Adrenal gland & paraganglia

Adrenal insufficiency

Primary adrenal insufficiency

Topic Completed: 1 February 2005

Minor changes: 3 May 2021

Copyright: 2002-2021,, Inc.

PubMed Search: Primary acute adrenal insufficiency

Nat Pernick, M.D.
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Cite this page: Pernick N. Primary adrenal insufficiency. website. Accessed December 3rd, 2021.
Definition / general
Primary adrenal insufficiency:
  • Often insidious in onset, patients may present in shock due to increased stress
  • Patients usually live normal lives after diagnosis (depending on cause); may be at higher risk for heart failure, hypertension or osteopenia
  • Patients with chronic adrenal insufficiency (primary or secondary) and acute stress require immediate increase in steroids
Primary adrenal insufficiency:
  • Rapid withdrawal of exogenous steroids (i.e. no taper) or failure to increase steroids with acute stress
  • Massive adrenal hemorrhage destroying adrenal cortex due to anticoagulation, coagulopathy and newborns with physiologic deficiencies in prothrombin time
  • Hypotension / shock that causes mild or massive corticomedullary necrosis, including Waterhouse-Friderichsen syndrome
  • Infections that destroy substantial adrenal cortical tissue
  • Amyloidosis
    • Rarely causes cortical hypofunction, only if extensive bilateral involvement
    • Usually associated with systemic amyloidosis-AA type
    • 68% of consecutive autopsies had adrenal amyloid deposits, often multinodular and probably due to aging
    • Typically affects zona fasciculata and reticularis
    • Acellular salmon-pink amorphous material is present between cortical cells, which ultimately become atrophic
    • Amyloidosis-AL type is typically deposited intravascularly
  • Drugs
    • Aminoglutethimide: inhibits enzyme converting cholesterol to pregnenolone, causes decrease in cortisol and aldosterone
    • Metapyrone: inhibits 11 beta hydroxylase, which inhibits cortisol and aldosterone synthesis
    • Mitotane: cytotoxic to zona fasciculata and reticularis, produces medical adrenalectomy; produces atrophic adrenal glands with fibrosis and residual islands of cortical cells
  • Radiation
    • May cause fibrosis, although cortex is relatively radioresistant
    • High doses (> 5000 roentgens) to abdomen, pelvis or lumbar region may cause hyaline fibrosis of reticularis and reduction of fasciculata, although does not necessarily affect cortical function
  • Autoimmune disorders (autoimmune adrenalitis or polyglandular autoimmune syndromes)
Isolated mineralocorticoid deficiency
  • Deficiency of aldosterone production by zona glomerulosa
  • Usually due to impaired release of renin from kidney due to diabetes mellitus, autoimmune disease, amyloidosis or sickle cell anemia; also heparin, rarely tumors or idiopathic
  • Primary (idiopathic) hypoaldosteronism may be due to autosomal recessive disorder associated with deficiency in CYP11B2 enzyme (converts 18-hydroxyl group to aldehyde at end of aldosterone biosynthesis)
  • Infants have failure to thrive, recurrent dehydration and salt wasting
Polyglandular automimmune syndromes
  • More common in women

    Type I polyglandular autoimmune syndrome:
    • Also called autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED)
    • Due to mutations in gene at 21q22.3
    • Rare with < 200 cases reported
    • Autosomal recessive; associated with adrenal insufficiency in 60% of cases, usually by age 13 years
    • Also chronic mucocutaneous candidiasis and hypoparathyroidism in childhood
    • Also autoimmune thyroiditis, diabetes mellitus; variable alopecia; most have autoantibodies to glutamic acid decarboxylase

    Type II polyglandular autoimmune syndrome:
    • Usually autosomal dominant
    • Adrenal insufficiency in all cases; more common than type I
    • 50% familial with onset between ages 20-40 years
    • Also autoimmune thyroiditis (Grave disease), insulin dependent diabetes mellitus
    • Also primary hypogonadism, myasthenia gravis and celiac disease; only rarely hypoparathyroidism
Wolman disease
  • Primary familial xanthomatosis
  • Rare, autosomal recessive lipid storage disorder due to deficiency of lysosomal acid lipase, causing accumulation of triglycerides and cholesterol esters in liver, spleen and adrenal glands
  • Usually causes death by age 6 months
  • Gross description: markedly enlarged adrenal glands with dystrophic calcifications but normal architecture
  • Microscopic (histologic) description: necrosis, fibrosis and calcification; zona fasciculata and reticularis cells have vacuolated cytoplasm
  • Differential diagnosis: Niemann-Pick disease, other storage diseases

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Markedly enlarged adrenal glands

Primary adrenal insufficiency:
  • Glucocorticoids, mineralocorticoids and IV fluids
  • In chronic patients, must give steroid boost during infections, prior to surgery or during pregnancy
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