title: Non-classic adrenal hyperplasia due to the deficiency of 21-hydroxylase and its relation to polycystic ovarian syndrome.
abstract: Non-classic adrenal hyperplasia (NCAH) is a disease in which a partial deficiency of the steroidogenic enzyme 21-hydroxylase produces mild to moderate hyperandrogenemia, hirsutism, polycystic ovaries, oligomenorrhea or amenorrhea, insulin resistance, male pattern baldness and subfertility. The resemblances between NCAH and polycystic ovary syndrome (PCOS) are manifest, and a relation between the two has been sought by many authors trying to identify subtle alterations in the CYP21 gene transcription end-products as the cause or a contributing cause of PCOS. On the other hand, the differences that may differentiate these two diseases have also been the focus of research by many groups, searching for clinical markers that might help to distinguish the two conditions. Insulin resistance or the polycystic ovarian morphology once thought to be hallmarks of PCOS have been proven to exist also in NCAH. Obesity, not being a diagnostic criterion of either but being very prevalent in PCOS women is also present in many NCAH women, and hence is not helpful in the distinction between the two. And if it is a fact that women with NCAH have a higher prevalence of normal ovulation and lower likelihood of having an LH/FSH ratio >2 or polycystic ovaries, in comparison to PCOS, it is also true that even in those parameters overlap does exist. Besides 17-OH-progesterone, progesterone, androstenedione and testosterone are elevated in most NCAH cases, similarly to what occurs in PCOS patients. The only exception in fact is the level of 17-OH-progesterone and progesterone that are not significantly elevated in PCOS, at least not to the levels attained in NCAH. Our recommendation, thus, is that NCAH should be excluded in all women presenting with hirsutism, oligomenorrhea and infertility. A basal follicular phase 17-hydroxyprogesterone level should be used as a screening tool, regardless of the presence of polycystic ovaries or metabolic dysfunction; in the case of doubt, an ACTH stimulation test is recommended. Levels above 10 ng/ml (30 nmol/l), either basal or after stimulation should be considered as diagnostic of NCAH, and some of those patients, particularly the ones that are planning to conceive, should be genotyped, mainly with the purpose of genetic counseling. Treatment of NCAH women normally requires the use of the same anti-androgenic weapons as PCOS but some may benefit from the administration of small doses of glucocorticoids. Curiously, some studies have demonstrated that PCOS cases too may benefit from the administration of glucocorticoids.
authors.affiliation: Department of Endocrinology, Hospital S João, PT–4200-319 Porto, Portugal. dpignatelli@ipatimup.pt
authors.forename: Duarte
authors.initials: D
authors.lastname: Pignatelli
mesh_terms: D019326:17-alpha-Hydroxyprogesterone / Q000097:blood; D000312:Adrenal Hyperplasia, Congenital / Q000175:diagnosis* / Q000188:drug therapy; D000324:Adrenocorticotropic Hormone; D002318:Cardiovascular Diseases / Q000209:etiology; D003937:Diagnosis, Differential; D005260:Female; D005938:Glucocorticoids / Q000627:therapeutic use; D006579:Heterozygote; D006628:Hirsutism / Q000209:etiology; D006801:Humans; D007247:Infertility, Female / Q000209:etiology; D007333:Insulin Resistance; D009765:Obesity / Q000150:complications; D009839:Oligomenorrhea / Q000209:etiology; D011085:Polycystic Ovary Syndrome / Q000175:diagnosis*; D012307:Risk Factors; D013255:Steroid 21-Hydroxylase / Q000235:genetics*
chemical_list: D005938:Glucocorticoids; D019326:17-alpha-Hydroxyprogesterone; D000324:Adrenocorticotropic Hormone; C531510:CYP21A2 protein, human; D013255:Steroid 21-Hydroxylase