What are the causes and management of Sheehan's syndrome in postpartum women?

Sheehan's Syndrome: Causes and Management

Etiology and Pathophysiology

Sheehan's syndrome results from ischemic necrosis of the pituitary gland following severe postpartum hemorrhage (PPH), with the physiologically enlarged pituitary during pregnancy becoming vulnerable to hypoperfusion when massive bleeding occurs. 1

Primary Cause

• Massive postpartum hemorrhage is the initiating event, causing impaired blood supply to the already enlarged pituitary gland 1
• The syndrome can develop after hemorrhage of approximately 5000 mL or more, though smaller volumes may suffice in predisposed individuals 2

Contributing Factors

• Small sella turcica size increases susceptibility by limiting space for the enlarged pituitary 1
• Vasospasm triggered by PPH compounds the ischemic insult 1
• Thrombosis associated with pregnancy or underlying coagulation disorders 1
• Autoimmunity may contribute to progressive worsening of pituitary function over time 1, 3
• Disseminated intravascular coagulation (DIC) can occur in severe hemorrhage cases (>80% when blood loss is massive) 3

Clinical Presentation

Timing of Presentation

• Chronic presentation (most common): Symptoms develop years after delivery, often going undiagnosed for decades 1, 4
• Acute presentation (rare but life-threatening): Symptoms appear within days to weeks postpartum, with median onset at 7-9 days for panhypopituitarism 2

Pattern of Hormone Deficiency

The location of hormone-secreting cells relative to pituitary vasculature determines the sequence of hormone loss 1:

1. Growth hormone (GH) - affected earliest and most commonly 1, 3
2. Prolactin - failure of postpartum lactation is the most common presenting symptom 1, 3
3. FSH/LH - failure to resume menses after delivery 3
4. TSH - hypothyroidism develops with more severe necrosis 1
5. ACTH - adrenal insufficiency occurs only with extensive pituitary damage 1

Clinical Manifestations by System

Acute Presentation (Life-Threatening):

• Adrenal crisis with hypotension and shock (12 cases in literature review, median 7.9 days postpartum) 2
• Seizures and altered consciousness progressing to coma 2
• Severe hypoglycemia 2
• Diabetes insipidus (4 cases, median 4 days postpartum) 2
• Ventricular arrhythmias (torsade de pointes) with prolonged QT interval 5
• Acute congestive heart failure with hemodynamic instability 5

Chronic Presentation:

• Failure to lactate postpartum (most common) 1, 3
• Amenorrhea or failure to resume menses 3
• Nonspecific symptoms: profound fatigue, cold intolerance, weakness 1, 4
• Skin changes: loss of axillary and pubic hair, dry skin 4
• Sexual dysfunction and loss of libido 4
• Cardiovascular complications and increased osteoporosis risk 4

Diagnostic Approach

Clinical Suspicion

Any woman with a history of severe postpartum hemorrhage who presents with failure to lactate, amenorrhea, or symptoms of hypopituitarism should be evaluated for Sheehan's syndrome, regardless of time elapsed since delivery. 1, 4

Laboratory Evaluation

• Baseline hormone levels: Measure TSH, free T4, cortisol (8 AM), prolactin, FSH, LH, estradiol, IGF-1 1
• Stimulation tests to confirm suspected deficiencies (ACTH stimulation test, insulin tolerance test if safe) 1
• Look for: Low cortisol, hypothyroidism, hypoprolactinemia, hypogonadotropic hypogonadism 5, 2
• In acute cases, check glucose (hypoglycemia common), electrolytes, and ECG (prolonged QT) 5, 2

Imaging

• MRI of pituitary is diagnostic, showing empty sella turcica with diminished and flattened pituitary gland and prominent intrasellar CSF 5, 1, 3
• Serial MRI changes may be documented in acute cases 2
• The majority of patients demonstrate empty sella on CT or MRI 3

Differential Diagnosis

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

Management

Acute Sheehan's Syndrome (Medical Emergency)

Immediate hormone replacement is essential and always results in dramatic clinical improvement when acute Sheehan's syndrome is diagnosed. 5

1. Corticosteroid replacement (FIRST):

   • Administer hydrocortisone immediately for suspected adrenal crisis 5, 2
   • Do NOT wait for laboratory confirmation if clinical suspicion is high 2
   • Stress-dose steroids if patient is critically ill 2

2. Thyroid hormone replacement:

   • Start levothyroxine ONLY AFTER corticosteroid replacement to avoid precipitating adrenal crisis 5, 2
   • Thyroxine administration improved respiratory distress and heart failure in documented cases 5

3. Supportive care:

   • Treat hypoglycemia aggressively 2
   • Monitor and correct electrolyte abnormalities 2
   • Cardiac monitoring for arrhythmias (QT prolongation) 5
   • Manage congestive heart failure if present 5

Chronic Sheehan's Syndrome

Lifelong hormone replacement therapy is the only available management option and must address all deficient axes. 1

1. Glucocorticoid replacement:

   • Hydrocortisone 15-25 mg daily in divided doses (typically 10 mg morning, 5 mg afternoon) 1
   • Essential to prevent life-threatening adrenal crisis 4
   • Increase doses during illness or stress 1

2. Thyroid hormone replacement:

   • Levothyroxine at appropriate doses based on free T4 levels 1, 4
   • Start AFTER adequate glucocorticoid replacement 1

3. Sex hormone replacement:

   • Estrogen/progesterone replacement in premenopausal women 1
   • Improves sexual function, bone density, and cardiovascular risk 4

4. Growth hormone replacement:

   • Consider in appropriate candidates for improved quality of life, body composition, and cardiovascular risk 1

5. Fertility management:

   • Ovulation induction is required for subsequent pregnancies 2
   • Successful pregnancies have been documented after acute Sheehan's syndrome with appropriate management 2

Monitoring and Follow-up

• Regular assessment of hormone levels to optimize replacement doses 1
• Monitor for cardiovascular complications and osteoporosis 4
• Patient education on stress-dose steroids and medical alert identification 1
• Long-term endocrinology follow-up is mandatory 4

Critical Pitfalls to Avoid

• Never start thyroid hormone before glucocorticoid replacement - this can precipitate fatal adrenal crisis 5, 2
• Do not dismiss vague symptoms (fatigue, cold intolerance) in women with history of PPH - diagnosis is often delayed for decades 4
• Acute Sheehan's syndrome can present up to 18 days postpartum; maintain vigilance beyond the immediate postpartum period 2
• The condition remains an important cause of hypopituitarism even in developed countries and should not be overlooked 4
• Failure to diagnose prevents life-saving treatment and leaves patients at risk for adrenal crisis 4