Key Facts

The endocrine system uses hormones as chemical messengers to regulate metabolism, growth, reproduction, and homeostasis. Hormones act via endocrine (distant), paracrine (local), or autocrine (self) signalling.

Epidemiology

Endocrine disorders are common: diabetes mellitus affects approximately 4.9 million people in the UK (90% type 2). Hypothyroidism affects ~2% of women, 0.2% of men. Primary hyperparathyroidism prevalence is ~1 in 1,000.

Aetiology

Hormones are classified by structure:

• Peptide/protein: Insulin, GH, PTH, ACTH — act via cell surface receptors
• Steroid: Cortisol, aldosterone, sex hormones — act via intracellular nuclear receptors (gene transcription)
• Amine: Thyroid hormones (T3/T4) — nuclear receptors; catecholamines — cell surface receptors

Pathophysiology

Negative feedback is the dominant regulatory mechanism:

• Hypothalamus releases stimulatory/inhibitory hormones → pituitary releases trophic hormones → target gland releases effector hormones → inhibit hypothalamus/pituitary

Key axes:

• HPA axis: CRH → ACTH → cortisol (suppressed by dexamethasone in Cushing's workup)
• HPT axis: TRH → TSH → T3/T4
• HPG axis: GnRH → LH/FSH → testosterone/oestrogen
• GH axis: GHRH → GH → IGF-1 (somatostatin inhibits)

Insulin signalling: Glucose entry into beta cell → ATP production → K-ATP channel closure → depolarisation → Ca²⁺ influx → insulin exocytosis. Sulphonylureas close K-ATP channels (hence insulin secretion).

Hypothyroidism

• Weight gain, cold intolerance, constipation, dry skin, bradycardia, fatigue
• Myxoedema (non-pitting oedema), delayed relaxation of reflexes

Hyperthyroidism

• Weight loss, heat intolerance, tremor, tachycardia/AF, diarrhoea, anxiety
• Graves' disease: Thyroid eye disease, pretibial myxoedema, diffuse goitre

Cushing's Syndrome

• Central obesity, moon face, buffalo hump, striae, thin skin, proximal myopathy
• Hypertension, hyperglycaemia, osteoporosis

Addison's Disease

• Fatigue, weight loss, postural hypotension, hyperpigmentation, hyponatraemia, hyperkalaemia

Diabetes Mellitus

• Polyuria, polydipsia, weight loss (type 1); often asymptomatic (type 2)
• Complications: Retinopathy, nephropathy, neuropathy, cardiovascular disease

Red Flags

• Adrenal crisis: Hypotension, hyponatraemia, hypoglycaemia — IV hydrocortisone 100mg stat
• Thyroid storm: Pyrexia, tachycardia, confusion — propranolol, carbimazole, hydrocortisone
• DKA: Glucose >11, ketones >3, pH <7.3 — insulin infusion, IV fluids

Bedside

• Blood glucose: Fasting, random, or OGTT
• Blood pressure: Hyper/hypotension in endocrine disease
• BMI: Obesity assessment, Cushing's

Bloods

• TFTs: TSH (most sensitive), free T4, free T3
• HbA1c: Diabetes diagnosis and monitoring
• 9am cortisol: <100 nmol/L abnormal, >450 nmol/L normal; 100-450 = Synacthen test needed
• Short Synacthen test: 250mcg IM/IV, measure cortisol at 0 and 30 min; >450 nmol/L at 30 min = normal
• Calcium, PTH, phosphate, vitamin D: Parathyroid assessment
• Prolactin: Pituitary tumour screening
• IGF-1: GH excess/deficiency screening

Imaging

• Pituitary MRI: Adenoma detection
• Thyroid USS: Nodule assessment, FNA guidance
• CT adrenals: Adrenal masses, Cushing's localisation
• DEXA scan: Osteoporosis in endocrine disease

Special Tests

• Overnight dexamethasone suppression test: 1mg at 11pm, 9am cortisol <50 nmol/L = normal
• Insulin tolerance test: Gold standard for GH and cortisol reserve
• Water deprivation test: Diabetes insipidus diagnosis
• OGTT: Diagnosis of gestational diabetes, acromegaly (GH not suppressed <1 µg/L)

Non-pharmacological

• Lifestyle modification for type 2 diabetes: Diet, exercise, weight loss
• Sick day rules for patients on steroids or insulin
• MedicAlert bracelet for adrenal insufficiency

Pharmacological

• Hypothyroidism: Levothyroxine 50-100mcg OD (start 25mcg in elderly/cardiac disease); titrate to TSH
• Hyperthyroidism: Carbimazole 20-40mg OD (block-replace or titration regimen); propranolol 40mg TDS for symptom control
• Type 2 diabetes (NICE NG28): Metformin 500mg OD-BD titrated to 1g BD → add SGLT2 inhibitor (empagliflozin 10mg) or GLP-1 RA (semaglutide) especially if CVD or HF
• Addison's disease: Hydrocortisone 15-25mg daily (split doses, 10mg on waking) + fludrocortisone 50-200mcg OD
• Adrenal crisis: Hydrocortisone 100mg IV stat, IV 0.9% saline

Surgical

• Thyroidectomy: Graves' disease, thyroid cancer, large goitre
• Transsphenoidal pituitary surgery: Cushing's disease, acromegaly, prolactinoma (if dopamine agonist-resistant)
• Adrenalectomy: Adrenal tumours, phaeochromocytoma

Referral Criteria

• Newly diagnosed type 1 diabetes — immediate endocrinology
• Suspected Cushing's or phaeochromocytoma — endocrinology
• Thyroid nodule — 2-week-wait if malignancy suspected

• Type 1 diabetes: Life expectancy reduced by ~8-13 years; intensive control (DCCT/EDIC trial) reduces microvascular complications by 50-76%
• Type 2 diabetes: UKPDS showed intensive glucose control reduces microvascular complications by 25%
• Hypothyroidism: Excellent prognosis with levothyroxine replacement
• Graves' disease: ~50% remission after 12-18 months of carbimazole; relapse rate ~50%
• Addison's disease: Normal life expectancy with adequate replacement; risk of adrenal crisis ~8% per year

Hypothalamic-Pituitary Axis Summary

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