual effects of any residual VP</li>
   <li>nephrogenic DI: Na and/or protein restriction helps with polyuria, thiazide diuretic</li>
   </ol>
   </li><li>Hypernatraemic dehydration, excess desmopressin elads to hyponatraemia</li><li>Depends on cause; cranial DI may be transient following head trauma; may be cured by removing the cause</li>

</output>

Question 6

Diabetes Mellitus Type 1

1. Definition
2. Aetiology/RF
3. Epidemiology
4. Presenting syx and sx
5. Investigations
6. Management
7. Complications
8. Prognosis

Answer 6

1. Metabolic hyperglycaemic condition caused by absolute insufficiency of pancreatic insulin production
2. Caused by destruction of pancreatic insulin-producing beta cells; AI process; occurs in genetically susceptible individuals with environmental trigger; auto-Ag associated with T1DM: glutamic acid decarboxylase, insulin, insulinoma-associated protein 2, cation efflux zinc transporter
3. 0.25% prevalence in UK
4. Juvenile onset (<30yrs), polyuria/nocturial, polydipsia, tiredness, weight loss
   
   1. DKA syx: N/V, adbo pain, polydipsia/uria, drowsiness, confusion, coma, kussmaul breathing, ketotic breathing, sx of dehydration
   2. sx of complications: fundoscopy (diabetic retinopathy), examine feet for evidence of neuropathy (monofilament test); monitor BP
   3. Sx of associated autoimmune conditions: vitiligo, addison’s disease, autoimmune thyroid disease
5. Blood glucose - fasting >7 or random bgl >11; HBA1c; FBC: MCV reticulocytes; U+Es monitor for nephropathy and hyperkalaemia; lipid profile; urine albumin creatinine ratio to detect microalbuminuria; urine - glycosuria, ketonuria, MSU;
   
   1. Investigations for DKA: FBC (raised WCC w/out infection), U+Es (raised urea/creatinine ), LFT, CRP, glucose, amylase, blood cultures, ABG (met acidosis with high anion gap), blood/urinary ketones
6. management:
   
   1. Glycaemic control: advice and pt education: short acting insulin (3/d = lispro, aspart, glulisine), long acting insuilin (1/d = isophane, glargine, detemir); insulin pumps, DAFNE courses (dose adjustment for eating), Monitor (regular cap BGT, HbA1c every 3-6m), screening and management of complications; tx of hypoglycaemia (reduced consciousness = 50ml of 50% glucose IV OR 1mg glucagon IM; consciousness = 50g oral glucose and starchy snack)
   2. DKA management: 50U soluble insulin in 50 mL of normal saline, continue until cap ketones <0.3, venous pH >7.30, venous bicarbonate >18mmol; then change to SC insulin and don’t stop insulin infusion until 1-2hrs after the SC insulin has restarted; 500ml normal saline over 15-30 min until SBP > 100; K replacement; monitor blood glucose, cap ketones, urine output hjourly; monitor U+Es and venous blood gas; broad spectrum Abx if infection; thromboprophylaxis; NBM for at least 6hrs, NGT if GCS reduced
7. DKA: can be precipitated by infection, errors in mx of dm, newly dx, idiopathic;
   
   1. Microvascular: retinopathy, neuropathy and nephropathy
   2. Macrovascular: Peripheral vascular disease, IHD, stroke/TIA
   3. Increased irsk of infection
   4. Complications of treatment: weight gain, fat hypertrophy and insulin injection site, hypoglycaemia (personality changes, fits, confusion, coma, pallor, sweating, tremor, tachycardia, palpitations, dizziness, hunger, focal neurological syx
8. Depends on early dx, good glycaemic control and compliance with tx and screening; vascular disease and renal failure are the main causes of increased mortality and morbidity

Question 7

Diabetes Mellitus type 2

1. Definition
2. Aetiology/RF
3. Epidemiology
4. Presenting Syx
5. Presenting Sx
6. Investigations
7. Management
8. Complications
9. Prognosis

Answer 7

1. Increased peripheral resistance to insulin action, impaired insulin secretion and increased hepatic glucose output
2. Genetic and env; few monogenic causes of DM; obesity increases risk; can be 2ry to pancreatic disease, endocrine (cushing’s, acromegaly, phaeo, glucagonoma) and drugs (corticosteroids, atypical antipsychotics, protease inhibitors
3. UK = 5-10%; asian, african and hispanic at greater risk; incidence increased over past 20yrs -> linked to increase obesity prevalence
4. Polyuria, polydipsia, tiredness, pts may present with hyperosmolar hyperglycaemic state, infections, assess cardiovascular risk factors: HTN, hyperlipidaemia and smoking
5. Calculate BMI, waist circumference, BP, diabetic foot sx (dry skin, reduced subcut tissue, ucleraton, gangrene, charcot’s arthropathy, weak foot pulses); skin changes (RARE): necrobiosis lipoidica diabeticorum, granuloma annulare , diabetic dermopathy
6. Dx if one or more present: syx of DM and random plasma glucose of >11.1mmol/L, fasting plasma glucose >7, 2-hr plasma glucose >11.1 after 75g oral glucose tolerance test; Monitor: HbA1c, U+Es, lipid profile, eGFR, urine albumin (creatinine ratio)
7. x
   
   1. Glycaemic control:
      
      1. at dx: lifestyle and metformin
      2. HBA1c >7% after 3m:
         
         1. lifestyle + metformin + sulphonylurea (can be monotherapy if metformin not tolerated)
         2. lifestyle +metformin + basal insulin
         3. And fasting blod glucose >7: add premeal rapid actign insulin
         4. NB: pioglitaqzone can be given alongside metformin and sulphonylurea
   2. Screening for complications: retinopathy, nephropathy, vascular disease, diabetic foot, cardiovascular risk factors
   3. Pregnancy: requiring strict glycaemic control and planning of conception
   4. Hyperosmolar hyperglycaemic state: mx similar to DKA, except 0.45% saline if serum Na >170mmol/L
8. x
   
   1. Hyperosmolar hyperglycaemic state: due to insulin def; marked dehydration, high Na, high glucose, high osmolality, no acidosis
   2. Neuropathy: distal symmetrical sensory neuropathy, painful, carpal tunnel syndrome, diabetic amyotrophy, mononeuritis, autonomic neuropathy, gastroparesis (abdo pain, N/V), impotence, urinary retention
   3. Nephropathy: microalbuminuria, proteinuria, renal failure, prone to UTI, renal papillary necrosis
   4. Retinopathy: background, pre-proliferative, proliferative,. maculopathy, prone to glaucoma/cataracts and transient visual loss
   5. Macrovascular: IHD, stroke, peripheral vascular disease
9. Good prognosis with good control; prediabetes can be dx based on fasting blood glucose and oral glucose tolerance test: Impaired fasting = FBG 5.6-6.9; impaired glucose tolerance = plasma glucose level 7.8-11 measured 2hrs after a 75g oral glucose tolerance test -> people with IFG or IGT are at high risk of developing T2DM

Question 8

Graves Disease

1. Definition
2. Aetiology/RF
3. Epidemiology
4. Presenting Syx
5. Presenting Sx
6. Investigations

Answer 8

1. The most common cause of hyperthyroidism; presence of TSH-receptor stimulating Ab that lead to hyperthyroidism due to loss of negative feedback
2. Caused by the presence of TSH receptor stimulating Ab; Rf: FHx, high iodine intake, smoking, trauma to thyroid gland, toxic multinodular goitre, HAART, childbirth
3. Common, graves is most common cause of hyperthyroidism (75%); rarely in children
4. Weight loss even though increased appetite; irritability, diarrhoea, sweating, tremor, anxiety, heat intolerance, loss of libido, oligomenorrhoea/amenorrhoea
5. palmar erythema, sweaty and warm palms, fine tremor, tachycardia (AF?), hair thinning, urticaria/pruritus, brisk refloexes, goitre, proximal myopathy, lid lag, gynaecomastia
6. TFTs - low TSH and high T3/T4; autoantibodies - anti-TPO antibodies (75%), anti-thyroglobulin antibodies, TSH-receptor ab (very sensitive/specific for graves); imaging - thyroid US, thyroid uptake scan; inflammatory markers - CRP/ESR raised in subacute thyroiditis

Question 9

Hyperparathyroidism

1. Definition
2. Aetiology/RF
3. Epidemiology
4. Presenting Syx and Sx
5. Investigations
6. Management
7. Complications
8. Prognosis

Answer 9

1. 1ry = increased PTH unrelated to plasma Ca conc; 2ry = increased PTH secondary to hypocalcaemia; 3ry = autonomous PTH secretion following chronic 2ry hyperparathyroidism
2. 1ry: parathyroid adenoma, parathyroid hyperplasia, parathyroid carcinoma, MEN syndrome; 2ry: chronic renal failure, vit D deficiency
3. 1ry incidence of 5/100,000; 2x as common in females;peak incidence = 40-60yrs
4. 1ry: many pts have mild hypercalcaemia and may be asyx; syx/sx of hypercalcaemia: polyuria, polydipsia, renal calculi, bone pain, abdo pain, nausea, constipation, psych depression, lethargy;
   
   1. 2ry: may present with sx/syx of HYPOcalcaemia or of underlying cause
5. U+Es, serum Ca (high in 1ry/3ry, low in 2ry), serum PO4, albumin, ALP, vit D, PTH, renal USS for renal calculi;
   
   1. primary hyperparathyroidism: hyperchloraemic acidosis, normal anion gap, due to PTH inhibition of renal reabsorption of bicarbonate, urine - high PTH in the presence of high Ca can also be caused by familial hypocalciuric hypercalcaemia (calcium:creatinine ratio can help differentiate between 1ry and FHH)
6. Acute hypercalcaemia = IV fluids, avoid factors that exacerbate hyperCa, maintain adequate hydration, moderate ca and vit D intake;
   
   1. surgical mx: subtotal/total parathyroidectomy
   2. 2ry herPTH: treat underlying cause and ca/vit D supplements may be needed
7. x
   
   1. 1ry: increased bone resoprtion/tubular ca reabsorption/1alpha-hydroxylation of vit D leading to hypercalcaemia
   2. 2ry: increased stimulation of osteoclasts and increased bone turnover; osteitis fibrosa cystica
   3. Surgery complications: hypocalcaemia, recurrent laryngeal nerve palsy
8. 1ry: surgery curative for benign disease in most cases; 2/3ry: same prognosis as chronic renal failure

Question 10

Hypogonadism (female)

