Cushing's Syndrome is caused by chronic excess cortisol. Features: Central (truncal) obesity with thin limbs (protein catabolism), Moon face (rounded face), Buffalo hump (fat pad between shoulder blades), Purple/violet striae (stretch marks - due to collagen breakdown), Hypertension, Diabetes (hyperglycaemia), Osteoporosis, Muscle weakness, thin skin, easy bruising, and Mood changes (depression, psychosis). Causes: Iatrogenic (most common - long-term steroid use), Cushing's Disease (pituitary ACTH-secreting adenoma - most common endogenous cause), Adrenal adenoma/carcinoma, Ectopic ACTH (small cell lung cancer). Diagnosis: 24-hr urine cortisol, low-dose dexamethasone suppression test, midnight salivary cortisol.

The Thymus Gland is a bilobed lymphoid organ located in the superior mediastinum (behind the sternum, in front of the heart). It is largest in childhood and involutes (atrophies) after puberty - in adults it is replaced largely by fat. Functions: Primary lymphoid organ - site of T-lymphocyte (T-cell) maturation. Immature lymphocytes (thymocytes) from bone marrow migrate to thymus - undergo positive and negative selection - mature T-cells released to blood/lymph. Produces Thymosin, Thymopoietin, Thymulin - hormones that promote T-cell development and maturation. DiGeorge syndrome (22q11 deletion): Thymus hypoplasia/aplasia causing deficient T-cell immunity, recurrent infections, cardiac defects, hypocalcaemia. Thymoma: Tumour of thymus - associated with Myasthenia Gravis.

The Endocrine System is a collection of ductless glands that produce and secrete hormones directly into the bloodstream (not through ducts), which then travel to target organs to produce specific effects. Key features: Ductless glands (unlike exocrine glands which have ducts e.g. salivary glands, sweat glands). Effects are slower but longer lasting compared to the nervous system. Regulates: Growth, metabolism, reproduction, mood, homeostasis, stress response. Major endocrine glands: Hypothalamus, Pituitary, Thyroid, Parathyroid, Adrenal, Pancreas, Gonads (testes/ovaries), Pineal, Thymus.

Addison's Disease (Primary Adrenal Insufficiency) is caused by destruction of the adrenal cortex causing deficiency of cortisol AND aldosterone. Most common cause: Autoimmune (70-80%) - anti-21-hydroxylase antibodies. Other causes: TB (historically most common), metastatic cancer, haemorrhage (Waterhouse-Friderichsen syndrome - meningococcal). Features: Hyperpigmentation (bronze skin) = Excess ACTH stimulates melanocytes (MSH action) - characteristic sign. Hypotension, postural hypotension (lack of aldosterone causing Na+ loss), Weakness, fatigue, weight loss, Hyponatraemia, Hyperkalaemia (lack of aldosterone), and Hypoglycaemia (lack of cortisol). Treatment: Hydrocortisone + Fludrocortisone (mineralocorticoid replacement). Addisonian crisis: Life-threatening - treat with IV hydrocortisone and saline.

Negative Feedback is the most common control mechanism in the endocrine system - it maintains hormone levels within a narrow range (homeostasis). How it works: A gland produces a hormone, hormone level rises, this rise feeds back (negatively) to inhibit further production. Classic example - HPT (Hypothalamo-Pituitary-Thyroid) axis: Hypothalamus produces TRH, pituitary produces TSH, thyroid produces T3/T4. Rising T3/T4 inhibits TRH and TSH causing thyroid to reduce production. Other examples: HPA axis (cortisol inhibits CRH and ACTH), HPG axis (sex hormones inhibit FSH and LH). Positive feedback is rare - example: Oxytocin/labour (cervical stretch causes more oxytocin causing more contractions) and LH surge (oestrogen stimulates LH surge causing ovulation).

A Hormone is a chemical messenger produced by endocrine glands, secreted into the bloodstream, and transported to target cells/organs where it produces a specific physiological effect by binding to specific receptors. Classification of hormones: Peptide/Protein hormones (Insulin, glucagon, ADH, GH, TSH - water-soluble - act on surface receptors), Steroid hormones (Cortisol, aldosterone, sex hormones - lipid-soluble - cross cell membrane - act on nuclear receptors), and Amine hormones (Adrenaline, noradrenaline, thyroid hormones - derived from amino acids). The concept of hormones was introduced by Ernest Starling (1905).

Aldosterone is a mineralocorticoid produced by the zona glomerulosa of the adrenal cortex. Regulated by: RAAS (Renin-Angiotensin-Aldosterone System), blood potassium levels (high K+ stimulates aldosterone), and ACTH (minor role). Actions on DCT and collecting duct of kidney: Increases Na+ reabsorption (water follows - increases blood volume and pressure), Increases K+ excretion (into urine - hypokalaemia in excess), and Increases H+ excretion (alkalosis in excess). Primary Hyperaldosteronism (Conn's Syndrome): Adrenal adenoma causing excess aldosterone, hypertension + hypokalaemia. Hypoaldosteronism (Addison's disease): Na+ loss, K+ retention, hypotension.

Diabetes Insipidus (DI) is characterised by polyuria (large volumes of very dilute urine - up to 20 L/day) and polydipsia (excessive thirst). Two types: Cranial DI (ADH deficiency - due to hypothalamic/posterior pituitary damage from head trauma, neurosurgery, tumour, infection. Treatment: Desmopressin/DDAVP - synthetic ADH analogue) and Nephrogenic DI (ADH resistance - kidneys fail to respond to ADH. Causes: Lithium toxicity, hypercalcaemia, hypokalaemia, genetic. Treatment: Thiazide diuretics - paradoxically reduce urine volume, and low sodium diet). Distinguished from Diabetes Mellitus by: Normal blood glucose, no glucose in urine, very low urine specific gravity (<1.005), very low urine osmolality. Water deprivation test + Desmopressin test differentiates cranial from nephrogenic DI.

The Pituitary Gland (Hypophysis) is called the master gland because it controls the activity of most other endocrine glands through its hormones. It is located at the base of the brain in a bony depression called the Sella Turcica (Turkish saddle) of the sphenoid bone. It is connected to the hypothalamus by the pituitary stalk (infundibulum). Two lobes: Anterior pituitary (Adenohypophysis) = Produces GH, TSH, ACTH, FSH, LH, Prolactin. Posterior pituitary (Neurohypophysis) = Stores and releases ADH and Oxytocin (produced by hypothalamus). However, the hypothalamus is considered the true master as it controls the pituitary.

Adrenaline (Epinephrine) is a catecholamine produced by chromaffin cells of the adrenal medulla (80% adrenaline, 20% noradrenaline). Derived from tyrosine via dopamine. Released in response to stress, hypoglycaemia, exercise. Effects (fight or flight): Heart (increased heart rate - tachycardia, increased force of contraction), Lungs (bronchodilation - opens airways), Blood (increased glucose via glycogenolysis and gluconeogenesis, increased free fatty acids), Blood vessels (vasoconstriction in skin/gut; vasodilation in muscles), and Pupils (dilation - mydriasis). Clinical use: Anaphylaxis treatment (IM adrenaline 1:1000), cardiac arrest (IV adrenaline in ALS protocol), and local anaesthetic additive (reduces bleeding).