Long-term control of hypercortisolism by vandetanib in a medullary thyroid carcinoma with a somatic RET mutation.

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Long-term control of hypercortisolism by vandetanib in a medullary thyroid carcinoma with a somatic RET mutation.

Thyroid. 2017 Jan 09;:

Authors: Paepegaey AC, Cochand-Priollet B, Louiset E, Sarfati PO, Alifano M, Burnichon N, Bienvenu-Perrard M, Lahlou N, Bricaire L, Groussin L

Abstract
CONTEXT: Medullary thyroid carcinomas (MTCs) complicated by ectopic Cushing's syndrome have a poor prognosis, partially due to the difficulties to control hypercortisolism by adrenal blocking drugs. Recent reports (including the initial follow-up of this patient) have suggested that tyrosine kinase inhibitors (TKIs) may be a therapeutic option due to an antisecretory action on ACTH. However, there is a lack of long-term follow-up studies.
CASE DESCRIPTION: We report the case of a 58 year-old man with a MTC-related Cushing's syndrome resistant to a combination of several anticortisolic drugs. Vandetanib, an oral multi-TKI that targets RET in particular, was initiated and a rapid reversal of the hypercortisolim was observed without any change in tumor size. Vandetanib was briefly interrupted twice, once during 45 days because of side effects and a second time during 10 days to schedule a surgical debulking. Each time plasma cortisol and calcitonin levels increased after TKI withdrawal and were rapidly lowered by vandetanib reintroduction. As described in other cases of Cushing's syndrome caused by MTC, a marked ACTH increase after desmopressin stimulation was observed before vandetanib therapy. In contrast, a blunted ACTH response to desmopressin was documented throughout the course of vandetanib treatment. This modulation of the tumoral ACTH production is a strong argument in favor of a TKI antisecretory action. A left thyroid lobectomy and a modified neck dissection were performed one year after the initiation of vandetanib to reduce the tumor mass. An activating M918T RET somatic mutation was identified in a lymph node metastasis. Three years and eight months after vandetanib initiation, there was no sign of recurrence of hypercortisolism.
CONCLUSION: This case illustrates the long-term effectiveness of vandetanib in maintaining the control of hypercortisolism in MTC-related Cushing's syndrome.

PMID: 28068878 [PubMed - as supplied by publisher]

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