1. Definition
2. Aetiology/RF
3. Epidemiology
4. Presenting Syx
5. Presenting Sx
6. Investigations

Answer 10

1. Characterised by impairment of ovarian function
2. 1ry: gonadal dysgenesis (due to chromosomal abnormalities), gonadal damage (autoimmune); 2ry: functional (stress, weight loss, excessive exercise eating disorder), pit/hypothalamic tumours and infiltrative lesions (pit adenomas, haemochromatosis), hyperprolactinaemia (prolactinoma), congenital GnRH deficiency (Kallman’s syndrome, idiopathic)
3. Oestrogen deficiency: night sweats, hot flushing, vaginal dryness, dyspareunia, decreased libido, infertility
4. 1. Pre-pubertal: delayed puberty (1ry amenorrhoea, absent breast development, no 2ry sex characteristics), eunuchoid (long legs, arm span greater than height);
   2. post-pubertal: regression of 2ry sex characteristics (loss of 2ry sex hair, breast atrophy), perioral and periorbital fine facial wrinkles, sx of underlying cause
   3. Hypothalamic/pit disease: visual field defects
   4. Kallman’s syndrome: anosmia
   5. turner’s syndrome: short stature, low post hair line, high arched palate, widely spaced nipples, wide carrying angle, short 4/5th metacarpals, congenital lymphoedema
   6. Autoimmune 1ry ovarian failure - may be signs of other AI diseases
5. Low serum oestradiol, serum FSH/LH (1ry = high, 2ry = low)
   
   1. 1ry: karyotype, pelvic imaging (US/MRI)
   2. Screen for FMR1 gene in pts with unexplained premature ovarian failure
   3. 2ry: pit function tests, visual field testing, hypothalamic-pit MRI, smell tests for anosmia, serum transferrin saturation
   4. Associated conditions: Turner’s syndrome: periodic echo, renal US; AI oophoritis: check autoimmune adrenal insufficiency

Question 11

Hypogonadism (male)

1. Definition
2. Aetiology/RF
3. Epidemiology
4. Presenting Syx
5. Presenting sx
6. Investigations

Answer 11

1. Syndrome of decreased testosterone production, sperm production or both
2. 1ry: gonadal dysgenesis (klinefelter’s syndrome, undescended testicles), gonadal damage (infection, torsion, trauma, AI), rare causes (defects in enzymes involved in testosterone synthesis)
   
   1. 2ry: pit/hypothalamic lesions, GnRH deficiency (Kallman’s syndrome), hyperprolactinaemia, systemic/chronic diseases, prader-willi syndrome (short, small hands, almond shape eyes, learning difficulty, postnatal hypotonia), laurence moon biedl syndrome (obesity, polydactyly, retinitis pigmentosa, learning difficulty); rare causes are genetic mutations
3. 1ry accounts for 30-40% of male infertility -> most common is Klinefelter’s syndrome (lower IQ, tall stature, poor muscle tone, reduced 2ry sexual characteristics, gynaecomastia, small testes/infertility); 2ry accounts for 1-2%
4. Delayed puberty, decreased libido, impotence, infertility, syx of underlying cause
5. Testicular volumem using Prader’s orchidometer (15-25mL);
   
   1. prepubertal: sx of delayed puberty (high pitched voice, decreased pubc/axillary/facial hair, small/undescended testicles, small penis), gynaecomastia, eunuchoid proportions, features of underlying cause
   2. Postpubertal: decreased pubic/axillary/facial hair, soft and small eyes, gynaecomastia, fine perioral wrinkles, features of underlying cause
6. serum total testosterone, sex hormone binding globulin, albumin, LH/FSH;
   
   1. ry: low testosterone, high LH and FSH, can be investigated using karyotyping
   2. ry low testosterone, inappropriately normal/low LH/FSH; pit function tests, MRI of the hypothalamic/pit area, visual field testing, smell testing, iron testing
   3. Assess bone age (risk of fx)

Question 12

Hypopituitarism

1. Definition
2. Aetiology/RF
3. Epidemiology
4. Presenting Syx and Sx
5. Investigations
6. Management
7. Complications
8. Prognosis

Answer 12

1. Deficiency in one or more of the hormones secreted by the anterior pit; panhypopituitary is deficiency of ALL pituitary hormones
2. Pit massess: most commonly adenomas; pit trauma: radiation, surgery, base of skull fractures; hypothalamic dysfunction: due to anorexia, starvation, over-exercise; infiltrative diseases: sarcoidosis, haemochromatosis, Langerhan’s cell histiocytosis; vascular: pit apoplexy, sheehans syndrome; infection: meningitis, encephalitis; genetic mutation: pit-1, prop-1 genes
3. Pit adenoma annual incidence 1/100,000
4. Depends on cause
   
   1. GH: children (short stature), adults (low mood, fatigue, reduced exercise capacity and muscle strength, increased abdo fat mass)
   2. LH/FSH: delayed puberty, Females: loss of 2ry sexual hair, breast atrophy, menstrual irregularities, dyspareunia, decreased libido, infertility; males: loss of 2ry sexual hair, gynaecomastia, small and soft testes, decreased libido, impotence
   3. ACTH: sx/syx of adrenal insufficiency
   4. TSH: sx/syx pf hypothyroidism
   5. Prolactin: absence of lactation (not usually noticed clinically)
   6. Pit apoplexy: headache, visual loss, cranial nerve palsies
5. Pit function tests:
   
   1. Basal tests: 9am cortisol, LH and FSH levels, testosterone levels, oestrogen levels, IGF-1 levels, prolactin levels, free T4/TSH levels
   2. Dynamic tests: RARE, insulin induced hypoglycaemic
   3. short synacthen test
   4. MRI/CT brain
   5. Visual field testing
6. Hormone replacement: hydrocortison, levothyroxine, sex hormones: testosterone in males, oestrogen with/out progesterone in females, growth hormone, desmopressin
7. Addisonian crisis, hypoglycaemia, myxoedema coma, infertility, osteoporosis, dwarfism; complications of pit mass: optic chiasm compression (bitemp hemianopia), hydrocephalus, temporal lobe epilepsy
8. Good prognosis with lifelong treatment

Question 13

Hypothyroidism

1. Definition
2. Aetiology/RF
3. Epidemiology
4. Presenting Syx
5. Presenting Sx
6. Investigation

Answer 13

1. The clinical syndrome resulting from insufficiency secretion of thyroid hormones
2. 1ry:
   
   1. Acquired: hashimoto’s thyroiditis (AI), iatrogenic (post-surgery, radioiodine, hyperthyroid medication), severe iodine deficiency, iodine excess (wolff-chaikoff effect), thyroiditis
   2. Congenital: thyroid dysgenesis, inherited defects in thyroid hormone biosynthesis
   3. 2ry: pit and hypothalamic disease: resulting in reduced TSH/TRH and reduced stimulation of thyroid hormone production
3. 0.1-2% of adults; 6x more common in females; most common age of onset >40yrs, iodine deficiency in mountainous areas
4. Insidious onset, cold intolerance, lethargy, weight gain, reduced appetite, constipation, dry skin, hair loss, hoarse voice, mental slowness, depression, cramps, ataxia, paraesthesia, menstrual disturbance (irregular cycles, menorrhagia), hx of surgery or radioiodine therapy for hyperthyroidism, personal/FHx of other autoimmune conditions; myxoedema coma: hypothermia, hypoventilation, hyponatraemia, HF, confusion, coma
5. x
   
   1. Hands: bradycardia, cold hands
   2. Head/neck/skin: pale puffy face, goitre, oedema, hair loss, dry skin, vitiligo
   3. Chest: pericardial effusion, pleural effusion
   4. Abdomen: ascites
   5. Neurological: slow relaxation of reflexes, signs of carpal tunnel syndrome
6. Bloods: TFTs, FBC (normocytic anaemia), U+Es (low Na), cholesterol (high)
7. x
   
   1. Chronic: levothyroxine (25-200mcg/d), important to rule out underlying adrenal insufficiency before starting THR, thyroid hormone replacement in the context of adrenal insufficiency can precipitate an addisonian crisis, adjust dose based on clinical picture and TFTs
   2. Myxoedema coma: oxygen, rewarming, rehydration, IV T4/3, IV hydrocortisone, treat underlying disease
8. Myxoedema coma, myxoedema madness (psychosis with delusions and hallucinations or dementia)
9. Lifelong thyroxine required; myxoedema coma mortality 80%

Question 14

Multiple Endocrine Neoplasia

1. Definition
2. Aetiology/RF
3. Epidemiology
4. Presenting Syx and sx
5. Investigations

Answer 14

1. Autosomal dominant condition characterised by a predilection to develop tumours of endocrine glands
2. Autosomal dominant inheritance. Patterns of features:
   
   1. Men1: pit adenomas, parathyroid tumours, pancreatic islet cell tumours (other GIT tumours), facial angiofibromas and collangenomas
   2. Men2a: parathyroid tumours, medullary thyroid cancer, phaeochromocytoma
   3. Men2b:same as Men2a and marfanoid appearance, neuromas of GIT
3. VERY RARE
4. x
   
   1. MEN1: age of onset of tumours is usually teenage years; however, syx of tumours may not become apparent for years, dx is commonly made in the 4th decade of life; herPTH (syx of hyperCa and nephrolithiasis), hergastrinaemia (Zollinger-Ellison syndrome), herinsulinaemia (hypoglycaemia), herProlactinaemia (amenorrhoea), hersomatotrophinaemia (acromegaly); pit tumours may cause visual defects
   2. MEN2: syx of medullary thyroid cancer, herPTH or phaeo; medullary thyroid cancer syx: HTN, episodic sweating, diarrhoea, pruritic skin lesions, lump in neck; herCa syx: constipation, polyuria/dipsia, depression, kidney stones, fatigue
5. x
   
   1. MEN1: screening 1st/2nd degree relatives; hormone hypersecretion blood tests, DNA testing
   2. MEN2: phaeo test (24hr urine metanephrines, followed by abdo MRI), medullary thyroid cancer test (elevated calcitonin conc; also investigated with US and FNA); Parathyroid tumours (simultaneously elevated Ca and PTH

Question 15

Obesity

1. Definiton
2. Aetiology/RF
3. Epidemiology
4. Presenting syx/sx
5. Investigations

Answer 15

1. BMI>30kg/m2; defined using waist circumference = Men (low risk <94cm, v. high risk >102cm), women (low risk <80cm, v.high risk >88cm
2. Genetic factors that affect the risk of becoming obese; few monogenic forms of obesity (leptin deficiency, prader-willi syndrome), common obesity is caused by energy intake > energy usage
3. 24% of men and 25% of women are obese
4. Noticing you’ve gained weight, routine health check, sx of complications (t2dm, CHD, obstructive sleep apnoea); hgih body weight, BMI and waist circumference
5. Measure serum lipids, measure HbA1c, hormone profile (check hormonal cause), TFTs, other investigations

Question 16

Osteoporosis

1. Definiton
2. Aetiology/RF
3. Epidemiology
4. Presenting syx
5. Presenting sx
6. Investigations

Answer 16

1. Reduced bone density (>2.5 sd below peak bone mass achieved by healthy adult resulting in bone fragility and increased fx risk
2. 1ry is idiopathic or post-menopausal; 2ry: malignancy (myeloma, metastatic carcinoma), endocrine (cushing’s disease, thyrotoxicosis, 1ry herPTH, hypogonadism), drugs (corticosteroids, heparin), rheumatological (RhA, AnkSpond), GI (malabsorption (coeliac, partial gastrectomy), liver disease and anorexia).
   
