title: Long-Term Control of Hypercortisolism by Vandetanib in a Case of Medullary Thyroid Carcinoma with a Somatic RET Mutation.
abstract: Medullary thyroid carcinomas (MTCs) complicated by ectopic Cushing's syndrome (CS) have a poor prognosis, partially due to the difficulty in controlling 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 anti-secretory action on ACTH. However, there is a lack of long-term follow-up studies.
  
  
  
  The case is reported of a 58-year-old man with MTC-related CS resistant to a combination of several anti-cortisolic drugs. Vandetanib, an oral multi-TKI that targets RET in particular, was initiated, and a rapid reversal of the hypercortisolism was observed without any change in tumor size. Vandetanib was briefly interrupted twice, once for 45 days because of side effects and a second time for 10 days to schedule 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 CS 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 anti-secretory action. A left thyroid lobectomy and a modified neck dissection were performed one year after the initiation of vandetanib in order to reduce the tumor mass. An activating M918T RET (c.2753T>C) 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. This case illustrates the long-term effectiveness of vandetanib in maintaining the control of hypercortisolism in MTC-related CS.
authors.affiliation: 1 Department of Endocrinology, Cochin Hospital , Assistance Publique Hôpitaux de Paris, Paris, France .|2 Université Paris Descartes , PRES Sorbonne Paris Cité, Faculté de Médecine, Paris, France .
authors.forename: Anne-Cécile
authors.initials: AC
authors.lastname: Paepegaey
authors.affiliation: 2 Université Paris Descartes , PRES Sorbonne Paris Cité, Faculté de Médecine, Paris, France .|3 Department of Pathology, Cochin Hospital , Assistance Publique Hôpitaux de Paris, Paris, France .
authors.forename: Béatrix
authors.initials: B
authors.lastname: Cochand-Priollet
authors.affiliation: 4 INSERM, Unité 982, Laboratory of Neuronal and Neuroendocrine Differentiation and Communication, Mont-Saint-Aignan, France; Institute for Research and Innovation in Biomedicine, Normandie Rouen University , Mont-Saint-Aignan, France .
authors.forename: Estelle
authors.initials: E
authors.lastname: Louiset
authors.affiliation: 5 Department of Digestive and Endocrine Surgery, Cochin Hospital , Assistance Publique Hôpitaux de Paris, Paris, France .
authors.forename: Pierre-Olivier
authors.initials: PO
authors.lastname: Sarfati
authors.affiliation: 2 Université Paris Descartes , PRES Sorbonne Paris Cité, Faculté de Médecine, Paris, France .|6 Department of Thoracic Surgery, Cochin Hospital , Assistance Publique Hôpitaux de Paris, Paris, France .
authors.forename: Marco
authors.initials: M
authors.lastname: Alifano
authors.affiliation: 2 Université Paris Descartes , PRES Sorbonne Paris Cité, Faculté de Médecine, Paris, France .|7 INSERM, UMR970, Paris-Cardiovascular Research Center , Paris, France .|8 Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou , Service de Génétique, Paris, France .
authors.forename: Nelly
authors.initials: N
authors.lastname: Burnichon
authors.affiliation: 9 Department of Nuclear Medicine, Cochin Hospital , Assistance Publique Hôpitaux de Paris, Paris, France .
authors.forename: Marie
authors.initials: M
authors.lastname: Bienvenu-Perrard
authors.affiliation: 2 Université Paris Descartes , PRES Sorbonne Paris Cité, Faculté de Médecine, Paris, France .|10 Department of Hormonal Biology, Cochin Hospital , Assistance Publique Hôpitaux de Paris, Paris, France .
authors.forename: Najiba
authors.initials: N
authors.lastname: Lahlou
authors.affiliation: 1 Department of Endocrinology, Cochin Hospital , Assistance Publique Hôpitaux de Paris, Paris, France .
authors.forename: Léopoldine
authors.initials: L
authors.lastname: Bricaire
authors.affiliation: 1 Department of Endocrinology, Cochin Hospital , Assistance Publique Hôpitaux de Paris, Paris, France .|2 Université Paris Descartes , PRES Sorbonne Paris Cité, Faculté de Médecine, Paris, France .
authors.forename: Lionel
authors.initials: L
authors.lastname: Groussin
mesh_terms: D002116:Calcitonin / Q000097:blood; D018278:Carcinoma, Neuroendocrine / Q000150:complications / Q000235:genetics* / Q000601:surgery; D003480:Cushing Syndrome / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D065426:Cytoreduction Surgical Procedures; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D008297:Male; D008875:Middle Aged; D037981:Neck Dissection; D010880:Piperidines / Q000627:therapeutic use*; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D051096:Proto-Oncogene Proteins c-ret / Q000235:genetics*; D011799:Quinazolines / Q000627:therapeutic use*; D013964:Thyroid Neoplasms / Q000150:complications / Q000235:genetics* / Q000601:surgery; D013965:Thyroidectomy
chemical_list: D010880:Piperidines; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D002116:Calcitonin; D051096:Proto-Oncogene Proteins c-ret; C099282:RET protein, human; D006854:Hydrocortisone; C452423:vandetanib
keywords: Cushing's syndrome; RET; hypercortisolism; medullary thyroid carcinoma; vandetanib