Hypopituitarism Workup
On this page
Direct answer
Pituitary hormones fail in a predictable order under a compressing mass — growth hormone first, then gonadotrophins, then TSH and ACTH, with prolactin rising (not failing) as stalk compression removes dopamine inhibition — so the workup is built as a structured screen, not a fishing expedition. Basal testing: 8–9 a.m. cortisol, free T4 (not TSH alone), testosterone in men or oestradiol in women with amenorrhoea, LH/FSH, prolactin, IGF-1, and electrolytes plus osmolality if diabetes insipidus is suspected. Dynamic tests confirm the axes that basal values cannot: the insulin tolerance test remains a gold standard (contraindicated in seizures and cardiac disease), with the short Synacthen test acceptable when recent onset is unlikely. The replacement rule that decides pass or fail: hydrocortisone before levothyroxine, never the reverse.
What you must remember
- Screening order under a sellar mass: GH → LH/FSH → TSH/ACTH; ADH involvement suggests invasion below the sella or stalk pathology.
- Free T4 is low in secondary hypothyroidism with a low or "normal" TSH — testing TSH alone misses the entire diagnosis.
- Morning cortisol interpretation (assay-dependent): clearly low (commonly <100–150 nmol/L) suggests deficiency; high (commonly >400–450 nmol/L) effectively excludes; the middle band needs stimulation testing.
- Insulin tolerance test: gold standard for the HPA axis and GH; short Synacthen (250 µg) is more practical but can miss very recent corticotroph loss because the still-responsive adrenal takes weeks to atrophy — a favourite viva nuance.
- Prolactin: exclude pregnancy and drugs (antipsychotics, metoclopramide) before imaging the stalk effect.
- Sheehan syndrome: postpartum haemorrhage with failure to lactate or menstruate — the classic Indian viva presentation of pituitary failure.
- Replacement sequence: glucocorticoid cover first (hydrocortisone 15–20 mg/day divided), then levothyroxine (1.6 µg/kg, T4 usually slightly lower than primary), then sex steroids, GH last and optional.
- Every hypopituitary patient carries a steroid alert and sick-day instructions; adrenal crisis remains the main preventable death.
A structured walkthrough
A 36-year-old woman presents a year after a delivery complicated by massive haemorrhage; she never lactated, has not menstruated since, feels exhausted, and has lost axillary hair. Sheehan syndrome leads the differential. Basal panel: 8 a.m. cortisol 85 nmol/L (low), free T4 8 pmol/L (low) with TSH 1.0 mIU/L (inappropriately normal — the pituitary is failing, not the thyroid), LH and FSH both low with oestradiol at menopausal-minus levels (she should be ovulating at 36), prolactin low, IGF-1 below the age range, sodium 128 mmol/L. The picture is panhypopituitarism; MRI shows the empty, partially infarcted sella of postpartum apoplexy. Treatment starts with hydrocortisone 10 mg morning and 5 mg evening, levothyroxine only after three days of steroid cover, then transdermal oestrogen-progestogen replacement, and GH replacement discussed for quality of life and bone.
The second scenario tests order of operations under time pressure: a macroprolactinoma with visual field loss and cortisol of 60 nmol/L. Before transsphenoidal surgery or even dopamine agonist therapy, steroid replacement begins — shrinking a mass or starting T4 in an unblocked, cortisol-deficient patient can precipitate adrenal crisis, because levothyroxine accelerates cortisol clearance. The reverse sequence — T4 first, steroids second — is the single most penalised error in this territory.
Where students slip
The commonest technical slip is screening with TSH alone and reporting "thyroids normal" in a patient whose free T4 is 6 pmol/L — central hypothyroidism is a free-T4 diagnosis. The second is over-trusting a "normal" Synacthen test in a patient whose pituitary damage is weeks old; the adrenal cortex has not yet atrophied, so cortisol rises appropriately and the deficiency is missed — the ITT or repeat testing later catches it. Third, candidates forget that the clinical context, not the stimulation test, diagnoses Sheehan: postpartum haemorrhage plus failure to lactate is nearly pathognomonic, and stimulation tests carry hypoglycaemia risk in such patients without prior steroid cover. Finally, do not replace GH before cortisol and thyroxine are stable.
Frequently asked questions
Which hormones are lost first in a growing pituitary mass?
Growth hormone, then the gonadotrophins LH and FSH, followed by TSH and ACTH; prolactin typically rises from stalk compression, and diabetes insipidus appears only with suprasellar or hypothalamic extension.
Why must hydrocortisone precede levothyroxine in hypopituitarism?
Starting thyroid hormone accelerates cortisol clearance and can precipitate adrenal crisis in an unrecognised ACTH-deficient patient; glucocorticoid cover first is the safe sequence — a rule examiners test directly.
What is the gold standard test for the hypothalamic-pituitary-adrenal axis?
The insulin tolerance test, inducing hypoglycaemia to stress the axis, with contraindications of epilepsy, ischaemic heart disease and pregnancy; the short Synacthen test is the practical alternative when recent-onset deficiency is not in question.
How does Sheehan syndrome present?
Postpartum haemorrhage followed by failure to lactate, amenorrhoea, fatigue, loss of axillary and pubic hair, and sometimes hyponatraemia — with an empty or partially empty sella on MRI; treatment is staged replacement beginning with hydrocortisone.
Is TSH reliable for monitoring replacement in secondary hypothyroidism?
No — the diseased pituitary cannot generate TSH appropriately, so replacement is titrated to free T4 levels (typically mid-normal) and clinical response rather than to TSH.