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. 1993 Feb;52(2):335–342.

The clinical implications of a positive calcitonin test for C-cell hyperplasia in genetically unaffected members of an MEN2A kindred.

R M Landsvater 1, A G Rombouts 1, G J te Meerman 1, J M Schillhorn-van Veen 1, M J Berends 1, R A Geerdink 1, A Struyvenberg 1, C H Buys 1, C J Lips 1
PMCID: PMC1682203  PMID: 8094268

Abstract

C-cell hyperplasia precedes the development of medullary thyroid carcinoma in multiple endocrine neoplasia type 2A (MEN2A). Identification of abnormal calcitonin levels after a provocative stimulus is a technique that has been widely used to diagnose this preneoplastic condition in an early stage during the development of medullary thyroid carcinoma, when total thyroidectomy is likely to be curative. In a MEN2A kindred, we identified seven individuals with abnormal calcitonin test results, whose carrier state was questionable. Five of these people were thyroidectomized, and C-cell hyperplasia was diagnosed. Four of these individuals were the offspring of a mother who is at risk for the development of MEN2A but who has had normal calcitonin test results throughout the years and of a father who is not at risk but who has had abnormal test results over a period of 10 years, without evidence of progressive elevation. None of these people developed other manifestations of MEN2A. DNA analysis using markers linked to the MEN2A gene demonstrated, with > 99% likelihood, that none of the individuals who could be genotyped was a gene carrier. C-cell hyperplasia due to some mechanism other than the presence of the MEN2A gene may also occur in MEN2A kindreds. DNA analysis offers an important additional tool for proper diagnosis in the clinical management of MEN2A families.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Albores-Saavedra J., Monforte H., Nadji M., Morales A. R. C-cell hyperplasia in thyroid tissue adjacent to follicular cell tumors. Hum Pathol. 1988 Jul;19(7):795–799. doi: 10.1016/s0046-8177(88)80262-4. [DOI] [PubMed] [Google Scholar]
  2. Easton D. F., Ponder M. A., Cummings T., Gagel R. F., Hansen H. H., Reichlin S., Tashjian A. H., Jr, Telenius-Berg M., Ponder B. A. The clinical and screening age-at-onset distribution for the MEN-2 syndrome. Am J Hum Genet. 1989 Feb;44(2):208–215. [PMC free article] [PubMed] [Google Scholar]
  3. Gagel R. F., Jackson C. E., Block M. A., Feldman Z. T., Reichlin S., Hamilton B. P., Tashjian A. H., Jr Age-related probability of development of hereditary medullary thyroid carcinoma. J Pediatr. 1982 Dec;101(6):941–946. doi: 10.1016/s0022-3476(82)80014-0. [DOI] [PubMed] [Google Scholar]
  4. Gagel R. F., Tashjian A. H., Jr, Cummings T., Papathanasopoulos N., Kaplan M. M., DeLellis R. A., Wolfe H. J., Reichlin S. The clinical outcome of prospective screening for multiple endocrine neoplasia type 2a. An 18-year experience. N Engl J Med. 1988 Feb 25;318(8):478–484. doi: 10.1056/NEJM198802253180804. [DOI] [PubMed] [Google Scholar]
  5. Gibson W. C., Peng T. C., Croker B. P. C-cell nodules in adult human thyroid. A common autopsy finding. Am J Clin Pathol. 1981 Mar;75(3):347–350. doi: 10.1093/ajcp/75.3.347. [DOI] [PubMed] [Google Scholar]
