313:
372:, trade name Cometriq, was granted marketing approval (November 2012) by the U.S. FDA for this indication. Cabozantinib which is a potent inhibitor of RET, MET and VEGF was evaluated in a double-blind placebo controlled trial. It was shown to improve overall survival by 5 months for the treated cohort vs. placebo, which was not statistically significant. However, cabozantinib was particularly effective in patients with the RET M918T mutation, extending overall survival by roughly 2 years, doubling survival vs. untreated patient (4 years vs. 2 year). Treatment with cabozantinib did require many dose reduction to mitigate side effects. It has been suggested that the trial dose of 140 mg was excessive, particularly in lower body mass patients. Ongoing trials have been scheduled to identify more optimal dosing regimes. Activity has been observed, in practice at doses of 1.2 mg/kg.
210:. Hereditary medullary thyroid cancer is inherited as an autosomal dominant trait, meaning that each child of an affected parent has a 50% probability of inheriting the mutant RET proto-oncogene from the affected parent. DNA analysis makes it possible to identify children who carry the mutant gene; surgical removal of the thyroid in children who carry the mutant gene is curative if the entire thyroid gland is removed at an early age, before there is spread of the tumor. The parathyroid tumors and pheochromocytomas are removed when they cause clinical symptomatology. Hereditary medullary thyroid carcinoma or multiple endocrine neoplasia (
51:
356:, which block the abnormal kinase proteins involved in the development and growth of medullary cancer cells, showed clear evidence of response in 10-30% of patients. In the majority of responders there has been less than a 30% decrease in tumor mass, yet the responses have been durable; responses have been stable for periods exceeding 3 years. The major side effects of this class of drug include hypertension, nausea, diarrhea, some cardiac electrical abnormalities, and thrombotic or bleeding episodes.
254:
337:
study wrote: "in 40 high risk patients (microscopic residual disease, extraglandular invasion, or lymph node involvement), the local/regional relapse free rate was 86% at 10 years with postoperative external beam radiation (25 patients), and 52% for those with no postoperative external radiation (p = 0.049). To optimize local/regional tumor control, we therefore continue to advise external beam radiation in patients at high risk of local/regional relapse."
321:
nerve damage, death or the need for second operation to clean out residual diseased lymph nodes left behind if the sentinel node biopsy was positive for cancerous spread. Extensive surgery can be effective when the condition is detected early, but a risk for recurrence remains, particularly in patients with multiple positive lymph nodes or extracapsular invasion. About half of patients have metastasis to regional lymph nodes at the time of diagnosis.
218:
those with a family history (screening is likely to be initiated at an early age in the hereditary form). Approximately 25-60% of sporadic medullary thyroid carcinomas have a somatic mutation (one that occurs within a single "parafollicular" cell) of the RET proto-oncogene. This mutation is presumed to be the initiating event, although there could be other as yet unidentified causes.
411:(CEA) concentrations in the blood was studied in 65 MTC patients who had abnormal calcitonin levels after surgery (total thyroidectomy and lymph node dissection). The prognosis correlated with the rate at which the postoperative calcitonin concentration doubles, termed the calcitonin doubling time (CDT), rather than the pre- or postoperative absolute calcitonin level:
324:
The
European Society of Endocrine Surgeons has published recommendations for managing this condition in gene carriers. The timing of surgery depends on the type of mutation present. For those in the highest risk group, surgery is recommended in the first year of life. In lower risk cases surgery may
217:
Seventy-five percent of medullary thyroid carcinoma occurs in individuals without an identifiable family history and is assigned the term "sporadic". Individuals who develop sporadic medullary thyroid carcinoma tend to be older and have more extensive disease at the time of initial presentation than
336:
is recommended when there is a high risk of regional recurrence, even after optimum surgical treatment. In this study, patients treated with external beam radiation were compared to a control group. Disease control with radiation was far superior in the group receiving radiation. The authors of the
320:
A total thyroidectomy with bilateral neck dissection is the gold standard for treating medullary thyroid cancer, and is the most definitive means of achieving a cure in patients without distant metastases or extensive nodal involvement. Risks of surgery include loss of vocal control, irreparable
284:: between 97.2% and 100%), these results had a high risk of bias due to design flaws of included studies. Overall, the value of routine testing of calcitonin for diagnosis and prognosis of Medullary Thyroid Carcinoma remains uncertain and questionable.
