Hypopituitarism and the order in which axes fail
Effect and feedback · GH first ACTH last Steroid before thyroxine
When the anterior pituitary is compressed or infarcted the axes usually fail in a set order: growth hormone, then the gonadotrophins, then TSH, then ACTH. Prolactin is lost last, or is raised instead when the stalk is involved.
Traced from the start
- Corticotrophin-releasing hormone (paraventricular nucleus)
- Corticotroph — ACTH cleaved from pro-opiomelanocortin
- Adrenal cortex — zona fasciculata and zona reticularis
- Thyrotrophin-releasing hormone (paraventricular nucleus)
- Thyrotroph — thyroid-stimulating hormone
- Thyroid follicular cell
- Gonadotrophin-releasing hormone pulse generator (arcuate nucleus)
- Gonadotroph — luteinising hormone and follicle-stimulating hormone
- Leydig cells and ovarian theca cells (the LH target)Sertoli cells and ovarian granulosa cells (the FSH target)
- GHRH and somatostatin (arcuate and periventricular nuclei)
- Somatotroph — growth hormone
- Hepatocyte — GH receptor and IGF-1 synthesis
- Tuberoinfundibular dopamine (prolactin-inhibiting factor)
- Supraoptic and paraventricular magnocellular neurones
- Lactotroph — prolactinPosterior pituitary — oxytocin release
- Mammary alveolus and myometrium
- CortisolThyroxine (T4) and triiodothyronine (T3)Testosterone and oestradiolInsulin-like growth factor 1Milk synthesis and the prolactin brake on GnRH
- Hypopituitarism and the order in which axes fail
Detail
- Order of loss
- GH, then LH and FSH, then TSH, then ACTH; prolactin deficiency is rare except in Sheehan syndrome, where failure to lactate is the first clue
- Causes
- Macroadenoma and its surgery or radiotherapy, craniopharyngioma, Sheehan syndrome, apoplexy, traumatic brain injury, hypophysitis including checkpoint inhibitor disease, sarcoidosis, haemochromatosis, empty sella
- Replacement order
- Hydrocortisone before levothyroxine — thyroxine raises cortisol clearance and metabolic demand and can precipitate an adrenal crisis in an unrecognised ACTH-deficient patient
- Monitoring
- Trophic hormones are useless for titration here: follow free T4, morning testosterone or symptoms, and IGF-1
When it goes wrong
Craniopharyngioma in a child
Growth failure with bitemporal hemianopia and suprasellar calcification, often with vasopressin deficiency as well
Checkpoint inhibitor hypophysitis (ipilimumab)
Headache and fatigue with ACTH and TSH deficiency weeks into treatment; give hydrocortisone and screen for the other axes
Levothyroxine started before hydrocortisone in a panhypopituitary patient
Adrenal crisis with hypotension and hyponatraemia
Practise this structure
2 questions in the bank tagged Pituitary.
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