UKMLA Endocrinology Masterclass: Diabetes to Addison

Endocrinology is the specialty that rewards integrated physiology more than any other on the UKMLA. One stem tests insulin deficiency, ketogenesis, and acid–base in the same breath. The next asks you to recognise Addisonian crisis from a serum sodium and a glucose. Candidates who try to memorise endocrinology as a list of isolated conditions hit a ceiling quickly.

This pillar binds the examinable endocrine surface — diabetes, thyroid, adrenal, pituitary, calcium, and sodium-water balance — into a coherent reference with UK guideline touchpoints at every step. If you can only revise one specialty the night before the AKT, this is the one where a structured reread pays the highest marginal return.

---

1. Why endocrine SBAs reward integrated physiology

Endocrine questions on the UKMLA rarely stop at "what is the diagnosis?" They extend into:

• Biochemical interpretation — glucose + ketones + bicarbonate + anion gap.
• Fluid and electrolyte consequences — hyponatraemia patterns, osmolality interpretation.
• Pharmacological ladders — T2DM NICE escalation, hyperkalaemia management ladder, thyrotoxicosis drug choice.
• Emergency recognition — Addisonian crisis, thyroid storm, myxoedema coma, DKA, HHS.

Because endocrine physiology integrates glucose, electrolytes, and haemodynamic control, questions can enter from any angle. Pair this pillar with the UKMLA Content Map 2026 to see which conditions sit where on the GMC syllabus, and with the NICE Guidelines + UK Prescribing pillar for the precise NG numbers the AKT loves.

---

2. T1DM vs T2DM — pathogenesis, presentation, management

T2DM diagnosis (any one of):

• HbA1c ≥48 mmol/mol (6.5%).
• Fasting glucose ≥7.0 mmol/L.
• Random glucose ≥11.1 mmol/L with symptoms.
• 2-hour OGTT ≥11.1 mmol/L.

Asymptomatic patients need two abnormal results.

NICE NG28 T2DM escalation (2022 update):

1. Lifestyle + metformin (titrate to tolerance). Modified-release if GI intolerance.
2. Add SGLT2 inhibitor if established CVD, heart failure, or high CV risk (QRISK ≥10%) — irrespective of HbA1c control.
3. If HbA1c ≥58 mmol/mol despite step 1 → dual therapy (metformin + SGLT2i OR DPP-4i OR sulfonylurea OR pioglitazone).
4. Triple therapy if still uncontrolled → add third oral agent OR insulin.
5. GLP-1 agonist if BMI ≥35 + obesity-related psychological problems, or BMI <35 when insulin would cause significant occupational issues (e.g., drivers).

T1DM management:

• Basal-bolus regimen — long-acting once/twice daily + rapid-acting with meals.
• Carbohydrate counting with DAFNE.
• HbA1c target ≤48 mmol/mol if safe.
• CGM/flash glucose offered to all T1DM adults (NICE NG17).
• Immunisation: pneumococcal + annual flu.

---

3. DKA — diagnosis, management protocol, monitoring

Diagnostic triad (JBDS 2023):

1. Ketosis — blood ketones ≥3 mmol/L OR urine ketones ≥2+.
2. Hyperglycaemia — glucose >11 mmol/L OR known diabetic.
3. Acidosis — pH <7.3 OR bicarbonate <15 mmol/L.

Precipitants (check all):

• Infection — pneumonia, UTI, cellulitis (send septic screen).
• MI — always ECG + troponin.
• Insulin non-adherence — pumps failing, new-onset T1DM.
• Pancreatitis.
• Medications — steroids, SGLT2 inhibitors (euglycaemic DKA).
• Pregnancy.

Management (JBDS):

Hour 0–1:

• 0.9% saline 1 L over 1 hour (unless shocked — 500 mL boluses).
• Fixed-rate IV insulin 0.1 units/kg/hr — do NOT bolus. Continue patient's long-acting SC insulin.
• Monitor ketones, glucose, pH, bicarbonate, K+, U&Es hourly.

