How does Sheehan's syndrome (postpartum pituitary necrosis after massive obstetric hemorrhage) present, how is it diagnosed, and what is the appropriate management?

Sheehan Syndrome: Clinical Presentation, Diagnosis, and Management

Clinical Presentation

Sheehan syndrome results from ischemic pituitary necrosis following severe postpartum hemorrhage, typically presenting with failure of postpartum lactation and amenorrhea, though acute life-threatening presentations can occur within days of delivery. 1, 2, 3

Acute Presentation (Rare but Life-Threatening)

• Adrenal crisis is the most common acute manifestation, presenting with seizures, altered mental status, or coma at a median of 7.9 days postpartum 2
• Diabetes insipidus may occur at a median of 4 days postpartum 2
• Acute hypothyroidism presents around 18 days postpartum 2
• Panhypopituitarism manifests at approximately 9 days postpartum 2
• Hypoglycemia, hyponatremia, and cardiovascular collapse may occur 2, 4

Chronic Presentation (Most Common)

• Failure of postpartum lactation (agalactorrhea) and failure to resume menses after delivery are the cardinal symptoms 3, 4
• Constitutional symptoms: profound fatigue, anhedonia, cold intolerance, weight changes 5, 6
• Secondary hypothyroidism occurs in 90% of cases 4
• Adrenal insufficiency affects 55% of patients 4
• Universal findings include hypogonadism, prolactin deficiency, and growth hormone deficiency 4
• Diagnosis is often delayed by decades (mean 26.8 years after delivery) 4, 6

Risk Factors and Pathophysiology

Maintain high clinical suspicion in any woman with history of postpartum hemorrhage exceeding 2000 mL, massive transfusion requirement, or peripartum hypotension/shock. 1

• Blood loss typically exceeds 5000 mL in acute cases 2
• The physiologically enlarged pituitary gland during pregnancy is particularly vulnerable to hypoperfusion 3
• Small sella size, disseminated intravascular coagulation, and autoimmunity may contribute to pathogenesis 3

Diagnostic Approach

Clinical History (Essential)

• Document obstetric history focusing on: estimated blood loss volume, transfusion requirements, hypotensive episodes, shock, and duration of hemorrhage 1
• Assess for failure of lactation immediately postpartum 4
• Evaluate menstrual history since delivery 4

Laboratory Evaluation

• Baseline and stimulated anterior pituitary hormone levels are required for all suspected cases 4
• Measure: TSH, free T4, cortisol, ACTH, prolactin, LH, FSH, estradiol, IGF-1, and growth hormone 4
• Inadequate prolactin and gonadotropin responses to stimulation tests are the most sensitive diagnostic markers 4
• Check serum sodium (hyponatremia present in 35% of cases) 4
• Morning cortisol and ACTH stimulation test to assess adrenal axis 4

Imaging

• MRI or CT of the pituitary reveals total or partially empty sella turcica in all cases 3, 4
• Serial MRI changes may document evolution of pituitary necrosis in acute cases 2
• Diabetes insipidus (posterior pituitary dysfunction) is notably absent in most cases 4

Differential Diagnosis

• Lymphocytic hypophysitis should be considered, particularly in peripartum presentations 3

Management

Acute Sheehan Syndrome (Medical Emergency)

Immediate hormone replacement is life-saving and must be initiated based on clinical suspicion without waiting for complete laboratory confirmation. 2

• Hydrocortisone: Administer stress-dose corticosteroids immediately (100 mg IV bolus, then 50-100 mg IV every 6-8 hours) for suspected adrenal crisis 2
• Levothyroxine: Initiate thyroid replacement only AFTER corticosteroid coverage to prevent precipitating adrenal crisis 2
• Treat hypoglycemia with IV dextrose 2
• Correct hyponatremia cautiously (risk of osmotic demyelination) 2
• Intensive monitoring for cardiovascular instability and seizures 2

Chronic Management

Lifelong hormone replacement therapy is required for all confirmed cases to prevent adrenal crisis, improve quality of life, and reduce cardiovascular and osteoporosis risk. 6

Hormone Replacement Regimen

• Glucocorticoid replacement: Hydrocortisone 15-25 mg daily in divided doses (typically 10 mg morning, 5 mg afternoon) 6
• Thyroid replacement: Levothyroxine titrated to normalize free T4 (start ONLY after adequate corticosteroid replacement) 2, 6
• Sex hormone replacement: Estrogen/progesterone therapy in premenopausal women 6
• Growth hormone replacement: Consider for improved quality of life, body composition, and cardiovascular risk reduction 6

Patient Education (Critical)

• Educate on stress-dose corticosteroid adjustment during illness, surgery, or trauma 6
• Provide emergency hydrocortisone injection kit 6
• Medical alert identification should be worn 6

Fertility Considerations

• Ovulation induction is required for subsequent pregnancies 2
• Successful pregnancy outcomes are possible with appropriate hormonal support 2
• Close endocrine and obstetric monitoring throughout pregnancy is essential 2

Clinical Pitfalls to Avoid

• Do not dismiss vague constitutional symptoms (fatigue, cold intolerance) in women with remote history of postpartum hemorrhage—diagnosis may be delayed for decades 6
• Never initiate thyroid replacement before corticosteroid coverage in suspected hypopituitarism—this can precipitate fatal adrenal crisis 2
• Do not assume Sheehan syndrome only occurs in developing countries—recent reports document cases in well-developed healthcare systems 3, 6
• Do not overlook the diagnosis in women without massive hemorrhage—rare cases occur after normal delivery 3
• Recognize that most patients have mild, insidious disease rather than acute presentation 3