Nonclassic Adrenal Hyperplasia Research Articles

SAT358 Race And Ethnicity Of Women With 21-hydroxylase Deficient Non-classic Adrenal Hyperplasia (NCAH) Compared With PCOS

Abstract Disclosure: L.A. Pace: None. K.L. VanHise: None. J.L. Chan: None. M.D. Pisarska: None. R. Azziz: Advisory Board Member; Self; Arora Forge. Consulting Fee; Self; Rani Therapeutics, Fortress Biotech, Spruce Biosciences, Core Access Surgical Technologies. Grant Recipient; Self; Foundation for Research and Education Excellence, Ferring Pharmaceuticals. Stock Owner; Self; Martin Imaging. Background: 21-hydroxylase (21-OH) deficient non-classic adrenal hyperplasia (NCAH) is found in 1-10% of androgen excess patients and is one of the most common autosomal recessive disorders in humans. In turn, PCOS has complex inheritance and is one of the most common endocrine disorders of women. Objective: To compare the racial and ethnic distribution of NCAH vs. PCOS in a referral population. Methods: We analyzed data from a database collected prospectively of consecutive female patients presenting with androgen excess at a tertiary care referral clinic. Results: Among 645 consecutive female patients with androgen excess who completed their evaluation, 15 (2.3%) had NCAH and 619 (96.0%) had PCOS defined by the Rotterdam 2003 criteria. Of 15 women with NCAH, 13 (86.7%) were White (10 White Non-Hispanic [WNH] and 3 White Hispanic [WH]), one (6.7%) was Asian, and one (6.7%) was of mixed race. Of PCOS subjects, 479 (77.4%) were White (347 WNH, 121 WH, and 11 of undocumented ethnicity), 65 (10.5%) were Black (55 Black Non-Hispanic [BNH], 5 Black Hispanic [BH], and 5 were Black of undocumented ethnicity), 47 (7.6%) were Asian Non-Hispanic (ANH), 6 (1.0%) were Native Hawaiian/Pacific Islander Non-Hispanic, 14 (2.3%) were of mixed race (4 Hispanic and 10 Non-Hispanic), and 7 (1.1%) were other or undocumented race. Comparing key phenotypic features, the mean (±SD) age at first visit for NCAH patients was 33.1 (±14.1) years vs. 28.9 (±6.9) for PCOS (p=0.03); mean BMI of NCAH patients was 27.7 (±8.2) kg/M2 vs. 30.2 (±8.2) in PCOS (p=0.26); mean Ferriman-Gallwey (FG) score for NCAH patients was 8.6 (± 6.2) vs. 6.7 (±5.1) PCOS (p=0.19); and mean menstrual cycles per year were 7.8 (±5.2) in NCAH vs. 6.0 (±3.9) in PCOS (p=0.12). Conclusions: Phenotypically, patients with NCAH were slightly older, but did not differ in BMI, degree of hirsutism, or menstrual dysfunction vs. PCOS patients, emphasizing the need to screen for NCAH using basal follicular-phase measurements of 17-hydroxyprogesterone. However, there were notable racial differences between the NCAH and PCOS cohorts. While 10% of PCOS patients were Black in this referral clinic database, no patient with NCAH was Black. The paucity of NCAH among Black individuals evaluated for androgen excess mirrors the ethnic/racial distribution in the classic form of 21-OH deficient adrenal hyperplasia. These data question whether Black women suspected of androgen excess or PCOS should be routinely screened for NCAH. Presentation Date: Saturday, June 17, 2023

Is there any link between non-classic adrenal hyperplasia (NCAH) and glucose metabolism?

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Nonclassic Adrenal Hyperplasia (NCAH) due to 21-hydroxylase deficiency: A cohort of 78 patients