Hours 1–12:

• Continue saline — next litre over 2 h, then 4 h, then 6 h, then 8 h.
• Add potassium once K+ falls below 5.5 (never add to first bag unless K+ known <3.5 at start):
  • K+ 3.5–5.5 → add 40 mmol/L KCl.
  • K+ <3.5 → senior review, ICU level replacement.
• Switch to 10% glucose with continued saline when glucose <14 mmol/L.

Resolution criteria (must achieve all):

• Ketones <0.6 mmol/L.
• pH >7.3.
• Bicarbonate >18.

Convert to SC insulin only after resolution AND patient eating/drinking — overlap by 30 min with SC rapid-acting if on basal-bolus.

Complications:

• Cerebral oedema (especially paediatrics) — too rapid fluid or sodium correction.
• Hypokalaemia — commonest cause of death.
• Hypoglycaemia — must add dextrose when glucose <14.
• VTE — start LMWH prophylaxis.

For the wider acute-emergency ABCDE and resus algorithms, see our UKMLA Emergency Presentations pillar.

---

4. HHS — differentiation from DKA and management

Hyperosmolar hyperglycaemic state (HHS) — typically T2DM, older patients, insidious onset over days.

Diagnostic features:

• Marked hyperglycaemia (>30 mmol/L).
• Hyperosmolality (≥320 mOsm/kg).
• No significant ketosis or acidosis (pH >7.3, bicarbonate >15, ketones <3).
• Profound hypovolaemia — often 8–12 L fluid deficit.

Precipitants: infection (commonest), MI, stroke, medications (steroids, thiazides), reduced fluid intake in confusion.

Management differences from DKA:

• Slower fluid replacement — 0.9% saline 1 L over 2–4 h initially, aim for a controlled drop in osmolality (no faster than 3–8 mOsm/kg/hr).
• Insulin only if significant ketonaemia (>1 mmol/L) OR glucose not falling with fluids alone — lower rate 0.05 units/kg/hr.
• Aim glucose fall 4–6 mmol/L per hour — slower than DKA to prevent cerebral oedema.
• LMWH prophylaxis mandatory — VTE risk extremely high (hyperviscosity).
• Foot care — neuropathic patients develop ulcers during prolonged admission.

Mortality is ~15% (higher than DKA). Suspect HHS in any elderly T2DM patient presenting confused with severe hyperglycaemia.

---

5. Hypoglycaemia — causes, Whipple's triad, treatment ladder

Whipple's triad — all three needed to diagnose hypoglycaemia:

1. Low blood glucose.
2. Symptoms consistent with hypoglycaemia.
3. Resolution of symptoms with glucose correction.

Causes:

• Diabetic — too much insulin, missed meals, alcohol, exercise.
• Non-diabetic fasting — insulinoma (high C-peptide, high insulin), Addisonian crisis, hypopituitarism, liver failure, severe sepsis.
• Reactive postprandial — post-gastric surgery, nesidioblastosis.
• Drugs — sulfonylureas, beta-blockers (mask symptoms and precipitate).
• Factitious — surreptitious insulin (high insulin, low C-peptide) or sulfonylurea ingestion (high insulin, high C-peptide — resembles insulinoma).

Treatment ladder:

Conscious, swallows safely:

• 15–20 g fast-acting carbohydrate (Lucozade 150 mL, 4 glucose tabs, 3 teaspoons of sugar).
• Recheck in 15 min; repeat up to 3 times.
• Follow with long-acting carbohydrate (toast, biscuits).

Conscious, cannot swallow:

• 1–2 tubes GlucoGel (buccal gel) rubbed into gums.
• IM glucagon 1 mg if no IV access.

Unconscious:

• IV 10% dextrose 150–200 mL over 15 min (preferred) OR IV 20% dextrose 75–100 mL over 10 min.
• Avoid 50% dextrose — high osmolality, vessel injury if extravasates.
• IM glucagon 1 mg if no IV access — ineffective in malnourished, alcoholics, liver failure (depleted glycogen).

Always identify and address cause. A sulfonylurea hypo risks rebound — admit for 24 h observation; 10% dextrose infusion if recurrent.

