OBJECTIVE: To describe a kindred with a rare RET germline mutation in codon 791 and discuss potential management strategies. METHODS: We present clinical and biochemical data as well as results of mutation analysis in our study subjects and provide an overview of related published reports. RESULTS: Multiple endocrine neoplasia type 2 (MEN 2) is a familial cancer syndrome characterized by the development of medullary thyroid carcinoma (MTC), pheochromocytoma, and parathyroid hyperplasia or adenoma. Germline mutations in RET are responsible for this autosomal dominant syndrome. Familial MTC is a variant of MEN 2A and can be caused by RET mutations in codon 791. Deaths from gene carriers with mutations in these codons have not yet been reported. In general, gene carriers with these RET mutations have late-onset MTC. Because only a few kindreds with this specific mutation have been identified and no long-term follow-up data are available, management of these patients can be a challenge. We illustrate the difficulties with decisions about not only when to perform thyroidectomy in these patients but also whether thyroidectomy should even be considered in such gene carriers with a benign course. Our reported kindred included four carriers with a codon 791 RET germline mutation, one of whom had the rare concomitant occurrence of acromegaly and MEN 2A. The 70-year-old mother had acromegaly and hyperparathyroidism but normal serum calcitonin levels and normal findings on thyroid ultrasound examination. She refused pentagastrin testing and any surgical intervention. The 37-year-old daughter had hypothyroidism, a small thyroid gland, and negative results of pentagastrin stimulation testing of calcitonin. The 18-year-old grandson also had a negative pentagastrin test result and normal thyroid ultrasound findings. The 5-year-old granddaughter had normal results of thyroid ultrasonography. In all patients, we recommended thyroidectomy. CONCLUSION: Prospective studies are needed to clarify which patients with codon 791 RET germline mutation should undergo thyroidectomy.
OBJECTIVE: To describe a kindred with a rare RET germline mutation in codon 791 and discuss potential management strategies. METHODS: We present clinical and biochemical data as well as results of mutation analysis in our study subjects and provide an overview of related published reports. RESULTS:Multiple endocrine neoplasia type 2 (MEN 2) is a familial cancer syndrome characterized by the development of medullary thyroid carcinoma (MTC), pheochromocytoma, and parathyroid hyperplasia or adenoma. Germline mutations in RET are responsible for this autosomal dominant syndrome. Familial MTC is a variant of MEN 2A and can be caused by RET mutations in codon 791. Deaths from gene carriers with mutations in these codons have not yet been reported. In general, gene carriers with these RET mutations have late-onset MTC. Because only a few kindreds with this specific mutation have been identified and no long-term follow-up data are available, management of these patients can be a challenge. We illustrate the difficulties with decisions about not only when to perform thyroidectomy in these patients but also whether thyroidectomy should even be considered in such gene carriers with a benign course. Our reported kindred included four carriers with a codon 791 RET germline mutation, one of whom had the rare concomitant occurrence of acromegaly and MEN 2A. The 70-year-old mother had acromegaly and hyperparathyroidism but normal serum calcitonin levels and normal findings on thyroid ultrasound examination. She refused pentagastrin testing and any surgical intervention. The 37-year-old daughter had hypothyroidism, a small thyroid gland, and negative results of pentagastrin stimulation testing of calcitonin. The 18-year-old grandson also had a negative pentagastrin test result and normal thyroid ultrasound findings. The 5-year-old granddaughter had normal results of thyroid ultrasonography. In all patients, we recommended thyroidectomy. CONCLUSION: Prospective studies are needed to clarify which patients with codon 791 RET germline mutation should undergo thyroidectomy.
Authors: Thereasa A Rich; Lei Feng; Naifa Busaidy; Gilbert J Cote; Robert F Gagel; Mimi Hu; Camilo Jimenez; Jeffrey E Lee; Nancy Perrier; Steven I Sherman; Steven G Waguespack; Anita Ying; Elizabeth Grubbs Journal: Thyroid Date: 2014-06-06 Impact factor: 6.568
Authors: Eugen Melcescu; Reed B Hogan; Keith Brown; Stewart A Boyd; Thomas L Abell; Christian A Koch Journal: Exp Mol Pathol Date: 2012-10-05 Impact factor: 3.362
Authors: F O F Valente; M R Dias da Silva; C P Camacho; I S Kunii; A U Bastos; C C N da Fonseca; H P C Simião; R Tamanaha; R M B Maciel; J M Cerutti Journal: J Endocrinol Invest Date: 2013-05-30 Impact factor: 4.256