Diagnosis of nonclassic adrenal hyperplasia (NCAH) due to 21-hydroxylase deficiency (21-OHD) may be challenging due to its occult manifestations. To characterize clinical and molecular features of NCAH patients due to 21-hydroxylase deficiency, we retrospectively included 78 NCAH patients. Their phenotype and genotype were presented and compared. The transcription activities of novel CYP21A2 promoter variants were investigated using a dual-reporter luciferase assay system. This cohort included 53 females (68 %) and 25 males (32 %). The median of onset age was 13 years old (female: 13 range from 7 to 38; male: 11 range from 6 to 71). Menstrual cycle disorder was the most common complaint in females (62 %, n = 33) and for males, it was adrenal incidentalomas (52 %, n = 13). A total of 17 (22 %) patients complained of infertility. The most frequently variant was p.Ile173Asn (20 %, n = 31). Importantly, five variants in the promoter region including − 103/− 126 and − 196/− 296 were found in 21 (27 %) patients. Patients with promoter variants showed older onset age and less impaired hormone levels of 17-hydroxyprogesterone, ACTH, progesterone, and androstenedione. Compared with the wild-type promoter, the basic transcription activity of − 103/− 126 and − 196/− 296 promoter variants were reduced by 57% and 25%, respectively. Therefore, females with menstrual cycle disorders or infertility and males with adrenal incidentaloma should be considered of NCAH due to 21-OHD. When genotyping patients with NCAH, the promoter region of the CYP21A2 gene should be also investigated.

P-548 IMPORTANCE OF EXPANDED CARRIER SCREENING AMONG OOCYTE DONORS - questions and concerns

Abstract Study question To examine the utility of a range of expanded screening panels for oocyte donors. Summary answer Expanded carrier screening with NGS data identified that 86% of gamete donors were carriers of at least one condition while 302 genes were tested. What is known already The level of genetic testing for oocyte donors is not regulated in most countries. The use of expanded carrier screening is recommended more widely. If the egg donor is a carrier, there is a 50% chance that the offspring will also be carriers. Expanded carrier screening is performed to determine the potential effects of positive carrier status, which guarantees safety for future pregnancy. From practical experience, more genes are tested for a donor, more potential mutations are detected. Study design, size, duration A cohort of 92 potential oocyte donor applicants aged 18-30 years old, who were qualified for oocyte donation after full screening, tested negative on an initial cystic fibrosis carrier test for 11 most common CFTR mutations (PCR panel), was further screened with expanded commercial carrier testing panel (302 genes) using next-generation sequencing (NGS) data. Participants/materials, setting, methods A cohort of 92 potential oocyte donor applicants aged 18-30 years old, who tested negative on an initial cystic fibrosis carrier test for 11 most common CFTR mutations (PCR panel), was further screened with expanded commercial carrier testing panel (302 genes) using next-generation sequencing (NGS) data. Main results and the role of chance Genotyping results for all donors were analyzed; 38% (35/92) of donors were identified as carriers for one condition, 34% (31/92)- for two conditions, 7% (6/92)- for three conditions and 7% (6/92)- for four conditions, including cystic fibrosis. Among the most prevalent conditions in our study were: Hemochromatosis: Type 1: HFE Related- 22%, Cystic Fibrosis: CFTR-related conditions 11%, Biotinidase deficiency– 7,6%, 21-Hydroxilase-Deficient Congenital Nonclassical Adrenal Hyperplasia- 6,5%, Krabbe disease – 6,5%, Usher syndrome: USH2A-related conditions – 6,5%, Nonsyndromic deafness: GJB2- related conditions- 5,4% and Smith-Lemli-Opitz syndrome (5,4%). Limitations, reasons for caution Each donor was consented for genetic testing Wider implications of the findings This study shows a need to provide the explicit requirement for oocyte donor genetic testing and guidelines to satisfy quality and safety and not reduce the number of donors carries of mutations, but to implement a practice of genetic matching. Trial registration number not applicable

Hormonal and metabolic features of the androgenic phenotypes of polycystic ovary syndrome and non-classic adrenal hyperplasia with various polymorphic variants in the CYP17A1 gene

The CYP17A1 gene encodes the most important stages of sex steroid biosynthesis by the adrenal glands and ovaries. The objective of this study was to evaluate the hormonal and metabolic status of patients with hyperandrogenia and the CYP17A1 rs743572 gene polymorphism. We examined 106 women with polycystic ovary syndrome androgen phenotypes A, B, and C and 28 women with latent non-classic congenital adrenal hyperplasia. It was found that there were no significant differences in the frequency of CYP17A1 alleles and genotypes between the three phenotype groups of patients with polycystic ovary syndrome. Body mass index and insulin resistance after glucose loading were comparable in individuals with these phenotypes of polycystic ovary syndrome. The CYP17A1 gene polymorphism in patients with different polycystic ovary syndrome phenotypes and in individuals with latent non-classic congenital adrenal hyperplasia did not associate with the concentration of estradiol and androgens in the blood. Neither did LH / FSH ratio differ between groups with different allelic variants of the CYP17A1 gene. These results show that patients with different polycystic ovary syndrome phenotypes do not require differentiated therapy. Serum levels of DHEA-S and cortisol were elevated in 38.7% of women with polycystic ovary syndrome without non-classic congenital adrenal hyperplasia, which indicates an adrenal cause of hyperandrogenia. We suppose that in the diagnosis of polycystic ovary syndrome, it is necessary to define not only phenotypes, but also a suprarenal source of androgens. The therapy of these patients may require application of corticosteroids besides the usual methods in planning of pregnancy.

