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Emergency: requires immediate attention
Secondary adrenal insufficiency
Other Resources UpToDate PubMed
Emergency: requires immediate attention

Secondary adrenal insufficiency

Contributors: Shea A. Nagle MPH, Benjamin L. Mazer MD, MBA, Michael W. Winter MD
Other Resources UpToDate PubMed


Secondary adrenal insufficiency is characterized by a deficiency in adrenal cortical hormones due to dysfunction of the hypothalamus or pituitary gland rather than dysfunction of the adrenal gland itself. Corticotropin-releasing hormone (CRH) from the hypothalamus stimulates the release of adrenocorticotropic hormone (ACTH) from the anterior pituitary gland. ACTH stimulates the production of glucocorticoids in the adrenal cortex. In secondary adrenal insufficiency, there is a deficiency of ACTH that disrupts the hypothalamic-pituitary-adrenal axis and causes a decrease in corticosteroid production.

Tumors of the pituitary or surrounding structures are the most common cause of secondary adrenal insufficiency. This includes adenomas, cysts, craniopharyngiomas, and other tumors. Traumatic brain injuries, especially those that result in trauma to the pituitary stalk, should also be considered.

Secondary adrenal insufficiency can cause hypotension, hypoglycemia, fatigue, and weight loss. Due to pituitary or hypothalamic dysfunction, other endocrine systems may also manifest deficiency. Visual impairment can occur if a tumor compresses the nearby optic chiasm.

Adrenal crisis is a potentially life-threatening complication. It is characterized by severe hypotension, vomiting, dehydration, abnormal electrolytes, and hypoglycemia. This requires immediate evaluation and treatment with intravenous (IV) fluid boluses and hormone replacement.


E27.40 – Unspecified adrenocortical insufficiency

16685009 – Hypocortisolism secondary to another disorder

Look For

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Diagnostic Pearls

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Differential Diagnosis & Pitfalls

  • Adrenal crisis – hypotension, mental status changes, vomiting, hypoglycemia, hyponatremia, hyperkalemia, hypercalcemia
  • Addison disease – autoimmune disorder, associated with elevated ACTH
  • Sarcoidosis – caused by granuloma in adrenal glands
  • Tuberculosis – most common cause of primary adrenal insufficiency worldwide
  • Opportunistic infections – disseminated fungal infections can cause primary adrenal insufficiency, especially in the setting of human immunodeficiency virus (HIV) infection
  • Waterhouse-Friderichsen syndrome – associated with bacterial infection, especially Neisseria meningitidis
  • Adrenal hemorrhage
  • Postpartum hypopituitarism (Sheehan syndrome) – hypopituitarism following severe postpartum hemorrhage
  • Malignancy (particularly metastasis to adrenal glands, primary adrenal tumors)
  • Shock (septic, hypovolemic, cardiogenic, etc)
  • Congenital adrenal hyperplasia – often associated with salt wasting and virilization
  • Trauma – especially traumatic brain injury
  • Genetic conditions – mutations in genes related to pituitary development (includes: HESX homeobox 1, orthodentical homeobox 2, LIM homeobox 4, SRY, congenital proopiomelanocortin deficiency, Prader-Willi syndrome)
  • Adrenoleukodystrophy – X-linked peroxisomal disease
  • Hemochromatosis
  • Amyloidosis (AA amyloidosis, AL amyloidosis)
  • Iatrogenic – medications include chlorpromazine, imipramine, etomidate, ketoconazole, fluconazole, suramin, phenytoin, barbiturates, mifepristone, rifampin, and opiates
  • Chronic corticosteroid use – common cause of tertiary adrenal insufficiency, suppresses hypothalamic-pituitary-adrenal axis
  • Hypoglycemia – exogenous insulin or oral antihyperglycemic drugs, malnourishment, or alcohol intoxication

Best Tests

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Management Pearls

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Drug Reaction Data

Below is a list of drugs with literature evidence indicating an adverse association with this diagnosis. The list is continually updated through ongoing research and new medication approvals. Click on Citations to sort by number of citations or click on Medication to sort the medications alphabetically.

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Last Reviewed:04/07/2019
Last Updated:05/16/2019
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Emergency: requires immediate attention
Secondary adrenal insufficiency
A medical illustration showing key findings of Secondary adrenal insufficiency : Abdominal pain, Fatigue, Hypotension, Nausea/vomiting, Hypoglycemia, Orthostatic hypotension, Asthenia
Copyright © 2023 VisualDx®. All rights reserved.