PCOS (Polycystic Ovary Syndrome) affects 5-15% of women of reproductive age. It is the most common cause of anovulatory infertility. Diagnosis (Rotterdam criteria - 2 of 3): Oligo/anovulation (irregular or absent periods), Clinical/biochemical hyperandrogenism (acne, hirsutism - excess body hair, alopecia, elevated testosterone), and Polycystic ovaries on ultrasound (>=12 follicles per ovary or ovarian volume >10 mL). Pathophysiology: Insulin resistance causes elevated insulin causing stimulation of ovarian androgen production causing excess LH causing LH:FSH ratio elevated (>2:1). Associated with: Metabolic syndrome, T2DM, cardiovascular risk, and endometrial cancer (from unopposed oestrogen). Treatment: Lifestyle changes (weight loss), OCP (regulates cycle), Metformin (insulin sensitiser), and Clomiphene/Letrozole (ovulation induction for fertility).

The Adrenal (Suprarenal) Glands are two small, triangular/pyramidal glands located on the superior pole of each kidney. Each weighs ~4-5 g. Two distinct regions: Adrenal Cortex (outer, 90%) - derived from mesoderm - produces steroid hormones: Zona Glomerulosa (outermost) = Aldosterone (mineralocorticoid - regulates Na+/K+), Zona Fasciculata (middle, largest) = Cortisol (glucocorticoid - stress response), and Zona Reticularis (innermost) = Androgens (DHEA - weak sex hormones). Adrenal Medulla (inner, 10%) - derived from neural crest (modified sympathetic ganglion) - produces Adrenaline (80%) + Noradrenaline (20%) (catecholamines). Mnemonic for cortex zones: GFR = Salt (Glomerulosa), Sugar (Fasciculata), Sex (Reticularis).

Prolactin (PRL) is produced by lactotroph cells of the anterior pituitary. Primary function: Stimulates and maintains milk production (lactogenesis) in breast tissue - acts on mammary gland alveolar cells. Regulation: Dopamine (PIH - Prolactin Inhibiting Hormone) = The main inhibitor of prolactin (tonically suppresses prolactin secretion). TRH (from hypothalamus) = Stimulates prolactin. Suckling = Stimulates prolactin release (neurogenic reflex). Prolactin suppresses ovulation (explains why breastfeeding can reduce fertility - lactational amenorrhoea). Hyperprolactinaemia: Most common cause = Prolactinoma (pituitary adenoma). Also: dopamine antagonists (metoclopramide, antipsychotics), hypothyroidism. Features: Galactorrhoea (nipple discharge), amenorrhoea, infertility, hypogonadism in men. Treatment: Dopamine agonists (cabergoline, bromocriptine).

Cortisol is the primary glucocorticoid produced by the zona fasciculata of the adrenal cortex under control of ACTH (from pituitary) and CRH (from hypothalamus). It is the stress hormone. Functions: Raises blood glucose (gluconeogenesis, glycogenolysis - anti-insulin, protein catabolism), Anti-inflammatory (suppresses immune response - inhibits prostaglandins, cytokines, phospholipase A2 - basis for steroid drugs), Fat redistribution (chronic excess) = central obesity, moon face, buffalo hump, Blood pressure maintenance (permissive effect on catecholamines), and Suppresses immune system. Diurnal variation: Highest in early morning, lowest at night (follows circadian rhythm).

The Pineal Gland is a small (~150 mg), pine cone-shaped gland located in the epithalamus (posterior diencephalon), between the two superior colliculi. Sometimes called the third eye. It produces Melatonin - synthesised from serotonin (which is derived from tryptophan). Regulation: Darkness causes sympathetic stimulation of the pineal causing increased melatonin (promotes sleep). Light (via retino-hypothalamic-pineal pathway) suppresses melatonin (promotes wakefulness). Functions of melatonin: Regulates circadian rhythm (sleep-wake cycle), influences seasonal reproductive cycles (photoperiodism), antioxidant properties. Clinical use: Jet lag, shift work disorder, insomnia treatment.