Non-Classic Adrenal Hyperplasia, Insulin Resistance, and Vitamin D

Non-Classic Adrenal Hyperplasia, Insulin Resistance, and Vitamin D

Association of Vitamin D Repletion with Normalization of Elevated Serum 17-OH-Progesterone

Insulin resistance is associated with a number of conditions, such as non-classic 21-hydroxylase deficiency and allied disorders. Serum vitamin D is often deficient/ insufficient in insulin resistant individuals. Disorders associated with insulin resistance are often mitigated in association with vitamin D repletion. Here we report a patient with type 2 diabetes mellitus, lower extremity infection, vitamin D insufficiency, and elevated unstimulated serum 17-OH-progesterone (17-OHP), which normalized during vitamin D repletion. Serum 25-OHvitamin D (25-OHD) rose by 32% while serum 17-OHP fell by 87% over the course of four weeks receiving 50,000 IU ergocalciferol orally weekly. Vitamin D repletion in this setting restored normal serum 25-OHD levels and was associated with normalization of elevated serum 17-OHP. Serum 25-OHD levels should be determined before commencing glucocorticoids or mineralocorticoids for the treatment of elevated serum 17-OHP in disorders like non-classic adrenal hyperplasia (NCAH) and levels of 17- OHP, should be re-measured when vitamin D levels are replete to determine whether glucocorticoid/ mineralocorticoid replacement is actually necessary.

Expanded carrier screening in gamete donors of Venezuela.

ObjectiveTo discuss the implications of expanded genetic carrier screening for preconception purposes based on our practice.MethodsOne hundred and forty-three potential gamete donors aged 20-32 years old (µ=24, 127 females and 16 males), signed informed consent forms and were selected according to the REDLARA guidelines. Blood or saliva samples were examined by one of these genetic carrier screening methods: Genzyme screening for Cystic Fibrosis (CF), Fragile X and Spinal Muscular Atrophy (SMA); Counsyl Universal panel or Recombine Carrier Map.ResultsGenotyping results for all donors were analyzed; 41% (58/143) of donors were identified as carriers for at least one condition. We found a carrier frequency of 1/24 for CF, 1/72 for SMA and 0/120 for Fragile X syndrome. Among the high-impact most prevalent conditions in our study (Carrier Map group) were: 21-Hydroxilase-Deficient Congenital Nonclassical Adrenal Hyperplasia (1/8), Factor V deficiency (1/12), Hemochromatosis: Type 1: HFE Related (1/12), Short Chain Acyl-CoA (1/14) and MTHFR deficiency 1/3 (39%).ConclusionsThe rate of gamete donors identified as carriers of at least one condition was 41%, which supports the offering of expanded carrier screening to our population. Studies in Latin American populations could help customize screening panels. The ART patient population has a unique opportunity to be offered expanded carrier screening and appropriate counseling, to make its best-informed decisions.

Polycystic Ovary Syndrome: An Apparently Simple yet Challenging Diagnosis.

Polycystic Ovary Syndrome: An Apparently Simple yet Challenging Diagnosis.

Diagnostic evaluation of patients presenting with hirsutism

Objective: Hirsutism, similar to men, is the presence of terminal hairs in androgen-to sensitive areas in women. The present report aimed to study etiology and determine the prevalence of the diseases that causes hirsutism in these patients. Methods: In this study, total number of 40 patients who admitted because of hirsutism to Department of Endocrinology and Metabolism clinic was enrolled. Demographic, clinical and laboratory parameters of the patients were evaluated. Results: Result of the study showed that polycystic ovary syndrome is the most common cause of hirsutism. The second most common cause was found as idiopathic hirsutism. Conclusion: By the present study, etiologic factors of hirsutism were examined firstly in our region in which Ethnic and cultural diversity is concentrated. In rare cases like Cushing's syndrome, hyperprolactinemia, non-classic adrenal hyperplasia, androgen-secreting tumors should be considered in the differential diagnosis of hirsutism.

