Late-Onset Adrenal Hyperplasia in Hirsutism

Abstract

We studied the incidence of late-onset adrenal hyperplasia as a cause of hirsutism, its association with the major histocompatibility complex, and its clinical expression. Twenty-four of 400 women seen because of hirsutism were found to have late-onset adrenal hyperplasia, diagnosed on the basis of a high plasma level of 17-hydroxyprogesterone, and its marked increase after ACTH stimulation. The degree of hirsutism varied widely. Plasma antigen levels were high, especially the level of androstenedione, whereas 5 alpha-reductase activity, considered to be a good index of peripheral androgen utilization, showed frequent normal or low values. The 24 patients were genotyped, along with 84 family members, and plasma hormones were measured in the family members. We found a high correlation between late-onset adrenal hyperplasia and HLA antigens B14 and Aw33. Similar biologic profiles were observed in the patients and those of their siblings who were HLA identical (n = 9), confirming that late-onset adrenal hyperplasia is linked to the histocompatibility complex. These nine siblings had no hirsutism. We therefore conclude that the role of skin sensitivity to androgens is important in determining the clinical expression of this disorder.

The Prevalence of Non-classical Congenital Adrenal Hyperplasia Due to 21-hydroxylase Deficiency in Greek Women with Hirsutism and Polycystic Ovary Syndrome

“…The previously reported findings not only in relation to the prevalence of NC-CAH-due to 21-OHdef but also concerning the HLA phenotypes, are compatible with those reported in the literature [5][6][7][8][9][10][11][12][14][15][16][17][18][19]. As previously reported, the prevalence of 21-OHdef varies from 1% to 20%-30% and it is particularly high around the Mediterranean, in Italians, in the Jewish Ashkenazi, in the Hispanics, in the Turks and in the Arabs [34][35][36][37][38].…”

“…These clinical characteristics of NC-CAH cases do not differ from those shown in patients with polycystic ovary syndrome (PCOS), idiopathic hirsutism or hyperinsulinemia [8][9][10][11][12][13]. The incidence of 21-OHdef among hirsute women varies between 1.2-20% [8][9][10][11][12]14]. The disparity in these findings could be due to the variability of the 21-OHdef gene in different populations, the variability in protocols of studies and the lack of similarity of the patient populations in different studies [7].…”

“…In women with CAH hyperandrogenism may be present, extending from virilization of external genitalia and salt wasting in C-CAH cases, to menstrual irregularity, obesity, short stature, infertility or subfertility and skin disorders (hirsutism, seborrhea and/or acne in peripubertal period) in NC-CAH cases. These clinical characteristics of NC-CAH cases do not differ from those shown in patients with polycystic ovary syndrome (PCOS), idiopathic hirsutism or hyperinsulinemia [8][9][10][11][12][13]. The incidence of 21-OHdef among hirsute women varies between 1.2-20% [8][9][10][11][12]14].…”

Genotype-phenotype associations in non-classical steroid 21-hydroxylase deficiency

“…Furthermore, while all the patients of group B presented in the ®rst decade with either premature/early pubarche, precocious/early puberty, clitoromegaly or growth acceleration, the presentation of group A subjects was much more variable; all the postpubertal patients belonged to this group, as well as the three`asymptomatic' parents who were detected by family screening. The explanations for the phenotypic heterogeneity among individuals carrying the same mutations are still hypothetical and include the presence of other still unidenti®ed mutations, the activity of other genes encoding proteins with extra-adrenal 21-hydroxylase activity (26), individual variation in the amount of protein produced (27), differences in intra-adrenal concentrations of progesterone (2), and differences in sensitivity to androgens (28).…”

Hirsutismo: diagnóstico

“…A hiperplasia adrenal congênita forma não clássica (HAC-NC) por deficiência da 21-hidroxilase (CYP21) é a causa mais frequente de hirsutismo de origem adrenal, embora sua Di retrizes em foco prevalência, entre mulheres hirsutas como um todo, seja relativamente baixa, variando entre 2% e 10% das pacientes consultando por hirsutismo 16,17 (C) 18 (d) No sul do Brasil, a frequência observada foi de 7,4% 6 (d). A apresentação clínica é variável, incluindo acne, hirsutismo, alopecia androgênica, distúrbio menstrual e anovulação crônica.…”