Chemistry, toxicology & urinalysis

Organ specific


Adrenal insufficiency-diagnosis

Topic Completed: 1 July 2009

Minor changes: 11 November 2021

Copyright: 2002-2021,, Inc.

PubMed Search: Adrenal insufficiency [title] chemistry

Renu Virk, M.D.
Page views in 2020: 710
Page views in 2021 to date: 512
Cite this page: Virk R. Adrenal insufficiency-diagnosis. website. Accessed December 3rd, 2021.
Definition / general
  • Clinical condition which occurs when there is more than 90% destruction of the adrenal gland
  • See also Adrenal gland chapter
Clinical features
  • Often insidious in onset, patients may present in shock due to increased stress
  • Malaise, lassitude, fatigue, weakness, anorexia, weight loss, nausea, vomiting, hypotension, hypoglycemia, hyponatremia, hyperkalemia and hyperpigmentation (with primary adrenal insufficiency)
  • Morning serum cortisol level >13 mcg/dL reliably rules out adrenal insufficiency (J Fam Pract 2009;58:281a)
  • Relative adrenal insufficiency: if patient's cortisol response is inadequate for the degree of illness or stress (J Perinatol 2009;29:S44)

Acute adrenal crisis:
  • Infection or major stress may transform chronic adrenal insufficiency into acute crisis
  • Patient usually presents in shock

Primary adrenal insufficiency:

Secondary and tertiary adrenal insufficiency:
  • See also Adrenal gland - Secondary adrenocortical insufficiency topic
  • Due to pituitary (secondary) or hypothalamic (tertiary) disease
  • Characterized by low ACTH levels, low morning serum cortisol, low morning salivary cortisol levels (Horm Metab Res 2009;41:834)
  • Note: androgens and cortisol levels are low because their production is influenced by ACTH, but androgens are less affected in males since they are also produced by testis; hypoglycemia is more common than with primary adrenal insufficiency
  • Serum aldosterone, sodium and potassium and plasma renin activity levels are usually normal, since they are controlled by renin-angiotensin axis, which is not under the control of ACTH
  • Causes (secondary): panhypopituitarism, isolated ACTH deficiency (very rare); traumatic brain injury
  • Causes (tertiary): chronic high dose glucocorticoid therapy, tumor, sarcoidosis, cranial irradiation
  • Low early morning serum cortisol levels (less than 3 mcg/dl)
  • Low basal urinary cortisol and 17-hydroxycorticosteroid levels
  • Salivary cortisol value at 8 am < 1.8ng/ml or an early morning serum cortisol level < 10 mcg/dl is suggestive of adrenal insufficiency
  • Normal levels of morning salivary cortisol exclude adrenal insufficiency
  • ACTH, aldosterone and plasma renin levels vary by cause (primary versus secondary / tertiary)

ACTH stimulation tests:
  • Patients with primary adrenal insufficiency show subnormal rise in cortisol after ACTH stimulation test
  • This test may not detect partial secondary adrenal insufficiency
  • 48-hour ACTH stimulation test reliably separates primary from secondary or tertiary adrenal insufficiency
  • ACTH test is the single best test for confirming the diagnosis of chronic adrenal insufficiency (Lancet 1999;354:179)

CRH stimulation test:
  • Differentiates secondary from tertiary adrenal insufficiency
  • Seldom used due to expense and a requirement for multiple blood samples
  • Secondary: have subnormal results
  • Tertiary: normal response
  • See CRH stimulation test in Adrenal hypercortisolism

Insulin induced hypoglycemia and metyrapone stimulation tests:
  • More helpful if partial secondary / tertiary adrenal insufficiency is suspected
  • Metyrapone test is less expensive
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