Endocrine Abstracts

Objective: The aim of this study was to determine genetic, anthropometric and metabolic features in an unselected population of adult Norwegian patients with classical 21-hydroxylase deficiency (21OHD).

Patients,

Methods, and design: Sixty-four 21OHD-patients participated (23 men, 41 women; mean age 40.3 (range 19–72) in a cross-sectional study including DNA sequencing of the CYP21A1P-CYP21A2 locus, anthropometric measurements including dual X-ray absorptiometry (DXA) scanning, and biochemical analyses. The results were compared with reference cohorts from the general population.

Results: We identified four novel and plausibly disease-causing CYP21A2 mutations. Gene deletions/conversions (42.1% of alleles), the point mutations I2splice (23.0%) and I172 N (22.2%) were common. The genotype corresponded to clinical phenotype in 89% of the patients. Reduced final height was more pronounced in the men; 168.2 cm (151–186) (mean and range) than in the women 159.1 cm (144–173). The prevalence of osteopenia was 44% in the men and 29% in the women. Both men and women had normal body mass index, but markedly increased fat mass compared with the normal population. Diastolic blood pressure was higher than normal. Only 20% of the women had testosterone levels in the normal range; 13% of the men had testosterone levels below normal.

Conclusion: In this population-based survey of 21OHD we identified four novel mutations and high concordance between genotype and phenotype. The patients had reduced final height, with high frequency of osteopenia in the men, increased fat mass, and increased diastolic blood pressure. These results indicate unfavourable metabolic status and need for improvement of the therapy.

Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.

Funding: This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.