Pituitary gonadal axis and child rate in males with classical 21-hydroxylase deficiency

Though appropriate glucocorticoid substitution therapy should abolish both cortisol deficiency and adrenal androgen excess in patients with 21-hydroxylase deficiency (21-OHD), the long-term outcome is not always satisfactory. There are several reports on low adult height in both male and female patients, and impaired fertility has been reported in females with 21-OHD. There are only few reports on gonadal function of adult male patients with 21 -OHD. In this study, we calculated the child rate of all the 29 diagnosed adult Finnish males with classical 21-OHD and compared it with the mean child rate of the whole Finnish male population with equal age distribution. Sixteen males with 21-OHD and their age-matched healthy controls were further examined in a cross-sectional study. Auxology and pituitary gonadal axis were examined in both patients and controls. Testicular ultrasonography of the patients was also performed. The mean child rate of the 29 males with 21-OHD was 0.07 which was significantly lower (p<0.001) than that in the Finnish male population of the same age (0.34). In the cross-sectional study, males with 21-OHD had serum testosterone, inhibin B, LH and FSH concentrations comparable to those of healthy controls and reference values. Serum DHEA-S concentrations were remarkably low, even in the undersubstituted males with 21-OHD (p<0.001, compared with the healthy controls). In the patient group, serum inhibin B concentration did not correlate with serum FSH concentration. Adrenal rest tumors of the testicles were found in two undersubstituted males with 21-OHD. In conclusion, our study suggests normal pituitary and gonadal function but reduced child rate in adult males with 21-OHD. This might be explained by suboptimal psychosocial adaptation to the chronic disease. However, the patients in this study were young and the final child rate may become essentially higher.