International Medical Journal, Vol. 26., Iss. 1, 2020, P. 11−15.
MULTIPLE ENDOCRINE NEOPLASIA IN PRACTICE OF PRIMARY CARE AND FAMILY PHYISICIANS
V. N. Karazin Kharkiv National University
Kharkiv Medical Academy of Postgraduate Education, Ukraine
Multiple endocrine neoplasia is characterized with a predisposition to tumors involving two or more endocrine glands. The four main forms of the disease are inherited as an autosomal dominant syndrome or may occur sporadically. In addition to these four forms, six other syndromes are associated with the presence of multiple endocrine and other neoplasms of the organs: hyperparathyroidism − jaw tumors, Carney complex, von Hippel−Lindau disease, neurofibromatosis type 1, Cowden syndrome and McCune − Albright syndrome. The diagnosis of multiple endocrine neoplasia syndrome can be established in humans by one of the three available criteria: clinical features, family history, genetic analysis. Mutation analysis during these syndromes is useful in clinical practice to confirm the clinical diagnosis; identifying family members who tolerate the mutation and need to be screened, and identifying family members who do not tolerate the mutation. Syndrome of multiple endocrine neoplasia (Wermer syndrome) is characterized by the presence of a triad of tumors, including tumors of the parathyroid glands, pheochromocytoma and tumors of the parathyroid gland. It occurs less frequently in combination with Hirschsprung's disease, caused by the absence of vegetative ganglion cells in the intestine terminal parts, that leads to colonic enlargement, severe constipation and obstruction. This syndrome may be associated with cutaneous lichen amyloidosis, the clinical manifestations of which are pruritus and lichenoid lesions, usually located in the upper back. A clinical case of MEN2 syndrome in a 52−year−old patient is presented. It is noted that for such patients, in addition to timely syndromic rather than component diagnosis of this endocrine multipathology, the spread of neoplastic process in medullary thyroid cancer to its capsule and surrounding tissues, as well as the presence of metastases in peripheral lymph nodes are important. As a rule, such patients cannot be timely cured.
Key words: multiple endocrine neoplasia, endocrine tumors, genetic analysis, family history.
1. Calender A. Multiple endocrine neoplasia: genetic aspects // Bull Acad. Natl Med. 2010. № 194. P. 81−95;
2. Harrison's Principles of Internal Medicine. 20th ed. / J. L. Jameson et al. N.−Y.: McGraw−Hill, 2018. 3790 p. URL: http://accessmedicine.mhmedical.com/books.aspx?book/D_2019
3. Sindrom mnozhinnoї endokrinnoї neoplazії 2a / N. І. Boiko ta іn. // Klіnіchna endokrinologіya. 2011.№ 1 (34). S. 19−21.
4. Multiple Endocrine Neoplasia Type 2A: A 25−Year Review / M. A. Iler et al. // J. of Pediatric Surgery. 1999. Vol. 34 (1). P. 92−97.
5. Bіlіns'kii B. Sindromi mnozhinnikh endokrinnikh neoplazіi // Medichnі nauki. 2015. T. XLIII. S. 34−48.
6. Thakker R. V. Multiple endocrine neoplasia type 1 (MEN1) and type 4 (MEN4) // Mol. Cell Endocrinol. 2014. № 386 (1−2). P. 2−15. doi: https://doi.org/10.1016/j.mce.2013.08.002
7. Lemos M. C., Thakker R. V. Multiple endocrine neoplasia type 1 (MEN1): analysis of 1336 mutations reported in the first decade following identification of the gene // Hum. Mutat. 2008. № 29 (1). P. 22−32. doi: https://doi.org/10.1002/humu.20605
8. Revised American Thyroid Association guidelines for the management of medullary thyroid carcinoma / S. A. Wells et al. // Thyroid. 2015. № 25 (6). P. 567−610. doi: https://doi.org/10.1089/thy.2014.0335
9. De Laat J. M., van Leeuwaarde R. S., Valk G. D. The Importance of an Early and Accurate MEN1 Diagnosis // Front. Endocrinol. 2018. doi.org/10.3389/fendo.2018.00533
10. Thakker Clinical Practice Guidelines for Multiple Endocrine Neoplasia Type 1 (MEN1) / R. V. Thakker et al. // The J. of Clin. Endocrinology & Metabolism. 2012. Vol. 97 (9). P. 2990−3011. doi: https://doi.org/10.1210/jc.2012−1230
11. Multiple endocrine neoplasia type 2a associated with cutaneous lichen amyloidosis / R. F. Gagel et al. // Ann. Intern. Med. 1989. Vol. 111 (10). P. 802−806. doi: https://doi.org/10.7326/0003−4819−111−10−802
12. Dermal Hyperneury and Multiple Sclerotic Fibromas in Multiple Endocrine Neoplasia Type 2A Syndrome / V. Alegría−Landa, M. Jo−Velasco, M. Robledo, L. Requena // JAMA Dermatol. 2017. Vol. 153 (12). P. 1298−1301. doi: https://doi.org/10.1001/jamadermatol.2017.3959
13. Multiple Endocrine Neoplasia Type 2A (including Familial Medullary Carcinoma) and Type 2B / M. S. Hughes, E. Feliberti, R. R. Perry, A. Vinik // Endotext. 2017. Vol. 2. P. 11−16.
14. Kumar P. C., Kumar M. L. Clark's Clinical Medicine. 9th ed. Elsevier, 2019. 1376 p.
15. Germ−line mutations in p27Kip1 cause a multiple endocrine neoplasia syndrome in rats and humans / N. S. Pellegata et al. // J. Proc. Natl. Acad. Sci. USA. 2006. Vol. 103 (42). P. 1558−1563. doi: https://doi.org/10.1073/pnas.0609565103
16. A heterozygous frameshift mutation in exon 1 of CDKN1B gene in a patient affected by MEN4 syndrome / F. Tonelli et al. // Eur. J. Endocrinol. 2014. Vol. 171 (2). P. 7−17. doi: https://doi.org/10.1530/eje−14−0080
17. Prophylactic thyroidectomy for medullary thyroid carcinoma in gene carriers of MEN2 syndrome / M. Lallier et al. // J. Pediatr. Surg. 1998. Vol. 33 (6). P. 846−848. doi: https://doi.org/10.1016/s0022−3468(98)90656−x
18. Roman S., Sosa L. R. Prognosis of medullary thyroid carcinoma: demographic, clinical, and pathologic predictors of survival in 1252 cases // J. A Cancer. 2006. Vol. 107 (9). P. 2134−2142. doi: https://doi.org/10.1002/cncr.22244
19. A Nationwide Study of Multiple Endocrine Neoplasia Type 2A in Norway: Predictive and Prognostic Factors for the Clinical Course of Medullary Thyroid Carcinoma / E. M. Opsahl et al. // Thyroid. 2016. Vol. 26 (9). P. 1225−1238. doi: https://doi.org/10.1089/thy.2015.0673
20. Management of endocrine disease: Outcome of adrenal sparing surgery in heritable pheochromocytoma / F. Castinetti et al. // Eur. J. Endocrinol. 2016. Vol. 174 (1). P. 9−18.