1138:
1123:
261:
Diagnosis is primarily performed via fine needle aspiration of the lesion of the thyroid to distinguish it from other types of thyroid lesions. Microscopic examination will show an amyloid stroma with hyperplasia of parafollicular cells.
312:
753:
Niederle B, Sebag F, Brauckhoff M (2013) Timing and extent of thyroid surgery for gene carriers of hereditary C cell disease-a consensus statement of the
European Society of Endocrine Surgeons (ESES).Langenbecks Arch
245:. In general, measurement of serum CEA is less sensitive than serum calcitonin for detecting the presence of a tumor, but has less minute to minute variability and is therefore useful as an indicator of tumor mass.
795:
Brierley J, Tsang R, Simpson WJ, Gospodarowicz M, Sutcliffe S, Panzarella T (1996). "Medullary thyroid cancer: analyses of survival and prognostic factors and the role of radiation therapy in local control".
399:
I, 98% at stage II, 81% at stage III and 28% at stage IV. The prognosis of MTC is poorer than that of follicular and papillary thyroid cancer when it has metastasized (spread) beyond the thyroid gland.
1238:
662:
Verbeek HH, de Groot JW, Sluiter WJ, Muller Kobold AC, van den Heuvel ER, Plukker JT, Links TP, et al. (Cochrane
Metabolic and Endocrine Disorders Group) (March 2020).
430:
41 patients out of 41 (100%) were alive at the end of the study. These included 1 patient whose calcitonin was stable, and 11 patients who had decreasing calcitonin levels.
152:, and either symptom may be the first manifestation of the disease. The flushing that occurs in medullary thyroid carcinoma is indistinguishable from that associated with
1029:
102:. Medullary tumors are the third most common of all thyroid cancers and together make up about 3% of all thyroid cancer cases. MTC was first characterized in 1959.
202:
is responsible for nearly all cases of hereditary or familial medullary thyroid carcinoma. Its germline mutation may also be responsible for the development of
1341:
424:
11 patients out of 12 (92%) survived 5 years. 3 patients out of 8 (37%) survived 10 years. 4 patients out of 12 (25%) survived to the end of the study.
1231:
970:
767:
1572:
122:
1567:
1562:
1153:
711:
Schlumberger M, Carlomagno F, Baudin E, Bidart JM, Santoro M (2008). "New therapeutic approaches to treat medullary thyroid carcinoma".
211:
118:
1224:
585:
276:
for
Medullary Thyroid Carcinoma. Although both basal and combined basal and stimulated calcitonin testing presented high accuracy (
164:). By comparison, the flushing and diarrhea observed in carcinoid syndrome is caused by elevated levels of circulating serotonin.
418:
3 patients out of 12 (25%) survived 5 years. 1 patient out of 12 (8%) survived 10 years. All died within 6 months to 13.3 years.
1051:"Prognostic impact of serum calcitonin and carcinoembryonic antigen doubling-times in patients with medullary thyroid carcinoma"
988:"Prognostic impact of serum calcitonin and carcinoembryonic antigen doubling-times in patients with medullary thyroid carcinoma"
304:
syndrome. Undiagnosed pheochromocytoma leads to a very high intraoperative risk of hypertensive crisis and, potentially, death.
1421:
1268:
198:
protein, termed RET (REarranged during
Transfection). RET is involved in the regulation of cell growth and development and its
161:
366:(FDA) for treatment of late-stage (metastatic) medullary thyroid cancer in adult patients who are ineligible for surgery.
1026:
125:. When medullary thyroid cancer due to a hereditary genetic disorder occurs without other endocrine tumours it is termed
1554:
931:
904:
363:
281:
277:
226:
While the increased serum concentration of calcitonin is not harmful, it is useful as a marker which can be tested in
644:
462:
333:
1411:
1388:
528:
Dionigi G, Bianchi V, Rovera F, et al. (2007). "Medullary thyroid carcinoma: surgical treatment advances".
292:
Surgery and radiation therapy have been the major treatments for medullary thyroid carcinoma. A plasma level of
1464:
1383:
1247:
1164:
439:
408:
353:
234:
195:
1593:
1374:
266:
50:
1090:
926:
899:
874:
479:
Stamatakos M, Paraskeva P, Stefanaki C, Katsaronis P, Lazaris A, Safioleas K, Kontzoglou K (January 2011).
1459:
1050:
1516:
142:
325:
be delayed up to the age of ten years, the precise timing depending on the mutation and other factors.