---

6. Insulin regimens and prescribing pitfalls

UK insulin categories:

Common regimens:

• Basal-bolus (T1DM gold standard) — long-acting OD/BD + rapid with meals.
• BD pre-mix — twice daily mixed; less flexible; useful for patients unable to manage complex regimens.
• OD long-acting + oral agents (T2DM starter) — add basal to metformin.

Prescribing rules that matter in the AKT:

• Write "units" in full — never "U" (mistaken for zero).
• Insulin infusion concentration — always 1 unit/mL in 0.9% saline.
• Never abbreviate insulin name — "Novomix 30" not "Novomix" alone.
• Sick day rules — do NOT stop insulin; increase if hyperglycaemia + ketosis; SADMANS drug cessation (SGLT2, ACE, diuretics, metformin, ARBs, NSAIDs, sulfonylureas) if dehydrated.

Pitfalls the UKMLA tests:

• Hypoglycaemia on hospital admission — continue long-acting, reduce/stop prandial if not eating.
• NBM pre-operative — stop rapid-acting; halve long-acting the night before; variable-rate IV insulin infusion during NBM.
• Steroid-induced hyperglycaemia — pre-lunch dose of intermediate insulin matches morning prednisolone peak.
• Pump patients — do NOT disconnect in DKA until fixed-rate IV insulin running.

For PSA-level prescribing depth, see our upcoming UKMLA Prescribing Safety pillar.

---

7. Thyroid disease: hyper- vs hypo-, Graves vs Hashimoto

Hyperthyroidism presentation: weight loss despite appetite, heat intolerance, palpitations, tremor, diarrhoea, anxiety, oligomenorrhoea, hyperreflexia, lid lag.

Graves' disease — autoimmune, TSH receptor antibodies (TRAb). Features: diffuse goitre + ophthalmopathy (exophthalmos, lid retraction), pretibial myxoedema, thyroid acropachy.

Toxic multinodular goitre / toxic adenoma — autonomous nodules, no eye signs. Isotope scan shows hot nodules.

Thyroiditis (transient hyperthyroid phase):

• De Quervain's — painful, tender, post-viral, raised ESR. Hypo phase follows. Treat with NSAIDs/steroids.
• Postpartum thyroiditis — 3–6 months post-delivery; hyper then hypo.
• Hashimoto's — can have initial hyperthyroid (Hashitoxicosis) then permanent hypothyroid.

Management of hyperthyroidism (NICE NG145):

• Beta-blocker (propranolol 40 mg QDS) for symptom control.
• Carbimazole — titration regimen 20–40 mg daily, reducing as euthyroid; OR block-and-replace.
• Propylthiouracil (PTU) — first trimester of pregnancy (teratogenicity of carbimazole); thyroid storm; severe adverse effects from carbimazole.
• Radioactive iodine — definitive; avoid in pregnancy, breastfeeding, active eye disease.
• Thyroidectomy — pregnancy 2nd trimester, large goitre, compressive symptoms, eye disease.

Carbimazole side effect of note: agranulocytosis — warn every patient about sore throat, fever → stop drug, FBC urgently.

Hypothyroidism causes: Hashimoto's (TPO antibodies), post-radioiodine, post-thyroidectomy, drugs (amiodarone, lithium, interferon), iodine deficiency, central (secondary).

Treatment: levothyroxine — start 1.6 μg/kg/day; 25–50 μg in elderly/ischaemic heart disease. Recheck TSH at 6–8 weeks.

Trap: a suppressed TSH + normal T4 and T3 = subclinical hyperthyroidism — monitor and treat if symptomatic or TSH <0.1.

---

8. Thyroid storm and myxoedema coma

Thyroid storm (Burch–Wartofsky score ≥45): fever >38.5°C, marked tachycardia, AF, agitation/psychosis/coma, vomiting/diarrhoea/jaundice. Precipitants: infection, surgery, iodine load, radioactive iodine, trauma.

Management:

1. Propylthiouracil 500 mg stat → 200–250 mg QDS (blocks synthesis + peripheral T4→T3 conversion).
2. Lugol's iodine 4 drops QDS (start at least 4 hours AFTER PTU — prevents iodine-fuelling synthesis).
3. Propranolol 60–80 mg QDS (heart rate + T4→T3 conversion).
4. Hydrocortisone 100 mg IV QDS (blocks conversion, covers adrenal reserve).
5. Cooling, fluids, treat precipitant.
6. ICU admission.

