Sanne Høxbroe Michaelsen1, Marie Juul Ornstrup2, Morten Møller Poulsen2, Finn Noe Bennedbaek3, Mette Gaustadnes4, Maria Rossing5, Peter Darling1, Peter Vestergaard6,7, Jes Sloth Mathiesen1,8. 1. Department of ORL, Head & Neck Surgery and Audiology, Odense University Hospital, Odense, Denmark. 2. Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark. 3. Department of Endocrinology, Herlev and Gentofte University Hospital, Herlev, Denmark. 4. Department of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark. 5. Center for Genomic Medicine, Copenhagen University Hospital, Copenhagen, Denmark. 6. Department of Clinical Medicine and Endocrinology, Aalborg University Hospital, Aalborg, Denmark. 7. Steno Diabetes Center North Jutland, Aalborg University Hospital, Aalborg, Denmark. 8. Department of Clinical Research, University of Southern Denmark, Odense, Denmark.
Abstract
BACKGROUND AND OBJECTIVES: Recently, a comprehensive study presented evidence that a long-disputed REarranged during Transfection (RET) variant, RET Y791F, should be classified as nonpathogenic. In spite of this, several subsequently published papers, including the revised American Thyroid Association guidelines for medullary thyroid carcinoma, refer to the variant as pathogenic. This study presents data from a unique national Danish cohort of RET Y791F carriers who have been followed by watchful waiting instead of being subjected to early thyroidectomy, to determine if any carrier shows evidence of multiple endocrine neoplasia 2A (MEN2A) at long-term follow-up. METHODS: A national cohort of all patients tested for RET mutations in Denmark from September 1994 to October 2017 was searched for carriers of RET Y791F. Medical records and laboratory reports of carriers were reviewed for signs of MEN2A at latest follow-up (medullary thyroid carcinoma, primary hyperparathyroidism, pheochromocytoma, cutaneous lichen amyloidosis, or Hirschsprung's disease). RESULTS: In total, twenty RET Y791F-carriers were identified, none of whom showed any evidence of MEN2A, despite an age range from 7 to 87 years. CONCLUSIONS: Our national cohort study of all Danish RET Y791F carriers substantiates the claim that the RET Y791F variant is nonpathogenic.
BACKGROUND AND OBJECTIVES: Recently, a comprehensive study presented evidence that a long-disputed REarranged during Transfection (RET) variant, RETY791F, should be classified as nonpathogenic. In spite of this, several subsequently published papers, including the revised American Thyroid Association guidelines for medullary thyroid carcinoma, refer to the variant as pathogenic. This study presents data from a unique national Danish cohort of RETY791F carriers who have been followed by watchful waiting instead of being subjected to early thyroidectomy, to determine if any carrier shows evidence of multiple endocrine neoplasia 2A (MEN2A) at long-term follow-up. METHODS: A national cohort of all patients tested for RET mutations in Denmark from September 1994 to October 2017 was searched for carriers of RETY791F. Medical records and laboratory reports of carriers were reviewed for signs of MEN2A at latest follow-up (medullary thyroid carcinoma, primary hyperparathyroidism, pheochromocytoma, cutaneous lichen amyloidosis, or Hirschsprung's disease). RESULTS: In total, twenty RETY791F-carriers were identified, none of whom showed any evidence of MEN2A, despite an age range from 7 to 87 years. CONCLUSIONS: Our national cohort study of all Danish RETY791F carriers substantiates the claim that the RETY791F variant is nonpathogenic.
Authors: Anna Reimer Hansen; Line Borgwardt; Åse Krogh Rasmussen; Christian Godballe; Morten Møller Poulsen; Filipe G Vieira; Jes Sloth Mathiesen; Maria Rossing Journal: Front Endocrinol (Lausanne) Date: 2021-12-01 Impact factor: 5.555