Hypopituitarism
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Direct answer
Hydrocortisone is replaced before levothyroxine in every patient with hypopituitarism — thyroid hormone accelerates cortisol clearance and, on corticotrophs that cannot respond, precipitates adrenal crisis; this ordering rule is the most examined single fact in the disease. The commonest cause in adults is a pituitary macroadenoma (usually clinically non-functioning) or the surgery and radiotherapy used to treat it; craniopharyngioma leads in children and young adults; and in Indian practice Sheehan syndrome after postpartum haemorrhage remains a fixture of ward rounds and vivas. Replacement then proceeds down the axes: hydrocortisone 15–20 mg daily in divided doses, levothyroxine titrated to free T4 because TSH is unreadable in central hypothyroidism, sex steroids, growth hormone where deficiency is proven, and desmopressin if the posterior lobe fails.
What you must remember
- Order of replacement: glucocorticoid, then thyroid, then gonadal steroid, then growth hormone — reversing the first two is the classic prescription error.
- No fludrocortisone is needed: aldosterone sits under renin–angiotensin control, not ACTH, so the zona glomerulosa still works in secondary adrenal insufficiency.
- Central hypothyroidism reads upside down: TSH is normal or low with a low free T4; dose levothyroxine by weight (about 1.3–1.6 μg/kg; start low if elderly or cardiac) and monitor free T4 alone.
- Sheehan ladder: failure to lactate is the earliest sign (the first postpartum clue), then amenorrhoea, loss of axillary and pubic hair, and years later fatigue and hyponatraemia — a woman who "never fed the baby" after a home delivery with haemorrhage is the textbook stem.
- Other causes to list on demand: pituitary apoplexy (sudden headache, visual loss, collapse — hydrocortisone before anything else), empty sella, infiltrative disease (sarcoidosis, tuberculosis, haemochromatosis), peripartum lymphocytic hypophysitis, and radiotherapy acting years later.
- Sick-day rules: double or triple oral hydrocortisone for fever or surgery; injectable hydrocortisone with vomiting; every patient carries a steroid card.
- The unmasking phenomenon: cortisol deficiency impairs free-water excretion, so coexisting diabetes insipidus is masked — starting hydrocortisone unmasks polyuria and is expected, not a drug reaction.
- Fertility and GH: gonadotrophin induction (FSH/hMG with hCG) replaces the absent LH/FSH; adult GH replacement, after dynamic testing, improves body composition, lipids and quality of life.
The postpartum woman whose TSH was "normal"
A 31-year-old delivers at home with heavy postpartum haemorrhage, never lactates, and stays amenorrhoeic. Three years later she presents with fatigue, cold intolerance and a serum sodium of 126 mmol/L. The thyroid profile shows free T4 0.6 ng/dL with TSH 1.2 mIU/L — reported as "normal thyroid" because the TSH is in range; this is the central-hypothyroidism trap, since a truly primary gland failure would drive TSH high. Morning cortisol is 2.1 μg/dL, LH and FSH are low despite amenorrhoea (a menopause would show them high). Sheehan syndrome with panhypopituitarism. Treatment order is the exam answer: hydrocortisone 10 mg morning, 5 mg evening starts first — and the hyponatraemia improves on steroid alone, cortisol deficiency having driven the water retention. Only after a week is levothyroxine introduced at roughly 1.3 μg/kg and titrated to a mid-range free T4, never to TSH. Oestrogen–progestogen replacement follows for bone and cardiovascular protection, with sick-day education and a steroid card. Had she presented instead with sudden collapse, the pathway is stress-dose intravenous hydrocortisone, urgent MRI for apoplexy, and neurosurgical decompression once the adrenals are covered.
Where students slip
The slip that harms patients is starting levothyroxine first — within days the unblocked increase in cortisol clearance tips a compensated patient into crisis; vivas probe exactly this. The second is biochemical: reading a "normal" TSH as euthyroidism in someone with a low free T4, or chasing the hyponatraemia with saline and salt restriction for days while cortisol sits unmeasured — every hyponatraemia workup includes a morning cortisol. Third, postpartum amenorrhoea attributed to anaemia or lactation for years while failed lactation and hair loss sit in the notes. And remember the two-way interaction with the posterior pituitary: glucocorticoid replacement unmasks diabetes insipidus, and untreated DI makes adrenal crisis likelier — adjust hydrocortisone upward when desmopressin is withheld or fever appears.
Frequently asked questions
Which hormone is replaced first in hypopituitarism and why?
Hydrocortisone — levothyroxine accelerates cortisol metabolism and precipitates adrenal crisis in uncorrected ACTH deficiency, so glucocorticoid cover must precede thyroid replacement.
What is the standard hydrocortisone regimen?
15–20 mg daily in two or three divided doses (for example 10 mg on waking, 5 mg early afternoon), doubled or tripled during illness and given injectably with vomiting; no mineralocorticoid is required.
Why is TSH useless in central hypothyroidism?
Pituitary TSH secretion is itself deficient, so TSH is low or inappropriately normal despite a low free T4; levothyroxine is titrated to the free T4 alone.
What is the earliest manifestation of Sheehan syndrome?
Failure to lactate after delivery complicated by postpartum haemorrhage, followed by persistent amenorrhoea and loss of axillary and pubic hair.
How does glucocorticoid replacement affect coexisting diabetes insipidus?
Cortisol deficiency impairs free-water clearance and masks polyuria; starting hydrocortisone unmasks or worsens diabetes insipidus, which should be anticipated rather than mistaken for deterioration.