Hypothalamic & Pituitary Drugs

Hypothalamic & Pituitary Drugs

1. Definition, scope & organising principles

• The control of metabolism, growth, and reproduction is mediated by an integrated neuroendocrine unit comprising the hypothalamus and pituitary gland; drugs in this class either mimic, replace, or block hypothalamic/pituitary hormones (Katzung 16e Ch.37, pp.703–4).
• The pituitary (~0.6 g) sits in the sella turcica at the base of the brain, adjacent to the optic chiasm and cavernous sinuses — anatomical proximity explaining the bitemporal visual-field defects and headaches seen with pituitary macroadenomas (Katzung 16e Ch.37, p.703).
• Two functional lobes (G&G 14e Ch.46, pp.923–4; KDT 8e Ch.17, pp.257):
  • Anterior lobe (adenohypophysis) — the "master endocrine gland"; secretes peptide trophic hormones into the systemic circulation under the control of hypothalamic releasing/inhibiting hormones delivered via the hypothalamic-adenohypophyseal portal venous system.
  • Posterior lobe (neurohypophysis) — not a true gland but the axon terminals of magnocellular hypothalamic neurons (supraoptic [SON] + paraventricular [PVN] nuclei); stores and releases oxytocin and arginine vasopressin (AVP/ADH) directly into the systemic circulation, bypassing any intermediate pituitary signal.
• Axis architecture — hypothalamic releasing hormone → amplified by anterior pituitary trophic hormone → regulated response from a target endocrine organ → target-organ hormone exerts negative feedback on both hypothalamus and pituitary (the feed-forward/feedback loop that permits precise homeostatic regulation) (G&G 14e Ch.46, pp.923–4).
• Pharmacologic applications fall into three areas (Katzung 16e Ch.37, p.704):
  • Replacement of a deficient hormone (e.g. somatropin for GH deficiency, desmopressin for central DI).
  • Antagonism of an over-produced hormone (e.g. somatostatin analogues / pegvisomant in acromegaly, dopamine agonists in hyperprolactinaemia, vaptans in SIADH).
  • Diagnostic testing (e.g. GnRH/leuprolide test for precocious puberty, oxytocin challenge test, vasopressin/renal-concentration test).