   1. RF: age, fhx, low BMI/Ca intake/exposure to sunlight, smoking, lack of physical exercise, alcohol abuse, late menarche, early menopause, hypogonadism
3. Common, in >50yrs: F1/3, M1/12; more common in caucasians than afrocaribbeans
4. Often asyx, until fx occur; neck of femur (minimal trauma), vertebral fx (loss of height, stooped posture and acute back pain on lifting), colles’ fx (distal radius after falling on outstretched hand
5. None until complications develop: tenderness on percussion over vertebral fx, thoracic kyphosis, severe pain when hip flexed and externally rotated
6. Bloods: Ca, PO4, ALP (NORMAL in 1ry); XR: to dx fx, often normal, can show biconcave vertebrae and crush fx; Isotope bone scan to highlight areas of stress and microfx; DEXA: T-score (no. of sd the BMD is above or below theyoung normal mean BMD) or Z-score (no of sd measurements below age-matched mean BMD

Question 17

Paget’s disease of the bone

1. Definiton
2. Aetiology/RF
3. Epidemiology
4. Presenting Syx
5. Presenting Sx
6. Investigations

Answer 17

1. Characterised by excessive bone remodelling at one or more sites resulting in bone that is structurally disorganised
2. Unkown; genetic and viral factors may play role; excessive bone resorption by abnormally large osteoclasts followed by increased bone formation by osteoblasts in a disorganised fashion; abnormal pattern of lamellar bone, marrow filled by excess of fibrous tissue with marked increase in blood vessels
3. common in elderly, 3%>50, 10%>80; M=F
4. May be asyx; present with insidious onset pain, aggravated by weight bearing and movement; headaches, deafness, increasing skull size
5. Bitemporal skull enlargment with frontal bossing (prominent protruding forehead); spinal kyphosis; anterolateral bowing of femur, tibia, forearm; skin over affected bone may be warm due to increased vascularity; sensorineural deafness (compression of vestibulocochlear nerve
6. Bloods: high ALP, normal Ca/PO4;
   
   1. bone radiographs: enlarged, deformed bones, lytic/sclerotic appearance, lack of distinction between cortex and medulla, skull changes: osteoporosis circumscripta, enlargment of frontal and occipital areas, cotton wool appearance;
   2. Bone scan: asessses extent of skeletal involvement, pagetic bone lesions are seen as areas with markedly increased uptake;
   3. Resorption markers: monitors disease activity, check urinary hydroxyproline

Question 18

Phaeochromocytoma

1. Definiton
2. Aetiology/RF
3. Epidemiology
4. Presenting Syx
5. Presenting Sx
6. Investigations

Answer 18

1. Catecholamine producing tumours that usually arise from chromaffin cells of the adrenal medulla, but are extra-adrenal in about 10% of cases:
   
   1. 10% bilateral
   2. 10% malignant
   3. 10% extraadrenal - paragangliomas
2. Sporadic cases are unknown aetiology, familial in up to 30% seen in pts with MEN2a, vHL syndrome and Neurofibromatosis type 1
3. Rare, <0.2% of HTN pts
4. Paroxysmal episodes; headaches, sweating, cardioresp syx: palpitations, chest pain, dyspnoea; GI: eigastric pain, nausea, constipation; neuropsych: weakness, tremor, anxiety
5. HTN, postural hypotension, pallor, tachycardia, fever, weight loss
6. 24hr urine collection for catecholamine levels and fractionated metanephrine levels; plasma free metanephrines; tumour localisation (MRI/CT), I-MIBG scintigraphy; screen for asociated conditions; genetic testing

Question 19

Pituitary tumours (non-functioning)

1. Definiton
2. Aetiology/RF
3. Epidemiology
4. Presenting Syx
5. Presenting Sx
6. Investigations

Answer 19

1. benign tumours of the pit gland formed from pit cells that don’t produce any active pit hormones
2. No specific caue; part of MEN1
3. Most common type of macroadenoma and pit tumour in pts >60
4. Very slowly, headaches, pressure on surrounding structures; optic chiasm (bitemp hemianopia), normal pit (panhypopit)
5. MRI, CT, bloods for hormone levels, visual field testing

Question 20

Polycysitic Ovarian syndrome

1. Definiton
2. Aetiology/RF
3. Epidemiology
4. Presenting Syx
5. Presenting Sx
6. Investigations

Answer 20

1. charcterised by Oligomenorhoea/amenorrhoea and hyperandrogenism; frequently associated with: obesity, insulin resistance, T2DM, dyslipidaemia
2. Environmental factors, genetic variants, hyperinsulinaemia resulting in increased ovarian androgen synthesis and reduced hepatic sex hormone binding globulin; leads to increase in free androgens
3. Most common cause of infertilty in women, affecting 6-8% of women
4. Menstrual irregularities dysfunctional uterine bleeding, infertility, syx of hyperandrogenism: hirsuitism, male pattern hair loss, acne
5. Hirsuitism, acne, acanthosis nigricans
6. Bloods: high LH/LH:FSH ration/testosterone, androstenedione and DHEAS, low sex hormone binding globulin; others: hyperprolactinaemia, hypo/erthyroidism, CAH (17OHP levels), cushing’s syndrome; impaired glucose tolerance: FBG and HbA1c; fasting lipid profile; transvaginal USS for ovarian follicles and increase in ovarian volume

Question 21

1ry hyperaldosteronism

1. Definiton
2. Aetiology/RF
3. Epidemiology
4. Presenting Syx
5. Presenting Sx
6. Investigations
7. Management
8. complications
9. Prognosis

Answer 21

1. Characterised by autonomous aldosterone overproduction from the adrenal gland with subsequent suppression of plasma renin activity
2. Adrenal adenoma (Conn’s) responsible for 70%; adrenal cortex hyperplasia (30%), RARE: glucocorticoid-suppressible hyperaldosteronism, aldosterone producing adrenal carcinoma; pathophysiology: excess aldosterone leads to increased Na and water retention = HTN and increased renal K loss = hypokalaemia; renin suppressed due to NaCl retention
3. 1-2% HTN; Conn’s more common in women and young pts; bilat adrenal hyperplasia more common in men and at older age
4. usually asyx, tends to be incidental finding on routine blood tests; syx of hypokalaemia: muscle weakness, polyuria, polydipsia (nephrogenic DI), paraesthesia, tetany
5. HTN and complications of HTN
6. Screening tests: low serum K (normal sNa), High urine K, high plasma aldosterone concentration, high aldosterone:renin activity ratio; confirmatory tests:
   
   1. Salt loading: failure of aldosterone suppression following salt load = 1ry
   2. postural test = measure plasma aldosterone, renin activity and cortisol when pt lying down at 8am, then measure again after 4hrs of pt being upright = aldosterone-producing adenoma = aldosterone decreases between 8am-12pm; bilat adrenal hyperplasia = adrenals respond to standing posture and increase renin production, increasing aldosterone production
   3. CT/MRI
   4. Bilat adrenal vein catheterisation = measuring aldosterone levels to distinguish between Conn’ sand BAH
   5. Radiolabelled cholesterol scanning = unilat uptake in adrenal adenomas, bilat uptake in BAH
7. BAH = spironolactone, eplerenone if spironolactone side effects intolerable, amiloride -> monitor serum K and creatinine and BO, can also add ACEi and CCBs; Aldosterone producing adenomas = adrenalectomy; adrenal carcinoma = surgery, post op mitotane (anti-neoplastic)
8. Complications of HTN
9. Surgery may cure HTN, or make it easier to treat with medication

Question 22

Prolactinoma

1. Definiton
2. Aetiology/RF
3. Epidemiology
4. Presenting Syx and Sx
5. Investigations
6. Management
7. Complications
8. Prognosis

Answer 22

1. Pit adenoma that overproduces prolactin
2. Different types: microadenomas <1cm, macro >1cm, giant pit adenomas >4cm, malignant prolactinomas (rare); cause unknown, but some due to MEN1; risk of enlargment during pregnancy
3. Relatively common, higher incidence in premenopausal women
4. Note: micro rarely become macro; women = ameno/oligomenorrhoea, galactorrhoea, infertility, hirsuitism, reduced libido; men = syx subtle and develop slowly, reduced libido, reduced beard growth, erectile dysfunction; syx by tumour size: headache, visual disturbance, cranial nerve palsies, hypopit
5. Exclude pregnancy; TFTs: hypothyroidism, high TRH which stim prolactin release; serum prolactin level (>5000mU/L suggests true prolactinoma; MRI; assessment of pit function
6. Goals: treat cause, relieve syx, prevent complications, restore fertility; DA agonists (cabergoline and bromocriptine) effective in most pts, long-term basis and if ineffective: surgery and RT
7. Hypogonadism: OP, reduced fertiltiy, erectile dysfunction; tumour size: visual loss, headache, pit apoplexy and CSF rhinorrhoea
8. Micro spontaneously resolve 1/3 cases; DA agonist withdrawal attempted after about 2-3 yrs if PL levels normalised and tumour volume reduced, high rates of recurrence

Question 23

SIADH

1. Definiton
2. Aetiology/RF
3. Epidemiology
4. Presenting Syx
5. Presenting Sx
6. Investigation
7. Management
8. Complication
9. Prognosis

Answer 23

1. Characterised by continued secretion of ADH, despite the absence of normal stimuli for scretion
2. x
   
   1. Brain: Haemorrhage/thrombosis, meningitis, abscess, trauma, tumour, Guillain Barre syndrome
   2. Lung: Pneumonia, TB, Other: abscess, aspergillosis, small cell carcinoma
   3. Tumours: Small cell lung cancer, lymphoma, leukaemia, others: pancreatic cancer, prostate cancer, mesothelioma, sarcoma, thymoma
   4. Drugs: Vincristine, opiates, carbamazepine, chlorpropamide
   5. Metabolic: porphyria, alcohol withdrawal
3. Hyponatraemia is most common electrolyte imbalance seen in hospital; <50% of severe hyponatraemia caused by SIADH
4. Mild hypoNa can by asyx; headache, N/V, muscle cramp/weakness, irritability, confusion, drowsiness, convulsions, coma, syx of underlying cause
5. Mild hypoNa = no sx; SEVERE hypoNa = reduced reflexes, extensor plantar reflexes; sx of underlying cause
6. Low serum Na, creatinine, glucose/serum protein/lipids to rule out pseudohypoNa; free T4 and TSH, short synacthen test
   
