Hypothalamic-pituitary axes
32 named structures.
Draft — not yet clinically reviewed. The structure of this map is checked automatically, but its wording has not been fact-checked against a textbook. Do not rely on it for an exam answer yet.
Hover or tab a structure to trace what it connects to. Some structures reveal further branches.
Clinical detail
- Corticotrophin-releasing hormone (paraventricular nucleus)CRH AVP co-secreted DiurnalPrednisolone above about 5 mg daily for more than three weeks2 questions
- Thyrotrophin-releasing hormone (paraventricular nucleus)TRH Gq Also drives prolactinLong-standing untreated primary hypothyroidism4 questions
- Gonadotrophin-releasing hormone pulse generator (arcuate nucleus)GnRH Kisspeptin PulsatileKallmann syndrome — failed migration of GnRH neurones with the olfactory placode
- GHRH and somatostatin (arcuate and periventricular nuclei)GHRH Somatostatin GhrelinInsulin tolerance test proposed in a patient with ischaemic heart disease or epilepsy
- Tuberoinfundibular dopamine (prolactin-inhibiting factor)Dopamine D2 Tonic inhibitionRisperidone or metoclopramide2 questions
- Supraoptic and paraventricular magnocellular neuronesADH Oxytocin NeurophysinLesion of the hypothalamic nuclei or high stalk (germinoma, craniopharyngioma, Langerhans cell histiocytosis, trauma)1 question
- Corticotroph — ACTH cleaved from pro-opiomelanocortinACTH POMC MC2RCorticotroph microadenoma (Cushing disease, about 70% of endogenous Cushing syndrome)2 questions
- Thyrotroph — thyroid-stimulating hormoneTSH Shared alpha subunit Gs to cAMPPituitary or hypothalamic damage (secondary hypothyroidism)4 questions
- Gonadotroph — luteinising hormone and follicle-stimulating hormoneLH FSH Shared alpha subunitPolycystic ovary syndrome2 questions
- Somatotroph — growth hormoneGH Pulsatile JAK2-STAT5Somatotroph macroadenoma in an adult (acromegaly)2 questions
- Lactotroph — prolactinProlactin D2 inhibited TRH stimulatedMicroprolactinoma in a woman2 questions
- Posterior pituitary — vasopressin releaseADH V2 kidney V1a vesselsSmall cell lung carcinoma, pneumonia, meningitis, SSRIs, carbamazepine or postoperative pain1 question
- Posterior pituitary — oxytocin releaseOxytocin Gq Ferguson reflexProlonged high-dose oxytocin infusion in hypotonic fluid
- Pituitary stalk and the hypophyseal portal veinsPortal veins Watershed supply SheehanSevere postpartum haemorrhage with hypotension (Sheehan syndrome)
- Adrenal cortex — zona fasciculata and zona reticularisMC2R StAR 21-hydroxylase21-hydroxylase deficiency, over 90% of congenital adrenal hyperplasia
- Thyroid follicular cellNIS TPO ThyroglobulinTSH-receptor stimulating antibody (Graves disease)4 questions
- Leydig cells and ovarian theca cells (the LH target)LH StAR Androgen synthesisExogenous testosterone or anabolic steroid use
- Sertoli cells and ovarian granulosa cells (the FSH target)FSH Aromatase Inhibin BSeminiferous tubule damage from chemotherapy, mumps orchitis or Klinefelter syndrome2 questions
- Hepatocyte — GH receptor and IGF-1 synthesisGH receptor JAK2-STAT5 IGFBP-3GH receptor mutation (Laron syndrome)
- Mammary alveolus and myometriumProlactin receptor Oxytocin receptor MyoepitheliumRetained placental fragments
- Collecting duct principal cell (V2 receptor)V2 cAMP Aquaporin-2Long-term lithium1 question
- CortisolZona fasciculata CBG bound DiurnalChronic glucocorticoid excess from any cause
- Thyroxine (T4) and triiodothyronine (T3)T4 prohormone D2 makes T3 Nuclear receptorSevere non-thyroidal illness (sick euthyroid syndrome)4 questions
- Testosterone and oestradiolAromatase 5-alpha reductase SHBGAromatase deficiency or an oestrogen receptor mutation in a man
- Insulin-like growth factor 1IGF-1 IGFBP-3 Growth plateAcromegaly confirmed on IGF-1 and OGTT
- Milk synthesis and the prolactin brake on GnRHCasein Alpha-lactalbumin GnRH suppressedProlactinoma in a man2 questions
- Aquaporin-2 mediated water reabsorptionAQP2 Free water Medullary gradientNon-osmotic ADH release from pain, nausea, opioids or hypovolaemia, combined with hypotonic maintenance fluid1 question
- Milk ejection and uterine contractionMyoepithelial Myometrial Gq Spiral artery clampActive management of the third stage with prophylactic oxytocin
- Long-loop negative feedback and how it localises a lesionLong loop Short loop Set pointLong-term prednisolone2 questions
- Positive feedback: the LH surge and the Ferguson reflexLH surge Ferguson reflex Self-limitingPolycystic ovary syndrome2 questions
- Plasma osmolality, thirst and the osmoreceptor loop275-295 mOsm/kg Thirst Free waterSmall cell lung carcinoma with sodium 118 mmol/L, urine osmolality 500 mOsm/kg and urine sodium 60 mmol/L1 question
- Hypopituitarism and the order in which axes failGH first ACTH last Steroid before thyroxineCraniopharyngioma in a child2 questions
Common questions
Why is TSH high in primary hypothyroidism but low or normal in secondary hypothyroidism?
