The Prevalence, Molecular Analysis and HLA Typing of Late-onset 21-Hydroxylase Deficiency in Turkish Woman with Hirsutism and Polycystic Ovary

Abstract

Abstract. We studied the incidence of late-onset congenital adrenal hyperplasia (LOCAH) due to 2l-hydroxylase (21-OH) deficiency, its molecular genotype expression, and its association with the major histocompatibility complex in 61 women with hirsutism and polycystic ovary. Ultrasound, clinical and hormonal parameters were used to define polycystic ovary syndrome (PCOS). Baseline and ACTH stimulated 17a-hydroxyprogesterone (17-OHP) levels were measured for screening of LOCAH during follicular phase. Forty-one women were diagnosed as having PCOS (67%) and 20 women were diagnosed as having had LOCAH due to 2l-OH deficiency (33%). In LOCAH patients, the most common mutation (Val281-Leu, V281L) was found in 10 patients (7 heterozygous/3 homozygous). The frequency of V281L mutation was found as 32.5% in 20 patients. All patients with the V281L mutation presented HLA-B14 (100%) and six of them presented DR1 (60%), confirming that LOCAH is linked to the histocompatibility complex. Although molecular analysis is a better and more accurate means for an exact and precise definition of LOCAH, it is not routinely available in our country. So, ACTH stimulation test combined with HLA-B14 typing should be more widely utilized in these patients. As a result, LOCAH due to 21-OH deficiency is unexpectedly high in Turkish patients with hirsutism and PCO.

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

“…These findings are in agreement with our previous paper on the high frequency and the positively genetic linkage disequilibrium of HLA phenotypes B14, DR 1 , B 35 , B 47 , B 22 and B 7 and 21-OHdef in Greece [41]. In group C (that, is the group of women with PCOS) there are a considerably great number of women with 17-OHP 60 values between 21 nmol/l and 32 nmol/l (10 out of 22) (45%).…”

“…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]. Recently published papers in Turkey, reported a high prevalence of NC-CAH due to 21-OHdef in women suffering from hirsutism and PCOS [11,34,35].…”

“…Recently published papers in Turkey, reported a high prevalence of NC-CAH due to 21-OHdef in women suffering from hirsutism and PCOS [11,34,35]. Kamel and Yarman reported a prevalence of 9.52% and 33%, respectively, in these women [34,35]. A high prevalence was also reported by Italians, Hispanics, Yugoslavians and Arabs.…”

The prevalence of non-classic adrenal hyperplasia among Turkish women with hyperandrogenism

“…Although there were some studies regarding the prevalence of NCAH due to 21-OH deficiency among hirsute Turkish women, these studies were local, not having any detailed genotype investigation and have been performed with relatively small number of patients [17,18] study investigating the prevalence of NCAH due to 21-OH deficiency among Greek women with hirsutism and PCOS showed a relatively higher (10.3%) prevalance compared with other European communities [21]. However, diagnosis of 21-OH deficiency has not been confirmed by molecular genetic analysis in these patients.…”

Late-onset Congenital Adrenal Hyperplasia with Cushing Syndrome

“…Another study found 21-hydroxylase deficiency to be present in 33% of patients with symptoms of PCOS and hirsutism (14). The largest study (n=205) from Turkey reported a frequency of LCAH of 9.75% among patients with hirsutism (15).…”