Height outcome and pubertal development in CYP21 genotyped CAH male patients

BACKGROUND: CYP21 genotyping permits to define better the CAH form of the patients, in particular in males without salt wasting. AIM: Retrospective evaluation of height outcome and pubertal developmental patterns in 22 male patients affected by 21-hydroxylase deficiency and classified by CYP21 genotype. METHODS: The patients were selected on the basis of male sex and completed linear growth (FH) and were classified into three groups, according to predicted mutation severity: Group A (n.10), homozygous or compound heterozygous for null or In2 splice mutations (residual enzymatic activity, RA <1%); Group B (n.5), homozygous for I172N or R341P mutations (RA about 2-3%), or compound heterozygous with any of the Group A or B mutations; and Group C (n.7), homozygous for P30L or V281L mutations (RA > 30%) or compound heterozygous with any of the Groups A, B or C mutations. RESULTS: Patients of Group B were shorter than males of Groups A and C. 79% of patients in Group A, 50% in Group B and 100% in Group C reached a final height above or equal to -1.8 SD of Tanner standards (3rd pct). 60% of patients of Group A, 25% of Group B and 43% of Group C reached a final height within 0.5 SD of target height (TH). The chronological age of Group B subjects at onset of puberty (testicular volume >3 ml) was advanced compared to both Groups A and C and the height age/bone age ratio was significantly higher in Group A than in Group B subjects (0.98±0.13 vs. 0.76±0.14; P<0.025). Mean duration of puberty was similar in the three groups. Group B patients showed a significantly lower height gain during puberty than males in Group C. Early diagnosed CAH patients who received lower cortisol equivalent doses during the first year of life, reached a better final height. Our results underline the importance of mineralocorticoid therapy, since CAH subjects in Groups A and B who did not receive this treatment showed a reduced final height. CONCLUSION: Early diagnosis, the use of more physiological cortisol equivalent dosages during the first year of life and the extension of mineralocorticoid therapy to all “classical” patients is shown to improve the auxological outcome.Genotypic analysis helped to interpret the height results of our cases and prospectively may represent a useful tool in improving the therapeutical choice and the height outcome