scholarly journals HEREDITARY ENDOCRINE TUMOURS: CURRENT STATE-OF-THE-ART AND RESEARCH OPPORTUNITIES: Early thyroidectomy in multiple endocrine neoplasia: a four decade experience

2020 ◽  
Vol 27 (8) ◽  
pp. T1-T8
Author(s):  
Elizabeth G Grubbs ◽  
Ronald M Lechan ◽  
Beth Edeiken-Monroe ◽  
Gilbert J Cote ◽  
Chardria Trotter ◽  
...  
Keyword(s):  
Multiple Endocrine Neoplasia ◽  
Disease Status ◽  
Serum Calcitonin ◽  
Central Lymph Node Dissection ◽  
Endocrine Neoplasia ◽  
Patients At Risk ◽  
Biomarker Testing ◽  
Central Lymph ◽  
Detectable Serum

Forty years ago, physicians caring for the J-kindred, a 100+ member family with multiple endocrine neoplasia type 2A (MEN2A), hypothesized that early thyroidectomy based on measurement of the biomarker calcitonin could cure patients at risk for development of medullary thyroid carcinoma (MTC). We re-evaluated 22 family members with proven RET proto-oncogene mutations (C634G) who underwent thyroidectomy and central lymphadenectomy between 1972 and 1994 based on stimulated calcitonin abnormalities. Current disease status was evaluated by serum calcitonin measurement and neck ultrasound in 18 of the 22 prospectively screened patients. The median age of the cohort at thyroidectomy was 16.5 years (range 9–24). The median duration of follow-up at the time of examination was 40 years (range 21–43) with a median current age of 52 years (range 34–65). Fifteen of the 18 patients had no detectable serum calcitonin (<2 pg/mL). Three had detectable serum calcitonin measurements, inappropriately elevated following total thyroidectomy. None of the 16 patients imaged had an abnormal ultrasound. Survival analysis shows no MTC-related deaths in the prospectively screened patients, whereas there were many in prior generations. Early thyroidectomy based on biomarker testing has rendered 15 of 18 MEN2A patients (83%) calcitonin-free with a median follow-up period of 40 years. There have been no deaths in the prospectively screened and thyroidectomized group. We conclude that early thyroidectomy and central lymph node dissection is an effective prophylactic treatment for hereditary MTC.

Impact of RET Screening on the Management of Multiple Endocrine Neoplasia Type 2A: 10 Years Experience and Follow-up in Three Families

2021 ◽  
Vol 21 ◽  
Author(s):  
Yue-Ping Wang ◽  
Fei-Ping Li ◽  
Hui-Hong Wang ◽  
Xu-Dong Fang ◽  
Zai-Sheng Zhu ◽  
...  
Keyword(s):  
Early Diagnosis ◽  
Multiple Endocrine Neoplasia ◽  
Multiple Endocrine Neoplasia Type ◽  
Term Outcome ◽  
Serum Calcitonin ◽  
Long Term Outcome ◽  
Endocrine Neoplasia ◽  
Endocrine Neoplasia Type ◽  
Younger Age

Background: Multiple endocrine neoplasia type 2A (MEN 2A) is mainly caused by germline RET codon C634 mutation and is characterized by medullary thyroid carcinoma (MTC), pheochromocytoma (PHEO), and hyperparathyroidism (HPTH). The early diagnosis and initial normative treatment are helpful for the long-term outcome of MEN2A. Methods: Three index cases and their 29 relatives from three families with MEN2A were included in this study. Genetic screening was performed on all participants. Demographic, clinical profiles, tumor histopathologic features, and follow-up records were systematically analyzed. Results: In total, RET C634Y mutation was identified in 10 individuals (10/32, 31.3%). Among them, 5 presented with MTC symptoms, whereas the other 5 did not show apparent clinical manifestation, and all were subjected to thyroidectomy with varying neck dissection. Compared to individuals in the former, the latter benefited greatly from RET screening with significantly younger age at diagnosis of MTC and surgery (18.1 ± 13.8 years vs. 39.0 ± 14.1 years, P =0.045), and less-aggressive MTC behavior (size: 0.74 vs. 2.82 cm, P =0.026; LN+/resected: 20.0% vs. 100.0%, P =0.048) and also lower recurrence rate of MTC (20.0% vs. 100.0%, P =0.048). The PHEO was identified in 6 of the 10 carriers (60.0%), and all had undergone adrenal-sparing surgery. During the 10 years of follow-up, one (16.7%) developed recurrence of PHEO. Conclusion: Integrated RET screening, serum calcitonin, and plasma metanephrine/normetanephrine levels can facilitate the early diagnosis and standardized MTC/PHEO surgery to improve the prognosis of MEN2A. Laparoscopic adrenal-sparing surgery prior to the bilateral total thyroidectomy is a preferred surgical approach for PHEO.

