title: Adrenal gland inclusions in patients treated with aldosterone antagonists (Spironolactone/Eplerenone): incidence, morphology, and ultrastructural findings.
abstract: BACKGROUND
  Spironolactone is often used to treat hypertension caused by hyperaldosteronism, and as a result, can form concentrically laminated electron dense spironolactone body inclusions within the adrenal gland. Spironolactone bodies have not been investigated in a contemporary cohort or in patients treated with the more recently approved aldosterone antagonist, eplerenone.
  
  
  METHODS
  Spironolactone bodies were retrospectively investigated in patients treated for hyperaldosteronism (n=15) from 2012-2013 that underwent a subsequent adrenalectomy.
  
  
  RESULTS
  Inclusions were identified in 33% of patients treated with aldosterone antagonists, far less than previously reported. Remarkably, 50% of patients treated with spironolactone had inclusions while no patients using eplerenone alone had inclusions. Two patients treated with spironolactone had bodies present longer than the duration described in prior studies. Inclusions unexpectedly persisted in 1 patient despite increased duration of discontinued pharmacological treatment. A spectrum of histologic and ultrastructural findings were encountered within an adrenal cortical adenoma from a patient treated with both spironolactone and eplerenone. Ultrastructural examination revealed laminated electron dense bodies with the appearance of classic spironolactone inclusions as well as electron dense bodies without laminations and laminated bodies without electron dense cores.
  
  
  CONCLUSIONS
  Our incidence rate of spironolactone bodies was much lower than previously reported, with no inclusions seen in patients treated solely with the newer aldosterone antagonist, eplerenone. Pathologists should be aware of these infrequently encountered inclusions, particularly as the clinical history of hyperaldosteronism and pharmacologic treatment may not be provided.
  The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/4597918761268031.
authors.forename: Kishan A
authors.initials: KA
authors.lastname: Patel
authors.forename: Edward P
authors.initials: EP
authors.lastname: Calomeni
authors.forename: Tibor
authors.initials: T
authors.lastname: Nadasdy
authors.affiliation: Department of Pathology, The Ohio State University Medical Center, 410 W 10th Ave, 401 Doan Hall, Columbus, OH 43210, USA. debra.zynger@osumc.edu.
authors.forename: Debra L
authors.initials: DL
authors.lastname: Zynger
mesh_terms: D000311:Adrenal Glands / Q000473:pathology* / Q000601:surgery / Q000648:ultrastructure; D000315:Adrenalectomy; D000328:Adult; D000368:Aged; D000077545:Eplerenone; D005260:Female; D006801:Humans; D006929:Hyperaldosteronism / Q000150:complications / Q000473:pathology* / Q000601:surgery; D006973:Hypertension / Q000188:drug therapy* / Q000209:etiology; D015994:Incidence; D002479:Inclusion Bodies / Q000473:pathology* / Q000648:ultrastructure; D008297:Male; D008875:Middle Aged; D000451:Mineralocorticoid Receptor Antagonists / Q000378:metabolism / Q000627:therapeutic use*; D012189:Retrospective Studies; D013148:Spironolactone / Q000031:analogs & derivatives* / Q000378:metabolism / Q000627:therapeutic use
chemical_list: D000451:Mineralocorticoid Receptor Antagonists; D013148:Spironolactone; D000077545:Eplerenone
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