Polycystic Ovary Syndrome and NC-CAH: Distinct Characteristics and Common Findings. A Systematic Review

Abstract

Background: Twenty-one-hydroxylase–deficient non-classic adrenal hyperplasia (NC-CAH) is a very common autosomal recessive syndrome with prevalence between 1:1,000 and 1:2,000 individuals and the frequency varies according to ethnicity. On the other hand, polycystic ovary syndrome has a familial basis and it is inherited under a complex hereditary trait. This syndrome affects 6 to 10% of women in reproductive age and it is the most common endocrine disorder in young women. Our aim was to investigate, through a systematic review, the distinct characteristics and common findings of these syndromes. Methods: The search period covered January 1970 to November 2018, using the scientific databases PubMed. Inclusion criteria were adult women patients with PCOS or NC-CAH. Search terms were “polycystic ovary syndrome,” “PCOS,” “non-classical adrenal hyperplasia,” “NC-CAH,” “21-hydroxylase deficiency.” From an initial 16,255 titles, the evaluations led to the final inclusion of 97 papers. Results: The clinical features of NC-CAH are hirsutism and ovulatory and menstrual dysfunction therefore; differentiation between these two syndromes is difficult based on clinical grounds only. Additionally, NC-CAH and PCOS are both associated with obesity, insulin resistance, and dyslipidaemia. Reproductive abnormalities are also common between these hyperandrogenemic disorders since in patients with NC-CAH polycystic ovarian morphology and subfertility are present as they are in women with PCOS. The diagnosis of PCOS, is confirmed once other disorders that mimic PCOS have been excluded e.g., conditions that are related to oligoovulation or anovulation and/or hyperandrogenism, such as hyperprolactinaemia, thyroid disorders, non-classic congenital adrenal hyperplasia, and androgen-producing neoplasms. Conclusions: The screening tool to distinguish non-classic adrenal hyperplasia from PCOS is the measurement of 17-hydroxyprogesterone levels. The basal levels of 17-hydroxyprogesterone may overlap, but ACTH stimulation testing can distinguish the two entities. In this review these two common endocrine disorders are discussed in an effort to unveil their commonalities and to illuminate their shadowed distinctive characteristics.

A study comparing the clinical and hormonal profile of late onset and persistent acne in adult females

“…In our study, in the persistent acne group, increased levels of 17‐OHP beyond 2 ng/ml were seen in eight patients thus by using the cut‐off values suggested by previous authors, only 15.38% of persistent acne patients can be been labeled as NCCAH (Table ). While an ACTH stimulation test could not be performed because of lack of ethical clearance, it must be noted that the cardinal test for confirmation of diagnosis of NCCAH is molecular genetic analysis of the CYP21A2 gene, a facility that we do not have at our center. Also it is pertinent to point out that a diagnosis of NCCAH generally will not change the best choice of treatment, because glucocorticoids are less effective than estrogen‐progestin contraceptives and/or antiandrogens for the treatment of chronic anovulation and hirsutism in women with NCCAH, both of which are notably also used for the treatment of adult female acne without NCCAH as well …”

Clinical outcomes and characteristics of P30L mutations in congenital adrenal hyperplasia due to 21-hydroxylase deficiency

“…There are no detailed data on fertility issues in patients with P30L mutation except the report of two female patients with P30L mutation and SV phenotype requiring genital surgery and several artificial assisted reproduction cycles [ 40 ]. In populations with a high prevalence of NC CAH, many females are diagnosed as PCOS [ 149 – 151 ]. NC CAH needs to be excluded before diagnosing PCOS [ 22 , 82 , 152 , 153 ].…”

Simultaneous quantitation of four androgens and 17‐hydroxyprogesterone in polycystic ovarian syndrome patients by LC‐MS/MS

“…39 Similarly, in present study, the However, according to their logistic regression study using forward stepping models, it was found that their large steroid panel was no According to the current PCOS diagnosis guideline, 38 it is required and necessary to exclude the possibility of NCAH mimicking the symptoms of PCOS. In a recent review article comparing PCOS and NCAH, 41 on average, 87% of NCAH patients and 25% of PCOS patients showed elevated serum 17-OHP levels, which was the only recommended screening assay to differentiate the two distinct diseases requiring different therapeutic treatments. By contrast, the common androgens such as T and DHEAS were also elevated in NCAH, limiting their applications in differentiating NCAH from PCOS.…”