Clinical and Biological Phenotypes in Late-Onset 21 Hydroxylase Deficiency

Abstract

We analyzed data from 20 patients with late-onset 21-hydroxylase deficiency (LOHD). Three clinical phenotypes could be distinguished among the 18 women. Seven (39%) presented with clinical features suggesting polycystic ovarian disease (PCOD). However, despite androgen levels similar to those of patients with typical PCOD, high serum LH to FSH ratios were not consistently found. Seven other women (39%) presented with isolated hirsutism, suggesting idiopathic hirsutism. The remaining 4 women (22%) had no manifestations of androgen excess and were considered to have the cryptic form of LOHD. Serum 17-hydroxyprogesterone (17-OHP) and androgen levels were similar in the 3 phenotypes, suggesting that the clinical expression of LOHD in women is modulated by individual factors, such as androgen sensitivity. The 2 men were detected by family study and were clinically normal. Since clinical diagnosis of LOHD is impossible, we concentrated on hormonal data with the aim of providing guidelines for the biological diagnosis of LOHD. Assay of basal serum 17-OHD at 0800 h in both sexes and in the early follicular phase in women was sufficient to establish the diagnosis of LOHD in most patients. If doubtful results are obtained, i.e. serum 17-OHP levels between 2 and 5 ng/ml, an ACTH test must be performed. Post-ACTH serum 17-OHP levels exceeding 10 ng/ml confirm the diagnosis of LOHD. Such results should avoid confusion with heterozygotes for 21-hydroxylase deficiency, whose frequency is high within the general population and may be even higher in patients with idiopathic hirsutism or PCOD.

The frequency of late-onset 21-hydroxylase and 11 beta-hydroxylase deficiency in women with polycystic ovary syndrome

“…Emans et al (31) have reported a patient with LOCAH diagnosed by ACTH testing and HLA studies, an elevated LH level, and PCO by laparoscopy. Dewailly et al (17) have found an elevated LH : FSH ratio in 23% of patients with LO 21-OH deficiency. In many patients with PCOS, dexamethasone treatment is associated with a frequency of ovulation, and can reverse symptoms of hyperandrogenism (5,30).…”

“…In addition, sonographic abnormalities of the ovaries may be similar in women with PCOS and women with adrenal enzyme defects (29,30). Although the classical laboratory findings in PCOS are an elevated level of serum LH and an elevated LH : FSH ratio, this can also be found in LOCAH (17,31,32) and approximately 60% of patients with PCOS do not have this inappropriate gonadotropin secretion (33,34). Emans et al (31) have reported a patient with LOCAH diagnosed by ACTH testing and HLA studies, an elevated LH level, and PCO by laparoscopy.…”

“…In many patients with PCOS, dexamethasone treatment is associated with a frequency of ovulation, and can reverse symptoms of hyperandrogenism (5,30). The clinical feature suggesting PCOS was identified in 39% of females with diagnosis of LO 21-OH deficiency (17). Hague et al (6) found polycystic ovaries in 83% of 36 adult patients with congenital adrenal hyperplasia due to 21-OH deficiency.…”

“…Animals given adrenal androgens develop a disorder equivalent to PCOS (15). PCOS may develop as a consequence of excessive adrenal androgen secretion in at least some patients (16,17). Polycystic ovaries have been noted on sonography moderately frequently in patients with LO 21-OH deficiency (6,18), 11b-hydroxylase (11b-OH) deficiency (19) and 3b-hydroxysteroid dehydrogenase deficiency (20).…”

Non-classic congenital adrenal hyperplasia

“…those with hyperandrogenic features or ovulatory/menstrual dysfunction). Various investigators have suggested the use of unstimulated levels of 17-OHP as a predictor of NCAH [24,57,87,88]. Levels of 170-300 ng/dL have been found to be useful as a screening tool, best if obtained in the morning and, most importantly (to reduce false positives), in the follicular (preovulatory) phase of the menstrual cycle Among 129 Portuguese women with hyperandrogenism and menstrual dysfunction, 87% of women with NCAH, 25% of lean women with PCOS, 20% of obese women with PCOS, and 7% of control women had basal 17-OHP concentrations >200 ng/dL [20].…”