Hiperplasia congénita da suprarrenal não clássica – aspetos relevantes para a prática clínica

AimNonclassical congenital adrenal hyperplasia is one of the most common autosomal recessive disorders and, in the majority of cases, is due to 21‐hydroxylase (21‐OH) enzyme deficiency. With this article we intend to review the relevant aspects of this disease in daily clinical practice, particularly in the areas of pediatrics, endocrinology and obstetrics. MethodsA bibliographic review was performed through the electronic database MEDLINE, for articles published between 1990 and 2013. The keywords used were “nonclassical adrenal hyperplasia” and “21‐hydroxylase deficiency.” ConclusionsThe clinical presentation of nonclassical adrenal hyperplasia is variable: it can be asymptomatic or cause symptoms related to androgen excess as premature pubarche, hirsutism, oligomenorrhea, acne or infertility. The diagnosis is confirmed by a tetracosactide stimulation test. Treatment is reserved for symptomatic individuals, must be individualized and its main goals are to avoid premature pubarch with premature epiphyseal fusion, to regulate the menstrual cycles, to promote fertility and to reduce hirsutism and acne.

Polycystic ovary syndrome, microbiomics and why you should be a little selfish with your time

Interview by Rona WilliamsonRicardo Azziz, MD, MPH, MBA, is Professor of Obstetrics and Gynecology (Ob/Gyn), Medicine and Medical Humanities, and President, at Georgia Regents University and CEO of the Georgia Regents Health System, Augusta, GA, USA. Georgia Regents University is one of Georgia’s four public comprehensive research universities, with recognized strengths in the health sciences, and including the state’s only academic health center. Formerly, Dr. Azziz served as Deputy Director for the Clinical and Translational Sciences Institute, Assistant Dean for Clinical and Translational Sciences, Vice-Chair of the Department of Ob/Gyn and co-Director of the Reproductive Endocrinology Fellowship Training Program at UCLA; and Director of the Center for Androgen-Related Disorders and Chair, Department of Ob/Gyn at the Cedars-Sinai Medical Center, Los Angeles, CA, USA. Dr. Azziz is an internationally recognized authority on androgen excess (disorders related to excess male hormones) in women, having published over 400 original peer-reviewed articles, book chapters and reviews. He has been funded by the NIH, among other entities, for his research for more than 25 years. Dr. Azziz’s laboratory has contributed significantly to the field of androgen excess research. This has included: establishing the populational prevalences and economic impact of the polycystic ovary syndrome (PCOS), the single most common form of androgen excess, idiopathic hirsutism and nonclassic adrenal hyperplasia, the most common form of an inherited defect of adrenal function in man; determining the familial risk for PCOS and elucidating some of the candidate genes that play a role in the disorder; identifying many of the molecular, genetic and physiologic mechanism(s) resulting in adrenal androgen excess in PCOS; and beginning to identify the unique defects in the molecular action of fat tissue in PCOS. In 2000, he received the President’s Achievement Award of the Society for Gynecologic Investigation for his research, and in that same year, he founded the Androgen Excess and PCOS Society, the only worldwide organization dedicated to promoting education and research in these disorders, where he currently serves as Senior Executive Director. His passion and focus for improving the care of women affected by reproductive endocrine disorders, and in particular androgen excess, has been recognized widely, including being named as one of, ‘America’s Top Doctors’ (Castle Connolly Medical Ltd, New York, NY, USA) from 2001 to present, and being recognized by various other lay press and patient-focused venues. Dr. Azziz’ musings on leadership, academics and healthcare can be seen at his blog site ‘Sculpting in Clay’ and now the Huffington Post .