   1. SIADH dx: low plasma osmolality, low serum Na conc, high urine osm, high urine Na -> absence of hypovolaemia, oedema, renal failure, adrenal insufficiency and hypothyroidism for dx;
   2. investigations for identifying the cause (CXR, CT, MRI)
7. Treat underlying cause, fluid restriction, VP, receptor antagonists (tolvaptan); severe cases = slow IV hypertonic saline and furosemide with close monitoring
8. Convulsions, coma, death, central pontine myelinolysis (occurs with rapid correction of hyponatraemia -> characterised by: quadriparesis, respiratory arrest, fits)
9. Depends on cause; Na <110mmol/L is associated with a high morbidity and morality; 50% morality with central pontine myelosis

Question 24

Thyroid cancer

1. Definition
2. Aetiology/RF
3. Epidemiology
4. Presenting Syx
5. Presenting Sx
6. Investigations

Answer 24

1. Malignancy arising in the thyroid gland. Types include: papillary, follicular, medullary, anaplastic
2. Unknown, RF: childhood exposure to radiation, medullary thyroid cancers may be familial and are associated with MEN2a/b, lymphoma is associated with Hashimoto’s thyroiditis
3. Rare, more common in Females; papillary: 20-40yrs; follicular: 40-50yrs; anaplastic more common in elderly
4. Slow-growing neck lump; discomfort swallowing; hoarse voice
5. Palpable nodules or diffuse enlargement of thyroid gland; cervical lymphadenopathy -> pt usually euthyroid
6. Bloods: TFTs, bone profile, tumour markers (thyroglobulin - pap and follicular; calcitonin - medullary); Fine-needle aspiration cytology allows historical dx; excision LN biopsy (cervical lymphadenopathy); isotope scan, CT/MRI for staging

Question 25

Thyroid nodules

1. Definition
2. Aetiology/RF
3. Epidemiology
4. Presenting Syx
5. Presenting Sx
6. Investigations

Answer 25

1. Abnormal growth of thyroid cells that forms a lump in the thyroid gland
2. Vast majority of thyroid nodules are benign but small proportion turn into thyroid cancer; most thyroid nodules are adenomatous and most are multiple; usually Non-functioning
3. 40% of the general popn have a single nodule or multiple nodules; more common in women; very small proportion of thyroid nodules will be malignant
4. Most asyx; usually found on self-exam or clinical exam; single isolated nodule is more likely to be malignant; can sometimes cause pain and will rarely compress the trachea or cause dysphagia
5. Ask the pt to drink some water and see if nodule moves when swallowing and check for regional lymphadenopathy
6. TFTs (euthyroid), US (character of nodules), FNA (cytological analysis), Radionuclide isotope scanning (iodine uptake), CT/MRI

Question 26

Thyroiditis

1. Definition
2. Aetiology/RF
3. Epidemiology
4. Presenting Syx and Sx
5. Investigations
6. Management
7. Complications
8. Prognosis

Answer 26

1. Inflammation of the thyroid gland
2. Hashimoto’s thyroiditis - AI condition, most common cause; other: de Quervain’s/post partum/drug-induced/acute or infectious/riedel’s thyroiditis; Pathogenesis: aggressive destruction of thyroid cells by the IS, environmental triggers have been hypothesised
3. True incidence is unknown; 15-20x more common in women, usually occurs in 30-50yrs
4. Syx of hypothyroidism: fatigue, constipation, dry skin, weight gain, cold intolerance, menstrual irregularities, depression, hair loss; syx caused by rapid enlargment of the thyroid gland: dyspnoea, dysphagia, tenderness
5. Based on clinical observations; histology: diffuse lymphocytic and plasma cell infiltration with formation of lymphoid follicles; TSH raised; antibodies: anti-TPO and anti-thyroglobulins’ thyroid US, radionuclide isotope scanning
6. Pharm: thyroide hormone replacement - oral levothyroxine sodium, titrate dose based on pts needs
   
   1. Surgical: considered if there is a large goitre that is causing syx due to compression of surrounding structures or if there is a malignant nodule
7. Thyroid hormone over-replacement -> bone loss + tachycardia; hyperlipidaemia, hashimoto’s encephalopathy, myxoedema, coma
8. Good prognosis with early diagnosis and levothyroxine replacement

Question 27

Vitamin D and osteomalacia

1. Definition
2. Aetiology/RF
3. Epidemiology
4. Presenting Syx
5. Presenting Sx
6. Investigations
7. Management
8. Complications
9. Prognosis

Answer 27

1. Osteomalacia is a disorder of mineralisation of bone matrix (osteoid); rickets is a disorder of defective mineralisation of cartilage in the epiphyseal growth plates of children
2. RF for vit D def: lack of exposure to sunlight, dietary deficiency, malabsorption, decreased 25OH of vit D (due to liver disease, anticonvulsants), decreased 1alpha OH of vit D (due to chronic kidney disease, hoPTH), vit D resistance
   
   1. Renal phosphate wasting: fanconi’s syndrome (phosphaturia, glycosuria, amino aciduria); renal tubular acidosis T2; hereditary hypophosphataemic rickets (X-linked/autosomal dominant); tumour induced osteomalacia
3. Common in industrialised countries; more common in females
4. Osteomalacia: bone pain, weakness, malaise; Rickets: hypotonia, growth retardation, skeletal deformities
5. OM: bone tenderness, proximal muscle weakness, waddling gait, sx of hypocalcaemia: trousseau’s sx and chvostek’s sx;
   
   1. Rickets: bossing of frontal and parietal bones, swelling of costochondral junctions, bow legs in early childhood, knock knees in later childhood, short stature
6. Bloods: low/normal Ca, low PO4, high ALP, low 25OH vit D, high PTH, check U+Es, check ABG, increased PO4 excreting
   
   1. Radiographs: may appear normal, may show OP, Looser’s zones = wide transverse lucenies traversing part way through a bone, usually at right angles to the involved cortex and are associated most frequently with OM and rickets
   2. Bone biopsy after double tetracycline labelling -> tetracycline deposited at the mineralisation front as a band; after 2 courses of tetracycline, the distance between the bands of deposited tetracycline is reduced in OM; not usually necessary for the dx of OM
7. Vit D and Ca replacement, monitor 24hr urinary calcium; also monitor: serum Ca, PO4, ALP, PTH, Vit D; treat underlying Cause
8. Bone deformities, hypocalcaemia can cause epileptic seizures; cardiac arrhythmias, hypocalcaemic tetany, depression, hypocalcaemia syx = CATs go NUMB: Convulsions, Arrhythmias, Tetany, NUMBness/paraesthesia
9. Syx and radiological appearances improve with vit D treatment; bone deformities in children tend to be permanent

Question 28

Definition

Acromegaly

Answer 28

1. Constellation of s/syx caused by hypersecretion of GH in adults, with excess before puberty leading to gigantism
2. Most caused by GH secreting pituitary adenoma;
3. rarely caused by excess GHRH causing somatotroph hyperplasia from ganglioneuroma, bronchial carcinoid or pancreatic tumours

Question 29

S+S

Acromegaly

Answer 29

1. very gradual progression over many years;
2. rings and shoes becoming tight, increased sweating, headaches, carpal tunnel syndrome,
3. hypopit syx: hypogonadism, hypothyroidism, hypoadrenalism;
4. visual disturbances, hyperprolactinaemia leading to irreg periods, decreased libido, impotence
5. Examination:
   
   1. Hands: large spade like hands; thick greasy skin, carpal tunnel syndrome sx, premature osteoarthritis
   2. Face: prominent eyebrow rdge, prominent cheeks, broad nose bridge, prominent nasolabial folds, thick lips, increased gap between teeth, large tongue, prognathism, husky resonant voice (thickening of vocal cords)
   3. Visual field loss: bitemporal superior quadrantopia progressing to bitemporal hemianopia
   4. Neck: multinodular goitre
   5. Feet: enlarged

Question 30

Investigation

Acromegaly

Answer 30

1. Serum IGF-1;
2. Oral glucose tolernce test (+ve, failure of suppression of GH after 75g of oral glucose load);
3. pit function tests: 9am cortisol, free T4 and TSH, LH/FSH, testosterone, prolactin;
4. MRI of brain

Question 31

Management

Acromegaly

Answer 31

1. Surgical: transphenoidal hypophysectomy
2. RT: adjunctive to surgery
3. Medical if surgery refused:
4. subcut Somatostatin analogues (e.g. octreotide/lanreotide) with side effects of abdo pain,steatorrhoea, glucose intolerance and gallstones;
5. Oral DA agonists (bromocriptine and cabergoline), side effects: N/V, constipation, postural hypotension, psychosis (rare);
6. GH antagonist = pegvisomant
7. Monitor: GH and IGF1 levels can be used to monitor

Question 32

Definition

Adrenal insufficiency

Answer 32

1. Deficiency of adrenal cortical hormones (mineralo/glucocorticoids and androgens)
2. Causes:
   
   1. 1ry adrenal insufficiency = addison’s disease (AI)
   2. 2ry adrenal insufficiency = pit/hypothalamic disease
   3. Infections = TB, meningococcal septicaemia (waterhouse-friderichsen syndrome), CMV, histoplasmosis
   4. Infiltration = metastasis (lung, breast, melanoma), lymphomas, amyloidosis
   5. Infarction = 2ry to thrombophilia
   6. Inherited = adrenoleukodystrophy, ACTH receptor mutation
   7. Surgical = after bilateral adrenalectomy
   8. Iatrogenic = sudden cessation of long-term steroid therapy

Question 33

S+S

Adrenal insufficency

Answer 33

1. Chronic presentation tend to be non-specific = dizziness, anorexia, weight loss, D/V, abdo pain, lethargy, weakness, depression
2. acute presentation: acute adrenal insufficiency, major haemodynamic collapse, precipitated by stress
3. Postural hypotension, increased pigmentation (more on buccal mucosa, scars, skin creases, nails and pressure points), loss of body hair in women (due to androgen deficiency), associated AI condition
4. Addisonian crisis: hypotensive shock, tachycardia, pale, cold, clammy, oliguria

