Detection of new potentially pathogenic mutations in two patients with primary pigmented nodular adrenocortical disease (PPNAD) - case reports with literature review

Endokrynol Pol. 2018;69(6):675-681. doi: 10.5603/EP.a2018.0063. Epub 2018 Sep 27.

Abstract

Introduction: Primary pigmented nodular adrenocortical disease (PPNAD) is a rare form of ACTH-independent Cushing's syndrome (CS). Half of patients with PPNAD are sporadic cases and the other half familial.

Material and methods: We present two patients with PPNAD confirmed by genetic analysis.

Results: In both patients there were no abnormal findings on diagnostic imaging of both adrenals and heart. Patients underwent bilateral two-stage adrenalectomy. Histopathological examination confirmed PPNAD. Genetic testing showed the following mutations in the PRKAR1A gene coding for the regulatory subunit type 1A of the protein kinase A enzyme: c.125dupG (patient 1) and c.15dupT (patient 2). Both these defects lead to inactivation of the PRKAR1A protein and are consequently causative of PPNAD in these patients.

Conclusions: The novel mutations presented in this article are considered to be pathogenic for PPNAD.

Keywords: Carney complex; Cushing’s syndrome; PPNAD; nodular adrenocortical disease.

Publication types

  • Case Reports
  • Review

MeSH terms

  • Adolescent
  • Adrenal Glands / surgery
  • Adrenalectomy
  • Cushing Syndrome / genetics*
  • Cushing Syndrome / metabolism
  • Cyclic AMP-Dependent Protein Kinase RIalpha Subunit / genetics*
  • DNA Mutational Analysis
  • Female
  • Humans
  • Male
  • Mutation*

Substances

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

Supplementary concepts

  • Acth-Independent Macronodular Adrenal Hyperplasia