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Case Reports
. 2022 Sep 28;11(6):e220032.
doi: 10.1530/ETJ-22-0032. Print 2022 Dec 1.

Rapid and long-lasting response to selpercatinib of paraneoplastic Cushing's syndrome in medullary thyroid carcinoma

Marine Sitbon  1 , Porhuoy Chou  2 , Seydou Bengaly  2 , Brigitte Poirot  3 , Marie Laloi-Michelin  4 , Laure Deville  1 , Atanas Pachev  5 , Ahouefa Kowo-Bille  2 , Clement Dumont  6 , Cécile N Chougnet  2
Affiliations
Case Reports

Rapid and long-lasting response to selpercatinib of paraneoplastic Cushing's syndrome in medullary thyroid carcinoma

Marine Sitbon et al. Eur Thyroid J. .

Abstract

The endocrine secretions of carcinomas can be life-threatening. Medullary thyroid carcinoma (MTC) is a rare cancer that is often associated with cortisol secretion, leading to paraneoplastic Cushing's syndrome. Mutations of the proto-oncogene RET are driver molecular events in 70% of MTC cases. Here, we report a case of a woman, born in 1956, who was diagnosed with sporadic MTC in 2005, with subsequent relapses treated with focal treatments. In April 2019, she presented with severe and rapidly progressive paraneoplastic Cushing's syndrome associated with lymph node, lung, liver and bone metastases. A supraclavicular lymph node biopsy revealed a somatic p.M918T (c.2753T>C) mutation in exon 16 of the RET proto-oncogene. The patient began treatment with selpercatinib in September 2019. Clinical efficacy was immediate. Chronic diarrhea disappeared within a few days. Clinical hypercorticism quickly disappeared, with quick improvements in muscle and skin conditions and fatigue. Two months after treatment initiation, urinary free cortisol normalized to 42 µg/24 h. Levels of the tumor markers carcinoembryonic antigen (CEA) and calcitonin also greatly decreased from baseline. After 34 months of treatment, selpercatinib elicits sustained clinical, biological and morphological responses. In summary, this case report illustrates the rapid and long-lasting antisecretory effect of selpercatinib associated with tumor control. As Cushing's syndrome associated with medullary thyroid cancer is associated with poor prognosis, this case report is very encouraging. In addition, this suggests the potential benefit of molecular testing in all cases of medullary thyroid cancer.

Keywords: Cushing’s syndrome; RET mutation; Selpercatinib; medullary thyroid cancer.

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Figures

Figure 1
Figure 1
Urinary free cortisol levels at the time of diagnosis and their outcome after selpercatinib oral treatment.
Figure 2
Figure 2
Changes in serum tumor markers: calcitonin and CEA levels at the time of diagnosis and their outcome after selpercatinib oral treatment.
See this image and copyright information in PMC

References

    1. Wirth LJ, Sherman E, Robinson B, Solomon B, Kang H, Lorch J, Worden F, Brose M, Patel J, Leboulleux Set al. Efficacy of selpercatinib in RET-altered thyroid cancers. New England Journal of Medicine 2020383825–835. ( 10.1056/NEJMoa2005651) - DOI - PMC - PubMed
    1. Wells SA, Asa SL, Dralle H, Elisei R, Evans DB, Gagel RF, Lee N, Machens A, Moley JF, Pacini Fet al. Revised American Thyroid Association guidelines for the management of medullary thyroid carcinoma. Thyroid 201525567–610. ( 10.1089/thy.2014.0335) - DOI - PMC - PubMed
    1. Lorusso L, Cappagli V, Valerio L, Giani C, Viola D, Puleo L, Gambale C, Minaldi E, Campopiano MC, Matrone Aet al. Thyroid cancers: from surgery to current and future systemic therapies through their molecular identities. International Journal of Molecular Sciences 202122 3117. ( 10.3390/ijms22063117) - DOI - PMC - PubMed
    1. Andreev-Drakhlin A, Cabanillas M, Amini B, Subbiah V. Systemic and CNS activity of selective RET inhibition with selpercatinib (LOXO-292) in a patient with RET-mutant medullary thyroid cancer with extensive CNS metastases. JCO Precision Oncology 20204 PO.20.00096. ( 10.1200/PO.20.00096) - DOI - PMC - PubMed
    1. Wijewardene AA, Glastras SJ, Learoyd DL, Robinson BG, Tsang VHM. ACTH-secreting medullary thyroid cancer: a case series. Endocrinology, Diabetes and Metabolism Case Reports 2017201716, -0110. ( 10.1530/EDM-16-0110) - DOI - PMC - PubMed

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