Updated: 12/16/2021

Secondary Adrenal Insufficiency

Review Topic
  • 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
    • 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 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

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