Molecular diagnosis and treatment of multiple endocrine neoplasia type 2B in Ethnic Han Chinese

2020 ◽  
Vol 20 ◽  
Author(s):  
Zhe-Wei Zhang ◽  
Xiao Guo ◽  
Xiao-Ping Qi
Keyword(s):  
Multiple Endocrine Neoplasia ◽  
Multiple Endocrine Neoplasia Type ◽  
Histopathological Examination ◽  
Diagnosis And Treatment ◽  
De Novo Mutation ◽  
Neck Lymph Node ◽  
Serum Calcitonin ◽  
Endocrine Neoplasia ◽  
Endocrine Neoplasia Type ◽  
Men 2B

Background: Multiple endocrine neoplasia type 2B (MEN 2B) is mainly caused by M918T RET germline mutation, and characterized by medullary thyroid carcinoma (MTC), pheochromocytoma (PHEO) and non-endocrine features. However, the diagnosis and treatment are usually delayed. Materials & Methods: This study reports 5 Chinese pedigrees with 5 individuals harboring germline RET-M918T, and systematically reviewed previous Chinese literatures. Results: All 5 patients initially presented MTC, but none had biochemically cured postoperatively. 2 also presented bilateral PHEO after adrenal-sparing surgery, 1 needed steroid replacement. Further, totally 32 MEN 2B patients from literatures were clustered with 28 available for analysis. 26 (92.8%) were diagnosed by endocrine-related symptoms; the remaining 2 (7.2%) due to RET testing and oral symptoms respectively. 25 patients underwent thyroidectomy with/without neck lymph node dissection at mean age of (23.3 ± 10.4) years. Histopathological examination revealed MTC (100%). Of them, 17 had definite TNM stage, with 1 in stage Ⅲ and others in Ⅳ. Other information of MEN 2B-related symptoms included penetrance of PHEO (60.7%), constipation (32.1%), Hirschsprung disease (25%), alacrima (17.8%), mucosal ganglioneuroma (96.4%) and marfanoid habitus (71.4%). 19 patients were verified harboring RET-M918T (c.2753T>C), of whom 15 (78.9%) were de novo mutation. The other 9 were clinically diagnosed as MEN 2B. Discussion & Conclusion : The initial diagnosis of MEN 2B is relatively later, and diagnosed by non-endocrine components is extremely lower. Recognition of MEN 2B and its non-endocrine-related components is still the utmost requirement for a Chinese physician. Combined RET screening and serum calcitonin detection can facilitate early diagnosis.

scholarly journals Usefulness of preoperative serum calcitonin in patients with nodular thyroid disease without suspicious history or cytology for medullary thyroid carcinoma

2013 ◽  
Vol 57 (4) ◽  
pp. 312-316 ◽  
Author(s):  
Pedro Weslley Rosário ◽  
Gustavo Cancela Penna ◽  
Kamilla Brandão ◽  
Bárbara Érika Souza
Keyword(s):  
Thyroid Carcinoma ◽  
Medullary Thyroid Carcinoma ◽  
Multiple Endocrine Neoplasia ◽  
Multiple Endocrine Neoplasia Type ◽  
Serum Calcitonin ◽  
Medullary Thyroid ◽  
Endocrine Neoplasia ◽  
Preoperative Serum ◽  
History Of

OBJECTIVE: To evaluate the usefulness of preoperative serum calcitonin (sCT) in patients with nodular disease without suspicion of medullary thyroid carcinoma (MTC) in history or cytology. PATIENTS AND METHODS: sCT was measured before thyroidectomy in 494 patients with nodular disease who had no family history of MTC or multiple endocrine neoplasia type 2, and no cytological suspicion of MTC. RESULTS: Basal sCT was < 10 ng/mL in 482 patients and none of them had MTC. One patient with basal sCT > 100 pg/mL had MTC. Among the 11 patients with basal sCT between 10 and 100 pg/mL, MTC was diagnosed in only one. The two patients with MTC were submitted to total thyroidectomy, combined with elective lymph node dissection indicated exclusively based on hypercalcitoninemia, and sCT was undetectable after six months. CONCLUSIONS: Preoperative sCT is useful for the detection of sporadic MTC in patients with nodular disease, even in the absence of suspicious history or cytology.

