Patients with advanced medullary thyroid carcinoma (MTC) who develop ectopic Cushing’s syndrome (ECS) may have a poorer prognosis than patients with MTC who do not develop ECS, according to a multicenter case series published in Clinical Endocrinology.

The results found that patients with MTC with ECS had a shorter median overall survival (OS) time of 87 months [95% CI, 64-111 months) after initial MTC diagnosis compared to patients with MTC without ECS (median, 190 months; 95% CI, 95-285 months).

Patients had a median OS of 14 months (95% CI, 0-44 months) after diagnosis with ECS and there was a median time of 29 months between MTC diagnosis and ECS diagnosis.

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“ECS mostly occurs in metastatic cases and significantly impairs prognosis: around 50% of the mortality in patients with ECS has been attributed to complications of hypercortisolism,” the authors said.

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A total of 8 (73%) of the patients with ECS received treatment for it and experienced complete resolution of symptoms along with control of their hypercortisolism. All 8 patients received adrenostatic treatment with either ketoconazole (n=2), mitotane (n=1), metyrapone (n=4), or a combination of ketoconazole with metyrapone (n=1).

Four patients then received bilateral adrenalectomy with subsequent replacement therapy to avoid adrenal crisis.

Multityrosine kinase inhibitors including vandetanib (Caprelsa®) and cabozantinib (Cometriq ) along with the RET inhibitors selpercatinib (Retevmo ) and pralsetinib (Gavreto ) were administered to 2 patients after resolution of ECS and in 1 patient as a treatment to resolve ECS.

“In one case, [multityrosine kinase inhibitor] treatment succeeded in the complete remission of hypercortisolism and sustained tumour control. [Multityrosine kinase inhibitors] might therefore be considered as an alternative to [bilateral adrenalectomy],” the authors suggested.

A total of 11 patients with MTC and ECS were included in the study from 1 Swiss and 3 German tertiary care centers. A total of 22 control patients with MTC without ECS were also included but matched by age at MTC diagnosis, sex, tumor stage, and calcitonin doubling time.


Koehler VF, Fuss CT, Berr CM, et al. Medullary thyroid cancer with ectopic Cushing’s syndrome: a multicentre case series. Clin Endocrinol. Published online November 6, 2021. doi:10.1111/cen.14617