21-Hydroxylase-deficient nonclassic adrenal hyperplasia is a progressive disorder: A multicenter study

OBJECTIVE: Our aim was to determine whether the clinical features of 21-hyd roxylase-deficient nonclassic adrenal hyperplasia are correlated with eithe r age at symptom onset or age at presentation, or both, and with the degree of adrenocortical abnormality. STUDY DESIGN: In a multicenter cohort design 220 women with nonclassic adrenal hy perplasia, with a basal or adrenocorticotropic hormone-stimulated 17-hydrox yprogesterone level >30.3 nmol/L, were studied, either prospectively (n = 3 9) or retrospectively (n = 181). Patients were stratified by age of present ation into 5 groups: (1) <10 years (n = 25), (2) 10 to 19 years (n = 64), ( 3) 20 to 29 years (n = 83), (4) 30 to 39 years (n = 30), and (5) 40 to 49 y ears (n = 16). Two patients >50 years old were excluded from the analysis b ecause of age. RESULTS: Ninety-two percent of patients <10 years old had premature pubarch e at presentation, whereas clitoromegaly and acne were each present in only 20% of these younger subjects. With only patients <greater than or equal t o>10 years old considered, presenting clinical features included hirsutism (59%), oligomenorrhea (54%), acne (33%); infertility (13%), clitoromegaly ( 10%), alopecia (8%), primary amenorrhea (4%), and premature pubarche (4%). Among the patients greater than or equal to 10 years old, the prevalence bu t not the degree of hirsutism increased significantly with age. Basal level s of 17-hydroxyprogesterone in adolescents were significantly higher than t he levels found either in children (<10 years old) or women 40 to 49 years old (P <.01 and P <.03, respectively), although no difference was noted in the stimulated 17-hydroxyprogesterone levels between age groups: The adreno corticotropic hormone-stimulated levels but not the basal levels of 17-hydr oxyprogesterone were significantly higher in patients with clitoromegaly th an in women without clitoromegaly. Alternatively, there were no differences in either basal or stimulated 17-hydroxyprogesterone levels between patien ts with and those without hirsutism, acne, or alopecia. CONCLUSION: In children <greater than or equal to>10 years old the most com mon presenting complaint was premature pubarche, whereas hirsutism and olig omenorrhea were more common in older patients. The prevalence of hirsutism increased with age, suggesting the progressive nature of nonclassic adrenal hyperplasia. Furthermore, the adrenocorticotropic hormone-stimulated level s of 17-hydroxyprogesterone were higher in patients with clitoromegaly, whi ch suggests that the degree of adrenocortical dysfunction in nonclassic adr enal hyperplasia determines, at least in part, the clinical presentation.