Rare case of ACTH-independent Cushing syndrome: diagnostic challenges and management
-
Luís Salazar
,
Sara Alves Araújo
Abstract
Objectives
To describe the clinical course, diagnosis, and management of a rare pediatric case of ACTH-independent Cushing syndrome (CS), associated with developmental delay.
Case presentation
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 months 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.
Conclusions
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’s non-pigmented micronodular adrenal hyperplasia and developmental delay.
-
Research ethics: Not applicable.
-
Informed consent: Informed consent was obtained from the legal guardians.
-
Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.
-
Use of Large Language Models, AI and Machine Learning Tools: None declared.
-
Conflict of interest: The authors state no conflict of interest.
-
Research funding: None declared.
-
Data availability: Not applicable.
References
1. Storr, HL, Chan, LF, Grossman, AB, Savage, MO. Paediatric Cushing’s syndrome: epidemiology, investigation and therapeutic advances. Trends Endocrinol Metabol 2007;18:167–74. https://doi.org/10.1016/j.tem.2007.03.005 [Epub 2007 Apr 6].Suche in Google Scholar PubMed
2. Funder, JW, Carey, RM, Mantero, F, Murad, MH, Reincke, M, Shibata, H, et al.. The management of primary aldosteronism: case detection, diagnosis, and treatment: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 2016;101:1889–916. https://doi.org/10.1210/jc.2015-4061 [Epub 2016 Mar 2].Suche in Google Scholar PubMed
3. Sharma, ST, Nieman, LK, Feelders, RA. Cushing’s syndrome: epidemiology and developments in disease management. Clin Epidemiol 2015;7:281–93. https://doi.org/10.2147/CLEP.S44336.Suche in Google Scholar PubMed PubMed Central
4. Concepción-Zavaleta, MJ, Armas, CD, Quiroz-Aldave, JE, García-Villasante, EJ, Gariza-Solano, AC, Durand-Vásquez, MDC, et al.. Cushing disease in pediatrics: an update. Ann Pediatr Endocrinol Metab 2023;28:87–97. https://doi.org/10.6065/apem.2346074.037 [Epub 2023 Jun 30].Suche in Google Scholar PubMed PubMed Central
5. Lacroix, A, Feelders, RA, Stratakis, CA, Nieman, LK. Cushing’s syndrome. Lancet 2015;386:913–27. https://doi.org/10.1016/S0140-6736(14)61375-1 [Epub 2015 May 21].Suche in Google Scholar PubMed
6. Barbot, M, Zilio, M, Scaroni, C. Cushing’s syndrome: overview of clinical presentation, diagnostic tools and complications. Best Pract Res Clin Endocrinol Metabol 2020;34:101380. https://doi.org/10.1016/j.beem.2020.101380 [Epub 2020 Jan 30].Suche in Google Scholar PubMed
7. Rothenbuhler, A, Stratakis, CA. Clinical and molecular genetics of Carney complex. Best Pract Res Clin Endocrinol Metabol 2010;24:389–99. https://doi.org/10.1016/j.beem.2010.03.003.Suche in Google Scholar PubMed
8. Bouys, L, Violon, F, Louiset, E, Sibony, M, Lefebvre, H, Bertherat, J. Bilateral adrenocortical nodular disease and Cushing’s syndrome. J Clin Endocrinol Metab 2024;109:2422–32. https://doi.org/10.1210/clinem/dgae419.Suche in Google Scholar PubMed
9. Daniel, E, Aylwin, S, Mustafa, O, Ball, S, Munir, A, Boelaert, K, et al.. Effectiveness of metyrapone in treating Cushing’s syndrome: a retrospective multicenter study in 195 patients. J Clin Endocrinol Metab 2015;100:4146–54. https://doi.org/10.1210/jc.2015-2616 [Epub 2015 Sep 9].Suche in Google Scholar PubMed PubMed Central
10. Pivonello, R, Fleseriu, M, Newell-Price, J, Bertagna, X, Findling, J, Shimatsu, A, et al.. Efficacy and safety of osilodrostat in patients with Cushing’s disease (LINC 3): a multicentre phase III study with a double-blind, randomised withdrawal phase. Lancet Diabetes Endocrinol 2020;8:748–61. https://doi.org/10.1016/S2213-8587(20)30240-0 [Epub 2020 Jul 27].Suche in Google Scholar PubMed
© 2025 Walter de Gruyter GmbH, Berlin/Boston
Artikel in diesem Heft
- Frontmatter
- Editorial
- Sunlight, supplements, and science: vitamin D as a tool for pediatric health care
- Mini Review
- Physical activity and vitamin D in children: a review of impacts on bone health and fitness
- Original Articles
- Association between overweight or obesity and vitamin D status in preschool children: an epidemiological survey in Beijing, China, 2021–2023
- Association between partial remission phase in type 1 diabetes and vitamin D receptor Fok1 rs2228570 polymorphism
- Optimal vitamin D status for Chinese infants in Hong Kong: insights from the relationship between serum 25-hydroxyvitamin D and parathyroid hormone levels
- Reviews
- The changing landscape in the evaluation of hypotonic polyuria in children and adolescents: the role of the new copeptin stimulation tests
- A systematic review and meta-analysis of the self-reported Pubertal Development Scale’s applicability to children
- Original Articles
- Assessing prediabetes and cardiometabolic risk in Danish youth with obesity
- Endocrinopathies in children with inborn errors of immunity: a single-center experience
- Relationship between blood lipids and bone mineral density in healthy preschoolers: a 12-month cohort study
- The causal role of endocrine disrupting chemicals in pubertal timing: a Mendelian randomization study
- Case Reports
- Vitamin D dependent rickets type 2A: a case series of two siblings with novel mutation in vitamin D receptor gene responded to high dose oral calcium and calcitriol
- Emergence of osteolysis as a new radiological feature in a case with a novel BMP2 gene variant
- Rare case of ACTH-independent Cushing syndrome: diagnostic challenges and management
Artikel in diesem Heft
- Frontmatter
- Editorial
- Sunlight, supplements, and science: vitamin D as a tool for pediatric health care
- Mini Review
- Physical activity and vitamin D in children: a review of impacts on bone health and fitness
- Original Articles
- Association between overweight or obesity and vitamin D status in preschool children: an epidemiological survey in Beijing, China, 2021–2023
- Association between partial remission phase in type 1 diabetes and vitamin D receptor Fok1 rs2228570 polymorphism
- Optimal vitamin D status for Chinese infants in Hong Kong: insights from the relationship between serum 25-hydroxyvitamin D and parathyroid hormone levels
- Reviews
- The changing landscape in the evaluation of hypotonic polyuria in children and adolescents: the role of the new copeptin stimulation tests
- A systematic review and meta-analysis of the self-reported Pubertal Development Scale’s applicability to children
- Original Articles
- Assessing prediabetes and cardiometabolic risk in Danish youth with obesity
- Endocrinopathies in children with inborn errors of immunity: a single-center experience
- Relationship between blood lipids and bone mineral density in healthy preschoolers: a 12-month cohort study
- The causal role of endocrine disrupting chemicals in pubertal timing: a Mendelian randomization study
- Case Reports
- Vitamin D dependent rickets type 2A: a case series of two siblings with novel mutation in vitamin D receptor gene responded to high dose oral calcium and calcitriol
- Emergence of osteolysis as a new radiological feature in a case with a novel BMP2 gene variant
- Rare case of ACTH-independent Cushing syndrome: diagnostic challenges and management
