By MRCSA in MRCS Part A — 04 Jul 2026

39 ENDOCRINOLOGY

# Endocrinology

Endocrine pathology underlies many "atypical" surgical patients. MRCS Part A rarely volunteers the diagnosis — recognise the hormonal pattern.

Detailed notes

The pituitary gland

Sits in the sella turcica beneath the optic chiasm, flanked by the cavernous sinuses (CN III, IV, V1, V2, VI). Two embryologically distinct lobes.

Anterior pituitary — from Rathke's pouch (oral ectoderm). Six hormones under hypothalamic control:

➡ ACTH — adrenocorticotrophic hormone, drives cortisol from zona fasciculata.

➡ TSH — thyroid-stimulating hormone.

➡ FSH and LH — gonadotrophins.

➡ GH — growth hormone, acts via IGF-1 from the liver.

➡ Prolactin — uniquely under tonic inhibition by hypothalamic dopamine.

Posterior pituitary — neural ectoderm; axonal terminus of supraoptic and paraventricular neurones. Releases:

➡ ADH — V2 receptors in collecting duct, inserts aquaporin-2.

➡ Oxytocin — uterine contraction, milk let-down.

👩‍⚕️ Mnemonic "FLAT PiG" — FSH, LH, ACTH, TSH, Prolactin, GH are anterior; ADH and oxytocin are posterior.

#### Pituitary adenomas

Benign anterior-lobe tumours. They harm by oversecreting a hormone or by mass effect.

Adenoma	Features	Treatment
Prolactinoma (commonest)	Galactorrhoea, amenorrhoea, infertility	Cabergoline / bromocriptine (medical)
GH-secreting	Acromegaly (adult) / gigantism (pre-pubertal)	Transsphenoidal; somatostatin analogues
ACTH-secreting	Cushing's disease	Transsphenoidal surgery
Non-functioning	Mass effect only	Surgery if symptomatic

Mass effect: chiasm compression → bitemporal hemianopia (crossing nasal fibres hit first). Cavernous sinus extension → cranial nerve palsies.

Pituitary apoplexy — infarction/haemorrhage into an adenoma. Thunderclap headache, visual loss, ophthalmoplegia, acute hypopituitarism. IV hydrocortisone first, then image. Sheehan's = post-partum variant, failed lactation.

The adrenal gland

Two embryologically distinct halves.

Adrenal cortex (mesoderm) — three zones, "GFR — Salt, Sugar, Sex":

Zone	Hormone	Stimulus	Action
Glomerulosa	Aldosterone	Angiotensin II, ↑K⁺	Na⁺ retention, K⁺/H⁺ excretion
Fasciculata	Cortisol	ACTH	Gluconeogenesis, immunosuppression, catabolism
Reticularis	Androgens (DHEA)	ACTH	Weak androgens

Adrenal medulla (neural crest) — chromaffin cells, modified post-ganglionic sympathetic neurones, secrete catecholamines (≈80% adrenaline, 20% noradrenaline).

Cushing's syndrome

The clinical state of chronic cortisol excess — not a single disease.

Type	ACTH	Cause
Iatrogenic (commonest overall)	Low	Exogenous glucocorticoid therapy
*Cushing's disease***	High	Pituitary ACTH-secreting adenoma (~70% of endogenous)
Ectopic ACTH	High	Small cell lung cancer, bronchial carcinoid
Adrenal adenoma/carcinoma	Low (suppressed)	Autonomous cortisol secretion

Features: moon face, buffalo hump, truncal obesity, purple striae, proximal myopathy, HTN, hyperglycaemia, osteoporosis.

Investigation: confirm with 24-hr urinary cortisol or low-dose dexamethasone suppression (failure to suppress = Cushing's). Then measure ACTH — low → adrenal source; high → high-dose dexamethasone (pituitary suppresses, ectopic does not) and MRI pituitary.

Conn's syndrome

Primary hyperaldosteronism — adrenal adenoma (⅔) or bilateral hyperplasia (⅓). Triad: HTN + hypokalaemia + alkalosis. Screen with aldosterone:renin ratio.

👩‍⚕️ Young patient with resistant HTN and low K⁺ — Conn's, not essential HTN.

Phaeochromocytoma

Catecholamine-secreting chromaffin cell tumour. Two examined hooks — the 10% rule and the α/β blockade order.

10% rule: bilateral, extra-adrenal (organ of Zuckerkandl), familial, malignant, paediatric, normotensive.

5 Ps: Pressure, Pain (headache), Perspiration, Palpitations, Pallor.

Investigation: plasma free metanephrines or 24-hr urinary metanephrines/VMA. Localise with CT/MRI and MIBG.

