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Иммуногистохимическое исследование экспрессии аберрантных/эутопических рецепторов у пациентов с макронодулярной гиперплазией надпочечников

https://doi.org/10.14341/probl12516

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Аннотация

Макронодулярная двусторонняя гиперплазия надпочечников (МДГН) является редкой причиной развития синдрома Иценко–Кушинга. Продукция кортизола при данной патологии может регулироваться как генетическими факторами, так и различными молекулярными механизмами. Наличие аберрантных или гиперэкспрессия эутопических рецепторов на мембране клеток кортикального слоя надпочечников может приводить к активации цАМФ/протеинкиназы А сигнального пути, что ведет к патологическому синтезу стероидных гормонов. Диагностика этого феномена с помощью предоперационных клинико-лабораторных тестов была признана нецелесообразной после доказательства эффективности односторонней адреналэктомии при МДГН, приводящей в большинстве случаев к длительной ремиссии гиперкортицизма. Тем не менее при отсутствии нормализации уровня кортизола в крови в послеоперационном периоде или при его рецидиве последующее консервативное лечение может быть предложено только в случае преобладания экспрессии/гиперэкспрессии тех или иных рецепторов. Их обнаружение становится возможным с помощью более надежных, чем клинико-лабораторные тесты, методов диагностики, таких как полимеразная цепная реакция (ПЦР) и иммуногистохимическое исследование (ИГХ), на данный момент широкое применение получил метод ПЦР-диагностики. В данной обзорной статье представлены накопленные данные о применении ИГХ при МДГН. 

Об авторах

А. Шевэ
Национальный медицинский исследовательский центр эндокринологии
Россия

117036, Москва, ул. Дм. Ульянова, д. 11



Л. С. Селиванова
Национальный медицинский исследовательский центр эндокринологии
Россия

к.м.н.,

117036, Москва, ул. Дм. Ульянова, д. 11



Н. С. Кузнецов
Национальный медицинский исследовательский центр эндокринологии
Россия

д.м.н., проф.,

117036, Москва, ул. Дм. Ульянова, д. 11



Д. А. Деркач
Национальный медицинский исследовательский центр эндокринологии

117036, Москва, ул. Дм. Ульянова, д. 11



М. Ю. Юкина
Национальный медицинский исследовательский центр эндокринологии
Россия

к.м.н.,

117036, Москва, ул. Дм. Ульянова, д. 11



Д. Г. Бельцевич
Национальный медицинский исследовательский центр эндокринологии
Россия

д.м.н., проф.,

117036, Москва, ул. Дм. Ульянова, д. 11



Список литературы

1. Fragoso MCBV, Pontes Cavalcante I, Meneses Ferreira A, et al. Genetics of primary macronodular adrenal hyperplasia. Press Medicale. 2018;47(7-8P2):139-149. doi: 10.1016/j.lpm.2018.07.002

2. Espiard S, Drougat L, Libé R, et al. ARMC5 mutations in a large cohort of primary macronodular adrenal hyperplasia: clinical and functional consequences. J Clin Endocrinol Metab. 2015;100(6):926-935. doi: 10.1210/jc.2014-4204

3. Assié G, Libé R, Espiard S, et al. ARMC5 mutations in macronodular adrenal hyperplasia with cushing’s syndrome. N Engl J Med. 2013;369(22):2105-2114. doi: 10.1056/NEJMoa1304603

4. Stratakis CA. Cushing syndrome in pediatrics. Endocrinol Metab Clin North Am. 2012;41(4):793-803. doi: 10.1016/j.ecl.2012.08.002

5. Carney JA, Young WF, Stratakis CA. Primary bimorphic adrenocortical disease: Cause of hypercortisolism in mccunealbright syndrome. Am J Surg Pathol. 2011;35(9):1311-1326. doi: 10.1097/PAS.0b013e31821ec4ce

6. Lerario AM, Moraitis A, Hammer GD. Genetics and epigenetics of adrenocortical tumors. Mol Cell Endocrinol. 2014;386(1-2):67-84. doi: 10.1016/j.mce.2013.10.028

7. Yoshida M, Hiroi M, Imai T, et al. A case of ACTH-independent macronodular adrenal hyperplasia associated with multiple endocrine neoplasia type 1. Endocr J. 2011;58(4):269-277. doi: 10.1507/endocrj.K10E-218

8. Gaujoux S, Pinson S, Gimenez-Roqueplo AP, et al. Inactivation of the APC gene is constant in adrenocortical tumors from patients with familial adenomatous polyposis but not frequent in sporadic adrenocortical cancers. Clin Cancer Res. 2010;16(21):5133-5141. doi: 10.1158/1078-0432.CCR-10-1497

9. Lacroix A. Heredity and cortisol regulation in bilateral macronodular adrenal hyperplasia. N Engl J Med. 2013;22(369):2147-2149. doi: 10.1056/NEJMe1312792