Non-classic adrenal hyperplasia (NCAH) in patients with bilateral adrenal incidentally discovered tumors

Non-classic adrenal hyperplasia (NCAH) in patients with bilateral adrenal incidentally discovered tumors

Management of congenital adrenal hyperplasia in childhood

Congenital adrenal hyperplasia (CAH) can present management challenges to the pediatric clinician. Glucocorticoid replacement remains the cornerstone of treatment; however, there are new formulations and delivery mechanisms being studied. Clinicians continue to discuss the optimal treatment of patients from the prenatal stage, through infancy to adulthood. As well, the role of genetics in the clinical care of patients with CAH, and screening for complications, remain topics of discussion. This review will highlight advances made in the past year, as they pertain to the management of pediatric patients with CAH. This article covers recent studies pertaining to optimal medication regimens, including prenatal dexamethasone treatment; medication delivery; monitoring of hormonal control; and the role of genotyping and genetics in the management of children with CAH. Much remains to be learned about the optimal management of children with CAH, including fludrocortisone replacement in simple-virilizing patients, frequency of specific monitoring strategies (e.g., electrolytes, bone age), catecholamine status, stress-dosing in nonclassical adrenal hyperplasia, and early screening for complications or metabolic sequelae. Further randomized and prospective studies are needed to address these issues.

Malignant Ovarian Sertoli-Leydig Cell Tumor Localized With Selective Ovarian Vein Sampling

Sertoli-Leydig cell tumors (SLCT) are rare, comprising less than 0.5% of ovarian neoplasms. They are most often diagnosed in premenopausal women and may produce androgens, resulting in hirsuitism, voice deepening, frontal balding, terminal hair growth, and clitoromegaly. SLCT are malignant in 15%–20% of cases. We discuss a 25-year-old patient with persistent hyperandrogenemia. Noninvasive imaging cannot conclusively differentiate between SCLT and other diagnoses such as polycystic ovary syndrome, ovarian hyperthecosis, idiopathic hyperandrogenism, idiopathic hirsuitism, and 21-hydroxylase-deficient nonclassic adrenal hyperplasia. Selective ovarian vein sampling revealed a 15-fold greater testosterone production from the right ovary compared with the left, which guided appropriate surgical management.

Non polycystic ovary syndrome–related endocrine disorders associated with hirsutism

Hyperandrogenism refers to classical androgen-dependent signs such as hirsutism, acne and androgenetic alopecia. Hirsutism is the main hyperandrogenic symptom, defined as an excess of body hair in the androgen-sensitive skin regions of the women. In this review, we attempt to focus on the pathogenesis of hirsutism related to disorders other than polycystic ovary syndrome (PCOS). Also, we will discuss their clinical and biochemical features as well as therapeutic options. Several original articles, meta-analysis and reviews have been screened in the field of hirsutism and hyperandrogenic disorders. Current English literature including our studies suggests that PCOS is the most common cause of hirsutism. The most important purpose for investigation is to identify those women with androgen-secreting tumours because of their life-threatening potential. In approximately 1-8% of the women with hirsutism, the underlying cause is nonclassical adrenal hyperplasia because of 21-hydroxylase deficiency. Depending on ethnicity and the geographic area, idiopathic hirsutism constitutes 5-17% of the patients with hirsutism. Approximately 3% of hyperandrogenic women were observed to suffer from hyperandrogenic-insulin-resistant acanthosis nigricans syndrome. More rare causes are glucocorticoid resistance syndrome, hyperprolactinemia, acromegaly, Cushing's syndrome and some drugs. Specific causes of hirsutism such as Cushing's syndrome and adrenal/ovarian tumours should be treated specifically. In other patients, pharmacological approach is the mainstay of therapy. A number of patients presenting with hirsutism and exhibiting similar features to PCOS may have other underlying diagnoses. Unlike PCOS, some of these disorders can occasionally be life threatening and require prompt diagnosis and treatment.

Characterization of Novel StAR (Steroidogenic Acute Regulatory Protein) Mutations Causing Non-Classic Lipoid Adrenal Hyperplasia

ContextSteroidogenic acute regulatory protein (StAR) is crucial for transport of cholesterol to mitochondria where biosynthesis of steroids is initiated. Loss of StAR function causes lipoid congenital adrenal hyperplasia (LCAH).ObjectiveStAR gene mutations causing partial loss of function manifest atypical and may be mistaken as familial glucocorticoid deficiency. Only a few mutations have been reported.DesignTo report clinical, biochemical, genetic, protein structure and functional data on two novel StAR mutations, and to compare them with published literature.SettingCollaboration between the University Children's Hospital Bern, Switzerland, and the CIBERER, Hospital Vall d'Hebron, Autonomous University, Barcelona, Spain.PatientsTwo subjects of a non-consanguineous Caucasian family were studied. The 46,XX phenotypic normal female was diagnosed with adrenal insufficiency at the age of 10 months, had normal pubertal development and still has no signs of hypergonodatropic hypogonadism at 32 years of age. Her 46,XY brother was born with normal male external genitalia and was diagnosed with adrenal insufficiency at 14 months. Puberty was normal and no signs of hypergonadotropic hypogonadism are present at 29 years of age.ResultsStAR gene analysis revealed two novel compound heterozygote mutations T44HfsX3 and G221S. T44HfsX3 is a loss-of-function StAR mutation. G221S retains partial activity (∼30%) and is therefore responsible for a milder, non-classic phenotype. G221S is located in the cholesterol binding pocket and seems to alter binding/release of cholesterol.ConclusionsStAR mutations located in the cholesterol binding pocket (V187M, R188C, R192C, G221D/S) seem to cause non-classic lipoid CAH. Accuracy of genotype-phenotype prediction by in vitro testing may vary with the assays employed.

