Sheehan syndrome
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Sheehan Syndrome
Definition
Sheehan syndrome is postpartum pituitary necrosis - ischemic infarction of the anterior pituitary gland occurring as a complication of severe peripartum hemorrhage and/or hypotension during or after delivery. It was first described by Harold Leeming Sheehan in 1937 and remains an important cause of hypopituitarism in women, particularly in lower-resource healthcare settings.
Pathophysiology
During pregnancy, the pituitary gland enlarges significantly under the influence of estrogen (predominantly lactotroph hyperplasia). This enlargement increases its metabolic demand while paradoxically making it vulnerable to ischemia because:
- The blood supply to the anterior pituitary (via the hypothalamo-hypophyseal portal system) is a low-pressure system
- Severe hemorrhage causes systemic hypotension and splanchnic vasoconstriction
- The enlarged gland is compressed within the sella turcica, further compromising the portal blood flow
- The result is ischemic necrosis of the adenohypophysis (anterior lobe)
There is no direct correlation between the severity of hemorrhage and the occurrence of Sheehan syndrome - but a large portion of the anterior pituitary must be destroyed before symptoms become clinically evident.
The posterior pituitary (neurohypophysis) is relatively spared because it has a direct arterial supply, though diabetes insipidus can still occur.
Epidemiology
- Uncommon in high-resource settings due to improved obstetrical care and blood transfusion
- Still a significant concern in developing countries
- Incidence estimated at 2-3 per 100,000 deliveries in developed countries; much higher elsewhere
- One large Turkish series (Diri et al.) of 114 patients found a mean diagnostic delay of 19.7 years - illustrating how insidious the condition can be
Clinical Features
Presentation ranges from acute (rare) to chronically progressive (most common).
Acute presentation (within 6 weeks postpartum)
- Failure of lactation (agalactia) - often the earliest and most characteristic sign
- Failure to resume menstruation (amenorrhea/oligomenorrhea)
- Persistent tachycardia and hypotension following hemorrhage
- Hyponatremia due to acute adrenal insufficiency (ACTH deficiency) - the most common acute emergency presentation
- Severe headache on the day of delivery (in some cases)
- Most acute cases present within the first 10 days postpartum
Chronic / delayed presentation
Symptoms depend on which pituitary hormones are deficient. Typically follow this rough order of loss (most to least sensitive to ischemia):
| Hormone Lost | Clinical Manifestation |
|---|---|
| GH (first and most sensitive) | Fatigue, reduced muscle mass, dyslipidemia |
| LH/FSH (gonadotropins) | Amenorrhea, loss of pubic/axillary hair, sexual dysfunction, infertility |
| TSH | Secondary hypothyroidism - fatigue, cold intolerance, weight gain, constipation, bradycardia |
| ACTH | Secondary adrenal insufficiency - fatigue, hypotension, hyponatremia, hypoglycemia (life-threatening during stress) |
| Prolactin | Failure of lactation (often the presenting complaint) |
| ADH (posterior pituitary - less common) | Diabetes insipidus |
Symptoms in the largest series were nonspecific in ~53%, adrenal-related in ~31%, and gonadal in ~10%. Just over half were panhypopituitary; the rest had partial hypopituitarism.
Diagnosis
Clinical clues
- History of peripartum hemorrhage or hypotension
- Postpartum failure to lactate + amenorrhea
- Symptoms of hypopituitarism developing months to years later
- Low serum thyroxine with low/normal TSH (secondary hypothyroidism pattern)
- Low morning cortisol; hyponatremia or hypotension, especially under physiologic stress
Biochemical evaluation
- Basal hormone levels: low/normal TSH + low free T4; low cortisol + low ACTH; low LH/FSH + low estradiol; low IGF-1 (GH surrogate)
- Dynamic stimulation tests: insulin tolerance test (ITT) for GH and cortisol reserve; TRH, GnRH stimulation; ACTH stimulation test
- Complete pituitary hormone panel recommended
Imaging
- MRI is the investigation of choice
- Early findings: absent or reduced pituitary enhancement, enlarged pituitary gland, intrasellar mass
- Late finding (months to years later): empty sella turcica - the hallmark chronic radiological finding as the necrotic gland is replaced and reabsorbed
- The empty sella is not exclusive to Sheehan syndrome but is highly suggestive in the correct clinical context
Differential Diagnosis
Key differentials for postpartum hypopituitarism:
| Condition | Distinguishing Features |
|---|---|
| Lymphocytic hypophysitis | Autoimmune; pituitary enlarged and enhancing on MRI; can occur in 3rd trimester or early postpartum; often posterior pituitary involved first |
| Pituitary apoplexy | Acute hemorrhage/infarction into a pre-existing adenoma; sudden severe headache, visual loss, ophthalmoplegia |
| Pituitary adenoma | Imaging shows mass; no hemorrhage history required |
| Empty sella syndrome (primary) | Incidental finding; no hypopituitarism in most cases |
Treatment
Treatment is lifelong hormone replacement therapy targeting each deficient axis:
- Adrenal insufficiency (highest priority) - hydrocortisone 15-25 mg/day (divided doses), with stress dosing instructions; this must be replaced BEFORE thyroid hormone to avoid precipitating adrenal crisis
- Hypothyroidism - levothyroxine; titrated to free T4 levels (not TSH, which is unreliable in central hypothyroidism)
- Hypogonadism - estrogen-progestogen replacement in premenopausal women; gonadotropin injections if pregnancy desired
- GH deficiency - recombinant human GH; improves body composition, lipid profile, quality of life
- Diabetes insipidus (if present) - desmopressin (DDAVP)
- Emergency management - IV hydrocortisone 100 mg during illness, surgery, or trauma; IV fluids for hypotension and hyponatremia
Key Points for Exam / Practice
- Sheehan syndrome = pituitary necrosis from peripartum hemorrhage → hypopituitarism
- Agalactia (failure to lactate) is the hallmark early sign
- Diagnosis is typically delayed by many years (mean ~20 years in reported series)
- MRI shows empty sella in chronic disease
- Hyponatremia in the acute setting = ACTH deficiency → treat with glucocorticoids
- A subsequent normal pregnancy does NOT exclude Sheehan syndrome
- Replace cortisol before thyroxine to avoid precipitating adrenal crisis
Sources:
- Creasy & Resnik's Maternal-Fetal Medicine, 8e (Ch. 62)
- Rosen's Emergency Medicine, 9e (Ch. 177)
- Goldman-Cecil Medicine, International Ed.
- Karaca Z & Kelestimur F. "Sheehan syndrome: a current approach to a dormant disease." Pituitary, 2025 Jan. PMID: 39863703 - recent review confirming long diagnostic delays and updated management approach
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