Adrenal gland & paraganglia

Adrenal cortical adenoma

Aldosterone producing

Last author update: 1 May 2014
Last staff update: 16 November 2022 (update in progress)

Copyright: 2003-2022,, Inc.

PubMed Search: Adenomas hyperaldosteronism

Carmen Perrino, M.D.
Debra L. Zynger, M.D.
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Cite this page: Perrino C, Zynger D. Aldosterone producing. website. Accessed December 3rd, 2022.
Definition / general
  • Benign neoplasm arising from adrenal cortical cells resulting in increased aldosterone levels in blood and urine and associated clinical symptoms
  • Adrenal cortical adenoma (ACA): discrete nodule in adrenal cortex
  • Bilateral adrenal hyperplasia (BAH): generalized thickening of adrenal cortex, usually without discrete nodules
  • Nodular adrenal hyperplasia (NAH): adrenal cortex contains multiple nodules with / without generalized thickening
    • Various cutoffs exist for macro versus micronodular hyperplasia (range 0.5 - 3.0 cm in diameter)
  • F > M, ages third to fifth decade
  • Unknown, theoretically zona glomerulosa, however cells may resemble any of the 3 layers of the adrenal cortex or a mixture of these cell types
  • Neoplastic proliferation of adrenal cortical cells
  • ↑Aldosterone → impacts distal tubules & collecting ducts of nephron → ↑sodium and water retention, ↓potassium retention → ↑blood pressure
Clinical features
  • Hypertension, proximal muscle weakness, headache, polyuria, hypokalemia, hypocalcemia, tachycardia with / without palpitations
  • Well circumscribed lesion comprised of cells resembling normal adrenal cortex
  • ↑Aldosterone, hypernatremia, hypokalemia
  • ↓Renin
  • Often ↑aldosterone: renin ratio, followed by confirmatory suppression testing (Orphanet J Rare Dis 2010;5:9)
Radiology description
Radiology images

Images hosted on other servers:

Left adrenal mass

(A) Plain CT and (B) contrast CT show left suprarenal mass

Prognostic factors
Case reports
  • Surgical excision is most common treatment
  • May initially attempt conservative medical management with blood pressure medications (i.e. spironolactone, an aldosterone receptor antagonist) (Endocr Relat Cancer 2008;15:693)
  • Prior to removal of adrenal gland, adrenal vein sampling may be performed to determine if aldosterone hypersecretion is unilateral (Orphanet J Rare Dis 2010;5:9)
    • Aldosterone and cortisol levels are determined in inferior vena cava (IVC) and both adrenal veins
    • Aldosterone secretion is lateralized to one side if aldosterone:cortisol ratio is 2 to 5 times higher on the dominant side
Gross description
  • Usually small (< 50 g, < 5 cm), well circumscribed, unilateral, solitary
  • Cut surface is homogeneous and bright golden yellow
  • Uninvolved adrenal gland is unremarkable or even hyperplastic but usually not atrophic
Microscopic (histologic) description
  • Pushing border, may be surrounded by a fibrous capsule / pseudocapsule
  • Architectural patterns include nesting, alveolar, cords, trabeculae
  • Cells may resemble all three layers of normal adrenal cortex, ranging from large pale lipid rich cells (zona fasciculata), to smaller cells with vacuolated eosinophilic cytoplasm (zona glomerulosa), to compact and possibly oncocytic cells (zona reticularis), to cells which resemble mixtures of these types
  • Often (~60%) associated with additional smaller adrenal cortical nodules
  • Spironolactone bodies may be identified due to prior medical management but may diminish / disappear with prolonged therapy (Am J Pathol 1981;103:404)
    • Spironolactone body: small eosinophilic intracytoplasmic inclusion with laminated, scroll-like appearance in zona glomerulosa (Lack: AFIP Atlas of Tumor Pathology, Series 4, 2007)
    • Frequency in ACA correlates with quantity of zona glomerulosa type cells in the lesion
Virtual slides

Images hosted on other servers:

ACA with hyperaldosteronism

Cytology description
  • Loose clusters of cells with round to oval, small, smooth, benign-appearing nuclei and abundant foamy, vacuolated cytoplasm
Positive stains
  • Usually positive: α inhibin, MelanA / Mart1, steroidogenic factor-1 (SF1), calretinin, Oil Red O (fresh frozen tumor, highlights intracytoplasmic lipid), BCL2 (Mod Pathol 1998;11:716), D2-40 (J Clin Pathol 2008;61:293)
  • Sometimes positive: synaptophysin, neuron specific enolase (NSE), low molecular weight cytokeratin (AE1 / AE3, CAM 5.2)
  • Rarely positive: vimentin (Am J Pathol 1990;136:1077)
  • Low Ki67 index (usually < 5%)
  • Spironolactone bodies: stain medium blue with Luxol fast blue, Sudan black B (Am J Pathol 1981;103:404)
Negative stains
  • EMA, CEA, B72.3, S100, chromogranin (stains adrenal medulla), vimentin, carbonic anhydrase IX (CAIX)
Electron microscopy description
  • Cells have features of normal adrenal cortical cells which they resemble on H&E histology
  • Since many patients have been treated with spironolactone, spironolactone bodies can be found (Am J Pathol 1981;103:404)
    • Spironolactone body: blue-black cytoplasmic inclusions, spherical laminated whorls with a central core with amorphous, electron dense material surrounded by smooth walled, concentric membranes continuous with endoplasmic reticulum (Lack: AFIP Atlas of Tumor Pathology, Series 4, 2007)
Electron microscopy images

Contributed by Dr. Edward Calomeni

Spironolactone bodies

Molecular / cytogenetics description
  • Clonal proliferation of adrenal cortical cells
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