  6. Goodfellow P. J., Myers S., Anderson L. L., Brooks-Wilson A. R., Simpson N. E. A new DNA marker (D10S94) very tightly linked to the multiple endocrine neoplasia type 2A (MEN2A) locus. Am J Hum Genet. 1990 Dec;47(6):952–956. [PMC free article] [PubMed] [Google Scholar]
  7. Landsvater R. M., Mathew C. G., Smith B. A., Marcus E. M., te Meerman G. J., Lips C. J., Geerdink R. A., Nakamura Y., Ponder B. A., Buys C. H. Development of multiple endocrine neoplasia type 2A does not involve substantial deletions of chromosome 10. Genomics. 1989 Apr;4(3):246–250. doi: 10.1016/0888-7543(89)90327-3. [DOI] [PubMed] [Google Scholar]
  8. Lichter J. B., Wu J. S., Genel M., Flynn S. D., Pakstis A. J., Kidd J. R., Kidd K. K. Presymptomatic testing using DNA markers for individuals at risk for familial multiple endocrine neoplasia 2A. J Clin Endocrinol Metab. 1992 Feb;74(2):368–373. doi: 10.1210/jcem.74.2.1346145. [DOI] [PubMed] [Google Scholar]
  9. Liou G. I., Li Y., Wang C., Fong S. L., Bhattacharya S., Bridges C. D. Bgl II RFLP recognized by a human IRBP cDNA localized to chromosome 10. Nucleic Acids Res. 1987 Apr 10;15(7):3196–3196. doi: 10.1093/nar/15.7.3196. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Lips C. J., Leo J. R., Berends M. J., Minder W. H., Blok A. P., Geerdink R. A., Hackeng W. H., Roelofs J. M., Vasen H. F., Vette J. K. Thyroid C-cell hyperplasia and micronodules in close relatives of MEN-2A patients: pitfalls in early diagnosis and reevaluation of criteria for surgery. Henry Ford Hosp Med J. 1987;35(2-3):133–138. [PubMed] [Google Scholar]
  11. Lips C. J., Minder W. H., Leo J. R., Alleman A., Hackeng W. H. Evidence of multicentric origin of the multiple endocrine neoplasia syndrome type 2a (Sipple's syndrome) in a large family in the Netherlands. Diagnostic and therapeutic implications. Am J Med. 1978 Apr;64(4):569–578. doi: 10.1016/0002-9343(78)90575-2. [DOI] [PubMed] [Google Scholar]
  12. Lips K. J., Van der Sluys Veer J., Struyvenberg A., Alleman A., Leo J. R., Wittebol P., Minder W. H., Kooiker C. J., Geerdink R. A., Van Waes P. F. Bilateral occurrence of pheochromocytoma in patients with the multiple endocrine neoplasia syndrome type 2A (Sipple's syndrome). Am J Med. 1981 May;70(5):1051–1060. doi: 10.1016/0002-9343(81)90866-4. [DOI] [PubMed] [Google Scholar]
  13. Livolsi V. A., Feind C. R. Incidental medullary thyroid carcinoma in sporadic hyperparathyroidism. An expansion of the concept of C-cell hyperplasia. Am J Clin Pathol. 1979 May;71(5):595–599. doi: 10.1093/ajcp/71.5.595. [DOI] [PubMed] [Google Scholar]
  14. Mathew C. G., Chin K. S., Easton D. F., Thorpe K., Carter C., Liou G. I., Fong S. L., Bridges C. D., Haak H., Kruseman A. C. A linked genetic marker for multiple endocrine neoplasia type 2A on chromosome 10. Nature. 1987 Aug 6;328(6130):527–528. doi: 10.1038/328527a0. [DOI] [PubMed] [Google Scholar]
  15. Mathew C. G., Easton D. F., Nakamura Y., Ponder B. A. Presymptomatic screening for multiple endocrine neoplasia type 2A with linked DNA markers. The MEN 2A International Collaborative Group. Lancet. 1991 Jan 5;337(8732):7–11. doi: 10.1016/0140-6736(91)93329-8. [DOI] [PubMed] [Google Scholar]