Myxoedema coma: severe hypothyroidism + hypothermia + altered consciousness + hypotension + bradycardia + hypoventilation.

Management:

1. ICU admission + airway support.
2. IV levothyroxine 500 μg loading, then 50–100 μg daily OR IV liothyronine (T3).
3. IV hydrocortisone 100 mg QDS — cover concurrent adrenal insufficiency (never give levothyroxine first).
4. Passive rewarming (not active — peripheral vasodilation precipitates shock).
5. Treat precipitant (usually sepsis).

Mortality 30–60% even with treatment.

---

9. Adrenal insufficiency — Addisonian crisis

Primary (Addison's) — 80% autoimmune in UK; TB and metastases elsewhere. Features: fatigue, weight loss, hyperpigmentation (ACTH drives MSH), postural hypotension, salt craving, hyponatraemia, hyperkalaemia, mild metabolic acidosis.

Secondary — pituitary cause, ACTH deficiency. No hyperpigmentation. No hyperkalaemia (aldosterone intact via RAAS).

Tertiary — long-term steroid use, abrupt withdrawal.

Diagnosis:

• Short Synacthen test — 0 and 30 min cortisol after 250 μg ACTH. Cortisol >500 nmol/L at 30 min = normal.
• ACTH level — high in primary, low/normal in secondary.
• Renin + aldosterone — high renin/low aldosterone = primary.
• 21-hydroxylase antibodies — autoimmune primary.

Addisonian crisis:

• Shock, vomiting, abdominal pain, confusion, hyponatraemia, hyperkalaemia, hypoglycaemia.
• Precipitants: infection, trauma, missed steroid dose, surgery without stress cover.

Immediate management:

1. IV hydrocortisone 100 mg bolus — do NOT wait for biochemistry.
2. 1 L 0.9% saline + dextrose if hypoglycaemic.
3. Further hydrocortisone 200 mg/24 h infusion or 50 mg QDS.
4. Identify and treat precipitant.
5. Discharge on oral hydrocortisone 20 mg morning + 10 mg noon + 10 mg evening (or patient's usual regimen), fludrocortisone 50–100 μg daily (primary only).

Sick day rules for known Addison's:

• Minor illness / fever — double oral hydrocortisone.
• Vomiting or unable to keep down dose — IM hydrocortisone emergency kit + ED.
• Major stress (surgery, sepsis) — IV hydrocortisone cover.

---

10. Cushing's syndrome — causes and tests

Cushing's syndrome = excess cortisol. Cushing's disease specifically = pituitary ACTH-secreting adenoma.

Causes:

• Exogenous (commonest) — long-term glucocorticoid therapy.
• Endogenous ACTH-dependent: pituitary adenoma (70%), ectopic ACTH (small cell lung cancer, carcinoid).
• Endogenous ACTH-independent: adrenal adenoma, carcinoma, nodular hyperplasia.

Clinical features: central obesity, moon face, buffalo hump, proximal myopathy, purple striae, easy bruising, hypertension, impaired glucose tolerance, osteoporosis, menstrual irregularity, depression/psychosis.

Screening tests (any of):

• Overnight dexamethasone suppression test — 1 mg at 11 pm; cortisol >50 nmol/L at 9 am next day = abnormal.
• 24-hour urinary free cortisol — raised.
• Late-night salivary cortisol — raised.

Localisation tests (after confirming hypercortisolism):

• Plasma ACTH:
  • Low → adrenal cause — CT adrenals.
  • High → ACTH-dependent — proceed to:
• High-dose dexamethasone suppression (8 mg) — suppresses pituitary adenoma (partial), not ectopic/adrenal.
• CRH test — pituitary responds, ectopic does not.
• MRI pituitary — adenoma.
• Inferior petrosal sinus sampling — gold standard for pituitary vs ectopic.

Management: treat cause — transsphenoidal surgery, adrenalectomy, tumour resection, steroid tapering, metyrapone/ketoconazole as medical pre-treatment.