> α-block BEFORE β-block. Phenoxybenzamine 10–14 days, then propranolol if tachycardic, then operate. β-blockade alone removes β2 vasodilatation, leaving α-vasoconstriction unopposed.

Associations: MEN 2A/2B, VHL, NF1.

Addison's disease (primary adrenal insufficiency)

Destruction of all three cortical zones → cortisol, aldosterone and androgen deficiency.

Causes: autoimmune (commonest in West; often polyglandular with T1DM, Hashimoto's, vitiligo); TB (commonest worldwide); metastases; adrenal haemorrhage (Waterhouse-Friderichsen).

➡ Hyponatraemia, hyperkalaemia, hypoglycaemia, mild metabolic acidosis.

Hyperpigmentation — pathognomonic of primary disease. Loss of cortisol feedback raises ACTH, cleaved from POMC alongside MSH → palmar creases, buccal mucosa, scars. Secondary (pituitary) disease has low ACTH — no pigmentation, no hyperkalaemia.

Diagnosis: Short Synacthen test. Paired ACTH separates primary (high) from secondary (low).

#### Addisonian crisis

Triggered by surgery, infection or steroid withdrawal in HPA-suppressed patients. Hypotension refractory to fluids, ↓Na⁺, ↑K⁺, ↓glucose.

> 100 mg IV hydrocortisone STAT, fluids, correct electrolytes, treat trigger.

👩‍⚕️ Long-term steroid patients need perioperative cover — failure is the textbook post-op crisis.

Diabetes insipidus

ADH-axis failure → dilute polyuria, compensatory polydipsia.

	Cranial (central) DI	Nephrogenic DI
Defect	↓ ADH production	ADH receptor unresponsive
Causes	Head trauma, pituitary surgery, tumour, sarcoid	Lithium, hypercalcaemia, hypokalaemia, hereditary
Plasma osmolality	High	High
Urine osmolality	Low (dilute)	Low (dilute)
Response to desmopressin (DDAVP)	Concentrates urine (osmolality rises)	No response

Water deprivation test: urine stays dilute in both. Then DDAVP — cranial concentrates (>50% rise); nephrogenic does not.

SIADH

The mirror of DI — too much ADH, water retained, Na⁺ diluted.

➡ ↓ Plasma Na⁺ and ↓ plasma osmolality.

➡ Inappropriately concentrated urine (osm > 100, Na⁺ > 20).

➡ Euvolaemia — the clinical sign that excludes hypovolaemic hyponatraemia.

Causes: SCLC (classic), CNS injury, pneumonia/TB, drugs (SSRIs, carbamazepine, opioids).

Treatment: fluid restriction. Symptomatic severe → cautious hypertonic saline. Refractory → demeclocycline/vaptans. Correct slowly (central pontine myelinolysis).

👩‍⚕️ Osmolality decoder:

- ↑ Plasma + ↓ urine → DI

- ↓ Plasma + ↑ urine → SIADH

- Both ↑ → dehydration

- Both ↓ → polydipsia

Diabetes mellitus — diagnosis

- Random ≥ 11.1 with symptoms — diagnostic.

- Fasting ≥ 7.0 (repeat if asymptomatic).

- OGTT 2-hr ≥ 11.1. HbA1c ≥ 48 mmol/mol.

- IFG = fasting 6.1–6.9; IGT = OGTT 2-hr 7.8–11.0.

Glucose transporters: GLUT1/3 brain (insulin-independent); GLUT2 liver/β-cell/gut; GLUT4 muscle/adipocytes (insulin-dependent); SGLT1/2 gut and PCT.

MEN syndromes

Autosomal dominant — learn the table.

	Gene	Tumours
MEN 1 ("3 Ps")	MEN1 (menin)	Parathyroid hyperplasia, Pituitary adenoma (prolactinoma), Pancreatic islet tumour (gastrinoma > insulinoma)
MEN 2A	RET	Medullary thyroid carcinoma, Phaeochromocytoma, Parathyroid hyperplasia
MEN 2B	RET	Medullary thyroid carcinoma, Phaeochromocytoma, Mucosal/intestinal neuromas, Marfanoid habitus

Pancreatic NETs (MEN1):

- Gastrinoma (Zollinger-Ellison) — peptic ulcers + diarrhoea.

- Insulinoma — fasting hypoglycaemia (Whipple's triad).

- Glucagonoma — diabetes, weight loss, necrolytic migratory erythema.

- VIPoma — WDHA (watery diarrhoea, hypokalaemia, achlorhydria).

