Hypopituitarism (Panhypopituitarism, Sheehan Syndrome)

Risk factors

• Pituitary adenoma (especially macroadenoma) and treatment (surgery, radiation)
• Severe postpartum hemorrhage with hypotension (Sheehan syndrome)
• Traumatic brain injury, subarachnoid hemorrhage
• Cranial irradiation (for nasopharyngeal carcinoma, brain tumors, leukemia prophylaxis)
• Lymphocytic hypophysitis (autoimmune; often peripartum, also seen with immune checkpoint inhibitors)
• Infiltrative disease: sarcoidosis, hemochromatosis, Langerhans cell histiocytosis, tuberculosis
• Pituitary apoplexy (hemorrhage or infarction of pre-existing adenoma)

Pathophysiology

Damage to the pituitary gland or hypothalamic-pituitary stalk disrupts trophic hormone secretion. Order of hormone loss in progressive disease (helpful mnemonic 'Go Look For The Adenoma Please'): GH first, then LH/FSH, TSH, ACTH, prolactin (ADH loss occurs only with stalk or posterior pituitary involvement). In Sheehan syndrome, peripartum hyperplasia of lactotrophs increases gland volume and metabolic demand without proportionate increase in arterial supply, predisposing to ischemic necrosis if perfusion drops.

Clinical presentation

Differential diagnosis

• Primary adrenal insufficiency (Addison disease) — Hyperpigmentation, hyperkalemia, hyponatremia, elevated ACTH; cosyntropin stimulation distinguishes primary from secondary
• Primary hypothyroidism — Elevated TSH with low free T4; central hypothyroidism shows inappropriately normal or low TSH with low free T4
• Primary gonadal failure — Elevated LH and FSH with low estradiol or testosterone; central hypogonadism shows low or inappropriately normal gonadotropins
• Anorexia nervosa — Functional hypothalamic hypogonadism, low BMI, and behavioral context; reversible with weight restoration
• Severe chronic illness (nonthyroidal illness, euthyroid sick syndrome) — Low T3, normal or low TSH and free T4, no clinical hypothyroidism; resolves with recovery
• Hemochromatosis — Iron overload affecting pituitary, liver, pancreas, heart; elevated ferritin and transferrin saturation; HFE gene testing
• Empty sella syndrome — Incidental imaging finding of CSF-filled sella; most are asymptomatic with normal function

Diagnostic workup

Diagnostic algorithm

Treatment

Complications

• Adrenal crisis — hypotension, hyponatremia, hypoglycemia, shock; precipitated by illness, surgery, or unrecognized cortisol deficiency
• Myxedema coma if profound untreated central hypothyroidism
• Osteoporosis from chronic hypogonadism and untreated GH deficiency
• Cardiovascular disease (increased mortality even on replacement, partly attributed to nonphysiologic glucocorticoid dosing)
• Infertility, sexual dysfunction
• Hyponatremia from glucocorticoid deficiency and SIADH-like state

PANCE pearls

• Always replace cortisol BEFORE thyroid hormone — starting levothyroxine first accelerates cortisol metabolism and can precipitate adrenal crisis.
• In central hypothyroidism, free T4 (not TSH) is used to monitor and titrate levothyroxine; aim for free T4 in the upper half of the reference range.
• Inability to lactate after delivery is the earliest and most specific feature of Sheehan syndrome — ask every postpartum woman with vague symptoms after hemorrhage about lactation.
• Pituitary apoplexy presents with sudden severe headache, visual disturbance, ophthalmoplegia, and altered mental status — it is an endocrine emergency requiring immediate stress-dose glucocorticoids and urgent neurosurgical evaluation.
• Educate every patient on stress-dosing rules and provide a medical alert bracelet plus a parenteral hydrocortisone emergency kit (Solu-Cortef 100 mg IM).

References

• Endocrine Society 2016 — Hormonal Replacement in Hypopituitarism in Adults: An Endocrine Society Clinical Practice Guideline (Fleseriu et al., J Clin Endocrinol Metab 2016)
• Endocrine Society 2016 — Diagnosis and Treatment of Primary Adrenal Insufficiency: An Endocrine Society Clinical Practice Guideline (Bornstein et al., J Clin Endocrinol Metab 2016)
• AACE/ACE 2019 — American Association of Clinical Endocrinologists and American College of Endocrinology Disease State Clinical Review: Postoperative Management Following Pituitary Surgery (Woodmansee et al., Endocr Pract 2019)
• Pituitary Society 2011 — Pituitary Society Guidelines on the Diagnosis and Management of Pituitary Apoplexy (Rajasekaran et al., Clin Endocrinol 2011)