Question 34

Investigation

Adrenal insufficiency

Answer 34

1. Dx: 9am serum cortisol (<100nmol/L and >550 makes it unlikely) or short Synacthen test (IM 250 ug tetrocosactrin - synth ACTH, serum cortisol <550nmol/L at 30 min = adrenal failure)
2. ID level of defect -> High in 1ry disease, Low in 2ry and Long synacthen test (1mg synth ACTH admin, measure serum cortisol at 0, 30, 60, 90 and 120 min and then measure again at 4, 6, 8, 12 and 24hrs; pts with 1ry show no increase after 6hrs)
3. ID the cause = AutoAb (against 21-OHase), abdoCT/MRI, other tests (adrenal biopsy, culture, PCR)
4. Check TFTs
5. In addisonian crisis = FBC, U+E (high urea, low Na, high K), CRP/ESR, Ca, glucose (low), blood cultures, urinalysis, culture and sensitivity

Question 35

Management

Adrenal insufficiency

Answer 35

1. Addisonian crisis =
   
   1. rapid IV fluid rehydration;
   2. 50mL of 50% dextrose to correct hypoglycaemia;
   3. IV 200mg hydrocortisone bolus, followed by 100mg 6hrly hydrocortisone until BP is stable, treat precipitating cause (Abx for infection), monitor
2. Chronic:
   
   1. replacement of glucocorticoids with hydrocortisone (3/d), mineralocorticoids with fludrocortisone;
   2. hydrocortisone dosage increased during times of acute illness or stress.
   3. NB: hydrocortisone before thyroxine if hypothyroidism
3. Advice: have a steroid warning card, wear a medic alert bracelet, emergency hydrocortisone on hand

Question 36

Definition

Carcinoid syndrome

Answer 36

1. Constellation of syx caused by systematic release of humoral factors from carcinoid tumours
2. Carcinoid tumours are slow growing neuroendocrine tumours, mostly derived from serotonin-producing enterochromaffin cells -> produce serotonin, histamine, tachykinins, kallikrein and prostaglandins
3. NB: hormones released into the portal circulation will be metabolised by the liver so syx don’t tend to appear until hepatic mets/release into systemic circulation from bronchial or extensive retroperitoneal

Question 37

S+S

Carcinoid syndrome

Answer 37

1. Paroxysmal flushing, diarrhoea, crampy abdo pain, wheeze, sweating, palpitations
2. Facial flushing, telangiectasia, wheeze, right-sided murmurs (tricuspid stenosis/regurg or pulm stenosis), nodular hepatomegaly in cases of mets disease
3. Carcinoid crisis sx: profound flushing, bronchospasm, tachycardia, fluctuating BP

Question 38

Investigations

Carcinoid syndrome

Answer 38

1. 24 hr urine collection (check 5-HIAA levels),
2. bloods (plasma chromogranin A/B and fasting gut hormones), CT/MRI scan (localise tumour),
3. radioisotope scan (radiolabelled somatostatin analogue helps localise the tumour),
4. investigations for MEN-1

Question 39

Definition

Cushing’s syndrome

Answer 39

1. Syndrome associated with chronic inapproriate elevation of free circulating cortisol
2. ACTH dependent (80% - excess from pit adenoma ‘disease’ - ectopic from lung cancer ‘syndrome’) and ACTH independent (20% - benign adrenal adenoma, adrenal carcinoma)

Question 40

S+S

Cushing’s syndrome

Answer 40

1. Increasing weight, fatigue, muscle weakness, myalgia, thin skin, easy bruising, poor wound healing, fractures, hirsuitism, acne, frontal balding, oligo/amenorrhoea, depression/psychosis
2. Moon face, facial plethora, interscapular fat pad, proximal muscle weakness, thin skin, bruises, central obesity, pink/purple striae on abdo/breasts/thighs, kyphosis, poorly healing wounds, hirsuitism, acne, frontal balding, HTN, ankle oedema, pigmentation in ACTH dependent cases

Question 41

Investigations

Cushing’s syndrome

Answer 41

1. Must be performed on pts with high pretest probability;
2. bloods (U+Es hypoK due to mineralocorticoid effect, BM high glucose)
3. Initial high sensitivity tests = urinary free cortisol, late night salivary cortisol, overnight/low dose dexamethasone suppression test (give 0.5mg DXM orally every 6hrs for 48hrs; failure to suppress below 50 nmol/L)
4. Test to determine underlying cause:
5. ACTH independent -> low plasma ACTH, CT/MRI of adrenals
6. ACTH dependent -> high plasma ACTH, pit MRI, high-dose DXM suppression test, inferior petrosal sinus sampling (superior to HDDST)
7. ACTH dependent ectopic -> lung cancer = CXR, sputum cytology, bronchoscopy, CT scan; radiolabelled octreotide scans can detect carcinoid tumours because they express somatostatin receotirs

Question 42

Management

Cushing’s syndrome

Answer 42

1. Iatrogenic = discontinue steroids, use lower dose or steroid-sparing agents
2. Medical = used pre-op or if unfit for surgery, inhibit cortisol synth with metyrapone or ketoconazole, treat osteoporosis, physio for muscle weakness
3. Surgical = pit adenomas (trans-sphenoidal resection), adrenal adenoma/carcinoma (surgical removal), ectopic ACTH (tx directed at the tumour)
4. RT = performed in those not cured and have persistent high cortisol after resection of tumour; bilat adrenalectomy may be performed in refractory cushing’s disease

Question 43

Definition

Diabetes insipidus

Answer 43

1. Disorder of inadequate secretion or of insensitivity to ADH leadig to hypotonic polyuria
2. Central DI: failure of ADH secretion by the post pit; nephrogenic DI: insensitivity of the Collecting duct to ADH; results in large volumes of hypotonic urine and polydipsia.​
3. Causes:
   
   1. Central: idiopathic, tumours (pit), infiltrative (sarcoidosis), infection (meningitis), vascular (aneurysms), trauma (head injury, neurosurgery)
   2. Nephrogenic: Idiopathic, drugs, post-obstructive uropathy, pyelonephritis, pregnancy, osmotic diuresis

Question 44

S+S

Diabetes insipidus

Answer 44

1. Polyuria, nocturia, polydipsia; children = enuresis, sleep disturbance;
2. other syx depend on aetiology
3. Central DI has few sx if pt drinks sufficiently to maintain levels;
4. urine output >3L/d; fluid intake

Question 45

Investigations

Diabetes insipidus

Answer 45

1. Bloods: U+Es, Ca, increased plasma osm, decreased urine osm
2. Water deprivation test = restricted for 8hrs;
   
   1. plasma and urine osm measured every hour for 8hrs;
   2. weigh the pt hourly to monitor level of dehydration;
   3. STOP the test body weight fall >3%.
   4. Desmopressin given after 8hrs and urine osm measured
3. Results = normal (water restriction causes): increased plasma osm, ADH secretion, water reabsorption, urine osm (>600mosmol/kg);
4. DI: Lack of ADH so urine osm LOW (<400), cranial means urine osm rises >50% after Desmopressin, nephrogenic means urine osm rises <45% after desmo

Question 46

Management

Diabetes insipidus

Answer 46

1. Treat the cause;
2. cranial DI: give DP and if mild chlorpropamide/carbamazepine to potentiate the residual effects of any residual VP
3. nephrogenic DI: Na and/or protein restriction helps with polyuria, thiazide diuretic

Question 47

Definition

Diabetes mellitus T1

Answer 47

1. Metabolic hyperglycaemic condition caused by absolute insufficiency of pancreatic insulin production
2. Caused by destruction of pancreatic insulin-producing beta cells;
3. AI process; occurs in genetically susceptible individuals with environmental trigger;
4. auto-Ag associated with T1DM: glutamic acid decarboxylase, insulin, insulinoma-associated protein 2, cation efflux zinc transporter

Question 48

S+S

DMT1

Answer 48

1. Juvenile onset (<30yrs), polyuria/nocturial, polydipsia, tiredness, weight loss
2. DKA syx: N/V, adbo pain, polydipsia/uria, drowsiness, confusion, coma, kussmaul breathing, ketotic breathing, sx of dehydration
3. sx of complications: fundoscopy (diabetic retinopathy), examine feet for evidence of neuropathy (monofilament test); monitor BP
4. Sx of associated autoimmune conditions: vitiligo, addison’s disease, autoimmune thyroid disease

Question 49

Management

DMT1

Answer 49

1. Glycaemic control:
   
   1. advice and pt education:
      
      1. short acting insulin (3/d = lispro, aspart, glulisine),
      2. long acting insuilin (1/d = isophane, glargine, detemir);
   2. insulin pumps,
   3. DAFNE courses (dose adjustment for eating),
   4. Monitor (regular cap BGT, HbA1c every 3-6m),
   5. screening and management of complications;
   6. tx of hypoglycaemia (reduced consciousness = 50ml of 50% glucose IV OR 1mg glucagon IM;
   7. consciousness = 50g oral glucose and starchy snack)
2. DKA management:
   
   1. 50U soluble insulin in 50 mL of normal saline, continue until cap ketones <0.3, venous pH >7.30, venous bicarbonate >18mmol;
   2. then change to SC insulin and don’t stop insulin infusion until 1-2hrs after the SC insulin has restarted;
   3. 500ml normal saline over 15-30 min until SBP > 100;
   4. K replacement;
   5. monitor blood glucose, cap ketones, urine output hourly;
   6. monitor U+Es and venous blood gas;
   7. broad spectrum Abx if infection;
   8. thromboprophylaxis;
   9. NBM for at least 6hrs, NGT if GCS reduced

Question 50

Investigations

DMT1

Answer 50

1. Blood glucose - fasting >7 or random bgl >11;
2. HBA1c;
3. FBC: MCV reticulocytes; U+Es monitor for nephropathy and hyperkalaemia; lipid profile;
   
   1. urine albumin creatinine ratio to detect microalbuminuria;
   2. urine - glycosuria, ketonuria, MSU;
4. Investigations for DKA: FBC (raised WCC w/out infection), U+Es (raised urea/creatinine ), LFT, CRP, glucose, amylase, blood cultures, ABG (met acidosis with high anion gap), blood/urinary ketones

Question 51

Definition

DMT2

Answer 51

1. Increased peripheral resistance to insulin action, impaired insulin secretion and increased hepatic glucose output
2. Genetic and env;
3. few monogenic causes of DM;
4. obesity increases risk;
5. can be 2ry to pancreatic disease, endocrine (cushing’s, acromegaly, phaeo, glucagonoma) and drugs (corticosteroids, atypical antipsychotics, protease inhibitors

