What is the appropriate work‑up for a postpartum woman with severe hemorrhage, failure to lactate, amenorrhea, and signs of hypothyroidism or adrenal insufficiency suggestive of Sheehan syndrome?

Sheehan Syndrome Work-Up

In a postpartum woman with severe hemorrhage, failure to lactate, amenorrhea, and signs of hypothyroidism or adrenal insufficiency, immediately obtain baseline pituitary hormone levels (prolactin, TSH, free T4, cortisol, ACTH, LH, FSH, IGF-1), perform dynamic pituitary function testing, and obtain brain MRI with dedicated pituitary imaging to confirm the diagnosis of Sheehan syndrome. 1

Clinical Recognition and Index of Suspicion

Maintain a high index of suspicion for Sheehan syndrome in any woman with a history of postpartum hemorrhage who presents with unexplained fatigue, amenorrhea, or inability to lactate. 1 The American College of Obstetricians and Gynecologists emphasizes particular vigilance when:

• Blood loss exceeded 2000 mL 1
• Massive transfusion was required 1
• Hypotension or shock occurred during or after delivery 1

The syndrome can present acutely (within days to weeks) or evolve slowly over months to years, making early recognition challenging. 2, 3

Essential Historical Elements

Obtain a detailed obstetric history focusing on:

• Severity of postpartum hemorrhage: Quantify estimated blood loss, number of transfusions, presence of hypotension or shock 1, 2
• Lactation failure: Complete inability to lactate or cessation of lactation shortly after delivery is a cardinal clue 3, 4
• Menstrual history: Failure to resume menses after delivery (amenorrhea) is highly suggestive 3, 4
• Timing of symptom onset: Acute presentations may occur 4-18 days postpartum with adrenal crisis, diabetes insipidus, or severe hypothyroidism 2

Physical Examination Findings

Look for specific signs of pituitary hormone deficiency:

• Loss of axillary and pubic hair (gonadotropin deficiency) 4
• Dry skin, periorbital edema, bradycardia (hypothyroidism) 5, 4
• Hypotension, weakness, hyperpigmentation absence (adrenal insufficiency) 2, 4
• Breast atrophy, absence of lactation (prolactin deficiency) 3, 6
• Visual field defects (rare, but warrant immediate neurological evaluation) 5

Laboratory Work-Up

Initial Hormone Panel

Obtain baseline measurements of all anterior pituitary hormones:

• Prolactin: Most commonly deficient; low or absent levels are highly suggestive 3, 6
• TSH and free T4: Central hypothyroidism shows low/normal TSH with low free T4 2, 4
• Morning cortisol and ACTH: Low cortisol with low/normal ACTH indicates secondary adrenal insufficiency 2, 4
• LH, FSH, and estradiol: Low gonadotropins with low estradiol confirm hypogonadotropic hypogonadism 6, 4
• IGF-1: Low levels suggest growth hormone deficiency 6, 4

Dynamic Pituitary Function Testing

The prolactin response to TRH (thyrotropin-releasing hormone) is the most sensitive screening test in patients with typical obstetric history. 6 Additional dynamic tests include:

• ACTH stimulation test: To assess adrenal reserve and confirm secondary adrenal insufficiency 4
• Insulin tolerance test or glucagon stimulation test: Gold standard for growth hormone deficiency (contraindicated in suspected adrenal crisis) 6
• GnRH stimulation test: May help confirm gonadotropin deficiency 4

Additional Laboratory Studies

• Complete blood count: Anemia and pancytopenia may be present 6
• Electrolytes: Hyponatremia suggests adrenal insufficiency or hypothyroidism 2
• Glucose: Hypoglycemia can occur with adrenal or growth hormone deficiency 2
• Bone density scan: Osteoporosis is common in chronic cases 6

Imaging Studies

Brain MRI with Pituitary Protocol

Brain MRI with dedicated pituitary imaging is essential to confirm the diagnosis and should be obtained promptly when Sheehan syndrome is suspected. 5 Characteristic findings include:

• Empty sella or partially empty sella (chronic phase) 5, 6
• Absence of posterior pituitary bright spot 6
• Pituitary gland atrophy or necrosis 2, 5
• Serial MRI changes: Acute phase may show enlarged pituitary with hemorrhage, evolving to atrophy over weeks to months 2

Acute Presentation Recognition

Acute Sheehan syndrome can be life-threatening and may present within the first 2-18 days postpartum. 2 Emergency presentations include:

• Adrenal crisis: Hypotension, shock, hyponatremia, hypoglycemia (median onset 7.9 days postpartum) 2
• Diabetes insipidus: Polyuria, polydipsia, hypernatremia (median onset 4 days postpartum) 2
• Severe hypothyroidism: Profound headache, seizures, coma (median onset 18 days postpartum) 2, 5
• Panhypopituitarism: Combined deficiencies presenting with multisystem failure (median onset 9 days postpartum) 2

Common Pitfalls to Avoid

• Do not dismiss vague symptoms such as fatigue, weakness, or mood changes in women with a history of postpartum hemorrhage; these may be the only early manifestations 5, 3
• Do not assume normal lactation excludes the diagnosis: Partial pituitary insufficiency can occur with preserved prolactin 6
• Do not delay imaging: Profound headache or visual disturbances warrant immediate brain MRI to rule out acute pituitary apoplexy or other neurological emergencies 5
• Do not overlook Sheehan syndrome in women without recognized severe hemorrhage: Rare cases can occur without obvious inciting factors 5
• Do not perform insulin tolerance testing in suspected adrenal crisis: This can be fatal; confirm and treat adrenal insufficiency first 4

Algorithmic Approach to Diagnosis

1. Identify high-risk patients: History of postpartum hemorrhage >2000 mL, massive transfusion, or hypotension 1
2. Screen for cardinal symptoms: Failure to lactate, amenorrhea, unexplained fatigue 3, 4
3. Obtain baseline hormone panel: Prolactin, TSH, free T4, cortisol, ACTH, LH, FSH, IGF-1 6, 4
4. Perform TRH stimulation test: Most sensitive screening test for Sheehan syndrome 6
5. Order brain MRI with pituitary protocol: Confirm diagnosis and assess extent of pituitary damage 5
6. Complete dynamic testing: ACTH stimulation, growth hormone stimulation as clinically indicated 6, 4
7. Assess for complications: Check for anemia, pancytopenia, osteoporosis, cognitive impairment 6

Monitoring After Severe Postpartum Hemorrhage

Monitor for complications including Sheehan syndrome in all women who experienced blood loss exceeding 1500 mL or required massive transfusion. 7, 8 Prolonged hypoperfusion may lead to pituitary necrosis manifesting weeks to months after delivery. 7