Multiple Endocrine Neoplasia (MEN) is a group of autosomal dominant hereditary conditions causing tumours (usually benign) in multiple endocrine glands: MEN 1 (Wermer's syndrome) - 3 Ps: Pituitary adenoma (prolactinoma most common), Parathyroid hyperplasia/adenoma (hyperparathyroidism - most common manifestation), and Pancreatic tumours (insulinoma, gastrinoma). Gene: MEN1 (Menin) - chromosome 11. MEN 2A (Sipple's syndrome) - 3 Cs: Medullary thyroid carcinoma (MTC - virtually 100%), Phaeochromocytoma, and Parathyroid hyperplasia. Gene: RET proto-oncogene - chromosome 10. MEN 2B: MTC + Phaeochromocytoma + Marfanoid habitus + Mucosal neuromas (no parathyroid). Gene: RET.

The Hypothalamo-Pituitary Portal System is a specialised blood vessel network that allows hypothalamic hormones to reach the anterior pituitary in very high concentrations without entering the general circulation: Hypothalamic neurons release hormones into primary capillary plexus in the median eminence, Blood flows down the portal veins (in the pituitary stalk), Reaches the secondary capillary plexus in the anterior pituitary, and Anterior pituitary cells respond and release their hormones into the general circulation. This portal system is essential because hypothalamic hormones are produced in tiny amounts - the portal system delivers them at high concentration directly to pituitary cells. Pituitary stalk disruption (trauma, tumour) causes hyperprolactinaemia (loss of dopamine inhibition) + pan-hypopituitarism.

Pan-hypopituitarism is deficiency of all anterior pituitary hormones. Features follow hormone deficiency order (GH usually lost first): GH deficiency (growth failure in children, fatigue, reduced muscle mass in adults), LH/FSH deficiency (hypogonadism - amenorrhoea, infertility, loss of libido, sexual dysfunction), TSH deficiency (secondary hypothyroidism - fatigue, weight gain), ACTH deficiency (secondary adrenal insufficiency - weakness, hypotension, hypoglycaemia - no hyperpigmentation unlike Addison's), and Prolactin deficiency (inability to lactate after delivery). Causes: Pituitary adenoma (most common), craniopharyngioma, Sheehan's syndrome (pituitary infarction post-partum haemorrhage), pituitary surgery/radiotherapy, haemochromatosis, sarcoidosis. Sheehan's Syndrome: Postpartum pituitary necrosis (pituitary enlarges in pregnancy - vulnerable to haemorrhagic infarction) - unable to breastfeed (no prolactin) is usually first sign.

Hypoglycaemia = blood glucose < 4 mmol/L (<70 mg/dL). The body activates counter-regulatory responses: 1) Glucagon (first response - alpha cells) = Stimulates glycogenolysis and gluconeogenesis. 2) Adrenaline = Stimulates glycogenolysis (liver), inhibits insulin release, produces symptoms (sweating, tremor, palpitations, anxiety - adrenergic symptoms). 3) Cortisol and GH = Longer-term - promote gluconeogenesis and reduce glucose utilisation. Symptoms: Adrenergic (sweating, trembling, palpitations, anxiety, hunger) and Neuroglycopenic (confusion, weakness, slurred speech, seizures, coma - brain deprived of glucose). Whipple's triad (for diagnosing hypoglycaemia): Symptoms of hypoglycaemia + Low blood glucose + Relief with glucose. Treatment: Oral glucose (if conscious), IV 50% dextrose (if unconscious), IM glucagon (if no IV access).

The Hypothalamus is the true master of the endocrine system - it controls the pituitary (which in turn controls most other endocrine glands). Hypothalamic hormones (all released into the hypothalamo-pituitary portal system): TRH (Thyrotrophin-Releasing Hormone) stimulates TSH release. CRH (Corticotrophin-Releasing Hormone) stimulates ACTH release. GnRH (Gonadotrophin-Releasing Hormone) stimulates FSH and LH release. GHRH (GH-Releasing Hormone) stimulates GH release. Somatostatin inhibits GH (and TSH). Dopamine (PIH) inhibits Prolactin. The hypothalamus also directly produces ADH and Oxytocin (stored in posterior pituitary).