IGF-1 (Insulin-like Growth Factor 1 / Somatomedin C) is produced primarily by the liver in response to Growth Hormone (GH) stimulation. It mediates most of GH's anabolic and growth-promoting effects: Stimulates bone lengthening (at epiphyseal plates) - chondrocyte proliferation, Promotes muscle protein synthesis and hypertrophy, Stimulates cell proliferation throughout the body, and Has insulin-like effects (can lower blood glucose at high concentrations). IGF-1 provides negative feedback on GH secretion (from hypothalamus/pituitary). Clinically: IGF-1 levels are used as a screening test for acromegaly and GH deficiency (more stable than GH which fluctuates throughout the day). IGF-1 is elevated in acromegaly and low in GH deficiency and malnutrition.

Somatostatin (Growth Hormone Inhibiting Hormone - GHIH) is a broad inhibitory hormone produced by: Hypothalamus (inhibits GH and TSH from anterior pituitary), Pancreatic delta cells (inhibits insulin and glucagon secretion from adjacent alpha and beta cells), and GI tract (inhibits gastrin, secretin, and other GI hormones). Functions: Inhibits GH (primary hypothalamic action), Inhibits TSH, Inhibits insulin AND glucagon (paracrine - from delta cells in islets), and Slows GI motility and reduces digestive secretions. Clinical use: Somatostatin analogues (Octreotide, Lanreotide) are used to treat: Acromegaly (reduce GH/IGF-1), Carcinoid syndrome (inhibit serotonin release), Variceal bleeding (reduce portal pressure), and VIPoma/glucagonoma (endocrine tumours).

Endocrine vs Exocrine Glands: Endocrine glands (internal secretion) = Ductless - secrete hormones directly into the bloodstream and transported to distant target organs. Examples: Pituitary, thyroid, adrenal, parathyroid, gonads, pancreatic islets. Exocrine glands (external secretion) = Have ducts - secrete substances onto epithelial surfaces (skin, GI tract, airways). Examples: Salivary glands (saliva), sweat glands, sebaceous glands (sebum), liver (bile - via bile duct), pancreatic acini (digestive enzymes - via pancreatic duct). Mixed glands = Both endocrine AND exocrine functions: Pancreas (exocrine: digestive enzymes; endocrine: insulin and glucagon) and Gonads (exocrine: sperm/eggs; endocrine: sex hormones). Paracrine secretion = Acts on nearby cells. Autocrine = Acts on the secreting cell itself.

Testosterone in Females is produced in smaller amounts than males by: Ovarian theca cells (stimulated by LH) and Adrenal cortex (zona reticularis - DHEA/androstenedione converted to testosterone). Physiological roles in females: Libido (sex drive) - primary androgen governing female sexual desire, Bone density and muscle strength (anabolic effects), Mood and energy levels, and Precursor for oestradiol (via aromatase enzyme: testosterone converts to oestradiol in granulosa cells). Excess testosterone in females causes: Hirsutism (excess body hair), Acne, Virilisation, Clitoromegaly, and Menstrual irregularity. Seen in PCOS (most common), Congenital Adrenal Hyperplasia (CAH), and androgen-secreting tumours.

Congenital Adrenal Hyperplasia (CAH) is a group of autosomal recessive disorders caused by deficiency of enzymes in the cortisol biosynthesis pathway. Most common: 21-hydroxylase deficiency (~95%). Cannot synthesise cortisol (and aldosterone). Low cortisol causes no negative feedback causing excess ACTH causing adrenal hyperplasia. Precursors shunted to androgen pathway causing excess androgens. Effects: Females = Virilisation (ambiguous genitalia at birth), clitoromegaly, labial fusion, early pubic hair. Males = Precocious puberty, enlarged genitalia. Salt-wasting (classical form) = Aldosterone deficiency causing life-threatening salt wasting, hypotension, hyperkalaemia in neonates. Non-classical (mild) = PCOS-like features in females (hirsutism, menstrual irregularity). Treatment: Hydrocortisone (replaces cortisol and suppresses excess ACTH) +/- Fludrocortisone (mineralocorticoid replacement).

