What is Sheehan syndrome?

Sheehan Syndrome: Definition and Pathophysiology

Sheehan syndrome is postpartum pituitary necrosis leading to hypopituitarism, caused by severe hemorrhage during delivery that results in ischemic necrosis of the enlarged pituitary gland. 1, 2

Underlying Mechanism

The pathophysiology involves several key factors:

• Pituitary vulnerability during pregnancy: The pituitary gland enlarges significantly during pregnancy (up to 135% of normal size), increasing its metabolic demands while blood supply remains relatively unchanged, making it particularly susceptible to ischemic injury 2

• Precipitating event: Massive postpartum hemorrhage (PPH) causes severe hypotension and hypovolemic shock, leading to impaired blood perfusion to the already vulnerable enlarged pituitary gland 1, 2, 3

• Predisposing anatomical factors: Small sella turcica size, vasospasms triggered by PPH, and/or thrombosis associated with pregnancy or coagulation disorders increase susceptibility to pituitary necrosis 2

• Progressive autoimmune component: Autoimmunity may contribute to the progressive worsening of pituitary function over time following the initial ischemic insult 2

Clinical Presentation Patterns

The syndrome manifests in two distinct temporal patterns:

Chronic Presentation (Most Common)

• Symptoms typically become evident years or even decades after the precipitating delivery, with diagnostic delays of 10-30 years being common 1, 2, 4
• Nonspecific symptoms include chronic fatigue, failure to lactate postpartum, amenorrhea (cessation of menses), cold intolerance, and progressive weakness 2, 5

Acute Presentation (Rare but Life-Threatening)

• Can develop within days after delivery (median 7-9 days for adrenal insufficiency manifestations) 3
• Presents with sudden onset seizures, altered consciousness or coma, severe hypoglycemia, and acute adrenal crisis 6, 3
• Requires immediate recognition and treatment to prevent mortality 3

Hormonal Deficiency Pattern

The pattern of hormone deficiency follows the anatomical distribution of hormone-secreting cells relative to the pituitary vasculature: 2

• Most commonly affected first: Growth hormone (GH) and prolactin deficiency—manifesting as failure to lactate postpartum 2, 5
• Intermediate severity: Follicle-stimulating hormone (FSH) and luteinizing hormone (LH) deficiency—causing amenorrhea and infertility 2
• Severe necrosis required: Thyroid-stimulating hormone (TSH) and adrenocorticotropic hormone (ACTH) deficiency—the latter being potentially life-threatening if unrecognized 2, 3

Epidemiology and Risk Context

• Developing countries: Remains an important cause of hypopituitarism due to inadequate obstetric care and higher rates of uncontrolled PPH 2, 5
• Developed countries: Has become rare due to improved obstetric management, but should still be considered in any woman with hypopituitarism and history of PPH 6, 2, 4
• The condition is frequently overlooked even when present, leading to significant diagnostic delays and preventable morbidity 1, 4

Diagnostic Approach

Diagnosis requires three key elements: 2, 5

• Clinical history: History of severe postpartum hemorrhage requiring transfusion, with failure to lactate and amenorrhea following delivery 2, 5
• Hormonal confirmation: Low or absent levels of pituitary hormones with inadequate response to stimulation tests 2
• Imaging findings: MRI typically shows empty sella turcica or small pituitary gland; acute cases may show serial changes on MRI including initial enlargement followed by involution 4, 3

Critical Clinical Pearls

Clinicians must maintain high suspicion in specific scenarios: 6, 3

• Any woman with history of massive PPH who develops unexplained altered mental status, seizures, or shock in the postpartum period requires immediate evaluation for acute Sheehan syndrome 3
• In placenta accreta spectrum cases with significant blood loss, attention to the "small but real possibility" of Sheehan syndrome is warranted given the clinical scenario and potential for hypoperfusion 6
• The triad of postpartum hemorrhage, failure to lactate, and amenorrhea should immediately trigger evaluation for Sheehan syndrome 5

Management Principles

Treatment consists solely of lifelong hormone replacement therapy: 1, 2, 4

• Immediate glucocorticoid replacement is critical to prevent life-threatening adrenal crisis 2, 3
• Thyroid hormone replacement (thyroxine) for TSH deficiency 4, 3
• Sex hormone replacement for gonadotropin deficiency 4
• Growth hormone replacement may improve quality of life, cardiovascular risk, and bone density 4

Early diagnosis and appropriate treatment significantly reduce morbidity and mortality, improve general energy, physical capacity, temperature regulation, and prevent potentially fatal adrenal crises. 1, 4, 5