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Clinical characteristics are secondary to insufficient gonadotropin secretion, caused by deficient gonadotropin-releasing hormone (GnRH) production, secretion, or action. Loss-of-function variants of the gonadotropin-releasing hormone receptor (GNRHR) are associated with CHH without anosmia. CHH was previously considered a permanent condition, but in the past two decades, cases of spontaneous recovery of CHH have been reported. The reversal of hypogonadism in CHH is currently unpredictable, and can happen unnoticed.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Case presentation<\/jats:title>\n                <jats:p>The male proband was diagnosed with CHH due to compound heterozygosity for two previously reported pathogenic missense variants in the <jats:italic>GNRHR<\/jats:italic> gene, NM_000406.2:c.416G\u2009&gt;\u2009A (NP_000397.1:p.Arg139His) and c.785G\u2009&gt;\u2009A (p.Arg262Gln) at 16\u00a0years of age. In addition to arrested partial puberty, he had a low testosterone level, gonadotropins in the range of early puberty, and a normal inhibin B level. A therapy with increasing doses of intramuscular testosterone undecanoate was received for 2.5\u00a0years, while there was no change in testicular volume. At the age of 19\u00a0years, testosterone supplementation was interrupted. During the next two years, he had spontaneous pubertal development to achieve a testicular volume of 20\u00a0mL, with normal adult levels of gonadotropins and testosterone.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>Genetic diagnostics can help discriminate congenital hypogonadotropic hypogonadism, deserving therapeutic intervention, from the self-limited constitutional delay of growth and puberty (CDGP). Patients with <jats:italic>GNRHR<\/jats:italic> associated hypogonadism can experience spontaneous recovery of the hypothalamic-pituitary\u2013gonadal axis. Spontaneous testis enlargement in patients with central hypogonadism not taking gonadotropins or pulsatile GnRH therapy can indicate recovery of hypogonadism.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s13052-022-01377-5","type":"journal-article","created":{"date-parts":[[2022,11,12]],"date-time":"2022-11-12T08:02:34Z","timestamp":1668240154000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["GNRHR-related central hypogonadism with spontaneous recovery \u2013 case report"],"prefix":"10.1186","volume":"48","author":[{"given":"Darja","family":"\u0160migoc Schweiger","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maja","family":"Davidovi\u0107 Pov\u0161e","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katarina","family":"Trebu\u0161ak Podkraj\u0161ek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tadej","family":"Battelino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0836-5114","authenticated-orcid":false,"given":"Magdalena","family":"Avbelj Stefanija","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,11,12]]},"reference":[{"issue":"5","key":"1377_CR1","doi-asserted-by":"publisher","first-page":"443","DOI":"10.1056\/NEJMcp1109290","volume":"366","author":"MR Palmert","year":"2012","unstructured":"Palmert MR, Dunkel L. 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Written informed consent was obtained from the patient and his parents.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Informed consent was obtained from all subjects involved in the study. The patient has given his informed consent for publication of anonymized case report.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no conflict of interest.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"184"}}