21-Hydroxylase Deficiency in Female Hyperandrogenism: Screening and Diagnosis

Abstract

21-Hydroxylase-deficient late-onset adrenal hyperplasia (LOAH) appears to affect 1-6% of hyperandrogenic women. Screening and diagnostic criteria for LOAH have not been well established, as these patients are clinically indistinguishable from other hyperandrogenic women. The following prospective study was undertaken to 1) determine the predictive value of screening hyperandrogenic women for LOAH with a morning follicular phase basal 17-hydroxyprogesterone (17-HP) level and 2) compare the various in vivo estimates of 21-hydroxylase activity after adrenal stimulation for the diagnosis of LOAH. Twenty-one euandrogenic control women (physically normal, without hirsutism, with regular menses, and a negative family history) were studied. The clinical population consisted of 164 consecutive unselected patients seen at the Division of Reproductive Endocrinology and Infertility of Johns Hopkins University School of Medicine between 1983 and 1987 demonstrating hirsutism and/or hyperandrogenic oligomenorrhea. Controls and patients underwent acute adrenal stimulation with 1 mg ACTH-(1-24), administered in the morning to fasting patients in the follicular phase of their menstrual cycle. Blood was sampled before and 30 min after ACTH-(1-24) administration. Steroid RIA determinations were performed for 17-HP, progesterone, testosterone, dehydroepiandrosterone sulfate, androstenedione, FSH, LH, and PRL. Three estimates of 21-hydroxylase activity were studied: the 17-HP level 30 min post-ACTH (17-HP30), the change in 17-HP (delta 17-HP0-30) and the summed rate of change in 17-HP and progesterone ([delta 17-HP0-30) + delta P0-30]/30 min). The upper 95th percentiles for these estimates of 21-hydroxylase activity in control women were 9.6 nmol/L (316 ng/dL), 8.8 nmol/L (292 ng/dL), and 0.39 nmol/L.min (13 ng/dL.min), respectively. Thirteen of 164 (7.9%) hyperandrogenic women had at least 1 abnormal 21-hydroxylase measurement. Four of these women (2.4%) had 17-HP measurements 3- to 20-fold above the upper normal 95th percentile (17-HP30 greater than 36.3 nmol/L or 1200 ng/dL) and were considered as suffering from LOAH. In our population the 3 measures of 21-hydroxylase studied clearly differentiated the LOAH women from all others, although a single 17-HP level 30 min post-ACTH was the simplest and most cost effective. Nine other hyperandrogenic women (5.5%) had at least 1 abnormal 21-hydroxylase measurement less than 3-fold the upper normal 95th percentile value and were designated as having mild 21-hydroxylase deficiency.(ABSTRACT TRUNCATED AT 400 WORDS)

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].…”

“…Group B (17-OHP60 values ≥33.2 nmol/l and <90.75 nmol/l) included patients with a moderate form of 21-OH def. In groups A and B all patients were considered as having NC-CAH, as reported in the literature [2][3][4][5][6][7][12][13][14][15][16][17][18][19].…”

“…Group D with 17-OHP60 values <15 nmol/l was composed of unaffected females from NC-CAH and probably a very small number of heterozygous 21-OHdef carriers. In groups C and D all patients were considered as having PCOS, because they did not meet the criterion of 17-OHP60 values >33 nmol/l, of 21-OHdef, as reported in the literature [7,13,17,18,19,21].…”

“…The accurate diagnosis of CAH can be confirmed by molecular gene analysis [12,14], but even today, in clinical practice, molecular biology is not routinely available. ACTH stimulation test remains the principal diagnostic tool [15][16][17][18][19]. The reason for a quick diagnosis of this enzymatic disorder in clinical practice using the adrenal stimulation test is the simplicity of this test.…”

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.…”