{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T11:58:11Z","timestamp":1789214291568,"version":"build-2803163510"},"reference-count":54,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2020,6,29]],"date-time":"2020-06-29T00:00:00Z","timestamp":1593388800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Congenital adrenal hyperplasia (CAH) is the most common cause of primary adrenal insufficiency in children and adolescents. It comprises several clinical entities associated with mutations in genes, encoding enzymes involved in cortisol biosynthesis. The mutations lead to considerable (non-classic form) to almost complete (classic form) inhibition of enzymatic activity, reflected by different phenotypes and relevant biochemical alterations. Up to 95% cases of CAH are due to mutations in CYP21A2 gene and subsequent 21\u03b1-hydroxylase deficiency, characterized by impaired cortisol synthesis and adrenal androgen excess. In the past two decades an alternative (\u201cbackdoor\u201d) pathway of androgens\u2019 synthesis in which 5\u03b1-androstanediol, a precursor of the 5\u03b1-dihydrotestosterone, is produced from 17\u03b1-hydroxyprogesterone, with intermediate products 3\u03b1,5\u03b1-17OHP and androsterone, in the sequence and with roundabout of testosterone as an intermediate, was reported in some studies. This pathway is not always considered in the clinical assessment of patients with hyperandrogenism. The article describes the case of a 17-year-old female patient with menstrual disorders and androgenization (persistent acne, advanced hirsutism). Her serum dehydroepiandrosterone sulfate and testosterone were only slightly elevated, along with particularly high values for 5\u03b1-dihydrotestosterone. In 24 h urine collection, an increased excretion of 16\u03b1-OHDHEA\u2014a dehydroepiandrosterone metabolite\u2014and pregnanetriolone\u2014a 17\u03b1-hydroxyprogesterone metabolite\u2014were observed. The investigations that we undertook provided evidence that the girl suffered from non-classic 21\u03b1-hydroxylase deficiency with consequent enhancement of the androgen \u201cbackdoor\u201d pathway in adrenals, peripheral tissues or both, using adrenal origin precursors. The paper presents diagnostic dilemmas and strategies to differentiate between various reasons for female hyperandrogenism, especially in childhood and adolescence.<\/jats:p>","DOI":"10.3390\/ijms21134622","type":"journal-article","created":{"date-parts":[[2020,6,29]],"date-time":"2020-06-29T11:17:17Z","timestamp":1593429437000},"page":"4622","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Non-Classic Disorder of Adrenal Steroidogenesis and Clinical Dilemmas in 21-Hydroxylase Deficiency Combined with Backdoor Androgen Pathway. Mini-Review and Case Report"],"prefix":"10.3390","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8434-1931","authenticated-orcid":false,"given":"Marta","family":"Sumi\u0144ska","sequence":"first","affiliation":[{"name":"Department of Pediatric Diabetes and Obesity, Poznan University of Medical Sciences, 60-527 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0063-6434","authenticated-orcid":false,"given":"Klaudia","family":"Bogusz-G\u00f3rna","sequence":"additional","affiliation":[{"name":"Department of Pediatric Diabetes and Obesity, Poznan University of Medical Sciences, 60-527 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominika","family":"Wegner","sequence":"additional","affiliation":[{"name":"Department of Pediatric Diabetes and Obesity, Poznan University of Medical Sciences, 60-527 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2865-7074","authenticated-orcid":false,"given":"Marta","family":"Fichna","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Metabolism and Internal Medicine, Poznan University of Medical Sciences, 60-653 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,6,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/j.ecl.2005.01.003","article-title":"Hypothalamic\u2013pituitary\u2013adrenocortical axis regulation","volume":"34","author":"Jacobson","year":"2005","journal-title":"Endocrinol Metab. 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