title: Questioning the pathogenic role of the pTyr791Phe mutation of the RET proto-oncogene: Insight from a case report.
abstract: The pTyr791Phe mutation of the RET proto-oncogene is associated with a low penetrance of medullar thyroid carcinoma (MTC). Thus, there is a lack in guidelines on management of these patients presenting without a thyroid disease.
  
  
  METHODS
  A 27-year-old woman presented with a history of severe hypertension, paroxysmal tachycardia, diaphoresis and headaches. Twenty-four-hour urinary norepinephrine and normetanephrine levels were exclusively up to 20 times the normal limit. CT-scan and MRI found a 35-mm diameter right adrenal tumor, highly intense in T2- and hypo-intense in T1-weighted image, enhanced after gadolinium injection. After alpha-adrenergic blocker treatment, a surgical resection of the tumor was performed; this latter proved to be a pheochromocytoma. Genetic screening only revealed a germline pTyr791Phe mutation of the RET proto-oncogene. However, the patient showed no evidence of MEN2: basal calcitonin was normal and calcium infusion test was negative. Thyroid ultrasound revealed a TIRADS 3 nodule with benign cytology. Total thyroidectomy was suggested but withheld due to the patient's refusal and a close follow-up was decided.
  
  
  CONCLUSIONS
  This rare case of pTyr791Phe mutation-related pheochromocytoma without evidence of MTC questions the indication for prophylactic thyroidectomy in mutation carriers, as recent data challenges its pathogenicity.
authors.affiliation: Department of Endocrinology and Metabolic Diseases, La Pitié-Salpêtrière Hospital, boulevard de l'Hôpital, 75013 Paris, France; Department of Endocrinology and Diabetes, University Hospital of Geneva, Geneva, Switzerland.
authors.forename: Maria
authors.initials: M
authors.lastname: Mavromati
authors.affiliation: Department of Endocrinology and Metabolic Diseases, La Pitié-Salpêtrière Hospital, boulevard de l'Hôpital, 75013 Paris, France. Electronic address: myriam.amsallem@gmail.com.
authors.forename: Myriam
authors.initials: M
authors.lastname: Amsallem
authors.affiliation: Department of Endocrinology and Metabolic Diseases, La Pitié-Salpêtrière Hospital, boulevard de l'Hôpital, 75013 Paris, France.
authors.forename: Christel
authors.initials: C
authors.lastname: Jublanc
authors.affiliation: Department of Endocrinology and Metabolic Diseases, La Pitié-Salpêtrière Hospital, boulevard de l'Hôpital, 75013 Paris, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Bruckert
authors.affiliation: Department of Nuclear Medicine, La Pitié-Salpêtrière Hospital, boulevard de l'Hôpital, 75013 Paris, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Leenhardt
authors.affiliation: Department of Endocrinology and Metabolic Diseases, La Pitié-Salpêtrière Hospital, boulevard de l'Hôpital, 75013 Paris, France.
authors.forename: Xavier
authors.initials: X
authors.lastname: Girerd
mesh_terms: D000310:Adrenal Gland Neoplasms / Q000175:diagnosis / Q000235:genetics*; D000328:Adult; D018278:Carcinoma, Neuroendocrine / Q000235:genetics; D005260:Female; D006801:Humans; D006973:Hypertension; D009154:Mutation / Q000235:genetics*; D010673:Pheochromocytoma / Q000175:diagnosis / Q000235:genetics*; D000090063:Proto-Oncogene Mas; D051096:Proto-Oncogene Proteins c-ret / Q000235:genetics*; D013964:Thyroid Neoplasms / Q000235:genetics
chemical_list: C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D051096:Proto-Oncogene Proteins c-ret; C099282:RET protein, human
keywords: Carcinome médullaire de la thyroïde; Medullary thyroid carcinoma; Pheochromocytoma; Phéochromocytome; Proto-oncogène RET; RET proto-oncogene