Classical congenital adrenal hyperplasia due to 21-hydroxylase deficiency (21-OHD) in adult males: Clinical presentation, hormone function and the detection of adrenal and testicular adrenal rest tumors (TARTs).

INTRODUCTION

21-hydroxylase deficiency (21-OHD) is the most common form of congenital adrenal hyperplasia (CAH). In adulthood, most studies are reported in females. By contrast, data on adult males are scarce.

OBJECTIVE

To describe a series of adult males with classic 21-OHD and to assess the presence of adrenal masses and testicular adrenal rest tumors (TARTs).

MATERIAL AND METHODS

Eight males (21-42 years) were included. We evaluated clinical presentation, 17-Hydroxyprogesterone (17-OHP), Testosterone (T), Δ4Androstenedione (Δ4A) ACTH, LH, FSH and plasma renin activitiy (PRA) levels at consultation. Molecular studies of the CYP21A2 gene, testicular ultrasound (US), semen analysis and adrenal computed tomography (CT) scan were performed. Treatment and compliance were assessed.

RESULTS

Basal 17-OHP levels were >20ng/ml in all patients. At consultation, median 17OH-P was 11.5 (2.3-81) ng/ml, FSH: 3 (0.3-4) mUI/ml, LH: 1.1 (0.1-6) mUI/ml, T: 4.3 (1.7-8) ng/ml, Δ4A: 5.7 (1.4-16) ng/ml, ACTH: 86.4 (76-334) pg/ml, PRA: 9.5 (1.3-23.6) ng/ml/h. Semen analysis was performed in 5/8 patients, showing azoospermia in two. Molecular genetic analysis was performed in 4/8 patients. TARTs were found in 5/6, being bilateral in four. Adrenal masses were found in 4/6. In the 7 patients diagnosed in childhood, their follow-up was referred to as irregular, both in their attendance at consultations and in compliance with the indicated treatment.

CONCLUSIONS

To our knowledge, this is the first series on adult males with classic 21-OHD which concomitantly assesses clinical presentation, molecular biology, adrenal and testicular imaging studies, semen analysis and compliance to treatment. A high prevalence of adrenal masses and TARTs was observed, possibly associated with poor treatment compliance leading to elevated ACTH and increased proliferation. Our findings on TARTs agree with reports in international publications of CAH in males, with adrenal imaging being added in our group. Although we are aware that further studies with a larger sample size and more data are needed, we consider that our findings contribute to the clinical management of classical 21-OHD in the male population.