Glucocorticoids (cortisol and synthetic equivalents) have powerful anti-inflammatory and immunosuppressive effects - the basis for their widespread clinical use. Drugs: Prednisolone, Dexamethasone, Hydrocortisone, Methylprednisolone, Budesonide. Clinical uses: Inflammatory diseases (Rheumatoid arthritis, IBD, vasculitis, SLE), Respiratory (Asthma, COPD, sarcoidosis), Neurology (Cerebral oedema, MS relapses, meningitis - dexamethasone), Oncology (Lymphoma, multiple myeloma - kills lymphocytes), Transplant (immunosuppression - prevent rejection), and Emergency (Anaphylaxis, Addisonian crisis, septic shock - fludrocortisone). Side effects of long-term steroids: Cushing's syndrome, osteoporosis, diabetes, hypertension, peptic ulcer, immunosuppression, cataracts, growth suppression in children, psychiatric effects. Patients on long-term steroids must NOT stop suddenly - adrenal suppression.

Oestrogen and Bone Health: Oestrogen inhibits osteoclast activity (reduces bone resorption) and promotes osteoblast survival. It maintains bone density throughout reproductive life. At menopause: Oestrogen levels fall dramatically causing osteoclast activity unchecked causing accelerated bone resorption causing rapid bone density loss (up to 3-5% per year in first 5-10 years post-menopause). This leads to postmenopausal osteoporosis - the most common cause of osteoporosis. Clinical significance: Osteoporosis risk in postmenopausal women, premature ovarian insufficiency, female athletes with amenorrhoea (low oestrogen). HRT (Hormone Replacement Therapy) = Oestrogen +/- progesterone protects bone at menopause. DEXA scan measures bone mineral density (BMD) to diagnose osteoporosis (T-score <=-2.5). Bisphosphonates (alendronate, risedronate) = First-line treatment for osteoporosis.

Steroid hormones (cortisol, aldosterone, oestrogen, progesterone, testosterone, Vitamin D, thyroid hormones) are lipid-soluble and can freely cross the lipid bilayer of cell membranes. Mechanism: Steroid hormone enters cell and binds to intracellular receptor (cytoplasmic or nuclear). Hormone-receptor complex enters the nucleus (if not already there). Binds to Hormone Response Elements (HREs) on DNA. Acts as a transcription factor causing activation or suppression of specific gene expression. New proteins synthesised causing biological response (slower onset, longer duration). Compare with Peptide/Protein hormones (insulin, GH, FSH) - water-soluble - cannot cross membrane - bind to surface receptors - use second messengers (cAMP, IP3, DAG) - rapid response. Thyroid hormones (T3/T4) are technically amines but act like steroids (nuclear receptors).

Gestational Diabetes Mellitus (GDM) is glucose intolerance first diagnosed during pregnancy (typically 2nd-3rd trimester). Mechanism: Placental hormones (HPL, progesterone, oestrogen, cortisol) cause progressive insulin resistance causing gestational diabetes in susceptible women (who cannot compensate with increased insulin production). Risk factors: Obesity, previous GDM, family history of T2DM, South Asian/Afro-Caribbean ethnicity, and previous macrosomic baby (>4 kg). Risks: Mother = Increased risk of T2DM later (50% develop T2DM within 10 years) and pre-eclampsia. Fetus = Macrosomia (large baby) causing difficult delivery, shoulder dystocia, neonatal hypoglycaemia (fetal hyperinsulinism), and prematurity. Diagnosis: Oral Glucose Tolerance Test (OGTT) at 24-28 weeks. Treatment: Dietary modification, Metformin, and Insulin if needed. Usually resolves after delivery - but mother needs follow-up OGTT at 6 weeks.

Inhibin is a peptide hormone (Inhibin A and Inhibin B) that provides important negative feedback specifically on FSH (not LH) from the pituitary. In Males: Produced by Sertoli cells in response to FSH stimulation and sperm production. When spermatogenesis is adequate, sufficient inhibin B suppresses FSH preventing over-stimulation. In azoospermia (no sperm): Sertoli cell damage causes low inhibin B causing elevated FSH (diagnostic marker of primary testicular failure). In Females: Inhibin B = Produced by growing follicles in the follicular phase causing suppression of FSH. Inhibin A = Produced by corpus luteum in luteal phase causing suppression of FSH. Inhibin A is part of the Down Syndrome Screening (Quadruple test): Elevated inhibin A in Down syndrome pregnancy. In ovarian failure (menopause, premature ovarian insufficiency): No follicles causing no inhibin causing elevated FSH - diagnostic of ovarian failure.