Endocrine

Autoimmune destruction of pancreatic β-cells (anti-GAD/IA-2/ZnT8 antibodies) causing absolute insulin deficiency, usually presenting in childhood/young adults with a short history of osmotic symptoms, weight loss and ketosis. Lifelong insulin is mandatory; DKA is the presenting or decompensating emergency.

Progressive insulin resistance with relative insulin deficiency, typically in older, overweight, inactive or high-risk-ethnicity patients. Often asymptomatic and found on screening; managed with lifestyle + a stepwise drug cascade anchored on metformin, with cardiovascular/renal protection from SGLT2 inhibitors and GLP-1 agonists. The exam tests the cascade and the contraindications.

Intermediate hyperglycaemia below diabetic thresholds — HbA1c 42–47 mmol/mol (6.0–6.4%), impaired fasting glucose or impaired glucose tolerance. A high-risk state for progression to T2DM and CVD; the intervention is intensive lifestyle change ± metformin.

A cluster of cardiometabolic risk factors — central obesity, raised fasting glucose/insulin resistance, raised triglycerides, low HDL and hypertension — that multiplies cardiovascular and T2DM risk. Managed by aggressive lifestyle change and treating each component.

Progressive glomerular damage from diabetes — the leading cause of end-stage renal disease. Earliest marker is moderately increased albuminuria (raised ACR); progresses through proteinuria to declining eGFR. Slowed by glycaemic and BP control with renin-angiotensin blockade and SGLT2 inhibition.

Nerve damage from chronic hyperglycaemia, most commonly a length-dependent symmetrical sensory polyneuropathy ('glove and stocking'). Drives foot ulceration (with peripheral vascular disease) and Charcot arthropathy. Also autonomic and mononeuropathies. Managed with glycaemic control, foot protection and neuropathic-pain agents.

Monogenic diabetes from a single autosomal-dominant gene defect (commonly HNF1A, HNF4A, glucokinase/GCK), presenting in young, non-obese, antibody-negative people with a strong vertical family history. Important because it is often misdiagnosed as T1DM (and over-insulinised) — many forms respond to sulfonylureas, and GCK-MODY needs no treatment.

Underactivity of the thyroid, most commonly autoimmune (Hashimoto/atrophic), also post-thyroidectomy/radioiodine, drugs (amiodarone, lithium) and iodine deficiency. Insidious tiredness, weight gain, cold intolerance and slowed everything. Treated with levothyroxine monotherapy titrated to TSH.

Excess thyroid hormone, most often Graves' disease (autoimmune TSH-receptor stimulation), toxic multinodular goitre/adenoma, or thyroiditis. Hypermetabolic features — weight loss, heat intolerance, tremor, palpitations. Beta-blockade controls symptoms; carbimazole/PTU, radioiodine or surgery are definitive. Radioiodine uptake distinguishes the cause.

The commonest cause of hyperthyroidism — TSH-receptor-stimulating autoantibodies drive diffuse thyroid overactivity, plus the extrathyroidal features unique to Graves: orbitopathy (thyroid eye disease), pretibial myxoedema and acropachy. Managed as hyperthyroidism, with specific attention to the eye disease.

Hyperthyroidism from autonomously functioning thyroid nodule(s) — a single toxic adenoma or a toxic multinodular goitre (Plummer's), typically in older patients. No eye signs (not autoimmune); the scan shows discrete 'hot' nodules. Definitive treatment is radioiodine or surgery.

Inflammation of the thyroid causing a release of preformed hormone — a transient thyrotoxic phase, then often hypothyroid, then recovery. Types: subacute (De Quervain, post-viral, painful), postpartum (painless), and Hashimoto (autoimmune, usually hypothyroid). Key point: LOW radioiodine uptake — treat the thyrotoxic phase with a beta-blocker, not antithyroid drugs.