Carcinoid tumours

Neuroendocrine, most often appendix or terminal ileum. Serotonin is metabolised by liver — carcinoid syndrome (flushing, diarrhoea, bronchospasm, right-heart valve disease) requires liver metastases or extra-portal drainage.

Investigation: 24-hr urinary 5-HIAA, chromogranin A, contrast CT, octreotide scintigraphy.

Management: appendix < 2 cm → appendicectomy. > 2 cm or positive margin/nodes → right hemicolectomy. Symptoms → octreotide.

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Test yourself

Which electrolyte abnormality is characteristic of Addison's disease?

((Hyperkalaemia::☑️ No aldosterone → K⁺ retention; paired with hyponatraemia and hypoglycaemia.))
((Hypokalaemia::Seen in Conn's syndrome and Cushing's, not Addison's.))
((Hypernatraemia::Aldosterone loss causes sodium loss, not retention.))
((Hypercalcaemia::Not a feature of adrenal insufficiency.))

👩‍⚕️ Addison's biochemical triad: ↓Na⁺, ↑K⁺, ↓glucose.

A woman on long-term prednisolone for RA and asthma presents with RIF pain, vomiting, BP 80/50, high K⁺, low Na⁺. Next best step?

((100 mg IV hydrocortisone::☑️ Adrenal crisis from HPA suppression — steroid first, fluids second.))
((IV antibiotics::Treat trigger only after steroid cover.))
((Urgent laparotomy::Premature — stabilise the crisis first.))
((IV insulin::No role; hypoglycaemia is part of the crisis.))

A 52-year-old on long-term steroids develops BP 80/50, Na⁺ 116, K⁺ 6.5 hours after hip replacement. Diagnosis?

((Adrenal insufficiency::☑️ Suppressed HPA cannot mount a stress response — classic post-op crisis.))
((Hypovolaemic shock::Doesn't fit the Na⁺/K⁺ pattern.))
((SIADH::Hyponatraemic but euvolaemic with normal K⁺.))
((Septic shock::Possible trigger, but biochemistry says adrenal failure.))

A 42-year-old with HTN, RA and PMR becomes delirious and hypotensive post-cholecystectomy. Na⁺ 132, K⁺ 5.3. Diagnosis?

((Addison's disease::☑️ Autoimmune polyglandular syndrome links Addison's with RA, PMR, Hashimoto's.))
((Conn's syndrome::HTN with hypokalaemia, not hyperkalaemia.))
((Phaeochromocytoma::Causes paroxysmal HTN, not post-op hypotension.))
((Graves' disease::Thyrotoxicosis, not adrenal crisis.))

Hyponatraemia, hyperkalaemia and hyperpigmentation. Which hormone to investigate?

((ACTH::☑️ High in primary adrenal failure; co-released MSH from POMC causes pigmentation.))
((Aldosterone::Low but doesn't explain pigmentation.))
((TSH::Unrelated.))
((Prolactin::Unrelated.))

Diagnostic test for adrenal insufficiency?

((Short Synacthen test::☑️ Failure of cortisol to rise after synthetic ACTH confirms adrenal failure.))
((Dexamethasone suppression::Used for Cushing's.))
((Water deprivation::Used for DI.))
((Oral glucose tolerance::Used for DM or acromegaly.))

A girl treated for TB has fatigue, weight loss, BP 90/55 and pigmentation. Best investigation?

((Short Synacthen test::☑️ TB is the commonest worldwide cause of adrenal destruction.))
((Aldosterone::Low but not diagnostic alone.))
((Random cortisol::Diurnal variation makes it unreliable.))
((OGTT::Wrong pathway.))

After head injury: urine output 350 mL/hr, high urine osm, low plasma osm, hyponatraemia. Which nephron segment?

((Collecting duct::☑️ ADH acts on V2 receptors here to insert aquaporin-2.))
((PCT::Bulk Na⁺ reabsorption, not ADH-sensitive.))
((Descending loop::Passively water-permeable, not ADH-regulated.))
((DCT::Aldosterone-sensitive, not ADH.))

A man with SCLC and SIADH. Main effect of high ADH?

((Decrease in plasma sodium::☑️ Excess water reabsorption dilutes plasma Na⁺.))
((Decrease in collecting-duct water permeability::ADH increases permeability.))
((Increase plasma osmolarity::It falls.))
((Increase vasa recta blood flow::Not the mechanism.))

Euvolaemic 54-year-old with hyponatraemia and concentrated urine. Diagnosis?

