What is the diagnosis and treatment for a postpartum woman suspected of having Sheehan syndrome, a condition characterized by hypopituitarism following significant blood loss during delivery?

Sheehan Syndrome: Diagnosis and Management

What is Sheehan Syndrome?

Sheehan syndrome is postpartum pituitary necrosis resulting in hypopituitarism, caused by ischemic injury to the enlarged pituitary gland following severe postpartum hemorrhage with hypotension or hemorrhagic shock. 1, 2

The physiologic enlargement of the pituitary gland during pregnancy (due to lactotroph hyperplasia) makes it particularly vulnerable to ischemic injury when severe hemorrhage and hypotension occur during or after delivery. 1, 3

Clinical Presentation

Acute Presentation (Rare)

• Onset typically 4-9 days postpartum with sudden deterioration including seizures, coma, severe hypoglycemia, and cardiovascular collapse 3
• Acute adrenal insufficiency is the most common acute presentation (12 of 21 reported cases), manifesting around day 7-8 postpartum 3
• Diabetes insipidus can occur acutely (median 4 days postpartum) 3
• This is a life-threatening emergency requiring immediate recognition and treatment 3

Chronic Presentation (More Common)

• Diagnosis is typically delayed by years or even decades due to nonspecific symptoms 1, 4, 5
• The classic triad to identify in history: failure to lactate postpartum, failure to resume menses, and history of severe postpartum hemorrhage 2, 5
• Progressive symptoms include: persistent fatigue, cold intolerance, loss of axillary and pubic hair, amenorrhea, decreased libido, and features of hypothyroidism and adrenal insufficiency 2, 4, 5
• The order of hormone deficiency is typically: growth hormone and prolactin first, then gonadotropins, followed by ACTH, and finally TSH 2

Diagnostic Approach

Key Historical Features to Elicit

• Detailed obstetric history focusing on postpartum hemorrhage severity, estimated blood loss (typically >2000-5000 mL), need for transfusion, hypotension, or shock 6, 3
• Inability to breastfeed immediately postpartum (agalactia) 2, 5
• Failure to resume menstruation after delivery 2, 5
• Timeline of symptom onset relative to the hemorrhagic delivery 1, 3

Laboratory Evaluation

• Measure baseline pituitary hormones: TSH, free T4, cortisol (8 AM), ACTH, prolactin, LH, FSH, estradiol, and IGF-1 2
• Perform dynamic testing with ACTH stimulation test and potentially insulin tolerance test or glucagon stimulation test to assess pituitary reserve 2
• Expected findings: low or inappropriately normal TSH with low free T4, low cortisol with low ACTH, low prolactin (key finding), low gonadotropins with low estradiol, and low IGF-1 2, 4

Imaging

• MRI of the pituitary typically shows empty sella turcica or partially empty sella in chronic cases 4
• In acute cases, serial MRI may show evolving changes from enlarged pituitary with hemorrhage to eventual atrophy 3

Treatment

Acute Management (If Presenting Acutely)

• Immediate administration of intravenous hydrocortisone (100 mg IV bolus, then 50-100 mg every 6-8 hours) is life-saving and must be given before thyroid hormone replacement 3
• Treat hypoglycemia with IV dextrose 3
• Monitor and treat electrolyte abnormalities 3
• Add levothyroxine only after glucocorticoid coverage is established 3

Chronic Hormone Replacement Therapy

• Glucocorticoid replacement is the most critical: hydrocortisone 15-25 mg daily in divided doses (typically 10 mg morning, 5 mg afternoon) 2, 4
• Levothyroxine replacement for secondary hypothyroidism: start at 50-75 mcg daily, titrate based on free T4 levels (not TSH) 2, 4
• Estrogen-progesterone replacement in premenopausal women for bone health, cardiovascular protection, and quality of life 4
• Growth hormone replacement may be considered in younger patients with documented deficiency 2

Critical Management Principles

• Always replace glucocorticoids before thyroid hormone, as thyroid hormone can precipitate adrenal crisis in untreated adrenal insufficiency 2
• Educate patients about stress-dose steroids during illness, surgery, or trauma (double or triple maintenance dose) 2
• Patients must wear medical alert identification and carry emergency hydrocortisone 2
• Regular monitoring of hormone levels and clinical response is essential 4

Prevention and Awareness

The American College of Obstetricians and Gynecologists guidelines emphasize vigilance for Sheehan syndrome in patients with severe postpartum hemorrhage, particularly when blood loss exceeds 2000 mL or requires massive transfusion. 6

While rare in developed countries due to improved obstetric care, clinicians should maintain a high index of suspicion in any woman with a history of postpartum hemorrhage who presents with unexplained fatigue, amenorrhea, or inability to lactate. 1, 5

Common Pitfalls to Avoid

• Do not dismiss vague symptoms of fatigue and cold intolerance in women with remote history of postpartum hemorrhage—always inquire about lactation failure and menstrual resumption 5
• Never start thyroid hormone replacement before ensuring adequate glucocorticoid coverage, as this can precipitate life-threatening adrenal crisis 2
• Do not rely on TSH levels to guide thyroid replacement in secondary hypothyroidism—use free T4 levels instead 2
• In acute postpartum deterioration following hemorrhage, consider Sheehan syndrome even if the hemorrhage occurred days earlier (median 7-9 days for acute presentation) 3