Diffuse or nodular thyroid enlargement, or a discrete nodule. Most nodules are benign (colloid, cyst, adenoma) but the task is to exclude malignancy and assess function and compression. Investigated with TFTs and ultrasound, and cytology (FNA) for suspicious nodules.

Thyroid malignancy — papillary (commonest, lymphatic spread, excellent prognosis), follicular (haematogenous, needs histology not cytology), medullary (parafollicular C cells, secretes calcitonin, MEN2-associated), and anaplastic (aggressive, elderly, poor prognosis). Usually a euthyroid solitary nodule; treated with surgery ± radioiodine, then TSH suppression.

Deficiency of adrenal cortical hormones. Primary (Addison's — autoimmune commonest in the UK, also TB worldwide, adrenal haemorrhage) loses BOTH cortisol and aldosterone → hyperpigmentation, hyponatraemia/hyperkalaemia. Secondary (pituitary ACTH deficiency, or abrupt steroid withdrawal) loses cortisol only — no hyperpigmentation, aldosterone preserved. The Addisonian crisis is the lethal emergency.

Chronic cortisol excess. Commonest cause is EXOGENOUS (prescribed steroids). Endogenous: ACTH-dependent (pituitary adenoma = Cushing's DISEASE, or ectopic ACTH from small-cell lung/carcinoid) or ACTH-independent (adrenal adenoma/carcinoma). Central obesity, striae, proximal myopathy, hypertension and hyperglycaemia. Confirm cortisol excess, then localise.

A catecholamine-secreting tumour of the adrenal medulla (phaeochromocytoma) or extra-adrenal sympathetic ganglia (paraganglioma). Episodic catecholamine surges cause paroxysmal hypertension, headache, palpitations and sweating. The '10% tumour' and strongly hereditary (MEN2, VHL, NF1, SDH). Alpha-blockade BEFORE beta-blockade is the life-saving rule before surgery.

Autonomous aldosterone overproduction — bilateral adrenal hyperplasia or an aldosterone-producing adenoma (Conn's). The commonest secondary/curable cause of hypertension. Causes hypertension with (sometimes) hypokalaemia and metabolic alkalosis. Screen with the aldosterone:renin ratio; treat with a mineralocorticoid antagonist or adrenalectomy.

Autosomal-recessive deficiency of a cortisol-synthesis enzyme (21-hydroxylase in ~90%), shunting precursors into androgens. Loss of cortisol ± aldosterone with androgen excess: classically a salt-wasting crisis and virilised (ambiguous) genitalia in a neonate. Managed with glucocorticoid (± mineralocorticoid) replacement. (Carded in depth on child health — referenced here for the adrenal axis.)

Growth hormone excess, almost always from a pituitary somatotroph adenoma (rarely ectopic GHRH). In adults (after growth plates fuse) it causes acromegaly — insidious soft-tissue and bony overgrowth; before fusion it causes gigantism. Diagnosed by failure of GH to suppress on an oral glucose tolerance test + raised IGF-1; treated by transsphenoidal surgery.

Raised prolactin — from a lactotroph adenoma (prolactinoma, the commonest functioning pituitary tumour), dopamine-antagonist drugs (antipsychotics, metoclopramide), pituitary stalk compression (loss of dopamine inhibition), hypothyroidism or pregnancy. Causes galactorrhoea, hypogonadism (amenorrhoea/low libido) and, with a macroadenoma, mass effects. Treated with a dopamine agonist (NOT surgery first).

Deficiency of one or more anterior pituitary hormones, from a pituitary/parasellar tumour (and its treatment), Sheehan syndrome (postpartum pituitary infarction), pituitary apoplexy, infiltration or trauma. Hormones are typically lost in the order GH → gonadotrophins → TSH → ACTH. The ACTH/cortisol deficiency is the dangerous one. Replace the deficient axes — glucocorticoid first.

