Endocrine Physiology

The endocrine system is the body's chemical communication network. Instead of sending electrical signals along nerves (fast, targeted, short-lived), it releases hormones — chemical messengers that travel through the blood and act on distant target organs. Hormone vs. nerve signal: - Nerve signal — travels in milliseconds, affects specific target, effect lasts milliseconds to seconds (e.g. moving a muscle) - Hormone — travels in seconds to minutes, affects multiple target tissues, effect lasts minutes to hours to days (e.g. regulating metabolism, growth, or reproduction) Both systems are essential — nerves handle immediate responses, hormones handle slower, sustained regulation. What hormones do: Hormones regulate virtually every physiological process: - Metabolism and energy use (thyroid hormones, insulin, glucagon, cortisol) - Growth and development (growth hormone, sex hormones, thyroid hormones) - Reproduction (oestrogen, progesterone, testosterone, FSH, LH) - Blood pressure and volume (aldosterone, ADH, adrenaline, ANP) - Blood glucose (insulin, glucagon, cortisol, adrenaline) - Calcium balance (parathyroid hormone, calcitonin, Vitamin D) - Stress response (cortisol, adrenaline) Major endocrine glands: - Hypothalamus — the master controller, links the nervous and endocrine systems - Pituitary gland — the "master gland," releases hormones that control other glands - Thyroid gland — regulates metabolic rate - Parathyroid glands — regulate calcium - Adrenal glands — stress hormones (cortisol, aldosterone, adrenaline) - Pancreas — blood glucose (insulin, glucagon) - Gonads (ovaries/testes) — sex hormones

A hormone in the bloodstream reaches every cell in the body — but it only affects cells that have the right receptor for it. Think of a hormone as a key, and the receptor as a lock. Only the right key opens the right lock. Two major receptor types based on hormone chemistry: 1. Cell surface receptors (for water-soluble hormones): Water-soluble hormones (peptides and amines) cannot cross the cell membrane — they are too large or too polar. They bind receptors on the cell surface. Binding triggers a cascade of reactions inside the cell using second messengers (like cAMP, calcium). Examples: insulin, glucagon, adrenaline, growth hormone, TSH, ADH 2. Intracellular receptors (for lipid-soluble hormones): Lipid-soluble hormones (steroids like cortisol, oestrogen, testosterone, and thyroid hormones) can diffuse through the cell membrane and bind receptors INSIDE the cell — often directly in the nucleus. They directly regulate gene expression — switching genes on or off. Examples: cortisol, oestrogen, progesterone, testosterone, aldosterone, thyroid hormones Why this matters clinically: - Steroid hormones (lipid-soluble) act slowly (hours) but have prolonged effects (days) because they change which proteins the cell makes - Adrenaline (water-soluble, cell surface receptor) acts in seconds via cAMP — used in emergencies (anaphylaxis, cardiac arrest) - Receptor abnormalities cause disease: insulin resistance (Type 2 diabetes) = receptors don't respond normally to insulin; androgen insensitivity syndrome = testosterone receptors are non-functional

The hypothalamus (a small region at the base of the brain) is the interface between the nervous system and the endocrine system. It monitors the body's internal state continuously and releases small amounts of releasing hormones or inhibiting hormones that travel a short distance to the anterior pituitary gland. The pituitary then releases its own hormones into the general circulation, which travel to and control other endocrine glands. This creates a hierarchical control system: Hypothalamus → Pituitary → Target gland → Hormone → Effects Key pituitary hormones and their targets: - TSH (thyroid-stimulating hormone) → thyroid → thyroid hormones (T3, T4) - ACTH (adrenocorticotropic hormone) → adrenal cortex → cortisol - FSH and LH (gonadotropins) → ovaries/testes → oestrogen, testosterone, egg/sperm production - GH (growth hormone) → liver + tissues → IGF-1 → growth and protein synthesis - Prolactin → mammary glands → milk production - ADH and Oxytocin — actually made in the hypothalamus, stored and released by the posterior pituitary Feedback regulation — negative feedback: Almost every axis is regulated by negative feedback. The hormone produced by the target gland feeds back to the hypothalamus and pituitary, suppressing further stimulation: Hypothalamus releases TRH → pituitary releases TSH → thyroid releases T3/T4 → T3/T4 feeds back and inhibits TRH and TSH release → levels stabilise. Clinical example — Hypothyroidism: Thyroid gland fails → low T3/T4 → no feedback suppression → hypothalamus releases more TRH → pituitary releases MORE TSH → TSH is very HIGH on blood test, even though T4 is low. This is how we diagnose hypothyroidism — the high TSH is the key finding.

