Pituitary hormones and prolactin

Anatomy that explains the physiology

• Anterior pituitary (adenohypophysis) comes from Rathke's pouch (oral ectoderm); posterior pituitary (neurohypophysis) is a downgrowth of the diencephalon.
• The superior hypophyseal artery feeds a capillary plexus in the median eminence; long portal veins carry releasing hormones down the stalk. The anterior lobe has almost no direct arterial supply, so it depends on low-pressure portal flow.
• The posterior lobe has its own inferior hypophyseal arteries, so it is usually spared when the anterior lobe infarcts.
• Median eminence, stalk and pituitary lie outside the blood–brain barrier: they enhance strongly on MRI, and domperidone raises prolactin despite barely entering the brain. On dynamic MRI the normal gland enhances early; a microadenoma stays dark and fills in later.
• The diaphragma sellae is the dural roof of the fossa (a tear at transsphenoidal surgery leaks CSF). Haemorrhage into an adenoma (apoplexy) can compress cranial nerve III in the cavernous sinus.
• On T1 MRI the posterior bright spot is stored vasopressin granules; it is lost in cranial diabetes insipidus.

Anterior pituitary cells and their controls

• POMC yields ACTH, MSH and beta-endorphin; in primary adrenal failure high ACTH darkens skin. In hypopituitarism the skin is pale.
• After oophorectomy, unrestrained gonadotrophs enlarge and vacuolate.
• In stress the first hormone of the axis to rise is CRH. CRH also suppresses GnRH pulses: hypothalamic amenorrhoea after bereavement, weight loss or heavy exercise has low FSH, LH and oestradiol.
• Kisspeptin drives GnRH neurones; loss of its receptor gives hypogonadotrophic hypogonadism with a normal sense of smell (anosmia suggests Kallmann syndrome).

Hypothalamic nuclei

Prolactin and its control

• The only anterior pituitary hormone under tonic inhibition, by dopamine on D2 receptors of lactotrophs.

• High prolactin suppresses GnRH pulses, so it causes amenorrhoea, infertility and bone loss from oestrogen deficiency.
• A very large tumour with a modestly raised result suggests the hook effect (antibody saturation): dilute and re-assay.
• Decidua produces the prolactin of amniotic fluid.
• Dopamine agonists: cabergoline (long acting; one dose suppresses lactation after stillbirth; high doses over years can cause valve fibrosis through 5-HT2B agonism) and bromocriptine (nausea from D2 stimulation in the area postrema). A macroadenoma growing upward compresses the optic chiasm (bitemporal hemianopia); a macroprolactinoma may grow this way in pregnancy under placental oestrogen.

Growth hormone

• Direct actions are anti-insulin: lipolysis (fatty acids as fuel in fasting), raised glucose. Via IGF-1 (liver): linear growth and protein synthesis. Hepatic IGF-1 generation needs insulin, so poorly controlled diabetes slows growth.
• Released in pulses in deep sleep, exercise, fasting and hypoglycaemia (the insulin tolerance test assesses GH and ACTH reserve).
• Fetal growth depends on insulin and IGF-2, not GH: babies without a pituitary have normal birth size.
• In late pregnancy a placental GH variant from syncytiotrophoblast raises IGF-1 and suppresses pituitary GH.
• High GH with low IGF-1 means a GH receptor defect. Excess GH before epiphyseal fusion gives gigantism, after it acromegaly (carpal tunnel from soft tissue swelling).

Posterior pituitary

• ADH and oxytocin are made in hypothalamic cell bodies with carrier neurophysins, transported down axons and stored in Herring bodies.
• ADH: V1 (Gq, IP3, vasoconstriction), V2 (Gs, cAMP, aquaporin-2 in collecting ducts). Osmoreceptors lie in the OVLT.
• Gestational diabetes insipidus: placental vasopressinase breaks down ADH in late pregnancy; desmopressin resists it.
• Oxytocin: half-life of only a few minutes, so infusions are titrated and contractions fade quickly when stopped. A rapid IV bolus causes vasodilatation and hypotension with reflex tachycardia; high doses have an antidiuretic effect. Carbetocin is a long-acting analogue.

Sheehan syndrome

• The pregnancy-enlarged anterior pituitary infarcts after massive PPH with shock.
• Earliest sign: failure of lactation, then amenorrhoea, hypothyroidism (low T4 with low TSH) and cortisol deficiency.
• The zona glomerulosa is preserved (aldosterone is under renin control), so potassium stays normal. Diabetes insipidus is uncommon. Later the sella looks empty.

Remember Prolactin is the only pituitary hormone that rises when the stalk is cut.

Exam trap In Sheehan syndrome aldosterone is preserved, so hyperkalaemia is not expected.

Exam trap Normal pregnancy doubles the pituitary by lactotroph hyperplasia; this is not an adenoma.