Pituitary hormones

How hormones act

• Peptides and catecholamines circulate free and act in seconds to minutes. Steroids and thyroid hormones travel bound to carriers (only the free fraction is active) and act over hours by changing protein synthesis.
• An activating Gs-alpha (GNAS) mutation in a mosaic pattern causes McCune–Albright syndrome: peripheral precocious puberty (suppressed LH and FSH), irregular café-au-lait patches and fibrous dysplasia, because Gs-linked receptors signal without their hormone.

Feedback

• Negative feedback is the commonest and most important control: each end hormone suppresses its hypothalamic and pituitary drivers. Primary gland failure therefore gives a high pituitary hormone (primary hypothyroidism: high TSH, low T4), while pituitary failure gives a low or inappropriately normal one.
• Positive feedback examples: the oestrogen-triggered LH surge (LH rises about 6–10-fold over the 1–2 days before ovulation), oxytocin in labour (Ferguson reflex), clotting cascade, and action potential upstroke.
• In males, inhibin from Sertoli cells inhibits FSH; testosterone inhibits LH.
• A TSH within the normal range is abnormal if free T4 is clearly high: think of a TSH-secreting pituitary adenoma (or thyroid hormone resistance).

Hypothalamic nuclei

Melatonin from the pineal gland is secreted mainly in darkness (light inhibits it via the retina and suprachiasmatic nucleus); it promotes sleep and can suppress gonadotrophins.

The hypothalamic–pituitary connections

• Anterior pituitary (from Rathke's pouch, oral ectoderm): hypothalamic hormones reach it through the hypophyseal portal veins in the stalk.
• Posterior pituitary (neural ectoderm): ADH and oxytocin are made in hypothalamic neurones (neurosecretion), carried down axons with neurophysins, stored and released. ADH and its stable co-product copeptin come from one precursor (neurophysin II); oxytocin uses neurophysin I.

Anterior pituitary hormones

Growth hormone

• Pulsatile; the largest pulse is in early slow-wave (deep) sleep. (Cortisol peaks in the early morning.)
• Increased by deep sleep, exercise, stress, fasting, hypoglycaemia, arginine and amino acids, puberty, ghrelin. Decreased by hyperglycaemia, somatostatin, IGF-1 feedback, obesity, cortisol excess.
• GH needs IGF-1 for most of its growth actions.
• The early-morning GH and cortisol surge raises fasting glucose in type 1 diabetes (dawn phenomenon), with normal 3 a.m. readings.
• Acromegaly (excess after epiphyseal fusion): enlarging hands, feet, jaw and tongue, sweating, hypertension, diabetes, bitemporal field loss. Screen with serum IGF-1; confirm with failure of GH to suppress during an oral glucose tolerance test. A random GH is unhelpful. Excess before fusion causes gigantism.

Prolactin

• Raised by pregnancy, suckling, stress, sleep, primary hypothyroidism (TRH), renal failure, dopamine D2 antagonists (risperidone and other antipsychotics, metoclopramide, domperidone), and stalk compression, which cuts the dopamine supply. Prolactin is the one anterior pituitary hormone that rises when the stalk is cut.
• High prolactin suppresses GnRH: amenorrhoea, galactorrhoea, infertility, low libido.
• Macroprolactin (prolactin bound to IgG) is biologically inactive but measured by assays: a high prolactin with regular periods, no galactorrhoea and normal MRI. Exclude it before treatment.
• Prolactinomas are treated first with dopamine agonists (cabergoline, bromocriptine).

Posterior pituitary

• ADH: water reabsorption (V2) and vasoconstriction (V1).
• Oxytocin: uterine contraction in labour and milk ejection (let-down) on suckling.
• Damage to the posterior pituitary or stalk reduces ADH (and oxytocin).

Puberty and gonadotrophins

Pituitary disease

• Pituitary apoplexy: haemorrhage into an adenoma, with sudden headache, vomiting, diplopia, visual loss, hypotension and hyponatraemia. Give IV hydrocortisone first; always replace cortisol before thyroxine.
• Sheehan syndrome: postpartum pituitary infarction after major haemorrhage; failure of lactation is often the first sign.
• Order of hormone loss with an expanding mass: GH and gonadotrophins first, then TSH, then ACTH; prolactin rises.
• Bitemporal hemianopia: chiasmal compression from below. Craniopharyngioma: Rathke's pouch remnant, calcified suprasellar mass in children.

Sodium problems after pituitary or brain injury

• Triphasic response after pituitary surgery: (1) cranial DI from shocked neurones (polyuria, dilute urine, rising sodium; give desmopressin); (2) about days 5–10, SIADH from unregulated ADH leaking from degenerating axons (desmopressin now causes dangerous hyponatraemia); (3) permanent DI once stores are exhausted.
• Cerebral salt wasting (after subarachnoid haemorrhage): natriuretic peptides cause renal salt loss, so the patient is hypovolaemic (weight loss, postural hypotension, rising urea and haematocrit) with high urine sodium. SIADH looks the same in the urine but the patient is euvolaemic. Treat salt wasting with saline; fluid restriction worsens vasospasm.

Remember Portal blood drives the front of the pituitary, axons fill the back; dopamine holds prolactin down; IGF-1 screens for acromegaly.

Exam trap Prolactin is controlled by dopamine inhibition; antipsychotics and stalk compression raise it.

Exam trap Insulin uses a tyrosine kinase; GH and prolactin use JAK–STAT; thyroid hormone uses a nuclear receptor.

How FCPS asks about this

• Posterior pituitary hormones: ADH and oxytocin, made in supraoptic and paraventricular nuclei.
• Lesion causing hyperphagia and obesity: ventromedial nucleus (satiety centre).
• Acromegaly: IGF-1 to screen; GH not suppressed by oral glucose to confirm.
• Galactorrhoea on risperidone: D2 blockade on lactotrophs removes dopamine inhibition.
• Delayed puberty with anosmia: Kallmann syndrome (low GnRH).
• GH peak: early slow-wave sleep; melatonin peaks in darkness.
• Hyponatraemia day 7 after pituitary surgery: ADH leaking from degenerating axons (second phase of the triphasic response).