Pituitary adenomas — functioning (prolactinoma, GH→acromegaly, ACTH→Cushing's disease, rarely TSH) or non-functioning. They present through hormone excess, hormone deficiency (compression of normal gland) or mass effect (bitemporal hemianopia from optic chiasm compression, headache, cavernous sinus involvement). Pituitary apoplexy is the acute haemorrhage/infarction.

Inability to concentrate urine from lack of ADH (cranial/AVP deficiency — pituitary surgery, tumour, trauma, idiopathic) or renal resistance to ADH (nephrogenic — lithium, hypercalcaemia, hypokalaemia, genetic). Causes large-volume dilute polyuria and intense thirst. The water-deprivation test (then desmopressin) distinguishes the type.

Inappropriate ADH secretion causing water retention and dilutional, EUVOLAEMIC hyponatraemia with inappropriately concentrated urine. Causes: malignancy (small-cell lung — paraneoplastic), CNS disease, lung disease, drugs (SSRIs, carbamazepine, etc.). A diagnosis of exclusion (euvolaemic, normal thyroid/adrenal). Treated by fluid restriction and the cause.

Autonomous overproduction of parathyroid hormone, usually from a single parathyroid adenoma (rarely hyperplasia/carcinoma; part of MEN1/2a). Causes hypercalcaemia with an inappropriately normal or raised PTH. Often asymptomatic (found on a calcium check); symptoms are 'bones, stones, abdominal groans and psychic moans'. Parathyroidectomy is curative.

Deficiency of PTH — most commonly after thyroid/parathyroid surgery, or autoimmune (± polyglandular syndrome), causing HYPOcalcaemia with HIGH phosphate and low/inappropriate PTH. Pseudohypoparathyroidism is end-organ PTH resistance (high PTH, with skeletal features). Treated with calcium and active vitamin D.

Raised serum (corrected) calcium. ~90% is either primary hyperparathyroidism (commonest in the well outpatient) or malignancy (commonest in the unwell inpatient — PTHrP, bony metastases, myeloma). PTH is the pivotal test: raised/normal = parathyroid; suppressed = malignancy/other. Severe hypercalcaemia is treated with IV fluids then a bisphosphonate.

Low corrected calcium, causing neuromuscular irritability. Causes split by PTH/phosphate: vitamin D deficiency and CKD (HIGH PTH = secondary hyperparathyroidism), hypoparathyroidism (LOW PTH, high phosphate), hypomagnesaemia, acute pancreatitis, and rhabdomyolysis/tumour lysis. Treated with calcium and (active) vitamin D; IV calcium if severe.

Reduced bone mass and microarchitectural deterioration causing fragility fractures (low-trauma fractures of hip, vertebrae, wrist). Often silent until a fracture. Risk is quantified with FRAX/QFracture and DXA (T-score ≤ -2.5 = osteoporosis). Treated with calcium/vitamin D and a bisphosphonate; exclude secondary causes.

Defective mineralisation of bone matrix, usually from vitamin D deficiency (low sunlight, malabsorption, CKD, anticonvulsants). In adults = osteomalacia (bone pain, proximal myopathy, pseudofractures); in children with open growth plates = rickets (bowing, swollen joints, growth failure). Biochemistry: low/normal calcium and phosphate with HIGH ALP and low vitamin D; treated with vitamin D (± calcium).

Localised disordered bone turnover — excessive osteoclastic resorption followed by disorganised osteoblastic formation, producing enlarged, structurally weak, deformed bone. Often asymptomatic with an isolated raised ALP; can cause bone pain, deformity (bowed tibia, skull enlargement), fractures, deafness, and (rarely) osteosarcoma. Calcium is normal. Treated with a bisphosphonate if symptomatic.

Raised plasma lipids (LDL cholesterol and/or triglycerides), a major modifiable driver of atherosclerotic cardiovascular disease. Managed by cardiovascular risk assessment (QRISK), lifestyle, and statins for primary (QRISK ≥10%) and secondary prevention, with ezetimibe/PCSK9 inhibitors/inclisiran as add-ons. Severe elevations suggest a familial disorder.