Question 52

S+S

DMT2

Answer 52

1. Polyuria, polydipsia, tiredness, pts may present with hyperosmolar hyperglycaemic state, infections,
2. assess cardiovascular risk factors: HTN, hyperlipidaemia and smoking
3. Calculate BMI, waist circumference, BP,
4. diabetic foot sx (dry skin, reduced subcut tissue, ucleration, gangrene, charcot’s arthropathy, weak foot pulses);
5. skin changes (RARE): necrobiosis lipoidica diabeticorum, granuloma annulare, diabetic dermopathy

Question 53

Investigations

T2DM

Answer 53

1. Dx if one or more present:
2. syx of DM and random plasma glucose of >11.1mmol/L, fasting plasma glucose >7, 2-hr plasma glucose >11.1 after 75g oral glucose tolerance test;
3. Monitor: HbA1c, U+Es, lipid profile, eGFR, urine albumin (creatinine ratio)

Question 54

Management

T2DM

Answer 54

1. Glycaemic control:
2. at dx: lifestyle and metformin
3. HBA1c >7% after 3m:
   
   1. lifestyle + metformin + sulphonylurea (can be monotherapy if metformin not tolerated)
   2. lifestyle +metformin + basal insulin
   3. And fasting blod glucose >7: add premeal rapid actign insulin
   4. NB: pioglitaqzone can be given alongside metformin and sulphonylurea
4. Screening for complications: retinopathy, nephropathy, vascular disease, diabetic foot, cardiovascular risk factors
5. Pregnancy: requiring strict glycaemic control and planning of conception
6. Hyperosmolar hyperglycaemic state: mx similar to DKA, except 0.45% saline if serum Na >170mmol/L

Question 55

Complications

T2DM

Answer 55

1. Hyperosmolar hyperglycaemic state: due to insulin def; marked dehydration, high Na, high glucose, high osmolality, no acidosis
2. Neuropathy: distal symmetrical sensory neuropathy, painful, carpal tunnel syndrome, diabetic amyotrophy, mononeuritis, autonomic neuropathy, gastroparesis (abdo pain, N/V), impotence, urinary retention
3. Nephropathy: microalbuminuria, proteinuria, renal failure, prone to UTI, renal papillary necrosis
4. Retinopathy: background, pre-proliferative, proliferative,. maculopathy, prone to glaucoma/cataracts and transient visual loss
5. Macrovascular: IHD, stroke, peripheral vascular disease

Question 56

Definition

Graves disease

Answer 56

1. The most common cause of hyperthyroidism;
2. presence of TSH-receptor stimulating Ab that lead to hyperthyroidism due to loss of negative feedback
3. Caused by the presence of TSH receptor stimulating Ab;
4. Rf: FHx, high iodine intake, smoking, trauma to thyroid gland, toxic multinodular goitre, HAART, childbirth

Question 57

S+S

Graves disease

Answer 57

1. Weight loss even though increased appetite;
2. irritability, diarrhoea, sweating, tremor, anxiety, heat intolerance, loss of libido, oligomenorrhoea/amenorrhoea
3. palmar erythema, sweaty and warm palms, fine tremor, tachycardia (AF?), hair thinning, urticaria/pruritus, brisk refloexes, goitre, proximal myopathy, lid lag, gynaecomastia

Question 58

Investigations

Graves disease

Answer 58

1. TFTs - low TSH and high T3/T4;
2. autoantibodies - anti-TPO antibodies (75%), anti-thyroglobulin antibodies, TSH-receptor ab (very sensitive/specific for graves);
3. imaging - thyroid US, thyroid uptake scan;
4. inflammatory markers - CRP/ESR raised in subacute thyroiditis

Question 59

Definition

Hyperparathyroidism

Answer 59

1. 1ry = increased PTH unrelated to plasma Ca conc;
   
   1. 1ry causes: parathyroid adenoma, parathyroid hyperplasia, parathyroid carcinoma, MEN syndrome;
2. 2ry = increased PTH secondary to hypocalcaemia;
   
   1. 2ry cause: chronic renal failure, vit D deficiency
3. 3ry = autonomous PTH secretion following chronic 2ry hyperparathyroidism

Question 60

S+S

Hyperparathyroidism

Answer 60

1. 1ry: many pts have mild hypercalcaemia and may be asyx;
2. syx/sx of hypercalcaemia: polyuria, polydipsia, renal calculi, bone pain, abdo pain, nausea, constipation, psych depression, lethargy;
3. 2ry: may present with sx/syx of HYPOcalcaemia or of underlying cause

Question 61

Investigations

Hyperparathyroidism

Answer 61

1. U+Es, serum Ca (high in 1ry/3ry, low in 2ry), serum PO4, albumin, ALP, vit D, PTH, renal USS for renal calculi;
2. primary hyperparathyroidism: hyperchloraemic acidosis, normal anion gap, due to PTH inhibition of renal reabsorption of bicarbonate,
3. urine - high PTH in the presence of high Ca can also be caused by familial hypocalciuric hypercalcaemia
4. (calcium:creatinine ratio can help differentiate between 1ry and FHH)

Question 62

Management

Hyperparathyroidism

Answer 62

1. Acute hypercalcaemia = IV fluids, avoid factors that exacerbate hyperCa, maintain adequate hydration, moderate ca and vit D intake;
2. surgical mx: subtotal/total parathyroidectomy
3. 2ry herPTH: treat underlying cause and ca/vit D supplements may be needed

Question 63

Definition

Hypogonadism - female

Answer 63

1. Characterised by impairment of ovarian function
2. 1ry: gonadal dysgenesis (due to chromosomal abnormalities), gonadal damage (autoimmune);
3. 2ry:
   
   1. functional (stress, weight loss, excessive exercise eating disorder),
   2. pit/hypothalamic tumours and infiltrative lesions (pit adenomas, haemochromatosis),
   3. hyperprolactinaemia (prolactinoma),
   4. congenital GnRH deficiency (Kallman’s syndrome, idiopathic)

Question 64

S+S

Hypogonadism - female

Answer 64

1. Pre-pubertal: delayed puberty (1ry amenorrhoea, absent breast development, no 2ry sex characteristics), eunuchoid (long legs, arm span greater than height);
2. post-pubertal: regression of 2ry sex characteristics (loss of 2ry sex hair, breast atrophy), perioral and periorbital fine facial wrinkles, sx of underlying cause
3. Hypothalamic/pit disease: visual field defects
4. Kallman’s syndrome: anosmia
5. turner’s syndrome: short stature, low post hair line, high arched palate, widely spaced nipples, wide carrying angle, short 4/5th metacarpals, congenital lymphoedema
6. Autoimmune 1ry ovarian failure - may be signs of other AI diseases

Question 65

Investigations

Hypogonadism female

Answer 65

1. Low serum oestradiol, serum FSH/LH (1ry = high, 2ry = low)
2. 1ry: karyotype, pelvic imaging (US/MRI)
3. Screen for FMR1 gene in pts with unexplained premature ovarian failure
4. 2ry: pit function tests, visual field testing, hypothalamic-pit MRI, smell tests for anosmia, serum transferrin saturation
5. Associated conditions: Turner’s syndrome: periodic echo, renal US; AI oophoritis: check autoimmune adrenal insufficiency

Question 66

Definition

Hypogonadism - male

Answer 66

1. Syndrome of decreased testosterone production, sperm production or both
2. 1ry:
   
   1. gonadal dysgenesis (klinefelter’s syndrome, undescended testicles),
   2. gonadal damage (infection, torsion, trauma, AI),
   3. rare causes (defects in enzymes involved in testosterone synthesis)
3. 2ry:
   
   1. pit/hypothalamic lesions,
   2. GnRH deficiency (Kallman’s syndrome),
   3. hyperprolactinaemia,
   4. systemic/chronic diseases,
   5. prader-willi syndrome (short, small hands, almond shape eyes, learning difficulty, postnatal hypotonia),
   6. laurence moon biedl syndrome (obesity, polydactyly, retinitis pigmentosa, learning difficulty);
   7. rare causes are genetic mutations

Question 67

S+S

Hypogonadism - male

Answer 67

1. Delayed puberty, decreased libido, impotence, infertility, syx of underlying cause
2. Testicular volumem using Prader’s orchidometer (15-25mL);
3. prepubertal:
   
   1. sx of delayed puberty (high pitched voice, decreased pubc/axillary/facial hair, small/undescended testicles, small penis),
   2. gynaecomastia,
   3. eunuchoid proportions,
   4. features of underlying cause
4. Postpubertal:
   
   1. decreased pubic/axillary/facial hair,
   2. soft and small eyes,
   3. gynaecomastia,
   4. fine perioral wrinkles,
   5. features of underlying cause

Question 68

Investigations

Hypogonadism - male

Answer 68

1. serum total testosterone, sex hormone binding globulin, albumin, LH/FSH;
2. 1ry: low testosterone, high LH and FSH, can be investigated using karyotyping
3. 2ry low testosterone, inappropriately normal/low LH/FSH; pit function tests, MRI of the hypothalamic/pit area, visual field testing, smell testing, iron testing
4. Assess bone age (risk of fx)

Question 69

Definition

Hypopituitarism

Answer 69

1. Deficiency in one or more of the hormones secreted by the anterior pit; panhypopituitary is deficiency of ALL pituitary hormones
2. Pit massess: most commonly adenomas;
3. pit trauma: radiation, surgery, base of skull fractures;
4. hypothalamic dysfunction: due to anorexia, starvation, over-exercise;
5. infiltrative diseases: sarcoidosis, haemochromatosis, Langerhan’s cell histiocytosis;
6. vascular: pit apoplexy, sheehans syndrome;
7. infection: meningitis, encephalitis;
8. genetic mutation: pit-1, prop-1 genes

Question 70

S+S

Hypopituitarism

Answer 70

Depends on cause

1. GH: children (short stature), adults (low mood, fatigue, reduced exercise capacity and muscle strength, increased abdo fat mass)
2. LH/FSH: delayed puberty, Females: loss of 2ry sexual hair, breast atrophy, menstrual irregularities, dyspareunia, decreased libido, infertility; males: loss of 2ry sexual hair, gynaecomastia, small and soft testes, decreased libido, impotence
3. ACTH: sx/syx of adrenal insufficiency
4. TSH: sx/syx pf hypothyroidism
5. Prolactin: absence of lactation (not usually noticed clinically)
6. Pit apoplexy: headache, visual loss, cranial nerve palsies

Question 71

Investigations

Hypopituitarism

Answer 71

1. Pit function tests:
2. Basal tests: 9am cortisol, LH and FSH levels, testosterone levels, oestrogen levels, IGF-1 levels, prolactin levels, free T4/TSH levels
3. Dynamic tests: RARE, insulin induced hypoglycaemic
4. short synacthen test
5. MRI/CT brain
6. Visual field testing

