Osilodrostat therapy in a 26-year-old patient after ineffective surgical treatment of Cushing Disease: a case report
DOI:
https://doi.org/10.12775/JEHS.2023.13.01.030Keywords
ACTH-dependent Cushing syndrome, Osilodrostat, Steroidogenesis InhibitorAbstract
Cushing’s Disease is caused by pituitary adenoma which produces adrenocorticotropic hormone causing hypercortisolemia. First-line treatment involves operative removal of the tumor, however, in some patients it proves ineffective. In those cases, pharmacological treatment is necessary as untreated Cushing’s Disease may be lethal. In 2020 a new steroidogenesis inhibitor – Osilodrostat - was approved by the European Medicines Agency and can be used in the treatment of patients who cannot undergo pituitary surgery or whose previous surgical treatment proved ineffective.
We present a case of a 26-year-old female patient who was diagnosed with endogenous Cushing’s Disease and underwent two consecutive operations to remove the tumor - both were ineffective. With deteriorating laboratory results and other pharmacological treatments exhausted Osilodrostat therapy was introduced.
Osilodrostat is becoming an important drug in patients with Cushing’s Disease refractory to other treatments.
References
Pivonello R, De Leo M, Cozzolino A, Colao A. The Treatment of Cushing's Disease. Endocr Rev. 2015 Aug;36(4):385-486. https://doi.org/10.1210/er.2013-1048
Pluta RM, Burke AE, Golub RM. Cushing Syndrome and Cushing Disease. JAMA. 2011;306(24):2742. https://doi.org/10.1001/jama.2011.1694
Sharma ST, Nieman LK, Feelders RA. Cushing's syndrome: epidemiology and developments in disease management. Clin Epidemiol. 2015 Apr 17;7:281-93. https://doi.org/10.2147/CLEP.S44336
Clayton RN, Mortality in Cushing's disease. Neuroendocrinology. 2010;92 Suppl 1:71-6. https://doi.org/10.1159/000315813
Nieman LK, Biller BMK, Findling JW, Murad MH, Newell-Price J, Savage MO, et all. (2015). Treatment of cushing’s syndrome: An endocrine society clinical practice guideline. Journal of Clinical Endocrinology and Metabolism 100, 2807–2831. https://doi.org/10.1210/jc.2015-1818
Pivonello R, Ferrigno R, De Martino MC, Simeoli C, Di Paola N, Pivonello C, et all. Medical Treatment of Cushing's Disease: An Overview of the Current and Recent Clinical Trials. Front Endocrinol (Lausanne). 2020 Dec 8;11:648. https://doi.org/10.3389/fendo.2020.00648
Castinetti F, Morange I, Jaquet P, Conte-Devolx B, Brue T. Ketoconazole revisited: a preoperative or postoperative treatment in Cushing's disease. Eur J Endocrinol. 2008 Jan;158(1):91-9. https://doi.org/10.1530/EJE-07-0514
Carballeira A, Fishman LM, Jacobi JD. Dual sites of inhibition by metyrapone of human adrenal steroidogenesis: correlation of in vivo and in vitro studies. J Clin Endocrinol Metab. 1976 Apr;42(4):687-95. https://doi.org/10.1210/jcem-42-4-687
Verhelst JA, Trainer PJ, Howlett TA, Perry L, Rees LH, Grossman AB, et all. Short and long-term responses to metyrapone in the medical management of 91 patients with Cushing's syndrome. Clin Endocrinol (Oxf). 1991 Aug;35(2):169-78. https://doi.org/10.1111/j.1365-2265.1991.tb03517.x
Fleseriu M, Castinetti F. Updates on the role of adrenal steroidogenesis inhibitors in Cushing's syndrome: a focus on novel therapies. Pituitary. 2016 Dec;19(6):643-653. https://doi.org/10.1007/s11102-016-0742-1
Nishioka H, Yamada S. Cushing's Disease. J Clin Med. 2019 Nov 12;8(11):1951. https://doi.org/10.3390/jcm8111951
Groselj U, Sikonja J, Battelino T. Osilodrostat for Cushing disease and its role in pediatrics. Horm Res Paediatr. 2022 Jan 19. https://doi.org/10.1159/000522054
Castinetti F, Nieman LK, Reincke M, Newell-Price J. Approach to the Patient Treated with Steroidogenesis Inhibitors. J Clin Endocrinol Metab. 2021 Jun 16;106(7):2114-2123. https://doi.org/10.1210/clinem/dgab122
Li L, Vashisht K, Boisclair J, Li W, Lin TH, Schmid HA, et all. (2015). Osilodrostat (LCI699), a potent 11β-hydroxylase inhibitor, administered in combination with the multireceptor-targeted somatostatin analog pasireotide: A 13-week study in rats. Toxicology and Applied Pharmacology, 286(3), 224–233. https://doi.org/10.1016/j.taap.2015.05.004
Gadelha M, Bex M, Feelders RA, Heaney AP, Auchus RJ, Gilis-Januszewska A, et all. Randomized Trial of Osilodrostat for the Treatment of Cushing Disease. J Clin Endocrinol Metab. 2022 Jun 16;107(7):e2882-e2895. https://doi.org/10.1210/clinem/dgac178
Fleseriu M, Biller BMK. Treatment of Cushing's syndrome with osilodrostat: practical applications of recent studies with case examples. Pituitary. 2022 Aug 24:1–15. https://doi.org/10.1007/s11102-022-01268-2
Witek P, Mehlich A, Stasiewicz A, Jawiarczyk-Przybyłowska A, Bolanowski M. Osilodrostat - an emerging drug for the medical management of Cushing's disease. Endokrynol Pol. 2022;73(2):371-374. https://doi.org/10.5603/EP.a2022.0009
Amodru V, Brue T, Castinetti F. Synergistic cortisol suppression by ketoconazole-osilodrostat combination therapy. Endocrinol Diabetes Metab Case Rep. 2021 Dec 1;2021:21-0071. https://doi.org/10.1530/EDM-21-0071
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2022 Magdalena Kamińska, Adam Strzoda, Wojciech Sowiński, Agata Juda, Kornelia Rojek, Anna Strzoda, Agnieszka Polak
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
The periodical offers access to content in the Open Access system under the Creative Commons Attribution-NonCommercial-ShareAlike 4.0
Stats
Number of views and downloads: 433
Number of citations: 0