((SIADH::☑️ Euvolaemic hyponatraemia with concentrated urine.))
((Addison's::Hypovolaemic with hyperkalaemia.))
((Diabetes insipidus::Causes hyper-natraemia.))
((Cardiac failure::Hypervolaemic with raised JVP and oedema.))

Three days post head trauma: headache, Na⁺ 128, serum osm 450, urine osm 850. Management?

((Fluid restriction::☑️ SIADH first-line — restrict free water.))
((Mannitol::Worsens the picture.))
((Thiazide::Causes hyponatraemia itself.))
((K⁺-sparing diuretic::Risks hyperkalaemia.))

Smoker with cough, Na⁺ 120 and a 3 cm right lung mass. Most likely cause?

((Small cell carcinoma::☑️ Neuroendocrine — ectopic ADH and ACTH.))
((Adenocarcinoma::Peripheral; not classically SIADH.))
((Squamous cell::Linked to PTHrP and hypercalcaemia.))
((Large cell::Far less commonly implicated.))

Progressive cough, weight loss and hyponatraemia. Which lung cancer?

((Small cell carcinoma::☑️ Central, neuroendocrine, paraneoplastic SIADH/Cushing's.))
((Adenocarcinoma::Peripheral; commonest in non-smokers.))
((Lung lymphoma::Not classically SIADH.))
((Adenosquamous::Not the classical culprit.))

Flushing, diarrhoea and SIADH. Most likely malignancy?

((Small cell lung cancer::☑️ Paraneoplastic ACTH, ADH and serotonin all possible.))
((Adenocarcinoma::Not the classical paraneoplastic source.))
((Squamous cell::PTHrP, not serotonin/ADH.))
((Hepatocellular::Different paraneoplastic profile.))

Heatwave, confused, plasma osm 310, urine osm 700. Diagnosis?

((Dehydration::☑️ Kidneys appropriately concentrate urine — physiology intact.))
((Central DI::Urine would be dilute.))
((Nephrogenic DI::Same — kidneys cannot concentrate.))
((SIADH::Plasma osm would be low.))

Polyuria, plasma osm 305, urine osm 250 → 600 after desmopressin. Diagnosis?

((Central diabetes insipidus::☑️ Dilute urine concentrates with exogenous ADH.))
((Nephrogenic DI::Kidneys wouldn't respond.))
((Primary polydipsia::Plasma osm would be low.))
((Dehydration::Urine osm already high.))

👩‍⚕️ Read plasma and urine osmolality together — the pattern names the diagnosis.

Overweight 52-year-old, nocturnal thirst and polyuria, random glucose 11.9. Diagnosis?

((Diabetes mellitus::☑️ Random ≥ 11.1 with symptoms is diagnostic.))
((Diabetes insipidus::Polyuria but normoglycaemic.))
((Impaired fasting glucose::Defined on fasting 6.1–6.9.))
((SIADH::Hyponatraemia, not hyperglycaemia.))

Random glucose 11.8 with polyuria, polydipsia, weight loss. Diagnosis?

((Diabetes mellitus::☑️ Classical triad + diagnostic glucose.))
((Diabetes insipidus::No hyperglycaemia.))
((IGT::Diagnosed on 2-hr OGTT 7.8–11.0.))
((IFG::Diagnosed on fasting 6.1–6.9.))

15-year-old post-parathyroidectomy now has abdominal pain and diarrhoea. Hormonal cause?

((Gastrin::☑️ Gastrinoma in MEN1 → Zollinger-Ellison.))
((Secretin::Not a clinical secretory syndrome.))
((Glucagon::Rash, diabetes, weight loss.))
((Calcitonin::Diarrhoea in medullary thyroid Ca (MEN2).))

Episodic fainting and sweating after exercise; past parathyroid disease. Diagnosis?

((Insulinoma::☑️ Pancreatic NET — fasting hypoglycaemia; MEN1.))
((Glucagonoma::Hyperglycaemia and migratory erythema.))
((VIPoma::WDHA syndrome.))
((Gastrinoma::Ulcers and diarrhoea.))

👩‍⚕️ Whipple's triad confirms hypoglycaemia: low glucose + symptoms + relief with glucose.

Skipping breakfast → sweats, confusion, resolves after eating. Diagnosis?

((Reactive (fasting) hypoglycaemia::☑️ Symptoms tied to meals and relieved by food.))
((Insulinoma::Hypoglycaemia at any time, not just meal-linked.))
((Addison's::Would include hypotension and electrolyte derangement.))
((Type 1 diabetes::Causes hyper-glycaemia.))

Which tissue has insulin-dependent glucose uptake?

