SN7 SHORT NOTE 5M

Describe the pituitary hormones and their analogues and antagonists.

Pharmacology · 2nd Professional — Para-Clinical

Anterior Pituitary Hormones and Their Analogues

Hormone	Agonists and their uses	Antagonists and their uses
Growth hormone	Somatropin (recombinant) — growth hormone deficiency in children, Turner syndrome, chronic renal failure, Prader-Willi syndrome, adult deficiency	Octreotide and lanreotide (somatostatin analogues); pegvisomant (a receptor antagonist) — for acromegaly
Prolactin	—	Dopamine agonists — cabergoline and bromocriptine. Dopamine is the physiological inhibitor of prolactin, so an agonist suppresses it: used for prolactinoma, hyperprolactinaemia and to suppress lactation. Cabergoline is better tolerated and given weekly
Gonadotrophins (FSH, LH)	Menotrophin, urofollitropin, recombinant FSH; hCG as an LH surrogate — ovulation induction and assisted reproduction	—
GnRH	Pulsatile GnRH stimulates gonadotrophin release — used in hypothalamic infertility	Continuous GnRH analogues (leuprorelide, goserelin) initially stimulate then down-regulate the receptor, causing chemical castration — prostate cancer, endometriosis, fibroids, precocious puberty, and IVF protocols. Degarelix is a direct antagonist with no initial flare
ACTH	Tetracosactide — diagnostic (short Synacthen test); infantile spasms	—
TSH	Recombinant TSH — before radioiodine scanning in thyroid cancer	—

CLINICAL PEARL

The same GnRH analogue stimulates or suppresses the gonads depending purely on whether it is given in pulses or continuously. Physiological release is pulsatile, and the pituitary responds to pulses. Give the analogue continuously and the receptors down-regulate within a fortnight, shutting the axis down completely. That is why leuprorelide is used for chemical castration in prostate cancer — the drug is an agonist, yet the clinical effect is suppression, and there is a transient "flare" in the first weeks that must be covered with an antiandrogen.

Posterior Pituitary Hormones

Hormone	Agonists	Antagonists
Vasopressin (ADH)	Desmopressin (DDAVP) — a V2-selective analogue with a long action and no vasoconstriction: used in central diabetes insipidus, nocturnal enuresis, and to release factor VIII and von Willebrand factor in mild haemophilia A and von Willebrand disease. Terlipressin and vasopressin (V1) cause splanchnic vasoconstriction — used in variceal bleeding and hepatorenal syndrome	Tolvaptan — a V2 antagonist ("aquaretic") producing water loss without sodium loss: used in hyponatraemia from SIADH and in polycystic kidney disease
Oxytocin	Oxytocin, carbetocin — labour and post-partum haemorrhage	Atosiban — tocolysis

Somatostatin Analogues

Octreotide and lanreotide mimic somatostatin, which physiologically inhibits growth hormone, insulin, glucagon, gastrin and other gut hormones
Uses — acromegaly; carcinoid syndrome and other neuroendocrine tumours (controlling flushing and diarrhoea); variceal bleeding; refractory sulphonylurea-induced hypoglycaemia; and high-output fistulae
Adverse effects — abdominal cramps, steatorrhoea, gallstones (from reduced gallbladder contraction), and both hyper- and hypoglycaemia

Applied Aspects

Dopamine agonists are first-line for prolactinoma, ahead of surgery — even large tumours shrink substantially, which is unusual among pituitary tumours and worth knowing
Check prolactin before investigating amenorrhoea or infertility further, and review the drug list — antipsychotics, metoclopramide and domperidone are common causes of hyperprolactinaemia and are frequently overlooked
Cover the initial GnRH agonist "flare" with an antiandrogen in prostate cancer; without it, a patient with spinal metastases may develop cord compression
Growth hormone must not be used for short stature that is not due to deficiency, and its misuse in sport and anti-ageing practice is both ineffective and harmful
Desmopressin causes hyponatraemia if fluid intake is not restricted; this is a real hazard in children treated for enuresis and in the elderly
Cabergoline in high doses causes cardiac valve fibrosis (as used in Parkinson disease); at the low doses used for prolactinoma the risk is small but echocardiography is considered with prolonged therapy
Octreotide causes gallstones in a substantial proportion with long-term use, and abdominal pain in such a patient should prompt an ultrasound rather than being attributed to the underlying tumour
Recombinant hormones removed the risk of transmitted disease — cadaveric growth hormone caused Creutzfeldt-Jakob disease, and pituitary-derived gonadotrophins carried similar hazards; this is a useful reminder of why source matters as much as molecule

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