Question 72

Management

Hypopituitarism

Answer 72

1. Hormone replacement:
   
   1. hydrocortisone,
   2. levothyroxine,
   3. sex hormones: testosterone in males, oestrogen with/out progesterone in females,
   4. growth hormone,
   5. desmopressin

Question 73

Definition

Hypothyroidism

Answer 73

1. The clinical syndrome resulting from insufficiency secretion of thyroid hormones
2. 1ry:
   
   1. Acquired: hashimoto’s thyroiditis (AI), iatrogenic (post-surgery, radioiodine, hyperthyroid medication), severe iodine deficiency, iodine excess (wolff-chaikoff effect), thyroiditis
   2. Congenital: thyroid dysgenesis, inherited defects in thyroid hormone biosynthesis
3. 2ry: pit and hypothalamic disease: resulting in reduced TSH/TRH and reduced stimulation of thyroid hormone production

Question 74

S+S

Hypothyroidism

Answer 74

1. Insidious onset,
2. cold intolerance, lethargy,
3. weight gain, reduced appetite,
4. constipation,
5. dry skin, hair loss,
6. hoarse voice,
7. mental slowness, depression,
8. cramps, ataxia, paraesthesia,
9. menstrual disturbance (irregular cycles, menorrhagia),
10. hx of surgery or radioiodine therapy for hyperthyroidism, personal/FHx of other autoimmune conditions;
11. myxoedema coma: hypothermia, hypoventilation, hyponatraemia, HF, confusion, coma
12. Hands: bradycardia, cold hands
13. Head/neck/skin: pale puffy face, goitre, oedema, hair loss, dry skin, vitiligo
14. Chest: pericardial effusion, pleural effusion
15. Abdomen: ascites
16. Neurological: slow relaxation of reflexes, signs of carpal tunnel syndrome

Question 75

Investigations

Hypothyroidism

Answer 75

Bloods: TFTs, FBC (normocytic anaemia), U+Es (low Na), cholesterol (high)

Question 76

Management

Hypothyroidism

Answer 76

1. Chronic:
   
   1. levothyroxine (25-200mcg/d), important to rule out underlying adrenal insufficiency before starting THR,
   2. thyroid hormone replacement in the context of adrenal insufficiency can precipitate an addisonian crisis,
   3. adjust dose based on clinical picture and TFTs
2. Myxoedema coma: oxygen, rewarming, rehydration, IV T4/3, IV hydrocortisone, treat underlying disease

Question 77

Definition

MEN

Answer 77

1. Autosomal dominant condition characterised by a predilection to develop tumours of endocrine glands
2. Autosomal dominant inheritance. Patterns of features:
   
   1. Men1: pit adenomas, parathyroid tumours, pancreatic islet cell tumours (other GIT tumours), facial angiofibromas and collangenomas
   2. Men2a: parathyroid tumours, medullary thyroid cancer, phaeochromocytoma
   3. Men2b:same as Men2a and marfanoid appearance, neuromas of GIT

Question 78

S+S

MEN

Answer 78

1. MEN1:
   
   1. age of onset of tumours is usually teenage years;
   2. however, syx of tumours may not become apparent for years, dx is commonly made in the 4th decade of life;
   3. herPTH (syx of hyperCa and nephrolithiasis),
   4. hergastrinaemia (Zollinger-Ellison syndrome),
   5. herinsulinaemia (hypoglycaemia),
   6. herProlactinaemia (amenorrhoea),
   7. hersomatotrophinaemia (acromegaly);
   8. pit tumours may cause visual defects
2. MEN2:
   
   1. syx of medullary thyroid cancer,
   2. herPTH or phaeo;
   3. medullary thyroid cancer syx:
   4. HTN,
   5. episodic sweating,
   6. diarrhoea,
   7. pruritic skin lesions,
   8. lump in neck;
   9. herCa syx: constipation, polyuria/dipsia, depression, kidney stones, fatigue

Question 79

Investigations

MEN

Answer 79

1. MEN1:
   
   1. screening 1st/2nd degree relatives;
   2. hormone hypersecretion blood tests,
   3. DNA testing
2. MEN2:
   
   1. phaeo test (24hr urine metanephrines, followed by abdo MRI),
   2. medullary thyroid cancer test (elevated calcitonin conc; also investigated with US and FNA);
   3. Parathyroid tumours (simultaneously elevated Ca and PTH

Question 80

Definition

Obesity

Answer 80

1. BMI>30kg/m2; defined using waist circumference =
   
   1. Men (low risk <94cm, v. high risk >102cm),
   2. women (low risk <80cm, v.high risk >88cm
2. Genetic factors that affect the risk of becoming obese;
3. few monogenic forms of obesity (leptin deficiency, prader-willi syndrome),
4. common obesity is caused by energy intake > energy usage

Question 81

S+S

Obesity

Answer 81

1. Noticing you’ve gained weight,
2. routine health check,
3. sx of complications (t2dm, CHD, obstructive sleep apnoea);
4. high body weight, BMI and waist circumference

Question 82

Investigations

Obesity

Answer 82

1. Measure serum lipids,
2. measure HbA1c,
3. hormone profile (check hormonal cause),
4. TFTs,
5. other investigations

Question 83

Definition

Osteoporosis

Answer 83

1. Reduced bone density (>2.5 sd below peak bone mass achieved by healthy adult resulting in bone fragility and increased fx risk
2. 1ry is idiopathic or post-menopausal;
3. 2ry:
   
   1. malignancy (myeloma, metastatic carcinoma),
   2. endocrine (cushing’s disease, thyrotoxicosis, 1ry herPTH, hypogonadism),
   3. drugs (corticosteroids, heparin),
   4. rheumatological (RhA, AnkSpond),
   5. GI (malabsorption (coeliac, partial gastrectomy),
   6. liver disease and anorexia).
4. RF: age, fhx, low BMI/Ca intake/exposure to sunlight, smoking, lack of physical exercise, alcohol abuse, late menarche, early menopause, hypogonadism

Question 84

S+S

Osteoporosis

Answer 84

1. Often asyx, until fx occur;
2. neck of femur (minimal trauma),
3. vertebral fx (loss of height, stooped posture and acute back pain on lifting),
4. colles’ fx (distal radius after falling on outstretched hand)
5. None until complications develop: tenderness on percussion over vertebral fx,
6. thoracic kyphosis,
7. severe pain when hip flexed and externally rotated

Question 85

Investigations

Osteoporosis

Answer 85

1. Bloods: Ca, PO4, ALP (NORMAL in 1ry);
2. XR: to dx fx, often normal, can show biconcave vertebrae and crush fx;
3. Isotope bone scan to highlight areas of stress and microfx;
4. DEXA: T-score (no. of sd the BMD is above or below theyoung normal mean BMD) or Z-score (no of sd measurements below age-matched mean BMD

Question 86

Definition

Paget’s disease of bone

Answer 86

1. Characterised by excessive bone remodelling at one or more sites resulting in bone that is structurally disorganised
2. Unknown;
3. genetic and viral factors may play role;
4. excessive bone resorption by abnormally large osteoclasts followed by increased bone formation by osteoblasts in a disorganised fashion;
5. abnormal pattern of lamellar bone, marrow filled by excess of fibrous tissue with marked increase in blood vessels

Question 87

S+S

Paget’s disease of bone

Answer 87

1. May be asyx; present with insidious onset pain, aggravated by weight bearing and movement; headaches, deafness, increasing skull size
2. Bitemporal skull enlargment with frontal bossing (prominent protruding forehead);
3. spinal kyphosis;
4. anterolateral bowing of femur, tibia, forearm;
5. skin over affected bone may be warm due to increased vascularity;
6. sensorineural deafness (compression of vestibulocochlear nerve

Question 88

Investigations

Paget’s disease of bone

Answer 88

1. Bloods: high ALP, normal Ca/PO4;
2. bone radiographs: enlarged, deformed bones, lytic/sclerotic appearance, lack of distinction between cortex and medulla,
   
   1. skull changes: osteoporosis circumscripta, enlargment of frontal and occipital areas, cotton wool appearance;
3. Bone scan: asessses extent of skeletal involvement, pagetic bone lesions are seen as areas with markedly increased uptake;
4. Resorption markers: monitors disease activity, check urinary hydroxyproline

Question 89

Definition

Phaeochromocytoma

Answer 89

1. Catecholamine producing tumours that usually arise from chromaffin cells of the adrenal medulla, but are extra-adrenal in about 10% of cases:
2. 10% bilateral
3. 10% malignant
4. 10% extraadrenal - paragangliomas
5. Sporadic cases are unknown aetiology, familial in up to 30% seen in pts with MEN2a, vHL syndrome and Neurofibromatosis type 1

Question 90

S+S

Phaeo

Answer 90

1. Paroxysmal episodes; headaches, sweating,
2. cardioresp syx: palpitations, chest pain, dyspnoea;
3. GI: eigastric pain, nausea, constipation;
4. neuropsych: weakness, tremor, anxiety
5. HTN, postural hypotension, pallor, tachycardia, fever, weight loss

Question 91

Investigations

Phaeo

Answer 91

1. 24hr urine collection for catecholamine levels and fractionated metanephrine levels;
2. plasma free metanephrines;
3. tumour localisation (MRI/CT), I-MIBG scintigraphy;
4. screen for asociated conditions;
5. genetic testing

Question 92

Definition

Non-functioning pituitary tumours

Answer 92

1. benign tumours of the pit gland formed from pit cells that don’t produce any active pit hormones
2. No specific cause; part of MEN1

Question 93

S+S

Non-functioning pituitary tumours

Answer 93

1. Very slowly, headaches,
2. pressure on surrounding structures;
3. optic chiasm (bitemp hemianopia),
4. normal pit (panhypopit)

Question 94

Investigations

Non-functioning pituitary tumours

Answer 94

1. MRI,
2. CT,
3. bloods for hormone levels,
4. visual field testing

Question 95

Definitions

PCOS

Answer 95

1. charcterised by Oligomenorhoea/amenorrhoea and hyperandrogenism;
2. frequently associated with: obesity, insulin resistance, T2DM, dyslipidaemia
3. Environmental factors,
4. genetic variants,
5. hyperinsulinaemia resulting in increased ovarian androgen synthesis and reduced hepatic sex hormone binding globulin;
   
   1. leads to increase in free androgens

Question 96

S+S

PCOS

Answer 96

1. Menstrual irregularities dysfunctional uterine bleeding,
2. infertility,
3. syx of hyperandrogenism: hirsuitism, male pattern hair loss, acne
4. acanthosis nigricans