  16. Nakamura Y., Carlson M., Krapcho K., Gill J., O'Connell P., Leppert M., Lathrop G. M., Lalouel J. M., White R. Isolation and mapping of a polymorphic DNA sequence pMCK2 on chromosome 10 [D10S15]. Nucleic Acids Res. 1988 Jan 11;16(1):374–374. doi: 10.1093/nar/16.1.374. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Nakamura Y., Lathrop M., Bragg T., Leppert M., O'Connell P., Jones C., Lalouel J. M., White R. An extended genetic linkage map of markers for human chromosome 10. Genomics. 1988 Nov;3(4):389–392. doi: 10.1016/0888-7543(88)90133-4. [DOI] [PubMed] [Google Scholar]
  18. Nakamura Y., Mathew C. G., Sobol H., Easton D. F., Telenius H., Bragg T., Chin K., Clark J., Jones C., Lenoir G. M. Linked markers flanking the gene for multiple endocrine neoplasia type 2A. Genomics. 1989 Aug;5(2):199–203. doi: 10.1016/0888-7543(89)90046-3. [DOI] [PubMed] [Google Scholar]
  19. Norum R. A., Lafreniere R. G., O'Neal L. W., Nikolai T. F., Delaney J. P., Sisson J. C., Sobol H., Lenoir G. M., Ponder B. A., Willard H. F. Linkage of the multiple endocrine neoplasia type 2B gene (MEN2B) to chromosome 10 markers linked to MEN2A. Genomics. 1990 Oct;8(2):313–317. doi: 10.1016/0888-7543(90)90287-5. [DOI] [PubMed] [Google Scholar]
  20. O'Toole K., Fenoglio-Preiser C., Pushparaj N. Endocrine changes associated with the human aging process: III. Effect of age on the number of calcitonin immunoreactive cells in the thyroid gland. Hum Pathol. 1985 Oct;16(10):991–1000. doi: 10.1016/s0046-8177(85)80276-8. [DOI] [PubMed] [Google Scholar]
  21. Schimke R. N. Genetic aspects of multiple endocrine neoplasia. Annu Rev Med. 1984;35:25–31. doi: 10.1146/annurev.me.35.020184.000325. [DOI] [PubMed] [Google Scholar]
  22. Scopsi L., Di Palma S., Ferrari C., Holst J. J., Rehfeld J. F., Rilke F. C-cell hyperplasia accompanying thyroid diseases other than medullary carcinoma: an immunocytochemical study by means of antibodies to calcitonin and somatostatin. Mod Pathol. 1991 May;4(3):297–304. [PubMed] [Google Scholar]
  23. Simpson N. E., Kidd K. K., Goodfellow P. J., McDermid H., Myers S., Kidd J. R., Jackson C. E., Duncan A. M., Farrer L. A., Brasch K. Assignment of multiple endocrine neoplasia type 2A to chromosome 10 by linkage. Nature. 1987 Aug 6;328(6130):528–530. doi: 10.1038/328528a0. [DOI] [PubMed] [Google Scholar]
  24. Troelstra C., Landsvater R. M., Wiegant J., van der Ploeg M., Viel G., Buys C. H., Hoeijmakers J. H. Localization of the nucleotide excision repair gene ERCC6 to human chromosome 10q11-q21. Genomics. 1992 Apr;12(4):745–749. doi: 10.1016/0888-7543(92)90304-b. [DOI] [PubMed] [Google Scholar]
  25. Wolfe H. J., Delellis R. A. Familial medullary thyroid carcinoma and C cell hyperplasia. Clin Endocrinol Metab. 1981 Jul;10(2):351–365. doi: 10.1016/s0300-595x(81)80027-8. [DOI] [PubMed] [Google Scholar]
  26. Wu J. S., Carson N. L., Myers S., Pakstis A. J., Kidd J. R., Castiglione C. M., Anderson L., Hoyle L. S., Genel M., Verdy M. The genetic defect in multiple endocrine neoplasia type 2A maps next to the centromere of chromosome 10. Am J Hum Genet. 1990 Mar;46(3):624–630. [PMC free article] [PubMed] [Google Scholar]

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