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Purpose: Polycystic Ovary Syndrome (PCOS) and Adrenal hyperplasia (CAH) are two pathologic conditions sharing several clinical features (hirsutism, acne, polycystic ovary morphology, metabolic alterations, ovulatory dysfunctions) and especially hyperandrogenism as a common clinical hallmark. Therefore, making a differential diagnosis of the two conditions still remains a great medical challenge., Methods: In particular, the comparison discussed in this review referred to non-classical form of adrenal hyperplasia (NCAH), which regards the adult population, and the Endocrine Metabolic Syndrome (EMS), following the new set of PCOS diagnostic criteria proposed by the Experts Group on Inositol and Clinical Research, and on PCOS (EGOI-PCOS). To support this review, a literature search was conducted using PubMed, Google Scholar and Web of Science, supplemented by articles known to the authors. Keywords included: polycystic ovary syndrome, non-classical adrenal hyperplasia, hyperandrogenism, and 17-Hydroxyprogesterone., Results: Considering the different pathophysiology of the two conditions, the recommended strategy to differentiate diagnosis is testing the blood values of 17-hydroxyprogesterone (17-OHP) in fertile aged women with suspicious hyperandrogenism. Basal values of 17-OHP higher than 2 ng/mL likely indicate NCAH, while values lower than 2 ng/mL exclude the diagnosis of NCAH; in case of borderline values stimulation test with adrenocorticotropic hormone may eventually confirm the diagnosis., Conclusion: This review contributes to make the differential diagnosis between hyperandrogenic PCOS and NCAH clearer, thus also aiming to achieve tailored therapeutic approaches for patients with hyperandrogenism., Competing Interests: Declarations. Conflict of interest: V.U., E.L., G.F. are employees of Lo.Li Pharma s.r.l. The other authors declare no conflict of interest., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Aim: Despite the high sensitivity of neonatal screening in detecting the classical form of congenital adrenal hyperplasia due to 21-hydroxylase deficiency, one of the unclear issues is identifying asymptomatic children with late onset forms. The aim of this nationwide study was to analyse the association between genotype and screened level of 17-hydroxyprogesterone in patients with the late onset form of 21-hydroxylase deficiency and to quantify false negativity., Methods: In the Czech Republic, 1,866,129 neonates were screened (2006-2022). Among this cohort, 159 patients were confirmed to suffer from 21-hydroxylase deficiency, employing the 17-hydroxyprogesterone birthweight/gestational age-adjusted cut-off limits, and followed by the genetic confirmation. The screening prevalence was 1:11,737. Another 57 patients who were false negative in neonatal screening were added to this cohort based on later diagnosis by clinical suspicion. To our knowledge, such a huge nationwide cohort of false negative patients has not been documented before., Results: Overall, 57 patients escaped from neonatal screening in the monitored period. All false negative patients had milder forms. Only one patient had simple virilising form and 56 patients had the late onset form. The probability of false negativity in the late onset form was 76.7%. The difference in 17-hydroxyprogesterone screening values was statistically significant (p<0.001) between severe forms (median 478.8 nmol/L) and milder (36.2 nmol/L) forms. Interestingly, the higher proportion of females with milder forms was statistically significant compared with the general population., Conclusions: A negative neonatal screening result does not exclude milder forms of 21-hydroxylase deficiency during the differential diagnostic procedure of children with precocious pseudopuberty., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Congenital adrenal hyperplasia (CAH) manifests as an autosomal recessive disorder characterized by defects in the enzymes responsible for steroid synthesis. This work aims to perform metabolic profiling of patients with CAH, screen key differential metabolites compared to the control group, and discover the associated metabolic pathways implicated in CAH. Serum samples obtained from 32 pediatric male patients with CAH and 31 healthy control group candidates were subjected to analysis using non-targeted metabolomics strategy using ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). A total of 278 differential metabolites were identified and annotated in KEGG. Operating characteristic curves (ROC) measurement exhibited 9 metabolites exhibiting high efficacy in differential diagnosis, as evidenced by an area under ROC curve (AUC) exceeding 0.85. Pathway analysis uncovered notable disruptions in steroid hormone biosynthesis (p <0.0001), purine metabolism and irregularities in lipid metabolism and amino acid metabolism, including tyrosine and alanine, in CAH patients. These findings demonstrate that metabolic pathways of purine, amino acid and lipid metabolism, apart from steroid hormone biosynthesis, may be disrupted and associated with CAH. This study helps provide insight into the metabolic profile of CAH patients and offers a new perspective for monitoring and administering follow-up care to CAH patients., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)