Статья
Генетические аспекты патогенеза первичного гиперальдостеронизма и феохромоцитомы
Наиболее частыми эндокринными причинами вторичной артериальной гипертензии (АГ) являются первичный гиперальдостеронизм и феохромоцитома (ФХ). У пациентов с гиперальдостеронизмом установлена частота соматических мутаций при альдостерон-продуцирующих аденомах (АПА), идентифицированы генетические мутации семейных форм заболевания. Исследователи сделали заключение, что область с альдостерон-продуцирующими клеточными кластерами, происходящая из клубочковой зоны, является следствием соматических мутаций и может быть представлена в качестве предшественника АПА. Наличие аутоантител и хроническая стимуляция ими клубочковой зоны, возможно, объясняет развитие двусторонней гиперплазии и АПА в надпочечниках. Выявление соматических и герминальных мутаций у пациентов с ФХ и параганглиомой способствуют ранней диагностике многих опухолей в рамках синдромальной неоплазии. Внедрение новых генетических исследований в практическую работу будет способствовать ранней диагностике заболеваний надпочечников, протекающих с АГ.
1. Asbach E, Williams TA, Reincke M. Recent developments in primary aldosteronism. Exp Clin Endocrinol Diabetes. 2016;124 (6):335–41. doi:10.1055/s‑0042–105278. Epub 2016 May 24.
2. Chao CT, Wu VC, Kuo CC, Lin YH, Chang CC, Chueh SJ et al. Diagnosis and management of primary aldosteronism: an updated review. J Annals of medicine. 2013;45(4):375–383. doi:10.3109/07853890.2013.785234.
3. Young WF. Minireview: primary aldosteronism-changing concepts in diagnosis and treatment. Endocrinology. 2003;144 (6):2208–2213. doi:10.1210/en.2003–0279.
4. Rossi GP, Bernini G, Caliumi C, Desideri G, Fabris B, Ferri C et al. A prospective study of the prevalence of primary aldosteronism in 1,125 hypertensive patients. J Am CollCardiol. 2006;48(11):2293–300.
5. AkerstromT, Crona J, Delgado Verdugo A, Starker LF, Cupisti K, Willenberg HS et al. Comprehensive re-sequencing of adrenal aldosterone producing lesions reveal three somatic mutations near the KCNJ5 potassium channel selectivity filter. PLoS ONE.2012:7e41926.
6. Boulkroun S, Beuschlein F, Rossi GP, Golib-Dzib JF, Fischer E, Amar L et al. Prevalence, clinical, and molecular correlates of KCNJ5 mutations in primary aldosteronism. Hypertension. 2012;59 (3):592–598. doi:10.1161/HYPERTENSIONAHA.111.186478.
7. Beuschlein F, Boulkroun S, Osswald A, Wieland T, Nielsen HN, Lichtenauer UD et al. Somatic mutations in ATP1A1 and ATP2B3 lead to aldosterone producing adenomas and secondary hypertension. Nature Genetics. 2013;45:440–444. doi:10.1038/ng.2550.
8. Zheng FF, Zhu LM, Nie AF, Li XY, Lin JR, Zhang K et al. Clinical characteristics of somatic mutations in Chinese patients with aldosterone-producing adenoma. J Hypertension. 2015;65 (3):622–628. doi:10.1161/HYPERTENSIONAHA.114.03346.
9. Williams TA, Monticone S, Schack VR, Stindl J, Burrello J, Buffolo F et al. Somatic ATP1A1, ATP2B3 and KCNJ5 mutations in aldosterone-producing adenomas. J Hypertension. 2014;63(1):188–195. doi:10.1161/HYPERTENSIONAHA.113.01733.
10. Lenzini L, Rossitto G, Maiolino G, Letizia C, Funder JW, Rossi GP. A meta-analysis of somatic KCNJ5 K(+) channel mutations in 1636 patients with an aldosterone-producing adenoma. J Clin Endocrinol Metab. 2015;100(8): E1089‑E1095. doi:10.1210/jc.2015–2149.
11. Boulkroun S, Beuschlein F, Rossi GP, Golib-Dzib JF, Fischer E, Amar L et al. Prevalence, clinical, and molecular correlates of KCNJ5 mutations in primary aldosteronism. J Hypertension. 2012;59 (3):592–598. doi:10.1161/HYPERTENSIONAHA.111.186478.
12. Stindl J, Tauber P, Sterner C, Tegtmeier I, Warth R, Bandulik S. Pathogenesis of adrenal aldosterone producing adenomas carrying mutations of the Na(+)/K(+)-ATPase. J Endocrinology. 2015;156(12):4582–4591. doi:10.1210/en.2015–1466.
13. Sutherland DJ, Ruse JL, Laidlaw JC. Hypertension, increased aldosterone secretion and low plasma renin activity relieved by dexamethasone. Can Med Assoc J. 1966;95(22):1109–1119.
14. Lifton RP, Dluhy RG, Powers M, Rich GM, Cook S, Ulick S et al. A chimaeric 11 beta-hydroxylase/aldosterone synthase gene causes glucocorticoid-remediable aldosteronism and human hypertension. J Nature. 1992;355(6357):262–265.
