Snapshot A 27-year-old, 2-week post-partum woman presents to the clinic complaining of weakness, fatigue, and inability to produce milk. Her pregnancy was unremarkable but she suffered significant blood loss during delivery. She reports that the first few days she was producing enough milk for her baby but the supply subsequently decreased. Laboratory testing demonstrates low serum cortisol and plasma ACTH levels. (Sheehan syndrome) Introduction A disorder characterized by decreased secretion of corticotropin (ACTH) by the pituitary gland leading to adrenal insufficiency (e.g., low levels of cortisol). the adrenal glands are intrinsically normal but may be atrophic because of chronic ACTH deficiency Epidemiology Risk factors exogenous steroid use traumatic brain injury chronic opioid use ETIOLOGY Pathogenesis any process that involves the pituitary and interferes with ACTH secretion can result in secondary adrenal insufficiency panhypopituitarism may occur secondary to pituitary tumors (e.g., craniopharyngioma), granulomas, infection, trauma, or infarction (e.g., Sheehan syndrome) isolated ACTH deficiency rare disorder likely caused by an autoimmune process medications patients with chronic steroid use may have insufficient ACTH secretion other medications associated with the condition includes high-dose progestins (e.g., megestrol acetate) and opiates Presentation Symptoms fatigue weakness weight loss muscle/joint pain psychiatric symptoms nausea/vomiting diarrhea Physical exam lack of hyperpigmentation (seen in primary adrenal insufficiency) hypotension auricular-cartilage calcification imaging Computed tomography (CT) of the brain indications best initial test to evaluate damage/abnormalities of the pituitary and/or hypothalamus imaging studies used to determine the cause of secondary adrenal insufficiency Magnetic resonance imaging (MRI) of the brain more sensitive test Studies Serum labs cortisol levels (e.g., morning serum cortisol) best initial test low serum cortisol (e.g., less than 5 ug/dL) strongly suggests adrenal insufficiency plasma ACTH concentration best initial test but often not quickly available low levels of ACTH (e.g., less than 5 pg/mL) with low cortisol suggest secondary or tertiary adrenal insufficiency ACTH stimulation test as the insufficiency is due to low ACTH levels, the stimulation test response will be normal CRH stimulation test differentiates between secondary vs. tertiary adrenal insufficiency absent or subnormal ACTH response indicates secondary adrenal insufficiency (tertiary adrenal insufficiency will demonstrate exaggerated or prolonged response) Diagnostic Laboratory Values for Secondary Adrenal Insufficiency Test Result Cortisol Low (5 ug/dL) ACTH Low (<5 pg/mL) ACTH stimulation test Normal CRH stimulation test Normal Differential Primary adrenal insufficiency distinguishing factor will have hyperpigmentation on physical examination will have high levels of ACTH Tertiary adrenal insufficiency distinguishing factor CRH stimulation test will demonstrate exaggerated or prolonged response DIAGNOSIS Diagnosis is often based on clinical presentation and confirmed via laboratory testing Imaging studies used to determine the cause of secondary adrenal insufficiency Treatment Treatment overview management is focused on treating the underlying cause (if any) and providing glucocorticoid replacement if panhypopituitarism, other pituitary deficiencies (e.g., growth hormone) should be addressed Pharmacologic glucocorticoid replacement therapy hydrocortisone or prednisone fludrocortisone is not indicated as aldosterone function is intact Complications Adrenal crisis medical emergency managed with scheduled IV glucocorticoid