Hypopituitarism — cortisol and TFT interpretation, and the pituitary mass viva

Interpretation

The examiner hands you a panel from a 50-year-old man with a year of fatigue, loss of libido and a recent headache: 9 am cortisol 90 nmol/L with ACTH low, free T4 8 pmol/L with TSH low/normal, testosterone low with LH/FSH low, IGF-1 low, prolactin mildly raised, sodium 128 mmol/L, potassium 4.2 mmol/L, and a note that he is pale with no pigmentation and a bitemporal visual field defect. The examiner asks: "Interpret these results, give the diagnosis, and outline the management."^[1]

• Interpretation: every axis shows a low target hormone with a low or inappropriately normal trophic hormone (low cortisol + low ACTH; low free T4 + low TSH; low testosterone + low LH/FSH; low IGF-1). This is hypopituitarism from a pituitary mass — the mild prolactin rise is a stalk effect (loss of dopaminergic inhibition), not a prolactinoma.^[1]
• The decisive discriminators the examiner will probe: no hyperpigmentation and a normal potassium localise the adrenal insufficiency to the PITUITARY (secondary), not the adrenal (primary Addison) — because ACTH is low, so there is no melanocyte stimulation, and aldosterone is spared by the intact RAAS so potassium stays normal.^[1]
• The mass effect — bitemporal hemianopia plus headache — points to a macroadenoma compressing the optic chiasm; a stalk-effect prolactin below about 200 ng/mL (roughly 4000 mU/L) supports a non-functioning macroadenoma over a macroprolactinoma (which is usually much higher and proportional to tumour size) — though a diagnostic grey zone exists below 200 ng/mL, so treat the whole picture, not one number.^[4]

Key points

The examiner will probe each; be ready to defend them at viva depth:

1. The trophic-hormone pattern — the diagnostic rule of hypopituitarism is a low target hormone with a low or inappropriately normal trophic hormone, across whichever axes are deficient; confirm the anatomy with pituitary MRI and assess the chiasm with formal visual-field perimetry.^[1]
2. Secondary vs primary adrenal insufficiency — secondary (ACTH deficiency) has no hyperpigmentation and no hyperkalaemia, does NOT need fludrocortisone (aldosterone/RAAS intact), and is caused by the pituitary; primary Addison has high ACTH (hyperpigmentation), low aldosterone (hyperkalaemia, salt-wasting) and needs fludrocortisone.^[1]
3. The hydrocortisone-before-levothyroxine rule — always replace glucocorticoid first; levothyroxine alone increases metabolic clearance of cortisol and precipitates adrenal crisis. In any suspected crisis give IV hydrocortisone 100 mg stat then 50 mg every 6 hours and fluids, and hold levothyroxine until the cortisol axis is covered.^[2][3]
4. Monitoring thyroid replacement — in central (secondary) hypothyroidism TSH is unreliable; titrate levothyroxine (~1.6 mcg/kg/day) to free T4, not TSH.^[1]
5. Order of hormone loss in a mass — GH, then LH/FSH, then TSH, then ACTH, then prolactin; ACTH loss is the most dangerous (adrenal crisis), and prolactin is often preserved or raised via the stalk effect.^[1]
6. The short Synacthen trap — the 250 mcg Synacthen test can be falsely normal early in secondary adrenal insufficiency, before the adrenal cortex atrophies; the insulin tolerance test (or metyrapone) is the gold standard for the HPA axis in hypopituitarism.^[2]
7. Pituitary apoplexy — the emergency — sudden thunderclap headache, cranial nerve III palsy, visual loss and acute adrenal insufficiency = haemorrhage or infarction into an adenoma; manage with emergency IV hydrocortisone and fluids, then urgent neurosurgery and ophthalmology for transsphenoidal decompression if there is visual loss or deterioration.^[1][2]
8. Replacement and sick-day education — hydrocortisone 15 to 25 mg/day divided (titrated clinically, no biochemical monitor), sex steroids, GH if proven deficient, desmopressin for diabetes insipidus; teach sick-day doubling/tripling, an emergency 100 mg IM hydrocortisone injection kit, and a MedicAlert bracelet.^[3]
9. Special causes to volunteer — Sheehan syndrome (postpartum necrosis: agalactia, amenorrhoea, hypopituitarism after severe PPH), traumatic brain injury/subarachnoid haemorrhage, empty sella (usually no deficiency), infiltrative disease (sarcoid, hemochromatosis), and immune-checkpoint-inhibitor hypophysitis (ipilimumab).^[2]

References

1. Yeliosof O, Gangat M. Diagnosis and management of hypopituitarism. Curr Opin Pediatr 2019.^[1]
2. Iglesias P. An Update on Advances in Hypopituitarism. J Clin Med 2024.^[2]
3. Fleseriu M, et al. Hormonal Replacement in Hypopituitarism in Adults. Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab 2016.^[3]
4. Harary M. Disentangling secretory ambiguity and the limitations of classical thresholds in defining prolactinomas. Pituitary 2026.^[4]

References4ShowHide

1. [1]Yeliosof O, Gangat M. Diagnosis and management of hypopituitarism. Current Opinion in Pediatrics, 2019.PMID 31082937
2. [2]Iglesias P. An Update on Advances in Hypopituitarism: Etiology, Diagnosis, and Current Management. Journal of Clinical Medicine, 2024.PMID 39458112
3. [3]Fleseriu M, Hashim IA, Karavitaki N, et al. Hormonal Replacement in Hypopituitarism in Adults: An Endocrine Society Clinical Practice Guideline. Journal of Clinical Endocrinology and Metabolism, 2016.PMID 27736313
4. [4]Harary M. Disentangling secretory ambiguity and the limitations of classical thresholds in defining prolactinomas Pituitary, 2026.PMID 42489804