An autosomal-dominant defect of LDL clearance (LDL-receptor, ApoB or PCSK9 gain-of-function) causing lifelong very high LDL cholesterol and premature atherosclerotic disease. Recognised by very high cholesterol, tendon xanthomata and a family history of early coronary disease. Needs early high-intensity statin (often + ezetimibe/PCSK9) and cascade testing of relatives.

Potentially fatal fluid and electrolyte shifts when nutrition is reintroduced to a malnourished/starved person. Refeeding carbohydrate triggers insulin release, driving phosphate, potassium and magnesium intracellularly and depleting thiamine — causing HYPOPHOSPHATAEMIA, hypokalaemia, hypomagnesaemia, fluid overload, arrhythmia and Wernicke's. Prevented by identifying risk, starting low and slow, and replacing electrolytes + thiamine.

Iron overload — hereditary (autosomal-recessive HFE mutations, commonest in those of northern European descent) or secondary (repeated transfusion). Iron deposits in liver, pancreas, heart, joints, skin and gonads. Classic late triad: 'bronze diabetes' + hepatomegaly/cirrhosis. Diagnosed by raised ferritin and transferrin saturation; treated by venesection.

Autosomal-recessive defect of copper excretion (ATP7B) causing copper accumulation in liver, brain and eyes. Presents in young people (children–30s) with liver disease (hepatitis/cirrhosis/acute liver failure) and/or neuropsychiatric features (tremor, dystonia, dysarthria, parkinsonism, personality/psychiatric change). Kayser-Fleischer rings, low caeruloplasmin; treated with copper chelation. (Also a neurology/GI differential.)

Autosomal-recessive deficiency of phenylalanine hydroxylase, so phenylalanine accumulates and is neurotoxic. Detected on the newborn blood-spot screen; untreated it causes intellectual disability, seizures, a 'musty' odour and fair pigmentation. Managed by a lifelong low-phenylalanine diet. Maternal PKU harms the fetus if control is poor in pregnancy.

Autosomal-recessive deficiency of galactose-1-phosphate uridyltransferase (classic galactosaemia), so galactose (from lactose) cannot be metabolised and toxic galactose-1-phosphate accumulates. The neonate becomes unwell on milk feeds — jaundice, hepatomegaly, vomiting, hypoglycaemia, cataracts and a predisposition to E. coli sepsis. Treated by a lifelong lactose/galactose-free diet.

A group of inherited (mostly autosomal-recessive; Fabry is X-linked) lysosomal enzyme deficiencies causing accumulation of un-degraded substrate. Examples: Gaucher (glucocerebrosidase — hepatosplenomegaly, bone crises, cytopenias), Niemann-Pick (sphingomyelinase — hepatosplenomegaly, cherry-red macular spot, neurodegeneration), Fabry (α-galactosidase — neuropathic pain, angiokeratomas, renal/cardiac), Tay-Sachs (hexosaminidase A — neurodegeneration, cherry-red spot, no hepatosplenomegaly). Some treated with enzyme replacement.

Autosomal-recessive deficiency of cystathionine β-synthase, causing homocysteine accumulation. A Marfan-like phenotype (tall, long limbs, lens dislocation) but with intellectual disability and, crucially, a strong thrombotic tendency. The lens dislocates DOWNWARD (vs upward in Marfan). Treated with pyridoxine (B6), diet and anti-thrombotic measures.

Generalised dysfunction of the proximal renal tubule causing urinary loss of glucose, amino acids, phosphate, bicarbonate, potassium and uric acid — producing a normal-anion-gap (type 2 proximal renal tubular) acidosis, hypophosphataemic rickets/osteomalacia, glycosuria with normal blood glucose, and polyuria. Causes: inherited (cystinosis, Wilson's, tyrosinaemia, galactosaemia) and acquired (drugs e.g. tenofovir, heavy metals, myeloma). (The packet's exemplar — congenital Fanconi ANAEMIA with short stature/absent radius is a separate haematological condition on child health.)