156:
syndrome. In MTC, the flushing, diarrhea, and itching (pruritus) are all caused by elevated levels of
253:
237:(CEA), also produced by medullary thyroid carcinoma, is released into the blood and it is useful as a
1598:
1506:
1336:
392:
381:
1511:
1399:
1142:
203:
95:
831:
Quayle FJ, Moley JF (2005). "Medullary thyroid carcinoma: including MEN 2A and MEN 2B syndromes".
778:
17:
1319:
856:
736:
553:
187:
167:
Medullary thyroid carcinoma may also produce a thyroid nodule and enlarged cervical lymph nodes.
110:
1498:
1346:
1327:
1263:
1193:
1072:
1009:
966:
848:
813:
728:
693:
624:
581:
545:
510:
269:
199:
178:), liver, lung, and bone. Spread to other sites such as skin or brain occurs but is uncommon.
74:
956:
664:"Calcitonin testing for detection of medullary thyroid cancer in people with thyroid nodules"
1476:
1416:
1361:
1062:
999:
840:
805:
720:
683:
675:
614:
537:
500:
492:
300:
since 25% of people found to have medullary thyroid cancer have the inherited form from the
297:
296:
should be checked before surgical thyroidectomy takes place to evaluate for the presence of
207:
106:
1539:
1471:
1429:
1295:
1033:
191:
65:
deposition (left of image). Near normal thyroid follicles are also seen (right of image).
1454:
1369:
688:
663:
505:
480:
396:
388:
384:
for medullary thyroid cancer is 80%, 83% or 86%, and the 10-year survival rate is 75%.
91:
1587:
1488:
1481:
1446:
1434:
466:
1147:
1036:
By the
American Cancer Society. In turn citing: AJCC Cancer Staging Manual (7th ed).
860:
740:
557:
257:
Medullary thyroid carcinoma on ultrasound with typical small calcifications (arrows)
1526:
1392:
1331:
1204:
679:
369:
293:
242:
66:
1169:
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1277:
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619:
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341:
238:
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79:
1304:
1291:
1286:
1273:
1216:
435:
404:
359:
273:
227:
157:
149:
99:
58:
603:"Calcitonin's fantastic voyage: from hormone to marker of a genetic disorder"
541:
1534:
1282:
1199:
1132:
481:"Medullary thyroid carcinoma: The third most common thyroid cancer reviewed"
362:, trade name Caprelsa, was the first drug (April 2011) to be approved by US
153:
1076:
1013:
852:
809:
732:
697:
628:
549:
514:
316:
A surgery for MTC showing the central lymph nodes and thyroid gland removed
817:
724:
1255:
1067:
1004:
987:
138:
1115:
496:
137:
The major clinical symptom of metastatic medullary thyroid carcinoma is
62:
844:
214:) accounts for approximately 25% of all medullary thyroid carcinomas.
1309:
1300:
1127:
340:
Unlike other differentiated thyroid carcinoma, there is no role for
986:
Barbet J, Campion L, Kraeber-Bodéré F, Chatal JF (November 2005).
311:
301:
252:
146:
1158:
580:(24th ed.). Philadelphia: Elsevier Saunders. pp. e76.
1220:
878:
174:
in the neck, lymph nodes in the central portion of the chest (
170:
Sites of spread of medullary thyroid carcinoma include local
927:"FDA approves Cometriq to treat rare type of thyroid cancer"
900:"FDA approves new treatment for rare form of thyroid cancer"
438:
doubling time was a better predictor of MTC survival than
1049:
Barbet J, Campion L, Kraeber-Bodéré F, Chatal JF (2005).
272:
assessed the diagnostic accuracy of basal and stimulated
875:"American Thyroid Association - Thyroid Clinical Trials"
465:
in Pazdur R, Wagman LD, Camphausen KA, Hoskins WJ (Eds)
105:
Approximately 25% of medullary thyroid cancer cases are
777:. National Comprehensive Cancer Network. Archived from
645:
National Cancer
Institute > Medullary Thyroid Cancer
955:
Numbers from
National Cancer Database in the US, from
1105:
992:
The
Journal of Clinical Endocrinology and Metabolism
961:
F. Grünwald; Biersack, H. J.; Grںunwald, F. (2005).
461:
Hu MI, Vassilopoulou-Sellin R, Lustig R, Lamont JP.