((Adipocytes::☑️ GLUT4 requires insulin to translocate to the membrane.))
((Liver::GLUT2 — insulin-independent.))
((Intestinal cells::SGLT1/GLUT2.))
((Brain::GLUT1/GLUT3.))

Pancreatitis + hyperparathyroidism. Which gland to investigate next?

((Pituitary::☑️ MEN1 = Parathyroid + Pancreas + Pituitary.))
((Thyroid::Medullary Ca is MEN2.))
((Adrenals::Phaeo is MEN2.))
((Gonads::Not part of MEN.))

Thyroid mass and BP 200/100. Diagnosis?

((Phaeochromocytoma::☑️ Medullary thyroid Ca + phaeo = MEN2.))
((Conn's::No thyroid mass.))
((Cushing's::Different phenotype.))
((Essential HTN::Doesn't explain the thyroid mass.))

Tall, thin 25-year-old with thyroid swelling, oral neuromas, BP 220/120, raised calcitonin and VMA. Cause of HTN?

((Phaeochromocytoma::☑️ Classic MEN2B — MTC + phaeo + mucosal neuromas + marfanoid.))
((Conn's::Wouldn't raise VMA.))
((Cushing's::Wrong phenotype.))
((Renal artery stenosis::Wouldn't raise calcitonin/VMA.))
((Essential HTN::Doesn't explain biochemistry.))

First-line investigation for phaeochromocytoma?

((Plasma or 24-hr urinary metanephrines/VMA::☑️ Catecholamine metabolites — first-line.))
((CT adrenals::Localises after biochemical confirmation.))
((MIBG scan::For occult/extra-adrenal disease, not first-line.))
((Adrenal biopsy::Contraindicated — risks crisis.))

👩‍⚕️ Pre-op: α-block (phenoxybenzamine) 10–14 days, then β-block, then operate.

4 cm appendix carcinoid with clear margins. Best next investigation?

((Contrast CT::☑️ Tumours > 2 cm need staging for liver/nodal spread.))
((Urinary 5-HIAA::For symptomatic carcinoid syndrome, not staging.))
((Abdominal USS::Insensitive.))
((PET scan::Not first-line.))

Drug for symptom control in carcinoid syndrome?

((Octreotide::☑️ Somatostatin analogue suppresses peptide release.))
((Dexamethasone::No role.))
((β-blocker::Used in phaeo.))
((Carbimazole::Used in hyperthyroidism.))

Best imaging investigation for suspected acromegaly?

((MRI pituitary::☑️ Gold standard for the GH-secreting adenoma.))
((CT skull::Less sensitive for soft tissue.))
((Skull X-ray::Outdated.))
((X-ray hands::Shows features, doesn't identify cause.))

👩‍⚕️ Biochemical confirmation of acromegaly is failure of GH suppression on OGTT, with raised IGF-1. MRI then localises.

Revision summary

➡ Anterior pituitary (FLAT PiG): FSH, LH, ACTH, TSH, Prolactin, GH. Posterior: ADH, oxytocin.

➡ Prolactinoma = commonest adenoma → cabergoline/bromocriptine. Chiasm compression → bitemporal hemianopia.

➡ Adrenal cortex (GFR — Salt, Sugar, Sex): aldosterone, cortisol, androgens. Medulla = chromaffin → catecholamines.

➡ Cushing's: ACTH-dependent (pituitary disease; ectopic SCLC) vs independent (adrenal). Dexamethasone suppression + 24-hr urinary cortisol.

➡ Conn's: HTN + hypokalaemia + alkalosis; aldosterone:renin ratio.

➡ Phaeochromocytoma: 10% rule; metanephrines; α-block before β-block; MEN2, VHL, NF1.

➡ Addison's: ↓Na⁺, ↑K⁺, ↓glucose, pigmentation. Autoimmune (West)/TB (worldwide). Synacthen. Crisis = 100 mg IV hydrocortisone.

➡ DI: ↑plasma osm, dilute urine. Cranial responds to DDAVP; nephrogenic doesn't.

➡ SIADH: ↓plasma osm, concentrated urine, euvolaemia. SCLC/CNS/drugs. Fluid restriction.

➡ DM: random ≥ 11.1 with symptoms / fasting ≥ 7.0 / HbA1c ≥ 48.

➡ MEN1 = 3 Ps. MEN2A = MTC + Phaeo + Parathyroid. MEN2B = MTC + Phaeo + Mucosal neuromas + Marfanoid.

➡ Carcinoid: appendix > 2 cm or nodal → right hemicolectomy. Octreotide for symptoms.