The commonest cancer in women. Usually a hard, irregular, fixed, painless lump ± nipple/skin change, detected by the patient or on screening (mammography, ages 50–70). Triple assessment (clinical + imaging + biopsy) confirms it; receptor status (ER/PR/HER2) guides treatment (surgery, radiotherapy, endocrine therapy, chemotherapy, anti-HER2).

The commonest benign breast tumour, typically in women under 35 — a smooth, firm, highly mobile, painless lump ('breast mouse'). Confirmed on triple assessment; most are left alone and many regress, with excision for large/growing/symptomatic lesions or patient choice.

A fluid-filled, benign breast lump, common in the perimenopausal years (40s–50s). Smooth, sometimes tender, can appear suddenly; confirmed on ultrasound and resolves on aspiration. Bloodstained aspirate or a residual mass after aspiration needs further assessment.

Inflammation/infection of the breast — most commonly LACTATIONAL (milk stasis → Staph aureus), also non-lactational periductal mastitis (smokers). Presents with a red, hot, tender, swollen segment ± systemic upset; if it forms a fluctuant collection it is an abscess (needs drainage). The crucial mimic is inflammatory breast cancer.

An eczema-like change of the NIPPLE caused by malignant ductal carcinoma cells spreading into the nipple epidermis — almost always associated with an underlying in-situ or invasive breast cancer. The trap is treating it as eczema. Unlike eczema, it starts on and destroys the NIPPLE (not the areola) and is unilateral and persistent.

A fibroepithelial breast tumour on a spectrum from benign to malignant — typically a rapidly growing, large lump in women in their 40s–50s. Resembles a giant fibroadenoma but grows fast and can recur or (rarely) metastasise (haematogenous). Treated with WIDE local excision (not enucleation).

Rare breast carcinoma in men, presenting as a hard, often retroareolar (subareolar) painless lump with nipple changes. Usually ER-positive; strongly associated with BRCA2, Klinefelter syndrome and oestrogen excess. The key is to distinguish a firm fixed eccentric mass from symmetrical, soft, central gynaecomastia.

Benign proliferation of male glandular breast tissue from a relative excess of oestrogen over androgen. Physiological (neonatal, puberty, older age), drug-induced (spironolactone, digoxin, antipsychotics, anti-androgens, cannabis), or from disease (liver cirrhosis, hypogonadism, hyperthyroidism, oestrogen-secreting or hCG-secreting tumours). A soft, symmetrical, mobile subareolar disc — the task is to find the cause and exclude male breast cancer and hormone-secreting tumours.

Dilatation and inflammation of the subareolar ducts, common around the menopause and in smokers. Causes a thick, often green/creamy or blood-stained nipple discharge, nipple retraction and a periareolar lump/inflammation. Benign, but discharge and retraction overlap with cancer — so triple assessment is needed.

A benign inflammatory reaction to injury of breast fat (trauma, surgery, radiotherapy, often in larger breasts). It produces a firm, sometimes irregular and skin-tethered lump that can clinically and radiologically MIMIC cancer — so it is diagnosed by triple assessment, not assumed from a trauma history.

A benign papillary tumour growing within a (usually subareolar) breast duct — the commonest cause of BLOODY single-duct nipple discharge, typically in women 40–50. Usually no palpable lump. Diagnosed by triple assessment/ductography and treated by microdochectomy (duct excision), partly to exclude an underlying malignancy.

The clinical syndrome of a serotonin- (and vasoactive amine-) secreting neuroendocrine tumour, usually midgut, that has metastasised to the liver (so the secreted amines bypass hepatic first-pass metabolism). Episodic FLUSHING, DIARRHOEA and bronchospasm, with right-sided cardiac valve fibrosis (TIPED) over time. Diagnosed by urinary 5-HIAA; treated with somatostatin analogues.