1553:
1525:
1497:
1445:
1360:
1318:
1254:
1179:
1109:
73:
40:
35:
27:
Malignant thyroid neoplasm originating from C-cells
117:. Medullary thyroid cancer is seen in people with
1093:. American Society of Clinical Oncology (ASCO).
467:Cancer Management: A Multidisciplinary Approach
1232:
8:
951:
949:
668:The Cochrane Database of Systematic Reviews
1239:
1225:
1217:
1106:
49:
32:
1066:
1044:
1042:
1003:
687:
618:
504:
442:but following both tests is recommended.
113:. When MTC occurs by itself it is termed
190:, located on chromosome 10, lead to the
145:episodes. Both occur particularly with
762:
760:
571:
569:
567:
451:
109:in nature, caused by a mutation in the
344:treatment in medullary-type disease.
98:(C cells), which produce the hormone
7:
1091:"ASCO Self-Evaluation Program (SEP)"
657:
655:
653:
640:
638:
457:
455:
61:of medullary thyroid carcinoma with
141:; occasionally a patient will have
119:multiple endocrine neoplasia type 2
403:The prognostic value of measuring
25:
18:Medullary carcinoma of the thyroid
463:"Thyroid and Parathyroid Cancers"
422:CDT between 6 months and 2 years:
380:Depending on source, the overall
127:familial medullary thyroid cancer
115:sporadic medullary thyroid cancer
1337:ACTH-secreting pituitary adenoma
1269:Pancreatic neuroendocrine tumor
713:Nat Clin Pract Endocrinol Metab
186:Mutations (DNA changes) in the
162:calcitonin gene-related peptide
1342:GH-secreting pituitary adenoma
1027:cancer.org > Thyroid Cancer
680:10.1002/14651858.CD010159.pub2
1:
160:gene products (calcitonin or
932:Food and Drug Administration
905:Food and Drug Administration
364:Food and Drug Administration
1248:Tumours of endocrine glands
620:10.1163/22977953-0640102004
1615:
1055:J. Clin. Endocrinol. Metab
530:Expert Rev Anticancer Ther
334:External beam radiotherapy
94:which originates from the
1032:October 18, 2013, at the
647:Last Modified: 12/22/2010
391:into stages I to IV, the
354:protein kinase inhibitors
348:Protein kinase inhibitors
57:
48:
1465:Adrenocortical carcinoma
578:Goldman's Cecil Medicine
542:10.1586/14737140.7.6.877
409:carcinoembryonic antigen
280:: between 82% and 100%;
235:carcinoembryonic antigen
196:receptor tyrosine kinase
88:Medullary thyroid cancer
36:Medullary thyroid cancer
1422:Squamous-cell carcinoma
416:CDT less than 6 months:
1460:Adrenocortical adenoma
810:10.1089/thy.1996.6.305
428:CDT more than 2 years:
317:
258:
784:on 25 September 2006.
725:10.1038/ncpendmet0717
315:
256:
1507:Parathyroid neoplasm
1068:10.1210/jc.2005-0044
1005:10.1210/jc.2005-0044
965:. Berlin: Springer.
393:5-year survival rate
382:5-year survival rate
96:parafollicular cells
1400:Parafollicular cell
768:"Thyroid Carcinoma"
497:10.3892/ol.2010.223
352:Clinical trials of
204:hyperparathyroidism
1180:External resources
576:Goldman L (2011).
318:
259:
188:RET proto-oncogene
133:Signs and symptoms
111:RET proto-oncogene
1581:
1580:
1347:Craniopharyngioma
1328:Pituitary adenoma
1264:Pancreatic cancer
1214:
1213:
998:(11): 6077–6084.
972:978-3-540-22309-2
845:10.1002/jso.20184
270:systematic review
233:A second marker,
200:germline mutation
92:thyroid carcinoma
85:
84:
30:Medical condition
16:(Redirected from
1606:
1477:Pheochromocytoma
1241:
1234:
1227:
1218:
1107:
1095:
1094:
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1080:
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1046:
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912:
896:
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889:
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877:. Archived from
871:
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772:
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755:
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601:Fragu P (2007).
598:
592:
591:
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562:
561:
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519:
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508:
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459:
298:pheochromocytoma
208:pheochromocytoma
53:
33:
21:
1614:
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1609:
1608:
1607:
1605:
1604:
1603:
1584:
1583:
1582:
1577:
1549:
1540:Pinealoblastoma
1521:
1493:
1441:
1430:Thyroid adenoma
1375:epithelial-cell
1356:
1314:
1296:Somatostatinoma
1250:
1245:
1215:
1210:
1209:
1175:
1174:
1118:
1104:
1099:
1098:
1089:
1088:
1084:
1061:(11): 6077–84.
