Sheehan syndrome is a state of postpartum hypopituitarism resulting from infarction of the pituitary secondary to postpartum hemorrhage or shock. The enlarged pituitary gland in pregnancy is more susceptible to ischemia following hemorrhage and severe hypotension, causing partial or complete loss of the anterior pituitary hormones (adrenocorticotropic hormone [ACTH], follicle-stimulating hormone [FSH], luteinizing hormone [LH], growth hormone [GH], prolactin [PRL], thyroid-stimulating hormone [TSH]) and their target organ functions.¹

• Failure to lactate or difficulty with lactation
• Failure to resume menses after delivery
• Failure of axillary or pubic hair growth
• Diminished libido
• Infertility
• Skin depigmentation (including areola)
• Breast atrophy
• Vaginal atrophy causing pain with intercourse
• Superinvolution of the uterus
• Hypothyroidism (cold intolerance, dry skin, fatigue, weight gain, constipation)
• ACTH insufficiency (fatigue, chronic hypotension)
• Diabetes insipidus (rare)

• Compromise of the blood supply to the low-pressure pituitary sinusoidal system may occur with postpartum hemorrhage or shock, enlarged pituitary, and/or small sella size, resulting in pituitary infarct and/or necrosis.
• The extent of damage to pituitary determines the severity of resulting hormonal dysfunction.
• Antibodies against hypothalamic and/or pituitary cells have been reported, suggesting an autoimmune cause.
• Severity of postpartum hemorrhage does not always correlate with the presence of Sheehan syndrome. Although rare, Sheehan syndrome has also been reported with normal postpartum bleeding.

• Postpartum autoimmune hypophysitis
• Chronic infections
• HIV
• Sarcoidosis
• Amyloidosis
• Rheumatoid disease
• Hemochromatosis
• Metastatic carcinoma
• Lymphocytic hypophysitis
• Pituitary tumor

• Target gland deficiency should be investigated by measuring levels of ACTH, FSH, LH, TSH (which may be normal or low), and T₄. Cortisol and estradiol (which may be low) should also be measured.
• Provocative testing of pituitary hormone reserves (e.g., metyrapone test, insulin tolerance test, and cosyntropin test): Normal, subnormal, or delayed responses may suggest the presence of islands of pituitary cells that no longer have the support of the hypothalamic-portal circulation.
• Measurement of insulin-like growth factor-1 to screen for GH deficiency: Subnormal levels suggest decreased GH.
• Impaired prolactin response to TRH or dopamine antagonist stimulation is frequently found.
• During pregnancy, adjustments must be made in interpreting both hormone levels and responses to various stimuli because of normal physiologic changes.

• MRI of the pituitary:
  1. Early findings: Enlarged enhancing pituitary
  2. Late findings: Empty sella
  3. Rules out mass lesion
• Computed tomography scan of the pituitary when MRI is unavailable or contraindicated

• Early identification and treatment are essential. Clinicians should have a high index of suspicion with any woman experiencing related symptoms following postpartum hemorrhage and/or shock.
• Acute form can be lethal, presenting with hypotension, tachycardia, failure to lactate, and hypoglycemia.
• Intravenous (IV) corticosteroids and fluid replacement should be given initially.
• Diagnosis is confirmed with a full endocrinologic workup.
• Treatment involves replacement of deficient pituitary hormones such as corticosteroids, levothyroxine, estrogen, and growth hormone.
• Most frequently observed deficiencies are growth hormone and prolactin.

• With late-onset disease (symptoms of general hypopituitarism, such as oligomenorrhea or amenorrhea, vaginal atrophic changes, and loss of libido): A full endocrinologic workup and replacement of the appropriate hormones are needed.
• With symptoms of adrenal insufficiency: Corticosteroids should be given.
  1. A maintenance dose of cortisone acetate or prednisone may be given.
  2. Adrenal production of cortisol is not entirely dependent on ACTH; thus, replacement of mineralocorticoids is rarely necessary.
  3. Stress doses of glucocorticoids should be administered during surgery or during labor and delivery.

• Patients who receive early diagnosis and adequate hormonal replacement may expect favorable outcomes, including subsequent pregnancy.
• Central adrenal insufficiency is the primary cause of mortality in Sheehan syndrome.

Patients should have yearly examinations by an endocrinologist.

Hypopituitarism (Related Key Topic)