An insulin-secreting pancreatic neuroendocrine tumour — the commonest functioning pancreatic NET. Causes fasting/exertional HYPOGLYCAEMIA with Whipple's triad. Diagnosed by inappropriately high insulin and C-peptide during hypoglycaemia (with low ketones); usually benign and resected. Part of MEN1 in a minority.

A gastrin-secreting neuroendocrine tumour (duodenum/pancreas) driving gastric acid hypersecretion — the Zollinger-Ellison syndrome. Causes multiple/refractory/atypically-sited peptic ulcers, diarrhoea and reflux. Diagnosed by a raised fasting gastrin (off PPIs) with high gastric acid; ~25% are part of MEN1. Treated with high-dose PPIs and tumour resection.

A rare glucagon-secreting pancreatic neuroendocrine tumour, classically presenting with the 4 D's: Dermatitis (NECROLYTIC MIGRATORY ERYTHEMA), Diabetes (mild), DVT/thromboembolism, Depression — plus weight loss and a sore red tongue/angular stomatitis. Diagnosed by a very high glucagon; treated with somatostatin analogues and resection.

A rare vasoactive-intestinal-peptide-secreting pancreatic neuroendocrine tumour causing the WDHA syndrome — Watery Diarrhoea, Hypokalaemia and Achlorhydria (pancreatic cholera). Profuse secretory diarrhoea persists when fasting, with dehydration and electrolyte loss. Diagnosed by a high VIP; treated with somatostatin analogues, fluid/electrolyte replacement and resection.

Paraneoplastic Cushing's syndrome from ectopic ACTH secretion by a non-pituitary tumour — classically small-cell lung cancer (rapid, severe) or a bronchial carcinoid (more indolent). Distinguished from pituitary Cushing's disease by very high ACTH, failure to suppress on high-dose dexamethasone, rapid onset with weight loss, marked hypokalaemic alkalosis and pigmentation.

The commonest cause of hypercalcaemia in inpatients/cancer patients — via PTH-related peptide (humoral, e.g. squamous lung, renal, breast cancer), osteolytic bony metastases, or myeloma (cytokine-driven), and rarely tumour 1,25-vitamin D. PTH is SUPPRESSED. Often rapid and symptomatic; treated with IV fluids then bisphosphonate/denosumab and the cancer.

Secondary polycythaemia from inappropriate (ectopic) erythropoietin production by a tumour — classically renal cell carcinoma, hepatocellular carcinoma, cerebellar haemangioblastoma (and uterine fibroids). Raised haemoglobin/haematocrit with a HIGH EPO and a normal JAK2 (distinguishing it from polycythaemia vera). Treated by removing the tumour.

Multiple Endocrine Neoplasia type 1 — an autosomal-dominant syndrome (MEN1 gene) of tumours of the '3 Ps': Parathyroid (primary hyperparathyroidism — usually the first/commonest), Pituitary (adenoma, e.g. prolactinoma), and Pancreas (neuroendocrine — gastrinoma, insulinoma). Recognised by combinations of these and a family history; managed by surveillance and treating each tumour.

Multiple Endocrine Neoplasia type 2 — autosomal-dominant RET proto-oncogene mutation. MEN2A: medullary thyroid cancer + phaeochromocytoma + parathyroid hyperplasia. MEN2B: medullary thyroid cancer + phaeochromocytoma + mucosal neuromas/marfanoid habitus (NO parathyroid disease). Medullary thyroid cancer is near-universal — RET-positive carriers are offered prophylactic thyroidectomy.

Autoimmune destruction of several endocrine glands together. APS type 1 (AIRE gene, childhood): the triad of chronic mucocutaneous candidiasis, hypoparathyroidism and Addison's disease. APS type 2 (Schmidt, adults, commoner): Addison's disease with autoimmune thyroid disease and/or type 1 diabetes. Recognise the clustering — one autoimmune endocrinopathy should prompt looking for the others.