TSH is made by the thyrotroph and suppressed by thyroid hormone. If the thyroid fails, feedback is lost and TSH rises steeply — the relationship is log-linear, so a small fall in free T4 gives a large TSH rise. If the pituitary or hypothalamus fails, the thyrotroph itself cannot respond, so free T4 falls while TSH stays low or inappropriately normal. That is why central hypothyroidism is missed if TSH is ordered alone, and why replacement is titrated against free T4 rather than TSH.
How do you distinguish a prolactinoma from the stalk effect?
By the size of the prolactin rise relative to the size of the tumour. Prolactin is under tonic dopamine inhibition, so any mass compressing the stalk removes that brake and raises prolactin modestly, usually under about 2000-3000 mIU/L (100-150 microgram/L), while the other anterior axes fail. In a true macroprolactinoma the level tracks tumour size and typically exceeds 5000 mIU/L (250 microgram/L). A large tumour with only a mildly raised prolactin should prompt serial dilution to exclude the hook effect.
Why is there no hyperkalaemia in secondary adrenal insufficiency?
ACTH drives the zona fasciculata and reticularis, but aldosterone comes from the zona glomerulosa, which is controlled by angiotensin II and potassium. When ACTH fails, cortisol is lost while aldosterone continues, so potassium stays normal and there is no pigmentation (ACTH is low, not high). Hyponatraemia can still occur, because cortisol deficiency permits unsuppressed ADH release.
How do you separate SIADH from arginine vasopressin deficiency at the bedside?
They are opposite ends of the same axis. In SIADH there is too much ADH: hyponatraemia with low plasma osmolality but urine osmolality above 100 mOsm/kg, urine sodium above 30-40 mmol/L, clinical euvolaemia and low urate. In arginine vasopressin deficiency (formerly central diabetes insipidus) there is too little: large volumes of dilute urine, thirst, and a rising sodium if the patient cannot drink; the urine concentrates by more than half after desmopressin, which it does not in vasopressin resistance (nephrogenic disease, classically from lithium).
Why must hydrocortisone be given before levothyroxine in hypopituitarism?
Thyroid hormone raises metabolic rate and accelerates cortisol clearance. In a patient who is also ACTH deficient, starting thyroxine first can exhaust the small remaining cortisol reserve and precipitate an adrenal crisis. Check cortisol (or simply cover with hydrocortisone) before starting replacement in anyone with pituitary disease, Sheehan syndrome or central hypothyroidism.
Which tests separate Cushing disease from ectopic ACTH secretion?
Both are ACTH-dependent, so ACTH is normal or high in each. A corticotroph adenoma retains partial feedback: cortisol falls by more than half on 8 mg dexamethasone and ACTH rises with CRH, and inferior petrosal sinus sampling shows a central-to-peripheral gradient. Ectopic secretion, typically from small cell lung carcinoma or a bronchial carcinoid, does not suppress and does not respond to CRH, and presents over weeks with weight loss, proximal weakness, pigmentation and hypokalaemic metabolic alkalosis rather than the classic cushingoid habitus.