Adrenal gland and paraganglia
Adrenocortical adenoma
Adenomas associated with hyperaldosteronism (Conn's syndrome)

Author: Carmen Perrino, M.D. (see Authors page)

Editor: Debra Zynger, M.D.

Revised: 20 January 2016, last major update May 2014

Copyright: (c) 2003-2016,, Inc.

PubMed Search: Adenomas [title] hyperaldosteronism
Cite this page: Adenomas associated with hyperaldosteronism (Conn's syndrome). website. Accessed March 24th, 2018.
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 cut-offs exist for macro- versus micronodular hyperplasia (range 0.5 cm to 3.0 cm in diameter)
  • F > M, ages 3rd to 5th 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

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
Gross images

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1.3 cm left adrenal adenoma

3×3 cm exophytic adrenal mass

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
Microscopic (histologic) images

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Multiple ACAs comprised of clear cells

Fine microvasculature
and spironolactone

Top: spironolactone bodies
Mid: Luxol fast blue
Bottom: renal clear cell carcinoma

Images hosted on Flickr:

Adenoma with spironolactone bodies

Virtual slides

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, CAM5.2)
  • Rarely positive: vimentin (Am J Pathol 1990;136:1077)
  • Low Ki-67 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

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Spironolactone bodies

Molecular / cytogenetics description
  • Clonal proliferation of adrenal cortical cells