15. Litchfield WR, Anderson BF, Weiss RJ, Lifton RP, Dluhy RG. Intracranial aneurysm and hemorrhagic stroke in glucocorticoid-remediable aldosteronism. J Hypertension. 1998;31 (1 Pt 2):445–450.
16. MacConnachie AA, Kelly KF, McNamara A, Loughlin S, Gates LJ, Inglis GC et al. Rapid diagnosis and identification of crossover sites in patients with glucocorticoid remediable aldosteronism. J Clin Endocrinol Metab. 1998;83(12):4328–4331.
17. So A, Duffy DL, Gordon RD, Jeske YW, Lin-Su K, New MI et al. Familial hyperaldosteronism type II is linked to the chromosome 7p22 region but also shows predicted heterogeneity. J Hypertension. 2005;23(8):1477–1484.
18. Geller DS, Zhang J, Wisgerhof MV, Shackleton C, Kashgarian M, Lifton RP. A novel form of human mendelian hypertension featuring nonglucocorticoid-remediable aldosteronism. J Clin Endocrinol Metab. 2008;93(8):3117–3123.
19. Choi M, Scholl UI, Yue P, Björklund P, Zhao B, Nelson-Williams C et al. K + channel mutations in adrenal aldosteroneproducing adenomas and hereditary hypertension. Science. 2011;331 (6018):768–772.
20. Mulatero P, Tauber P, Zennaro MC, Monticone S, Lang K, Beuschlein F et al. KCNJ5 mutations in European families with nonglucocorticoid remediable familial hyperaldosteronism. Hypertension. 2012;59(2):235–240.
21. Charmandari E, Sertedaki A, Kino T, Merakou C, Hoffman DA, Hatch MM et al. A novel point mutation in the KCNJ5 gene causing primary hyperaldosteronism and early-onset autosomal dominant hypertension. J Clin Endocrinol Metab. 2012;97(8): E1532‑E1539.
22. Petramala L, Savoriti C, Zinnamosca L, Marinelli C, Settevendemmie A, Calvieri C et al. Primary aldosteronism with concurrent primary hyperparathyroidism in a patient with arrhythmic disorders. Intern Med. 2013;52(18):2071–2075.
23. Scholl UI, Stolting G, Nelson-Williams C, Vichot AA, Choi M, Loring E et al. Recurrent gain of function mutation in calcium channel CACNA1H causes early-onset hypertension with primary aldosteronism. eLife. 2015;4: e06315.
24. Nishimoto K, Nakagawa K, Li D, Kosaka T, Oya M, Mikami S et al. Adrenocortical zonation in humans under normal and pathological conditions. J Clin Endocrinol Metab. 2010;95 (5):2296–2305.
25. Nishimoto K, Tomlins SA, Kuick R, Cani AK, Giordano TJ, Hovelson DH et al. Aldosterone-stimulating somatic gene mutations are common in normal adrenal glands. Proc Natl Acad Sci USA. 2015;112(33): E4591‑E4599.
26. Wallukat G, Homuth V, Fischer T, Lindschau C, Horstkamp B, Jüpner A et al. Patients with preeclampsia develop agonistic autoantibodies against the angiotensin AT1 receptor. J Clin Invest. 1999;103(7):945–952.
27. Kem DC, Li H, Velarde-Miranda C, Liles C, Vanderlinde-Wood M, Galloway A et al. Autoimmune mechanisms activating the angiotensin AT1 receptor in ‘primary’ aldosteronism. J Clin Endocrinol Metab. 2014;99(5):1790–1797.
28. Li H, Yu X, Cicala MV, Mantero F, Benbrook A, Veitla V et al. Prevalence of angiotensin II type 1 receptor (AT1R)-activating autoantibodies in primary aldosteronism. J Am Soc Hypertens. 2015;9(1):15–20.
29. Zubera SM, Kantorovich V, Pacak K. Hypertension in pheochromocytoma: characteristics and treatment. J Endocrinol Metab Clin North Am. 2011;40(2):295–311.
30. Ulchaker JC, Goldfarb DA, Bravo EL, Novick AC. Successful outcomes in pheochromocytoma surgery in the modern era. J Urol. 1999;161(3):764–767.
31. Santos P, Pimenta T, Taveira-Gomes A. Hereditary phaeochromocytoma. Int J Surg Pathol. 2014;22(5):393–400.
32. Pillai S, Gopalan V, Smith RA, Lam AK. Updates on the genetics and the clinical impacts on phaeochromocytoma and paraganglioma in the new era. Crit Rev Oncol Hematol. 2016;100:190–208.
33. Lenders JW, Duh QY, Eisenhofer G, Gimenez-Roqueplo AP, Grebe SK, Murad MH et al. Pheochromocytoma and paraganglioma: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2014;99(6):1915–1942.
34. Jafri M, Whitworth J, Rattenberry E, Vialard L, Kilby G, Kumar AV et al. Evaluation of SDHB, SDHD and VHL gene susceptibility testing in the assessment of individuals with nonsyndromicphaeochromocytoma, paraganglioma and head and neck paraganglioma. Clin Endocrinol (Oxf). 2013;78(6):898– 906.
