Familial Forms of Cushing Syndrome in Primary Pigmented Nodular Adrenocortical Disease Presenting with Short Stature and Insidious Symptoms: A Clinical Series

Horm Res Paediatr. 2018;89(6):423-433. doi: 10.1159/000488761. Epub 2018 Jun 15.


Cushing syndrome (CS) is a rare disease in children, frequently associated with subtle or periodic symptoms that may delay its diagnosis. Weight gain and growth failure, the hallmarks of hypercortisolism in pediatrics, may be inconsistent, especially in ACTH-independent forms of CS. Primary pigmented nodular adrenocortical disease (PPNAD) is the rarest form of ACTH-independent CS, and can be associated with endocrine and nonendocrine tumors, forming the Carney complex (CNC). Recently, phenotype/genotype correlations have been described with particular forms of CNC where PPNAD is isolated or associated only with skin lesions. We present four familial series of CS due to isolated PPNAD, and compare them to available data from the literature. We discuss the clinical and molecular findings, and underline challenges in diagnosing PPNAD in childhood.

Keywords: Carney complex; Cushing syndrome; PRKAR1A gene; Primary pigmented nodular adrenocortical disease.

Publication types

  • Case Reports

MeSH terms

  • Adolescent
  • Adrenal Cortex Diseases* / diagnosis
  • Adrenal Cortex Diseases* / genetics
  • Adrenal Cortex Diseases* / pathology
  • Adult
  • Child
  • Child, Preschool
  • Cushing Syndrome* / diagnosis
  • Cushing Syndrome* / genetics
  • Cushing Syndrome* / pathology
  • Female
  • Humans
  • Male
  • Middle Aged

Supplementary concepts

  • Pigmented Nodular Adrenocortical Disease, Primary, 1
  • Pigmented Nodular Adrenocortical Disease, Primary, 2