Endocrine Abstracts

Congenital adrenal hyperplasia (CAH) is a disorder due to mutations of genes coding for adrenal steroidogenesis enzymes, commonly caused by 21α-hydroxylase enzyme deficiency. Severe impairment of 21α-hydroxylase synthesis results in the classic form of CAH (c-CAH) characterized by cortisol and aldosterone deficiency (salt wasting form - SW), or partial enzyme deficiency characterized by cortisol deficiency (simple virilizing form - SV); mild impairment of 21α-hydroxylase synthesis results in the non-classic form of CAH (nc-CAH) potentially characterized by cortisol deficiency. Moreover, CAH is characterized by androgen excess which may promote secondary hypogonadism; furthermore, male patients suffering from CAH may present other andrological disorders including testis hypotrophy, testicular adrenal rest tumours (TARTs) and impaired spermatogenesis. The aim of the current study was to evaluate testis function in males with CAH due to 21α-hydroxylase deficiency. Data were retrieved from GONADIS, a national registry on gonadal status and reproductive and psycho-sexual function in patients affected by pituitary and adrenal disorders. Twenty one male patients aged 18-64 years suffering from CAH on chronic replacement therapy with glucocorticoids were evaluated, including 12/21 patients (57.2%) with c-CAH, 9/21 patients (42.8%) with nc-CAH. Prevalence of testis hypotrophy as well as semen parameters were assessed in the overall cohort of CAH patients and in a subanalysis a comparison between c-CAH vs nc-CAH was performed. The control of disease was defined as serum androstenedione levels within/above the normal range. In the overall cohort of CAH patients, 13/18 (72.2%) reached disease control. Unilateral/bilateral testis hypotrophy was detected in 11/20 (55%) and TARTs in 11/19 (57.9%) of patients; concerning seminal parameters, oligozoospermia was detected in 3/19 (15.8%), azoospermia in 6/19 (31.6%), asthenozoospermia in 4/13 (30.7%), teratozoospermia in 3/13 (23%) and oligo-astheno-teratozoospermia in 3/13 (23%) of patients. In a subanalysis on c-CAH vs nc-CAH patients, significantly lower ACTH (P=0.04) and higher testosterone (P=0.01) levels were detected in the c-CAH, compared to nc-CAH group; a significantly higher prevalence of TARTs (P=0.03), lower total sperm count (P=0.002) and sperm concentration (P=0.04), and higher prevalence of azoospermia (P=0.01), were detected in the c-CAH compared to nc-CAH group. This study demonstrated an overall high prevalence of pathological testis and semen parameters in male patients with CAH. Moreover, a significantly worse semen quality was highlighted in patients with c-CAH, which were also characterized by a significantly higher prevalence of azoospermia and TARTs, therefore suggesting that alterations in semen parameters might be predominantly due to testis damage induced by TARTs.