Adrenal morphology and associated comorbidities in congenital adrenal hyperplasia

Abstract

Objective Adrenonodular hyperplasia and tumour formation are potential long‐term complications of congenital adrenal hyperplasia (CAH) with little known regarding the clinical implications. Our aim was to describe volumetric adrenal morphology and determine the association between radiological findings and comorbidities in adults with classic CAH. Design This was a cross‐sectional study of 88 patients (mean age 29.2 ± 13 years, 47 females) with classic CAH seen in a tertiary referral centre. Methods CT imaging, performed at study entry or when reaching adulthood, was used to create 3‐dimensional volumetric models. Clinical, genetic and hormonal evaluations were collected and correlated with adrenal morphology and tumour formation. Results Over one‐third of the cohort was obese. 53% had elevated 17‐OH‐progesterone or androstenedione; and 60% had adrenal hyperplasia. Tumours included 11 myelolipomas, 8 benign adrenocortical adenomas, 1 pheochromocytoma and 50% of men had testicular adrenal rest tissue. CAH patients with adrenal hyperplasia had significantly higher number of comorbidities than those with morphologically normal adrenals (P = 0.03). Variables that positively correlated with adrenal volume included hypogonadal/oligomenorrhoeic status, hypertension, androstenedione, aldosterone, and triglyceride levels, and in women, low HDL and insulin resistance. Elevated aldosterone was observed in a subset of patients with simple virilizing CAH. Conclusions Adrenocortical hyperplasia is associated with a number of comorbidities, especially hypogonadism. Aldosterone production associated with adrenal enlargement may play a role in the development of metabolic risk factors. Further studies are needed to assess the long‐term impact of the excess adrenal steroid milieu associated with adrenal enlargement to develop improved management strategies for CAH.

Prevalence and Characteristics of Adrenal Tumors and Myelolipomas in Congenital Adrenal Hyperplasia: A Systematic Review and Meta-Analysis

“…Forty-seven publications were considered eligible for inclusion. Only seven of these studies investigated the prevalence of adrenal tumors in CAH (9,10,(20)(21)(22)(23)(24). Two of them reported on the same patient cohort (9,20) so only the most recent study was used in the meta-analysis (9).…”

“…These six cohort studies included 215 patients and 63 of them had an adrenal tumor. Three of the studies (9,22,24) had defined an adrenal mass ≥ 5mm but we also extracted data on tumors ≥ 10mm. The other 38 papers were case reports with adrenal (10,22,.…”

“…Three of the studies (9,22,24) had defined an adrenal mass ≥ 5mm but we also extracted data on tumors ≥ 10mm. The other 38 papers were case reports with adrenal (10,22,. We identified cases with other types of CAH than 21OHD with myelolipoma.…”

“…The prevalence of myelolipoma in CAH was 7.4% and in patients with verified CYP21A2 mutations 8.2%. The prevalence of myelolipoma when including only the two largest studies with unselected patients with CAH (10,22) The proportion of myelolipoma in the adrenal tumors was 25.4% and raised to 36.6% when only the studies with verified CYP21A2 mutations were included (Table 1). A pheochromocytoma with a diameter 165 mm (10) and another of 28 mm ( 22) were reported in two separate studies.…”

“…Most tumors were found on the left side (56.8%). Nermoen et al (10) and El-Maoche et al (22) had not published information on tumor side but data were provided after contact with the corresponding authors. The median diameter of the tumors was 24.0 (4-165) mm (Table 2).…”