scholarly journals Active Surveillance in RET Gene Carriers Belonging to Families with Multiple Endocrine Neoplasia

Cancers ◽  
2021 ◽  
Vol 13 (21) ◽  
pp. 5554
Author(s):  
Alessandro Prete ◽  
Antonio Matrone ◽  
Carla Gambale ◽  
Valeria Bottici ◽  
Virginia Cappagli ◽  
...  
Keyword(s):  
Active Surveillance ◽  
Thyroid Surgery ◽  
Multiple Endocrine Neoplasia ◽  
Ret Gene ◽  
Ret Mutation ◽  
Gene Carriers ◽  
Endocrine Neoplasia ◽  
Group A ◽  
Group B

Multiple Endocrine Neoplasia 2 (MEN2) is a hereditary cancer syndrome for developing medullary thyroid cancer (MTC) due to germline mutations of RET gene. Subjects harboring a germline RET mutation without any clinical signs of MTC are defined as gene carriers (GCs), for whom guidelines propose a prophylactic thyroid surgery. We evaluate if active surveillance of GCs, pursuing early thyroid surgery, can be safely proposed and if it allows safely delaying thyroid surgery in children until adolescence/adulthood. We prospectively followed 189 GCs with moderate or high risk germline RET mutation. Surgery was planned in case of: elevated basal calcitonin (bCT) and/or stimulated CT (sCT); surgery preference of subjects (or parents, if subject less than 18 years old); other reasons for thyroid surgery. Accordingly, at RET screening, we sub-grouped GCs in subjects who promptly were submitted to thyroid surgery (Group A, n = 67) and who were not (Group B, n = 122). Group B was further sub-grouped in subjects who were submitted to surgery during their active surveillance (Group B1, n = 22) and who are still in follow-up (Group B2, n = 100). Group A subjects presented significantly more advanced age, bCT and sCT compared to Group B. Mutation RETV804M was the most common variant in both groups but it was significantly less frequent in Group A than B. Analyzing age, bCT, sCT and genetic landscape, Group B1 subjects differed from Group B2 only for sCT at last evaluation. Group A subjects presented more frequently MTC foci than Group B1. Moreover, Group A MTCs presented more aggressive features (size, T and N) than Group B1. Accordingly, at the end of follow-up, all Group B1 subjects presented clinical remission, while 6 and 12 Group A MTC patients had structural and biochemical persistent disease, respectively. Thank to active surveillance, only 13/63 subjects younger than 18 years at RET screening have been operated on during childhood and/or adolescence. In Group B1, three patients, while actively surveilled, had the possibility to reach the age of 18 (or older) and two patients the age of 15, before being submitted to thyroid surgery. In Group B2, 12 patients become older than 18 years and 17 older than 15 years. In conclusion, we demonstrated that an active surveillance pursuing an early thyroid surgery could be safely recommended in GCs. This patient-centered approach permits postponing thyroid surgery in children until their adolescence/adulthood. At the same time, we confirmed that genetic screening allows finding hidden MTC cases that otherwise would be diagnosed much later.

scholarly journals Prophylactic thyroidectomy for asymptomatic 3-year-old boy with positive multiple endocrine neoplasia type 2A mutation (codon 634)

2014 ◽  
Vol 142 (1-2) ◽  
pp. 72-74 ◽  
Author(s):  
Maja Jesic ◽  
Milina Tancic-Gajic ◽  
Milos Jesic ◽  
Vladan Zivaljevic ◽  
Silvija Sajic ◽  
...  
Keyword(s):  
Multiple Endocrine Neoplasia ◽  
Multiple Endocrine Neoplasia Type ◽  
Prophylactic Thyroidectomy ◽  
Urinary Catecholamines ◽  
Serum Calcitonin ◽  
Long Term Outcome ◽  
Endocrine Neoplasia ◽  
Endocrine Neoplasia Type ◽  
Men 2A

