{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T15:54:09Z","timestamp":1768406049774,"version":"3.49.0"},"reference-count":10,"publisher":"Walter de Gruyter GmbH","issue":"7","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,7,28]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec id=\"j_jpem-2025-0056_abs_001\">\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>To describe the clinical course, diagnosis, and management of a rare pediatric case of ACTH-independent Cushing syndrome (CS), associated with developmental delay.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec id=\"j_jpem-2025-0056_abs_002\">\n                  <jats:title>Case presentation<\/jats:title>\n                  <jats:p>A three-year-old boy with global developmental delay, was referred for evaluation of rapid weight gain over the preceding three months, accompanied by increased body hair, a moon-shaped face, and sleep disturbances. Biochemical testing revealed undetectable ACTH levels and elevated cortisol levels, leading to the diagnosis of ACTH-independent CS. Abdominal magnetic resonance imaging demonstrated adrenal asymmetry, with a larger left adrenal gland, and further investigation using PET scan excluded the presence of adrenal adenomas\/carcinomas. The patient was initially treated with metyrapone, which effectively reduced cortisol levels. However, after two months, a left adrenalectomy was performed. Pathological examination confirmed micronodular non-pigmented adrenal hyperplasia. One year later, cortisol levels increased again with undetectable ACTH, prompting the re-initiation of metyrapone. Due to intolerance to this medication, osilodrostat, an off-label treatment, was introduced. At the time of follow-up, 15\u00a0months after initiation of osilodrostat, both serum and urinary cortisol levels remained within normal ranges, ACTH levels remained undetectable, and the clinical symptoms of CS were well controlled.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec id=\"j_jpem-2025-0056_abs_003\">\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>This case underscores the diagnostic and therapeutic challenges associated with rare pediatric cases of ACTH-independent CS. The treatment course, which included metyrapone, adrenalectomy, and off-label use of osilodrostat, resulted in significant improvement in cortisol control and clinical symptoms. Ongoing genetic analysis is being conducted to explore potential underlying genetic factors contributing to the patient\u2019s non-pigmented micronodular adrenal hyperplasia and developmental delay.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1515\/jpem-2025-0056","type":"journal-article","created":{"date-parts":[[2025,4,24]],"date-time":"2025-04-24T02:58:57Z","timestamp":1745463537000},"page":"772-778","source":"Crossref","is-referenced-by-count":2,"title":["Rare case of ACTH-independent Cushing syndrome: diagnostic challenges and management"],"prefix":"10.1515","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3760-5121","authenticated-orcid":false,"given":"Lu\u00eds","family":"Salazar","sequence":"first","affiliation":[{"name":"Servi\u00e7o de Pediatria, Centro Materno Infantil do Norte , 674892 Unidade Local de Sa\u00fade de Santo Ant\u00f3nio , Porto , Portugal"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sara Alves","family":"Ara\u00fajo","sequence":"additional","affiliation":[{"name":"Servi\u00e7o de Pediatria , Unidade Local de Sa\u00fade Entre o Douro e Vouga , Santa Maria da Feira , Portugal"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M\u00e1rio Rui","family":"Correia","sequence":"additional","affiliation":[{"name":"Servi\u00e7o de Cirurgia Pedi\u00e1trica, Centro Materno Infantil do Norte , 674892 Unidade Local de Sa\u00fade de Santo Ant\u00f3nio , Porto , Portugal"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jorge Diogo","family":"da Silva","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Centro de Gen\u00e9tica M\u00e9dica Dr. Jacinto Magalh\u00e3es, Cl\u00ednica de Gen\u00e9tica e de Patologia, Centro Hospitalar Universit\u00e1rio de Santo Ant\u00f3nio , 674892 Unidade Local de Sa\u00fade de Santo Ant\u00f3nio , Porto , Portugal"},{"name":"Unit for Multidisciplinary Research in Biomedicine , Instituto de Ci\u00eancias Biom\u00e9dicas de Abel Salazar, Universidade do Porto , Porto , Portugal"},{"name":"ITR-Laboratory for Integrative and Translational Research in Population Health , Porto , Portugal"},{"name":"Life and Health Sciences Research Institute, School of Medicine, University of Minho , Braga , Portugal"},{"name":"ICVS\/3B\u2019s\u00a0\u2013 PT Government Associate Laboratory , Braga\/Guimar\u00e3es , Portugal"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Catarina","family":"Matos de Figueiredo","sequence":"additional","affiliation":[{"name":"Servi\u00e7o de Pediatria , Unidade Local de Sa\u00fade Entre o Douro e Vouga , Santa Maria da Feira , Portugal"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Catarina","family":"Prior","sequence":"additional","affiliation":[{"name":"674892 Unidade de Neurodesenvolvimento, Centro Materno Infantil do Norte, Unidade Local de Sa\u00fade de Santo Ant\u00f3nio , Porto , Portugal"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cla\u00fadia","family":"Amaral","sequence":"additional","affiliation":[{"name":"Servi\u00e7o de Endocrinologia, Diabetes e Metabolismo , 674892 Unidade Local de Sa\u00fade de Santo Ant\u00f3nio , Porto , Portugal"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Jo\u00e3o","family":"Oliveira","sequence":"additional","affiliation":[{"name":"674892 Unidade de Endocrinologia Pedi\u00e1trica, Centro Materno Infantil do Norte, Unidade Local de Sa\u00fade de Santo Ant\u00f3nio , Porto , Portugal"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ribeiro","family":"Castro","sequence":"additional","affiliation":[{"name":"Servi\u00e7o de Cirurgia Pedi\u00e1trica, Centro Materno Infantil do Norte , 674892 Unidade Local de Sa\u00fade de Santo Ant\u00f3nio , Porto , Portugal"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Teresa","family":"Borges","sequence":"additional","affiliation":[{"name":"674892 Unidade de Endocrinologia Pedi\u00e1trica, Centro Materno Infantil do Norte, Unidade Local de Sa\u00fade de Santo Ant\u00f3nio , Porto , Portugal"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"374","published-online":{"date-parts":[[2025,4,25]]},"reference":[{"key":"2025071812031909538_j_jpem-2025-0056_ref_001","doi-asserted-by":"crossref","unstructured":"Storr, HL, Chan, LF, Grossman, AB, Savage, MO. 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