What is the management of Sheehan syndrome?

Management of Sheehan Syndrome

Sheehan syndrome requires lifelong hormone replacement therapy targeting all deficient pituitary axes, with the priority being immediate glucocorticoid replacement to prevent life-threatening adrenal crisis, followed by thyroid hormone replacement, and then sex hormone and growth hormone replacement as indicated. 1

Immediate Recognition and Acute Management

Clinical Presentation Requiring Urgent Intervention

• Adrenal crisis is the most life-threatening complication and can be precipitated by acute stressors such as infections (including dengue fever), surgery, or trauma 2
• Patients may present acutely with hypotension, hypoglycemia, hyperthermia, and severe dehydration requiring immediate glucocorticoid replacement 2
• Some patients present with profound headache and/or visual disturbances in the immediate postpartum period, warranting neurological evaluation and early brain MRI with pituitary imaging 3

Diagnostic Confirmation

• Diagnosis is based on clinical manifestations combined with a history of severe postpartum hemorrhage 1
• Brain MRI typically reveals an empty sella turcica 2, 3
• Hormone levels and/or stimulation tests confirm clinical suspicion, with anterior pituitary hormone levels significantly decreased 1, 2
• The secretion of growth hormone and prolactin is most commonly affected, followed by FSH and LH; severe necrosis also affects TSH and ACTH secretion 1

Hormone Replacement Therapy Algorithm

First Priority: Glucocorticoid Replacement

• Hydrocortisone must be initiated before thyroid hormone replacement to prevent precipitating adrenal crisis 2
• In acute adrenal crisis, manage conservatively with intravenous hydrocortisone and supportive care 2
• Maintenance hydrocortisone therapy is required lifelong 2, 3

Second Priority: Thyroid Hormone Replacement

• Levothyroxine should be initiated only after adequate glucocorticoid coverage is established 2, 3
• Thyroid profile analysis typically shows secondary hypothyroidism with low TSH and low free T4 2

Third Priority: Sex Hormone Replacement

• Estrogen replacement therapy is indicated for women with secondary hypogonadism 3
• This addresses symptoms of amenorrhea, vaginal dryness, and prevents long-term complications of estrogen deficiency 3

Fourth Priority: Growth Hormone Replacement

• GH replacement therapy should be considered after stabilization of other hormone axes 4, 5
• Starting dose: 0.15 mg per day in month 1, increased to 0.30 mg per day in month 2, with maintenance at 0.66 mg per day adjusted to achieve age-appropriate IGF-I levels 4
• Patients with Sheehan syndrome have more severe GHD compared to other causes of hypopituitarism 5

Expected Benefits of Treatment

Growth Hormone Replacement Outcomes

• After 18 months of GH replacement therapy: significant improvements in lipid profile (decreased total cholesterol and LDL-cholesterol, increased HDL-cholesterol), decreased waist circumference and waist-to-hip ratio 4
• After 1-2 years: increased lean body mass, improved quality of life scores, and favorable changes in body composition 4, 5
• Quality of life is significantly reduced at baseline in Sheehan syndrome patients compared to other causes of hypopituitarism, but improves significantly with GH replacement 5
• Note: Bone mineral density may not improve significantly after 18 months of GH replacement therapy 4

Overall Hormone Replacement Benefits

• Symptoms including agalactia, dry skin, mood changes, and amenorrhea improve and ultimately resolve with appropriate multi-hormone replacement 3
• The duration of untreated GHD correlates with severity of metabolic abnormalities, particularly waist circumference 4

Long-Term Monitoring

Follow-up Requirements

• Lifelong hormone replacement therapy is the only available management option 1
• Regular monitoring of hormone levels to adjust replacement doses appropriately 1
• IGF-I levels should be monitored to maintain age-adjusted normal ranges during GH replacement 4
• Periodic assessment of lipid profile, body composition, and quality of life measures 4, 5

Critical Pitfalls to Avoid

• Never initiate thyroid hormone replacement before glucocorticoid replacement, as this can precipitate fatal adrenal crisis 2
• Maintain high index of suspicion in any woman with history of severe postpartum hemorrhage presenting with symptoms of endocrine dysfunction, even years after delivery 1, 2
• Recognize that symptoms usually become evident years after delivery but can develop acutely in rare cases 1, 3
• Be aware that Sheehan syndrome can present without recognized inciting factors such as documented postpartum hemorrhage 3
• The majority of patients (78%) have panhypopituitarism requiring replacement of multiple hormone axes 4