Introduction. The multiple endocrine neoplasia type 2A (MEN 2A) syndrome, comprising medullary thyroid carcinoma (MTC), pheochromocytoma and primary hyperparathyroidism (PHPT) is most frequently caused by codon 634 activating mutations of the RET (rearranged during transfection) proto-oncogene on chromosome 10. For this codon-mutation carriers, earlier thyroidectomy (before the age of 5 years) would be advantageous in limiting the potential for the development of MTC as well as parathyroid adenomas. Case Outline. This is a case report of 3-year-old boy from the MEN 2A family (the boy?s father and grandmother and paternal aunt) in which cysteine substitutes for phenylalanine at codon 634 in exon 11 of the RET proto-oncogene, who underwent thyroidectomy solely on the basis of genetic information. A boy had no thyromegaly, thyroidal irregularities or lymphadenopathy and no abnormality on the neck ultrasound examination. The pathology finding of thyroid gland was negative for MTC. Two years after total thyroidectomy, 5-year-old boy is healthy with permanent thyroxine replacement. His serum calcitonin level is <2 pg/ml (normal <13 pg/ml), has normal serum calcium and parathyroid hormone levels and negative urinary catecholamines. Long-term follow-up of this patient is required to determine whether very early thyroidectomy improves the long-term outcome of PHPT. Conclusion. Children with familial antecedents of MEN 2A should be genetically studied for the purpose of determining the risk of MTC and assessing the possibilities of making prophylactic thyroidectomy before the age of 5 years.

Single Centre Experience in Patients with Primary Hyperparathyroidism: Sporadic, Lithium-associated and in Multiple Endocrine Neoplasia

2019 ◽  
Vol 128 (10) ◽  
pp. 693-698
Author(s):  
Sabine Dillenberger ◽  
Detlef K. Bartsch ◽  
Elisabeth Maurer ◽  
Peter Herbert Kann
Keyword(s):  
Primary Hyperparathyroidism ◽  
Multiple Endocrine Neoplasia ◽  
University Hospital ◽  
Primary Surgery ◽  
Endocrine Neoplasia ◽  
Single Centre Experience ◽  
Significant Difference ◽  
History Of ◽  
The University

Abstract Purpose It is assumed that primary hyperparathyroidism (pHPT) in Multiple Endocrine Neoplasia (MEN) and lithium-associated pHPT (LIHPT) are associated with multiple gland disease (MGD), persistence and recurrence. The studies purpose was to determine frequencies, clinical presentation and outcome of sporadic pHPT (spHPT), LIHPT and pHPT in MEN. Additional main outcome measures were the rates of MGD and persistence/recurrence. Methods Retrospective analysis of medical records of 682 patients with pHPT who had attended the University Hospital of Marburg between 01–01–2004 and 30–06–2013. All patients were sent a questionnaire asking about their history of lithium medication. Results Out of 682 patients, 557 underwent primary surgery (532 spHPT, 5 LIHPT, 20 MEN), 38 redo-surgery (31 spHPT, 7 MEN), 55 were in follow-up due to previous surgery (16 spHPT, 1 LIHPT, 38 MEN) and 37 were not operated (33 spHPT, 1 LIHPT, 3 MEN). Primary surgeries were successful in 97.4%, revealed singular adenomas in 92.4%, double adenomas in 2.9% and MGD in 3.4% of the cases. Rates of MGD in MEN1 (82.35%) were significantly higher than in spHPT (3.8%), while there was no significant difference between LIHPT (20%) and spHPT. Rates of persistence/recurrence did not significantly differ due to type of surgery (bilateral/unilateral) or type of HPT (spHPT/LIHPT/MEN). Conclusions History of lithium medication is rare among pHPT patients. While MGD is common in MEN1, rates of MGD, persistence or recurrence in LIHPT were not significantly higher than in spHPT.

LONG-TERM FOLLOW-UP OF A KINDRED WITH MULTIPLE ENDOCRINE NEOPLASIA TYPE IIA

1989 ◽  
Vol 59 (9) ◽  
pp. 683-689 ◽  
Author(s):  
StephenR. Munn ◽  
JonA. Van Heerden ◽  
GlenW. Sizemore ◽  
J. Aidan Carney ◽  
Edward Paloyan ◽  
...  
Keyword(s):  
Multiple Endocrine Neoplasia ◽  
Multiple Endocrine Neoplasia Type ◽  
Endocrine Neoplasia ◽  
Endocrine Neoplasia Type ◽  
Long Term Follow Up
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