Adrenal gland & paraganglia
Adrenal insufficiency
Primary and secondary adrenal insufficiency
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Last staff update: 4 October 2023
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PubMed Search: Primary acute adrenal insufficiency
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Cite this page: Pernick N. Primary and secondary adrenal insufficiency. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/adrenalprimaryadrenalinsuff.html. Accessed April 20th, 2024.
Primary adrenal insufficiency
Definition / general
- 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
Etiology
- 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)
Treatment
- Glucocorticoids, mineralocorticoids and IV fluids
- In chronic patients, must give steroid boost during infections, prior to surgery or during pregnancy
Secondary adrenal insufficiency
Definition / general
- Caused by any disorder of pituitary gland which decreases ACTH production and causes adrenal cortical atrophy
- Causes: pituitary macroadenoma, craniopharyngioma, tuberculosis or other infections, sarcoidosis, lymphocytic hypophysitis, head trauma, aneurysms, postpartum pituitary necrosis (Sheehan syndrome), pituitary apoplexy or metastases; also mutations in pro-opiomelanocortin gene
- Similar atrophic changes are caused by exogenous steroids, which also decrease ACTH production
- No hyperpigmentation since ACTH levels are low
- May be associated with hypopituitarism
Laboratory
- Serum aldosterone, sodium and potassium levels are usually normal, since they are controlled by renin-angiotensin axis, which is not under the control of ACTH
- Androgens and cortisol levels are low since their production is influenced by ACTH, although androgens are less affected in males since they are also produced by testis
- Hypoglycemia is more common than with primary adrenal insufficiency
Treatment
- Exogenous ACTH causes rise in serum cortisol levels
- May also need to replace other pituitary hormones
Gross description
- Atrophic adrenal glands with retention of architecture, often fibrotic capsule, bright yellow (due to lipid accumulation) and prominent medulla
Microscopic (histologic) description
- Normal thickness of zona glomerulosa, thinner fasciculata and reticularis
- Usually no lymphoplasmacytic infiltration
Tertiary adrenocortical insufficiency
- Due to disorders of hypothalamus reducing release of corticotropin releasing hormone (CRH); some include this within secondary adrenocortical insufficiency
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
Definition / general
- 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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