Question 97

Investigations

PCOS

Answer 97

1. Bloods: high LH/LH:FSH ration/testosterone, androstenedione and DHEAS, low sex hormone binding globulin;
2. others:
   
   1. hyperprolactinaemia,
   2. hypo/erthyroidism,
   3. CAH (17OHP levels),
   4. cushing’s syndrome;
   5. impaired glucose tolerance:
   6. FBG and HbA1c;
   7. fasting lipid profile;
3. transvaginal USS for ovarian follicles and increase in ovarian volume

Question 98

Definition

1ry hyperaldosteronism

Answer 98

1. Characterised by autonomous aldosterone overproduction from the adrenal gland with subsequent suppression of plasma renin activity
2. Adrenal adenoma (Conn’s) responsible for 70%; adrenal cortex hyperplasia (30%),
3. RARE: glucocorticoid-suppressible hyperaldosteronism, aldosterone producing adrenal carcinoma;
4. pathophysiology: excess aldosterone leads to increased Na and water retention = HTN and increased renal K loss = hypokalaemia;
5. renin suppressed due to NaCl retention

Question 99

S+S

1ry hyperaldosteronism

Answer 99

1. usually asyx, tends to be incidental finding on routine blood tests;
2. syx of hypokalaemia: muscle weakness, polyuria, polydipsia (nephrogenic DI), paraesthesia, tetany
3. HTN and complications of HTN

Question 100

Investigations

1ry hyperaldosteronism

Answer 100

1. Screening tests: low serum K (normal sNa), High urine K, high plasma aldosterone concentration, high aldosterone:renin activity ratio;
2. confirmatory tests:
   
   1. Salt loading: failure of aldosterone suppression following salt load = 1ry
   2. postural test = measure plasma aldosterone, renin activity and cortisol when pt lying down at 8am, then measure again after 4hrs of pt being upright =
      
      1. aldosterone-producing adenoma = aldosterone decreases between 8am-12pm;
      2. bilat adrenal hyperplasia = adrenals respond to standing posture and increase renin production, increasing aldosterone production
   3. CT/MRI
   4. Bilat adrenal vein catheterisation = measuring aldosterone levels to distinguish between Conn’ sand BAH
   5. Radiolabelled cholesterol scanning = unilat uptake in adrenal adenomas, bilat uptake in BAH

Question 101

Management

1ry hyperaldosteronism

Answer 101

1. BAH = spironolactone, eplerenone if spironolactone side effects intolerable, amiloride -> monitor serum K and creatinine and BO, can also add ACEi and CCBs;
2. Aldosterone producing adenomas = adrenalectomy;
3. adrenal carcinoma = surgery,
4. post op mitotane (anti-neoplastic)

Question 102

Definition

Prolactinoma

Answer 102

1. Pit adenoma that overproduces prolactin
2. Different types: microadenomas <1cm, macro >1cm, giant pit adenomas >4cm,
3. malignant prolactinomas (rare); cause unknown, but some due to MEN1;
4. risk of enlargment during pregnancy

Question 103

S+S

Prolactinoma

Answer 103

1. Note: micro rarely become macro;
2. women = ameno/oligomenorrhoea, galactorrhoea, infertility, hirsuitism, reduced libido;
3. men = syx subtle and develop slowly, reduced libido, reduced beard growth, erectile dysfunction;
4. syx by tumour size: headache, visual disturbance, cranial nerve palsies, hypopit

Question 104

Investigations

Prolactinoma

Answer 104

1. Exclude pregnancy;
2. TFTs: hypothyroidism, high TRH which stim prolactin release;
3. serum prolactin level (>5000mU/L suggests true prolactinoma;
4. MRI;
5. assessment of pit function

Question 105

Management

Prolactinoma

Answer 105

1. Goals: treat cause, relieve syx, prevent complications, restore fertility;
2. DA agonists (cabergoline and bromocriptine) effective in most pts, long-term basis and
3. if ineffective: surgery and RT

Question 106

Definition

SIADH

Answer 106

1. Characterised by continued secretion of ADH, despite the absence of normal stimuli for scretion
2. Brain: Haemorrhage/thrombosis, meningitis, abscess, trauma, tumour, Guillain Barre syndrome
3. Lung: Pneumonia, TB, Other: abscess, aspergillosis, small cell carcinoma
4. Tumours: Small cell lung cancer, lymphoma, leukaemia, others: pancreatic cancer, prostate cancer, mesothelioma, sarcoma, thymoma
5. Drugs: Vincristine, opiates, carbamazepine, chlorpropamide
6. Metabolic: porphyria, alcohol withdrawal

Question 107

S+S

SIADH

Answer 107

1. Mild hypoNa can by asyx;
2. headache,
3. N/V,
4. muscle cramp/weakness,
5. irritability,
6. confusion,
7. drowsiness,
8. convulsions,
9. coma,
10. syx of underlying cause
11. Mild hypoNa = no sx;
12. SEVERE hypoNa = reduced reflexes, extensor plantar reflexes

Question 108

Investigations

SIADH

Answer 108

1. Low serum Na, creatinine, glucose/serum protein/lipids to rule out pseudohypoNa;
2. free T4 and TSH, short synacthen test
3. SIADH dx: low plasma osmolality, low serum Na conc, high urine osm, high urine Na -> absence of hypovolaemia, oedema, renal failure, adrenal insufficiency and hypothyroidism for dx;
4. investigations for identifying the cause (CXR, CT, MRI)

Question 109

Management

SIADH

Answer 109

1. Treat underlying cause,
2. fluid restriction,
3. VP, receptor antagonists (tolvaptan);
4. severe cases = slow IV hypertonic saline and furosemide with close monitoring

Question 110

Definition

Thyroid cancer

Answer 110

1. Malignancy arising in the thyroid gland.
2. Types include: papillary, follicular, medullary, anaplastic
3. Unknown,
4. RF: childhood exposure to radiation, medullary thyroid cancers may be familial and are associated with MEN2a/b, lymphoma is associated with Hashimoto’s thyroiditis

Question 111

S+S

Thyroid cancer

Answer 111

1. Slow-growing neck lump;
2. discomfort swallowing;
3. hoarse voice
4. Palpable nodules or diffuse enlargement of thyroid gland;
5. cervical lymphadenopathy -> pt usually euthyroid

Question 112

Investigations

Thyroid cancer

Answer 112

1. Bloods: TFTs, bone profile, tumour markers (thyroglobulin - pap and follicular;
2. calcitonin - medullary);
3. Fine-needle aspiration cytology allows historical dx;
4. excision LN biopsy (cervical lymphadenopathy);
5. isotope scan,
6. CT/MRI for staging

Question 113

Definition

Thyroid nodules

Answer 113

1. Abnormal growth of thyroid cells that forms a lump in the thyroid gland
2. Vast majority of thyroid nodules are benign but small proportion turn into thyroid cancer;
3. most thyroid nodules are adenomatous and most are multiple;
4. usually Non-functioning

Question 114

S+S

Thyroid nodules

Answer 114

1. Most asyx; usually found on self-exam or clinical exam;
2. single isolated nodule is more likely to be malignant;
3. can sometimes cause pain and will rarely compress the trachea or cause dysphagia
4. Ask the pt to drink some water and see if nodule moves when swallowing and check for regional lymphadenopathy

Question 115

Investigations

Thyroid nodules

Answer 115

1. TFTs (euthyroid),
2. US (character of nodules),
3. FNA (cytological analysis),
4. Radionuclide isotope scanning (iodine uptake),
5. CT/MRI

Question 116

Definition

Thyroiditis

Answer 116

1. inflammation of the thyroid gland
2. Hashimoto’s thyroiditis - AI condition, most common cause;
3. other: de Quervain’s/post partum/drug-induced/acute or infectious/riedel’s thyroiditis;
4. Pathogenesis: aggressive destruction of thyroid cells by the IS, environmental triggers have been hypothesised

Question 117

S+S

Thyroiditis

Answer 117

1. Syx of hypothyroidism: fatigue, constipation, dry skin, weight gain, cold intolerance, menstrual irregularities, depression, hair loss;
2. syx caused by rapid enlargment of the thyroid gland: dyspnoea, dysphagia, tenderness

Question 118

Investigations

Thyroiditis

Answer 118

1. Based on clinical observations;
2. histology: diffuse lymphocytic and plasma cell infiltration with formation of lymphoid follicles;
3. TSH raised;
4. antibodies: anti-TPO and anti-thyroglobulins’ thyroid US, radionuclide isotope scanning

Question 119

Management

Thyroiditis

Answer 119

1. Pharm: thyroide hormone replacement - oral levothyroxine sodium, titrate dose based on pts needs
2. Surgical: considered if there is a large goitre that is causing syx due to compression of surrounding structures or if there is a malignant nodule

Question 120

Definition

Vit D deficiency and osteomalacia

Answer 120

1. Osteomalacia is a disorder of mineralisation of bone matrix (osteoid);
2. rickets is a disorder of defective mineralisation of cartilage in the epiphyseal growth plates of children
3. RF for vit D def: lack of exposure to sunlight, dietary deficiency, malabsorption, decreased 25OH of vit D (due to liver disease, anticonvulsants), decreased 1alpha OH of vit D (due to chronic kidney disease, hoPTH), vit D resistance
4. Causes:
   
   1. Renal phosphate wasting: fanconi’s syndrome (phosphaturia, glycosuria, amino aciduria);
   2. renal tubular acidosis T2;
   3. hereditary hypophosphataemic rickets (X-linked/autosomal dominant);
   4. tumour induced osteomalacia

Question 121

S+S

Vit D deficiency and Osteomalacia

Answer 121

1. Osteomalacia: bone pain, weakness, malaise, bone tenderness, proximal muscle weakness, waddling gait,
   
   1. sx of hypocalcaemia: trousseau’s sx and chvostek’s sx;
2. Rickets: hypotonia, growth retardation, skeletal deformities, bossing of frontal and parietal bones, swelling of costochondral junctions, bow legs in early childhood, knock knees in later childhood, short stature

Question 122

Investigations

Vit D deficiency and osteomalacia

Answer 122

1. Bloods: low/normal Ca, low PO4, high ALP, low 25OH vit D, high PTH, check U+Es, check ABG, increased PO4 excreting
2. Radiographs: may appear normal, may show OP, Looser’s zones = wide transverse lucenies traversing part way through a bone, usually at right angles to the involved cortex and are associated most frequently with OM and rickets
3. Bone biopsy after double tetracycline labelling -> tetracycline deposited at the mineralisation front as a band;
   
   1. after 2 courses of tetracycline, the distance between the bands of deposited tetracycline is reduced in OM;
   2. not usually necessary for the dx of OM

Question 123

Management

Vit d Deficiency and osteomalacia

Answer 123

1. Vit D and Ca replacement,
2. monitor 24hr urinary calcium;
3. also monitor: serum Ca, PO4, ALP, PTH, Vit D;
4. treat underlying Cause