Bit · Endo
Sheehan vs Simmonds vs Empty Sella
Three causes of anterior pituitary failure in adults. Each has a signature setup story.
Mechanism
All three produce hypopituitarism — deficiency of one or more anterior pituitary hormones (GH, prolactin, TSH, ACTH, LH/FSH). The clinical presentation depends on which hormones are lost, but the underlying mechanism differs:
- Sheehan syndrome — ischemic infarction of the anterior pituitary following severe postpartum hemorrhage. During pregnancy, the pituitary enlarges (lactotroph hyperplasia) and outgrows its blood supply; a hypotensive episode then causes infarction. The most common presenting feature is failure to lactate (loss of prolactin) — lactotrophs are the most metabolically active and the most vulnerable.
- Simmonds disease — historical term for adult panhypopituitarism from any cause (tumour, trauma, irradiation, infiltrative disease). Now mostly used synonymously with severe non-postpartum hypopituitarism. Often the result of a non-functioning pituitary adenoma compressing normal tissue.
- Empty sella syndrome — the sella turcica appears empty on imaging because CSF herniates into it through an incompetent diaphragma sellae, flattening the pituitary against the floor. Most cases are an incidental finding in obese, hypertensive, middle-aged women and pituitary function is preserved. A minority develop hypopituitarism.
Differentiator Table
| Sheehan | Simmonds | Empty sella | |
| Mechanism | Ischemic infarction of enlarged pituitary after postpartum hemorrhage | Pituitary destruction from tumour, trauma, surgery, irradiation, autoimmune (lymphocytic hypophysitis), infiltrative disease | CSF herniation through defective diaphragma sellae |
| Typical setting | Woman, recent delivery with massive bleeding/hypotension | Adult with pituitary mass or prior cranial event | Often incidental on MRI in obese, hypertensive middle-aged woman |
| First clinical clue | Failure to lactate | Variable — depends on hormones lost | Often asymptomatic |
| Other features | Loss of pubic/axillary hair, amenorrhea, fatigue, hypothyroidism, adrenal insufficiency | Same range; bitemporal hemianopia if adenoma compresses chiasm | Headache, mild visual changes if any |
| MRI finding | Pituitary may appear small or partially empty over years | Mass lesion or surgical defect | CSF density occupying sella; pituitary flattened against floor |
| Pituitary function | Variably reduced (commonly multi-axis) | Variably reduced | Usually preserved |
| Treatment | Hormone replacement for deficient axes | Treat cause + replace deficient hormones | Observe if asymptomatic; replace hormones if deficient |
The Pivot
The setup almost always tells you which one:
- Postpartum hemorrhage + failure to lactate? → Sheehan.
- Adult with a known pituitary mass, surgery, or radiation, now with hypopituitarism? → Simmonds (or just 'panhypopituitarism').
- Asymptomatic obese middle-aged woman with an MRI showing empty-appearing sella? → Empty sella.
NBME-Style Stem
A 28-year-old woman who delivered her first child 6 weeks ago presents with fatigue, cold intolerance, and inability to breastfeed. Her delivery was complicated by uterine atony and a 2-litre postpartum hemorrhage requiring transfusion. Labs show low free T4 with inappropriately low TSH, and low morning cortisol. Which of the following is the most likely diagnosis?
Concept Anchor
Pregnancy enlarges the pituitary until it depends on a tenuous blood supply; a postpartum hemorrhage drops perfusion below threshold and the most active cells die first — lactotrophs — which is why Sheehan announces itself as the milk that never comes.