The phenotype of hirsute women: a comparison of polycystic ovary syndrome and 21-hydroxylase–deficient nonclassic adrenal hyperplasia

The phenotype of hirsute women: a comparison of polycystic ovary syndrome and 21-hydroxylase–deficient nonclassic adrenal hyperplasia

O286 Comparison of corticoid substitution versus combined oral contraception administration in the treatment of nonclassic adrenal hyperplasia (NCAH)

International Journal of Gynecology & ObstetricsVolume 107, Issue S2 p. S174-S174 Free communication (oral) presentations O286 Comparison of corticoid substitution versus combined oral contraception administration in the treatment of nonclassic adrenal hyperplasia (NCAH) M. Fanta, M. FantaSearch for more papers by this authorM. Hill, M. HillSearch for more papers by this authorJ. Vrbikova, J. VrbikovaSearch for more papers by this authorJ. Belacek, J. BelacekSearch for more papers by this authorD. Cibula, D. CibulaSearch for more papers by this author M. Fanta, M. FantaSearch for more papers by this authorM. Hill, M. HillSearch for more papers by this authorJ. Vrbikova, J. VrbikovaSearch for more papers by this authorJ. Belacek, J. BelacekSearch for more papers by this authorD. Cibula, D. CibulaSearch for more papers by this author First published: 20 November 2009 https://doi.org/10.1016/S0020-7292(09)60658-5AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume107, IssueS2Abstracts of XIX FIGO World Congress of Gynecology and ObstetricsOctober 2009Pages S174-S174 RelatedInformation

The phenotype of hirsute women: a comparison of polycystic ovary syndrome and 21-hydroxylase–deficient nonclassic adrenal hyperplasia

To test the hypothesis that women with polycystic ovary syndrome (PCOS) are distinguishable from those with 21-hydroxylase-deficient nonclassic adrenal hyperplasia on the basis of having polycystic ovaries and metabolic dysfunction. Prospective observational. Tertiary care center. Fifty-two lean and 54 obese women with PCOS according to the 1990 National Institutes of Health criteria, 23 women with nonclassic adrenal hyperplasia, and 27 controls. History and physical examination, blood sampling, ovarian sonography, oral glucose tolerance, and acute adrenocorticotropin stimulation testing. The frequency of clinical, biochemical, and metabolic features. Women with PCOS had a higher frequency of oligomenorrhea or amenorrhea than those with nonclassic adrenal hyperplasia. Mean androstenedione and DHEAS levels were highest in nonclassic adrenal hyperplasia. The degree of metabolic dysfunction was greatest in obese women with PCOS; women with nonclassic adrenal hyperplasia and lean women with PCOS did not differ in degree of metabolic dysfunction. Women with nonclassic adrenal hyperplasia had a lower prevalence of polycystic ovaries than those with PCOS. The proportion of patients with an LH/FSH ratio >2 was greater in women with PCOS, compared with those with nonclassic adrenal hyperplasia. Basal 17-hydroxyprogesterone levels >2 ng/mL were found in 87%, 25%, 20%, and 7% of women with nonclassic adrenal hyperplasia, lean women with PCOS, obese women with PCOS, and controls, respectively. Nonclassic adrenal hyperplasia should be excluded in all women presenting with hirsutism, with use of a basal follicular phase 17-hydroxyprogesterone level, regardless of the presence of polycystic ovaries or metabolic dysfunction; however, women with nonclassic adrenal hyperplasia have a higher prevalence of normal ovulation and lower likelihood of having an LH/FSH ratio >2 or polycystic ovaries.