10. Bourdeau I, Oble S, Magne F, et al. ARMC5 mutations in a large French-Canadian family with cortisol-secreting β-adrenergic/vasopressin responsive bilateral macronodular adrenal hyperplasia. Eur J Endocrinol. 2016;174(1):85-96. doi: 10.1530/EJE-15-0642

11. Faucz FR, Zilbermint M, Lodish MB, et al. Macronodular adrenal hyperplasia due to mutations in an armadillo repeat containing 5 (ARMC5) Gene: A clinical and genetic investigation. J Clin Endocrinol Metab. 2014;99(6):1113-1119. doi: 10.1210/jc.2013-4280

12. Vélayoudom-Céphise FL, Haissaguerre M, Tabarin A. Etiopathogeny of primary adrenal hypercortisolism. Front Horm Res. 2016;46:39-53. doi: 10.1159/000443863

13. Lefebvre H, Duparc C, Chartrel N, et al. Intraadrenal adrenocorticotropin production in a case of bilateral macronodular adrenal hyperplasia causing Cushing’s syndrome. J Clin Endocrinol Metab. 2003;88(7):3035-3042. doi: 10.1210/jc.2002-030014

14. Юкина М.Ю., Нуралиева Н.Ф., Бельцевич Д.Г., и др. Макронодулярная двусторонняя гиперплазия надпочечников: диагностика аберрантных рецепторов и современные аспекты лечения // Consilium Medicum. — 2016. — Т. 10. — С. 29-33. [Yukina MYu, Nuralieva NF, Beltsevich DG, et al. Macronodular bilateral adrenal hyperplasia: diagnose the aberrant receptors and current aspects of treatment. Consilium Medicum. 2016;18(10):29-33. (in Russ.)]. doi: 10.26442/2075-1753_2016.10.29-33

15. Debillon E, Velayoudom-Cephise FL, Salenave S, et al. Unilateral adrenalectomy as a first-line treatment of cushing’s syndrome in patients with primary bilateral macronodular adrenal hyperplasia. J Clin Endocrinol Metab. 2015;100(12):4417-4424. doi: 10.1210/jc.2015-2662

16. Osswald A, Quinkler M, Di Dalmazi G, et al. Long-Term Outcome of Primary Bilateral Macronodular Adrenocortical Hyperplasia after Unilateral Adrenalectomy. J Clin Endocrinol Metab. 2019;104(7):2985-2993. doi: 10.1210/jc.2018-02204

17. Sheikh-Ahmad M, Dickstein G, Matter I, et al. Unilateral Adrenalectomy for Primary Bilateral Macronodular Adrenal Hyperplasia: Analysis of 71 Cases. Exp Clin Endocrinol Diabetes. 2020;128(12):827-834. doi: https://doi.org/10.1055/a-0998-7884

18. Albiger NM, Ceccato F, Zilio M, et al. An analysis of different therapeutic options in patients with Cushing’s syndrome due to bilateral macronodular adrenal hyperplasia: A singlecentre experience. Clin Endocrinol (Oxf ). 2015;82(6):808-815. doi: 10.1111/cen.12763

19. Xu Y, Rui W, Qi Y, et al. The role of unilateral adrenalectomy in corticotropin-independent bilateral adrenocortical hyperplasias. World J Surg. 2013;37(7):1626-1632. doi: 10.1007/s00268-013-2059-9

20. Terzolo M, Boccuzzi A, Ali A, et al. Cushing’s syndrome due to ACTHindependent bilateral adrenocortical macronodular hyperplasia. J Endocrinol Invest. 1997;20(5):270-275. doi: 10.1007/BF03350299

21. Gu YL, Gu WJ, Dou JT, et al. Bilateral adrenocortical adenomas causing adrenocorticotropic hormone-independent Cushing’s syndrome: A case report and review of the literature. World J Clin Cases. 2019;7(8):961-971. doi: 10.12998/wjcc.v7.i8.961

22. Antonini SR, Baldacchino V, Tremblay J, Hamet P, Lacroix A. Expression of ACTH receptor pathway genes in glucosedependent insulinotrophic peptide (GIP)-dependent Cushing’s syndrome. Clin Endocrinol (Oxf). 2006;64(1):29-36. doi: 10.1111/j.1365-2265.2005.02411.x

23. Vassiliadi DA, Tsagarakis S. Diagnosis and management of primary bilateral macronodular adrenal hyperplasia. Endocr Relat Cancer. 2019;26(10):567-581. doi: 10.1530/ERC-19-0240

24. Wada N, Kubo M, Kijima H, et al. Adrenocorticotropinindependent bilateral macronodular adrenocortical hyperplasia: Immunohistochemical studies of steroidogenic enzymes and postoperative course in two men. Eur J Endocrinol. 1996;134(5):583-587. doi: 10.1530/eje.0.1340583

25. Larose S, Bondaz L, Mermejo LM, et al. Coexistence of Myelolipoma and Primary Bilateral Macronodular Adrenal Hyperplasia With GIP-Dependent Cushing’s Syndrome. Front Endocrinol (Lausanne). 2019;10(September):1-9. doi: 10.3389/fendo.2019.00618