The thyroid gland sits in the front of the neck and produces two main hormones — T3 (triiodothyronine) and T4 (thyroxine). These hormones set the body's basal metabolic rate — the rate at which cells use oxygen and produce heat at rest. Think of thyroid hormones as a volume knob for the body's engine: - Too much → everything speeds up (hyperthyroidism) - Too little → everything slows down (hypothyroidism) Effects of thyroid hormones (T3 and T4): - Increase metabolic rate in virtually all cells → more oxygen consumed, more heat produced - Increase heart rate and cardiac output - Increase gut motility (bowel movements) - Essential for brain development in foetuses and newborns (severe deficiency = cretinism — permanent intellectual disability) - Stimulate bone growth (moderate levels) but cause bone loss (excess) - Permissive effects for other hormones (growth hormone, adrenaline) — many hormones work less effectively without adequate thyroid hormones Hypothyroidism (underactive thyroid): Too little T3/T4. Causes: Hashimoto's thyroiditis (autoimmune — most common in developed countries), iodine deficiency (most common worldwide), post-thyroidectomy. Symptoms reflect a slowed metabolism: fatigue, weight gain, cold intolerance, constipation, bradycardia (slow heart rate), dry skin, hair loss, depression. Treatment: levothyroxine (synthetic T4) once daily. Hyperthyroidism (overactive thyroid): Too much T3/T4. Most common cause: Graves' disease (autoimmune — antibodies mimic TSH, continuously stimulating the thyroid). Symptoms reflect a sped-up metabolism: weight loss despite increased appetite, heat intolerance, sweating, palpitations (fast heart rate), tremor, anxiety, diarrhoea, exophthalmos (bulging eyes — in Graves' disease specifically). Treatments: carbimazole (blocks hormone production), radioactive iodine (destroys thyroid tissue), or thyroidectomy.

The adrenal glands sit like caps on top of each kidney. Each has two distinct regions with completely different functions: Adrenal medulla (inner part): - Releases adrenaline (epinephrine) and noradrenaline in response to acute stress or danger - Part of the sympathetic nervous system's rapid response - Effects: increased heart rate, blood pressure, blood glucose; dilated pupils; redistributed blood flow to muscles Adrenal cortex (outer part): Produces three classes of steroid hormones: 1. Glucocorticoids (mainly cortisol) — the stress hormone 2. Mineralocorticoids (mainly aldosterone) — regulates sodium and blood pressure (covered in the renal lesson) 3. Androgens — weak sex hormones (small contribution compared to gonads) Cortisol — the stress hormone: Released by the adrenal cortex in response to ACTH (from the pituitary). Cortisol rises in the morning and falls at night (diurnal rhythm), and surges with physical or psychological stress. What cortisol does: - Raises blood glucose — stimulates gluconeogenesis (new glucose from amino acids) in the liver; inhibits insulin's effects on cells (to preserve glucose for the brain during stress) - Suppresses the immune system — reduces inflammation (why synthetic steroids like prednisolone are used for inflammatory conditions) - Breaks down proteins — muscle is broken down to provide amino acids for gluconeogenesis - Mobilises fat from peripheral stores Clinical diseases of cortisol: Cushing's syndrome — too much cortisol. Causes: steroid medication (most common), pituitary tumour producing excess ACTH, or adrenal tumour. Symptoms: weight gain (central obesity), round "moon face", stretch marks (striae), muscle weakness, hypertension, diabetes, fragile skin, poor wound healing, osteoporosis. Addison's disease — too little cortisol (and often aldosterone). Usually autoimmune destruction of the adrenal cortex. Symptoms: fatigue, weight loss, low blood pressure, hyperpigmentation (skin goes darker — excess ACTH has a pigment-stimulating side effect), low blood glucose, craving for salt. Life-threatening during illness or surgery (adrenal crisis) — these patients must take hydrocortisone replacement daily.

Growth Hormone (GH): Produced by the anterior pituitary. Essential for childhood growth — stimulates protein synthesis and cell division in virtually all tissues. In adults, it continues to maintain muscle mass, bone density, and fat distribution. GH stimulates the liver to produce IGF-1 (insulin-like growth factor 1), which mediates most of GH's growth-promoting effects. GH secretion follows a pulsatile pattern, with the largest pulse occurring during deep sleep — this is one physiological reason why sleep is essential for growth and recovery. Too much GH: - In children (before growth plates close): gigantism — very tall stature - In adults: acromegaly — bones in the hands, feet, and face continue to enlarge (acral = extremities). The face takes on characteristic features: prominent jaw, enlarged nose, widely spaced teeth. Also causes carpal tunnel syndrome, diabetes, heart disease. - Cause: usually a pituitary tumour (adenoma) Too little GH in childhood: GH deficiency → short stature. Treatable with recombinant GH injections. --- Calcium Regulation: Blood calcium must be kept within 2.1–2.6 mmol/L. Even small deviations cause serious problems: - Hypocalcaemia (low calcium) → muscle cramps, tetany (involuntary muscle contractions), seizures - Hypercalcaemia (high calcium) → "bones, stones, groans, and psychic moans": bone pain, kidney stones, constipation/abdominal pain, depression/confusion Three hormones regulate calcium: Parathyroid hormone (PTH) (from parathyroid glands — four tiny glands embedded behind the thyroid): - Released when calcium FALLS - Raises calcium: breaks down bone (releases Ca²⁺), increases Ca²⁺ absorption in kidneys, activates Vitamin D in kidneys - Hyperparathyroidism (most commonly a benign adenoma) → excess PTH → hypercalcaemia → bone loss + kidney stones Calcitonin (from thyroid C cells): - Released when calcium RISES - Lowers calcium by inhibiting bone breakdown - Physiologically minor in adults (mainly important in fish and birds) Vitamin D (calcitriol): - Activated in kidneys → promotes calcium absorption from the gut - Deficiency → rickets in children (soft, deformed bones), osteomalacia in adults (soft bones, bone pain) - Most people in northern climates are mildly Vitamin D deficient — supplementation is widely recommended