---

11. Phaeochromocytoma — triad and workup

Phaeochromocytoma — catecholamine-secreting tumour of adrenal medulla.

Classic triad: episodic headache + sweating + palpitations. Plus paroxysmal hypertension, tremor, pallor, anxiety, chest pain.

Associations: MEN2a/2b (RET mutation), von Hippel–Lindau, neurofibromatosis type 1, familial paraganglioma syndromes (SDHB/D).

Diagnosis:

• Plasma or 24-hour urine metanephrines (first-line; more sensitive than catecholamines).
• CT/MRI abdomen for localisation once biochemistry positive.
• MIBG scan for extra-adrenal/metastatic disease.

Management:

1. Alpha-blockade first — phenoxybenzamine 10 mg BD, titrate to symptomatic postural drop.
2. Beta-blockade second (propranolol) — after full alpha-blockade to prevent unopposed alpha-mediated hypertensive crisis.
3. IV fluids to re-expand contracted vascular volume before surgery.
4. Surgical excision once blocked for ≥2 weeks.

Hypertensive crisis — IV phentolamine (short-acting alpha-blocker).

---

12. PCOS and hyperprolactinaemia

PCOS Rotterdam criteria — 2 of 3:

1. Oligo/anovulation.
2. Clinical or biochemical hyperandrogenism (hirsutism, acne, raised testosterone/free androgen index).
3. Polycystic ovaries on USS (≥12 follicles 2–9 mm OR ovarian volume >10 mL).

Management:

• Lifestyle — weight loss 5–10% restores ovulation in many.
• Menstrual regulation — COCP (first-line if no contraindication; co-cyprindiol if hirsutism). Cyclic progestogens if COCP contraindicated.
• Hirsutism — eflornithine cream, laser, COCP. Spironolactone or finasteride as add-on.
• Fertility — letrozole (first-line per NICE 2024 update), clomiphene, metformin, ovarian drilling, IVF.
• Screen for metabolic complications — T2DM (OGTT), sleep apnoea, NAFLD, endometrial hyperplasia (induce withdrawal bleeds 3-monthly).

Hyperprolactinaemia:

• Physiological — pregnancy, breastfeeding, stress.
• Drugs — antipsychotics (risperidone, haloperidol), antiemetics (metoclopramide, domperidone), opioids, methyldopa.
• Pituitary — prolactinoma (micro <10 mm, macro ≥10 mm), stalk effect (compression → disinhibition).
• Other — hypothyroidism (TRH → prolactin), renal failure.

Presentation: galactorrhoea, amenorrhoea, infertility, low libido, bitemporal hemianopia (macroadenoma).

Management:

• Cabergoline (preferred, BD weekly) or bromocriptine — dopamine agonists shrink tumour.
• Surgery — transsphenoidal if drug-resistant or large with compression.

---

13. Hypercalcaemia — primary hyperPTH vs malignancy + management

Causes:

• Primary hyperparathyroidism — solitary adenoma (85%), hyperplasia, carcinoma. High Ca, high or inappropriately normal PTH.
• Malignancy — commonest cause in hospitalised patients. PTHrP (squamous cell, breast), bone mets, haematological (myeloma). Low PTH.
• Vitamin D toxicity / granulomatous disease — sarcoid, TB.
• Thiazide diuretics.
• Milk-alkali syndrome.
• Familial hypocalciuric hypercalcaemia (FHH) — inherited, asymptomatic, low urinary calcium.

Presentation: "stones, bones, abdominal groans, psychic moans" — renal stones, bone pain, abdominal pain/constipation/pancreatitis, confusion/depression, polyuria, polydipsia.

ECG: shortened QT.

Investigations:

• Corrected calcium (adjust for albumin).
• PTH — high vs low splits diagnosis.
• Urinary calcium:creatinine ratio — low in FHH, high in primary hyperPTH.
• Myeloma screen if low PTH — SPEP, serum free light chains, urinary Bence-Jones.
• Sestamibi scan / neck USS for parathyroid adenoma localisation.

