Adrenal gland and paraganglia
Adrenal hyperfunction / hyperplasia
Acquired (non-congenital) adrenocortical hyperplasia

Author: Nat Pernick, M.D. (see Authors page)

Revised: 14 January 2016, last major update February 2013

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Definition / General
  • Defined as non-neoplastic increase in adrenal cortical cells
  • Diffuse (62%) or nodular (20%) or hyperplasia with ectopic ACTH syndrome due to tumors (18%)
  • Diffuse cases are usually bilateral, associated with elevated ACTH produced by pituitary gland, ACTH-producing tumor or excess corticotropin-releasing factor production and rarely due to ACTH receptor autoantibodies (as with Grave disease)
  • Nodular cases usually are unrelated to ACTH production; may represent a later stage of diffuse hyperplasia, in which the lesion has evolved from ACTH-dependent to adrenal gland dependent
  • Associated with MEN1 (not neoplastic in one case, Mod Pathol 1999;12:919; also thyroid neoplasms, leiomyomas, hepatic focal nodular hyperplasia and renal angiomyoliomas
Case Reports
Gross Description
  • Nodular variant: at least one nodule 0.5 cm in diameter, often diffusely nodular adrenal cortex which weighs 6+ grams without fat; glands have rounded edges
Gross Images

Bilateral cortical hyperplasia

Nodular

Micro Description
  • Increased thickness of zona reticularis and fasciculata
  • Cells in fasciculata may appear lipid depleted
  • Atypical cells with large hyperchromatic nuclei may be present in nodules (“endocrine atypia”)
  • Small micronodules may be present near central vein, containing lipid-laden clear cells similar to zona fasciculata
Micro Images

Diffuse hyperplasia

Lipomatous metaplasia

Molecular / Cytogenetics Description
  • Cells may be aneuploid or polyploid
Electron Microscopy Description
  • Abundant smooth endoplasmic reticulum, long microvilli
Differential Diagnosis