Endocrine Abstracts

Background: Nonclassic congenital adrenal hyperplasia (NCAH) is a condition associated with adrenal masses and suggested by current European guidelines to be considered in case of bilateral adrenal lesions. NCAH is caused by different mutations in the CYP21A2 gene coding for the 21-hydoxylase enzyme in the glucocorticoid synthesis leading to mild cortisol deficiency and elevated androgen and steroid precursor levels. 17-hydroxyprogesterone (17OHP) is the most important steroid precursor and used to diagnose NCAH. Elevated ACTH levels lead to development of adrenocortical hyperplasia and adrenal masses. NCAH is one of the most common autosomal recessive disorders and with an estimated prevalence of around 0.1% in the general population but up to 2-4% in some ethnic groups. The prevalence of NCAH in a population with adrenal incidentaloma (AI) is unknown but assumed to be higher than in the general population. The main reason to exclude NCAH is that a correct diagnosis can enable glucocorticoid replacement that can improve quality of life for individuals with symptoms of hyperandrogenism. The aim of this study was to investigate the prevalence of NCAH in a population of adrenal incidentalomas (AIs).

Method: After overnight fasting serum cortisol and 17OHP were measured before and 30 and 60 minutes after an intravenous injection of 0.25 mg ACTH (Synacthen®) in subjects, >18 years with AI fulfilling ESE’s definition of AI at a single centre in Regional Sweden. A 17OHP >30 nmol/l before or after ACTH-stimulation was classified as NCAH.

Results: An ACTH-stimulation test was performed in 222 subjects (median age 66 (25–87) years, 58.6% women). None of the subjects presented a basal 170HP >30 nmol/l. Eight subjects (3.6%) presented a 17OHP >30 nmol/l (median 38 nmol/l (33–62) which could be compatible with NCAH. Four subjects (50%) with 17OHP >30 nmol/l had bilateral lesions.

Conclusion: The prevalence of NCAH based on the level of 17HOP after ACTH-stimulation in a population of patients with AI was 3.6%. The prevalence based on genetic analysis is probably lower, as the secretion of 17OHP can be slightly increased even from lesions without CAH. However, the prevalence of NCAH appears to be significant higher in a population diagnosed with AI than in the general population. Thus, screening for NCAH in AI may be considered even without bilateral AIs.