Primary pigmented nodular adrenocortical disease: the original 4 cases revisited after 30 years for follow-up, new investigations, and molecular genetic findings

Am J Surg Pathol. 2014 Sep;38(9):1266-73. doi: 10.1097/PAS.0000000000000220.


The original 4 patients with Cushing syndrome who underwent bilateral adrenalectomy for primary pigmented nodular adrenocortical disease were followed up for an average of 31 years to determine whether they or any of their primary relatives had developed Carney complex or its components. None had. Three of the patients were alive and well; the fourth had died of an unrelated condition. All the adrenal glands contained multiple small, black or brown cortical nodules, up to 4 mm in diameter. The extracapsular extension of the micronodules was limited to the immediate pericapsular adipose tissue and was not considered evidence of low-grade malignancy. Immunocytochemically, the nodules were positive for synaptophysin, inhibin-A, and melan A and negative for vimentin and CD56. Ki-67 antibody stained the cytoplasm of cells in the micronodules but not that of the atrophic cortical cells. The 4 patients had the PRKAR1A deletion that has been associated with the isolated form of primary pigmented nodular adrenocortical disease.

MeSH terms

  • Adolescent
  • Adrenal Cortex Diseases / genetics*
  • Adrenal Cortex Diseases / metabolism
  • Adrenal Cortex Diseases / pathology
  • Adrenal Cortex Diseases / surgery
  • Adrenalectomy
  • Biomarkers / analysis
  • Biomarkers / urine
  • Carney Complex / genetics*
  • Carney Complex / metabolism
  • Carney Complex / pathology
  • Child
  • Cushing Syndrome / genetics*
  • Cushing Syndrome / metabolism
  • Cushing Syndrome / pathology
  • Cushing Syndrome / surgery
  • Cyclic AMP-Dependent Protein Kinase RIalpha Subunit / genetics*
  • Dexamethasone / administration & dosage
  • Female
  • Follow-Up Studies
  • Gene Deletion*
  • Genetic Predisposition to Disease
  • Humans
  • Hydrocortisone / urine
  • Immunohistochemistry
  • Male
  • Phenotype
  • Polymerase Chain Reaction*
  • Predictive Value of Tests
  • Time Factors
  • Treatment Outcome
  • Young Adult


  • Biomarkers
  • Cyclic AMP-Dependent Protein Kinase RIalpha Subunit
  • PRKAR1A protein, human
  • Dexamethasone
  • Hydrocortisone