Management of acute hypercalcaemia (Ca >3.0 with symptoms):

1. IV 0.9% saline 3–4 L in 24 h — dilution + renal excretion.
2. IV bisphosphonate (zoledronic acid 4 mg) — peak effect at 48–72 h.
3. Calcitonin — faster but short-lived; for refractory/severe.
4. Haemodialysis — if severe + renal failure.
5. Avoid loop diuretics unless fluid-overloaded.
6. Address cause — parathyroidectomy, chemotherapy, steroid for granulomatous.

---

14. Diabetes insipidus vs SIADH — osmolality interpretation

SIADH (syndrome of inappropriate ADH):

• Hyponatraemia, low plasma osmolality, inappropriately high urine osmolality (>100 mOsm/kg), urine sodium >40 mmol/L, euvolaemia, normal renal/thyroid/adrenal function.
• Causes: CNS (stroke, meningitis, head injury, SAH), lung (SCLC, pneumonia, TB), drugs (SSRI, carbamazepine, cyclophosphamide, opioids), post-operative.
• Management: fluid restriction (800–1,000 mL/day), treat cause. Tolvaptan (V2 receptor antagonist) if refractory. Never correct Na >10 mmol/L in 24 h — osmotic demyelination (central pontine myelinolysis).

Diabetes insipidus (DI):

• Polyuria (>3 L/day), polydipsia, low urine osmolality, normal or high plasma osmolality, high-normal sodium.
• Cranial DI — pituitary/hypothalamic cause (tumour, surgery, trauma, sarcoid, autoimmune). Responds to desmopressin.
• Nephrogenic DI — kidney insensitive to ADH. Lithium, hypercalcaemia, hypokalaemia, inherited (X-linked). Does not respond to desmopressin.

Water deprivation test differentiates:

• Normal — urine concentrates during deprivation.
• Primary polydipsia — urine concentrates slowly during deprivation.
• Cranial DI — urine fails to concentrate during deprivation but concentrates after desmopressin.
• Nephrogenic DI — fails to concentrate even after desmopressin.

Management:

• Cranial DI — intranasal or oral desmopressin.
• Nephrogenic DI — treat cause (stop lithium), low-salt/low-protein diet, thiazide diuretic (paradoxical concentrating effect).

For the nephrology integration — hyponatraemia volume triage, hypernatraemia management, and the five-step ABG algorithm — see our UKMLA Renal & Electrolyte Emergencies pillar.

---

15. Exam technique: interpreting endocrine panels under time pressure

Step 1 — spot the biochemical fingerprint:

Step 2 — recognise the emergency signature:

• Shock + hyponatraemia + hyperkalaemia → Addisonian crisis → 100 mg hydrocortisone.
• Fever + AF + psychosis + thyroid history → thyroid storm → PTU + iodine + propranolol + hydrocortisone.
• Confused + hypothermic + bradycardic → myxoedema coma → IV levothyroxine + hydrocortisone.
• Glucose >30 + osmolality >320 + no ketones → HHS → slow saline, late insulin.

Step 3 — stabilise before localising: every endocrine crisis gets steroid + fluid + glucose control first. Localisation investigations (MRI pituitary, MIBG, petrosal sampling) are week-two problems.

---

Summary — five reflexes that win endocrine SBAs

1. Hypoglycaemia → 10% dextrose IV (not 50%) or IM glucagon if no access. Identify cause.
2. DKA → fluids, fixed-rate insulin, potassium when <5.5. Resolution = ketones <0.6 + pH >7.3 + bicarbonate >18.
3. Addisonian crisis → 100 mg hydrocortisone IV before anything else. Don't wait for biochemistry.
4. Thyroid storm → PTU, then Lugol's 4h later, propranolol, hydrocortisone. Cooling, fluids, treat precipitant.
5. Hypercalcaemia → IV saline 3–4 L + bisphosphonate. Differentiate hyperPTH from malignancy by PTH level.

Pair this pillar with the Emergency Presentations pillar for sepsis integration, and with the Nephrology pillar for hyponatraemia and hyperkalaemia depth. Endocrine SBAs reward pattern → ladder fluency — rehearse each crisis recipe until the first three management steps fire automatically.