What is the diagnosis and treatment for a postpartum female with a history of ectopic pregnancy and recent postpartum hemorrhage, presenting with hypothyroidism (low Thyroid-Stimulating Hormone (TSH), low thyroxine (T4), and low triiodothyronine (T3) levels) while on levothyroxine, suspected to have Sheehan syndrome?

Sheehan Syndrome: Diagnosis and Treatment

Immediate Diagnostic Confirmation

In a postpartum woman with recent hemorrhage presenting with hypothyroidism (low TSH, low T4, low T3) while on levothyroxine, Sheehan syndrome is the diagnosis until proven otherwise, and you must immediately assess cortisol levels before adjusting thyroid hormone to prevent life-threatening adrenal crisis. 1, 2

Critical Diagnostic Features

• Central hypothyroidism pattern: Low TSH with low free T4 and T3 distinguishes Sheehan syndrome from primary hypothyroidism, where TSH would be elevated 3
• History of postpartum hemorrhage: The enlarged pituitary gland during pregnancy undergoes ischemic necrosis when severe bleeding causes hypoperfusion 1, 4
• Timing of presentation: Acute Sheehan syndrome typically presents 7-9 days postpartum with adrenal insufficiency, though hypothyroidism may manifest later (median 18 days) 1
• Multiple pituitary hormone deficiencies: Expect panhypopituitarism with deficiencies in cortisol, thyroid hormone, prolactin (failure to lactate), and gonadotropins 1, 2

Distinguish from Postpartum Thyroiditis

• Postpartum thyroiditis shows elevated or normal TSH with low T4 during the hypothyroid phase, not the suppressed TSH seen here 3
• The triphasic pattern of postpartum thyroiditis (thyrotoxic→hypothyroid→euthyroid) can briefly mimic central hypothyroidism during transition, but obstetric hemorrhage history and failure to lactate point to Sheehan syndrome 3
• Goiter presence suggests postpartum thyroiditis rather than Sheehan syndrome 3

Life-Saving Treatment Protocol

Step 1: Assess and Replace Cortisol FIRST

Never start or increase levothyroxine before ruling out adrenal insufficiency—this precipitates adrenal crisis and can be fatal. 5, 6, 2

• Measure 9 AM cortisol immediately: Levels <500 nmol/L indicate adrenal insufficiency 6
• Start hydrocortisone 15-25 mg daily (divided doses: 10 mg morning, 5 mg afternoon, 5 mg evening) before any thyroid hormone adjustment 5, 2
• Wait at least 1 week after initiating corticosteroids before starting thyroid replacement 5, 6
• Clinical improvement is often dramatic within days of corticosteroid initiation 2

Step 2: Initiate Thyroid Hormone Replacement

• Start levothyroxine 25-50 mcg daily after cortisol replacement is established 6
• Titrate slowly by 12.5-25 mcg increments every 6-8 weeks based on free T4 levels (not TSH, which remains unreliable in central hypothyroidism) 6, 3
• Target free T4 in upper half of normal range to ensure adequate replacement 7
• Monitor free T4 and clinical symptoms, as TSH cannot guide therapy in pituitary disease 6, 3

Step 3: Address Other Hormone Deficiencies

• Prolactin deficiency: Failure to lactate is a hallmark sign; no specific replacement needed 1, 4
• Gonadotropin deficiency: Spontaneous pregnancy is rare but possible; may require ovulation induction for future fertility 1, 8
• Growth hormone: Consider evaluation if persistent fatigue despite adequate cortisol/thyroid replacement 4

Diagnostic Imaging

• MRI pituitary 3-4 weeks postpartum: Shows diminished, flattened pituitary gland with prominent intrasellar CSF ("empty sella") 1, 2
• Serial MRI changes document evolution from acute hemorrhagic necrosis to chronic empty sella 1

Critical Pitfalls to Avoid

• Never increase levothyroxine without checking cortisol first in any postpartum woman with hemorrhage history—thyroid hormone accelerates cortisol metabolism and unmasks adrenal crisis 5, 6, 2
• Do not rely on TSH for monitoring: Use free T4 levels and clinical response, as TSH remains inappropriately low in central hypothyroidism 6, 3
• Recognize acute presentation: Seizures, coma, hypoglycemia, and cardiovascular collapse can occur within days of delivery, requiring emergency hormone replacement 1, 2
• Cardiac complications: Ventricular arrhythmias, prolonged QT interval, and congestive heart failure may develop from untreated hypopituitarism 2
• Diagnostic delay increases mortality: Nonspecific symptoms lead to average diagnostic delays of years, but acute cases require immediate recognition 4

Long-Term Management

• Lifelong hormone replacement: Hydrocortisone and levothyroxine are required indefinitely 4, 2
• Stress dosing: Double or triple hydrocortisone during illness, surgery, or stress 6
• Annual monitoring: Free T4, cortisol, electrolytes, and clinical assessment 6
• Future pregnancy: Possible with ovulation induction; requires close endocrine monitoring and increased hormone doses during pregnancy 7, 8
• Patient education: Wear medical alert identification; understand sick-day rules for corticosteroid dosing 6

Prognosis with Treatment

• Dramatic clinical improvement occurs within days to weeks of appropriate hormone replacement 2
• Untreated mortality is high due to adrenal crisis, cardiovascular collapse, or hypoglycemic coma 1, 4
• With treatment, normal life expectancy and potential for future pregnancy 8