Congenital adrenal hyperplasia is a very rare cause of adrenal incidentalomas in Sweden

Front Endocrinol (Lausanne). 2022 Dec 5:13:1017303. doi: 10.3389/fendo.2022.1017303. eCollection 2022.


Background: Undiagnosed congenital adrenal hyperplasia (CAH) can cause adrenal incidentalomas, but the frequency is unclear.

Objectives: This study aimed to investigate the prevalence of CAH in a population with adrenal incidentalomas and report the clinical characterization.

Material and methods: This was a prospective study performed at a regional hospital from 2016 to 2021. Patients with adrenal incidentalomas were investigated with an adrenocorticotropic hormone (ACTH)-stimulation test in addition to hormonal workup. Serum cortisol and 17-hydroxyprogesterone (17OHP) were analyzed. Individuals with a basal or stimulated 17OHP ≥30 nmol/L were classified as suspicious non-classic CAH, and a CYP21A2-gene analysis was performed in these subjects.

Results: In total, 320 individuals with adrenal incidentalomas were referred to the center, and of these individuals, an ACTH-stimulation test was performed in 222 (median age, 67 (24-87) years; 58.6% women; and 11.7% with bilateral lesions). None of the individuals presented a basal 17OHP ≥30 nmol/L, but there were 8 (3.6%) who did after ACTH stimulation. Four of these subjects (50%) presented bilateral lesions, and the tumor size was larger compared to that of the individuals with a stimulated 17OHP <30 nmol/L (median, 38 (19-66) vs. 19 (11-85) mm, p=0.001). A CYP21A2 variation (p.Val282Leu) was detected in one of the eight subjects with a stimulated 17OHP ≥30 nmol/L, i.e., the patient was a heterozygotic carrier. None of the eight subjects presented with cortisol insufficiency or clinical signs of hyperandrogenism.

Conclusions: The prevalence of non-classic CAH in an adrenal incidentaloma cohort was 3.6% based on stimulated 17OHP and 0% based on gene analysis. CAH should be considered in AI management in selected cases and confirmed by genetic analysis.

Keywords: 17-hydroxyprogesterone; 21-hydroxylase deficiency; CYP21A2 variations; adrenal tumor; adrenocorticotropic hormone.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 17-alpha-Hydroxyprogesterone
  • Adrenal Gland Neoplasms* / complications
  • Adrenal Gland Neoplasms* / epidemiology
  • Adrenal Gland Neoplasms* / genetics
  • Adrenal Hyperplasia, Congenital* / complications
  • Adrenal Hyperplasia, Congenital* / diagnosis
  • Adrenal Hyperplasia, Congenital* / epidemiology
  • Adrenocorticotropic Hormone
  • Adult
  • Aged
  • Aged, 80 and over
  • Female
  • Humans
  • Hydrocortisone
  • Male
  • Middle Aged
  • Prospective Studies
  • Steroid 21-Hydroxylase / genetics
  • Sweden
  • Young Adult


  • 17-alpha-Hydroxyprogesterone
  • Adrenocorticotropic Hormone
  • CYP21A2 protein, human
  • Hydrocortisone
  • Steroid 21-Hydroxylase

Supplementary concepts

  • Adrenal incidentaloma