35. Martucci VL, Pacak K. Pheochromocytoma and paraganglioma: Diagnosis, genetics, management and treatment. Curr Probl Cancer. 2014;38(1):7–12.
36. Favier J, Amar L, Gimenez-Roqueplo AP. Paraganglioma and phaeochromocytoma: from genetics to personalized medicine. Nat Rev Endocrinol. 2015;11(2):101–111.
37. Dahia PL. Pheochromocytoma and paraganglioma pathogenesis: learning from genetic heterogeneity. Nat Rev Cancer. 2014;14(2):108–119.
38. Yang C, Zhuang Z, Fliedner SM, Shankavaram U, Sun MG, Bullova P et al. Germ-line PHD1 and PHD2 mutations detected in patients with pheochromocytoma/paraganglioma-polycythemia. J Mol Med (Berl). 2015;93(1):93–104.
39. Neumann HPH, Bausch B, Mcwhinney SR, Bender BU, Gimm O, Franke G et al. Germ-line mutations in nonsyndromic pheochromocytoma. N Engl J Med. 2002;346(19):1459–1466.
40. Kimura N, Takayanagi R, Takizawa N, Itagaki E, Katabami T, Kakoi N et al. Pathological grading for predicting metastasis in phaeochromocytoma and paraganglioma. Endocr Relat Cancer. 2014;21(3):405–414.
41. Yankovskaya V, Horsefield R, Törnroth S, Luna-Chavez C, Miyoshi H, Léger C et al. Architecture of succinate dehydrogenase and reactive oxygen species generation. Science. 2003;299 (5607):700–704.
42. Korpershoek E, Favier J, Gaal J, Burnichon N, Bram van Gessel, Oudijk L et al. SDHA immunohistochemistry detects germline SDHA gene mutations in apparently sporadic paragangliomas and pheochromocytomas. J Clin Endocrinol Metab. 2011;96(9): E1472‑E1476.
43. Brouwers FM, Eisenhofer G, Tao JJ, Kant JA, Adams KT, Linehan WM et al. High frequency of SDHB germline mutations in patients with malignant catecholamine-producing paragangliomas: implications for genetic testing. J Clin Endocrinol Metab. 2006;91 (11):4505–4509.
44. Loriot C, Burnichon N, Gadessaud N, Vescovo L, Amar L, Libé R et al. Epithelial to mesenchymal transition is activated in metastatic pheochromocytomas and paragangliomas caused by SDHB gene mutations. J Clin Endocrinol Metab. 2012;97(6): E954‑E962.
45. Amar L, Baudin E, Burnichon N, Peyrard S, Silvera S, Bertherat J et al. Succinate dehydrogenase B gene mutations predict survival in patients with malignant pheochromocytomas or paragangliomas. J Clin Endocrinol Metab. 2007;92(10):3822–3828.
46. Brouwers FM, Eisenhofer G, Tao JJ, Kant JA, Adams KT, Linehan WM et al. High frequency of SDHB germline mutations in patients with malignant catecholamine producing paragangliomas: implications for genetic testing. J Clin Endocrinol Metab. 2006;91 (11):4505–4509.
47. McWhinney SR, Pasini B, Stratakis CA. International carney triad and Carney–Stratakis syndrome consortium familial gastrointestinal stromal tumors and germline mutations. N Engl J Med. 2007;357(10):1054–6.
48. Pasini B, Stratakis CA. SDH mutations in tumorigenesis and inherited endocrine tumours: lesson from the phaeochromocytomaparaganglioma syndromes. J Intern Med. 2009;266(1):19–42.
49. Ricketts C, Woodward ER, Killick P, Morris MR, Astuti D, Latif F et al. Germline SDHB mutations and familial renal cell carcinoma. J Natl Cancer Inst. 2008;100(17):1260–2.
50. Raue F, Frank-Raue K. Multiple endocrine neoplasia type 2. Update Horm Res. 2007;68:101–4.
51. Machens A, Brauckhoff M, Holzhausen HJ, Thanh PN,Lehnert H, Dralle H. Codon-specific development of pheochromocytoma in multiple endocrine neoplasia type 2. J Clin Endocrinol Metab. 2005;90(7):3999–4003.
52. Brandi ML, Gagel RF, Angeli A, Bilezikian JP, Beck-Peccoz P, Bordi C et al. Guidelines for diagnosis and therapy of MEN type 1 and type 2. J Clin Endocrinol. 2001;86(12):5658–71.
53. Pacak K, Eisenhofer G, Ilias I. Diagnosis of pheochromocytoma with special emphasis on MEN 2 syndrome. Hormones (Athens). 2009;8(2):111–6.
54. Eng C, Clayton D, Schuffenecker I, Lenoir G, Cote G, Gagel RF et al. The relationship between specific RET protooncogene mutations and disease phenotype in multiple endocrine neoplasia type 2. International RET mutation consortium analysis. J Am Med Assoc. 1996;276(19):1575–9.