1048:
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1034:Wayback Machine
1025:
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674:(3): CD010159.
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1110:Classification
1103:
1102:External links
1100:
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1038:
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978:
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963:Thyroid cancer
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613:(1–2): 69–92.
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587:978-1437727883
586:
563:
520:
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469:. 11 ed. 2008.
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389:cancer staging
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1489:Paraganglioma
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1482:Neuroblastoma
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1470:
1466:
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1447:Adrenal tumor
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1372:(malignant):
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881:on 2007-12-12
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854:
850:
846:
842:
838:
834:
827:
824:
819:
815:
811:
807:
804:(4): 305–10.
803:
799:
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747:
742:
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536:(6): 877–85.
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90:is a form of
89:
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78:
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68:
67:H&E stain
64:
60:
56:
52:
47:
43:
39:
34:
19:
1527:Pineal gland
1404:
1393:Hurthle cell
1378:
1373:
1332:Prolactinoma
1198:
1187:
1163:
1152:
1137:
1122:
1085:
1058:
1054:
1022:
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991:
981:
962:
936:. Retrieved
930:
921:
909:. Retrieved
903:
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883:. Retrieved
879:the original
869:
839:(3): 122–9.
836:
833:J Surg Oncol
832:
826:
801:
797:
790:
779:the original
774:
749:
719:(1): 22–32.
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610:
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533:
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523:
491:(1): 49–53.
488:
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379:
370:Cabozantinib
368:
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243:tumor marker
232:
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126:
114:
104:
87:
86:
1599:Amyloidosis
1545:Pineocytoma
1499:Parathyroid
1352:Pituicytoma
1278:Glucagonoma
1189:MedlinePlus
938:29 November
395:is 100% at
387:By overall
342:radioiodine
282:specificity
278:sensitivity
176:mediastinum
172:lymph nodes
80:ENT surgery
41:Other names
1588:Categories
1412:Anaplastic
1389:Follicular
1305:Gastrinoma
1287:Insulinoma
885:2007-12-21
485:Oncol Lett
446:References
436:calcitonin
405:calcitonin
360:Vandetanib
274:calcitonin
192:expression
158:calcitonin
150:metastasis
100:calcitonin
59:Micrograph
1535:Pinealoma
1517:Carcinoma
1405:Medullary
1384:Papillary
1379:carcinoma
1320:Pituitary
1200:eMedicine
376:Prognosis
329:Radiation
288:Treatment
265:A recent
249:Diagnosis
241:or blood
154:carcinoid
75:Specialty
1417:Lymphoma
1256:Pancreas
1205:med/2272
1077:16091497
1030:Archived
1014:16091497
861:31436486
853:15719378
741:25818628
733:18084343
698:32176812
629:17982960
607:Gesnerus
558:37519975
550:17555398
515:22870127
267:Cochrane
182:Genetics
143:flushing
139:diarrhea
1512:Adenoma
1472:Medulla
1426:Benign
1362:Thyroid
1170:D013964
957:Page 10
911:7 April
818:8875751
798:Thyroid
689:7075519
506:3412473
308:Surgery
222:Markers
107:genetic
63:amyloid
1455:Cortex
1310:VIPoma
1194:000374
1159:155240
1075:
1012:
969:
859:
851:
816:
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121:A and
857:S2CID
782:(PDF)
771:(PDF)
737:S2CID
554:S2CID
397:stage
302:MEN2A
239:serum
228:blood
147:liver
1165:MeSH
1154:OMIM
1143:9-CM
1073:PMID
1010:PMID
967:ISBN
959:in:
940:2012
913:2011
849:PMID
814:PMID
754:Surg
729:PMID
694:PMID
672:2020
625:PMID
582:ISBN
546:PMID
511:PMID
434:The
407:and
212:MEN2
206:and
1555:MEN
1148:193
1139:ICD
1133:C73
1124:ICD
1063:doi
1000:doi
841:doi
806:doi
721:doi
684:PMC
676:doi
615:doi
538:doi
501:PMC
493:doi
440:CEA
44:MTC
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1573:2B
1568:2A
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560:.
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495::
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20:)
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