26. St-Jean M, Ghorayeb N El, Bourdeau I, Lacroix A. Aberrant G-protein coupled hormone receptor in adrenal diseases. Best Pract Res Clin Endocrinol Metab. 2018;32(2):165-187. doi: 10.1016/j.beem.2018.01.003

27. Schorr I, Ney RL. Abnormal hormone responses of an adrenocortical cancer adenyl cyclase. J Clin Invest. 1971;50(6):1295-1300. doi: 10.1172/JCI106608

28. De Groot JWB, Links TP, Themmen APN, et al. Aberrant expression of multiple hormone receptors in ACTH-independent macronodular adrenal hyperplasia causing Cushing’s syndrome. Eur J Endocrinol. 2010;163(2):293-299. doi: 10.1530/EJE-10-0058

29. Miyamura N, Taguchi T, Murata Y, et al. Inherited adrenocorticotropinindependent macronodular adrenal hyperplasia with abnormal cortisol secretion by vasopressin and catecholamines: Detection of the aberrant hormone receptors on adrenal gland. Endocrine. 2002;19(3):319-325. doi: 10.1385/ENDO:19:3:319

30. Lacroix A, Bourdeau I, Lampron A, et al. Aberrant G-protein coupled receptor expression in relation to adrenocortical overfunction. Clin Endocrinol (Oxf ). 2010;73(1):1-15. doi: 10.1111/j.1365-2265.2009.03689.x

31. Libé R, Coste J, Guignat L, et al. Aberrant cortisol regulations in bilateral macronodular adrenal hyperplasia: A frequent finding in a prospective study of 32 patients with overt or subclinical Cushing’s syndrome. Eur J Endocrinol. 2010;163(1):129-138. doi: 10.1530/EJE-10-0195

32. Bornstein SR, Stratakis CA, Chrousos GP. Adrenocortical tumors: Recent advances in basic concepts and clinical management. Ann Intern Med. 1999;130(9):759-771. doi: 10.7326/0003-4819-130-9-199905040-00017

33. Schorr I, Rathnam P, Saxena BB, Ney RL. Multiple specific hormone receptors in the adenylate cyclase of an adrenocortical carcinoma. J Biol Chem. 1971;246(18):5806-5811.

34. Hirata Y, Uchihashi M, Sueoka S, et al. Presence of ectopic β-adrenergic receptors on human adrenocortical cortisolproducing adenomas. J Clin Endocrinol Metab. 1981;53(5):953-957. doi: 10.1210/jcem-53-5-953

35. Katz MS, Kelly TM, Dax EM, et al. Ectopic β-adrenergic receptors coupled to adenylate cyclase in human adrenocortical carcinomas. J Clin Endocrinol Metab. 1985;60(5):900-909. doi: 10.1210/jcem-60-5-900

36. Cortez V, Santana M, Marques AP, et al. Regulation of catecholamine release in human adrenal chromaffin cells by β-adrenoceptors. Neurochem Int. 2012;60(4):387-393. doi: 10.1016/j.neuint.2011.12.018

37. Mazzuco TL, Thomas M, Martinie M, et al. Cellular and molecular abnormalities of a macronodular adrenal hyperplasia causing betablocker-sensitive Cushing’s syndrome. Arq Bras Endocrinol Metabol. 2007;51(9):1452-1462. doi: 10.1590/s0004-27302007000900007

38. Bertherat J, Contesse V, Louiset E, et al. In Vivo and in Vitro screening for illegitimate receptors in adrenocorticotropin-independent macronodular adrenal hyperplasia causing cushing’s syndrome: Identification of two cases of gonadotropin/gastric inhibitory polypeptide-dependent hypercortisolism. J Clin Endocrinol Metab. 2005;90(3):1302-1310. doi: 10.1210/jc.2004-1256

39. Spagnolo EV, Mondello C, Cardia L, et al. Post-mortem immunohistochemical evidence of β2-adrenergic receptor expression in the adrenal gland. Int J Mol Sci. 2019;20(12):1-12. doi: 10.3390/ijms20123065

40. Assie G, Louiset E, Sturm N, et al. Systematic analysis of G proteincoupled receptor gene expression in adrenocorticotropinindependent macronodular adrenocortical hyperplasia identifies novel targets for pharmacological control of adrenal Cushing’s syndrome. J Clin Endocrinol Metab. 2010;95(10):253-262. doi: 10.1210/jc.2009-2281

41. Arnaldi G, de Keyzer Y, Gasc JM, et al. Vasopressin receptors modulate the pharmacological phenotypes of Cushing’s syndrome. Endocr Res. 1998;24(3-4):807-816. doi: 10.3109/07435809809032691

42. Suzuki S, Uchida D, Koide H, et al. Hyper-responsiveness of adrenal gland to vasopressin resulting in enhanced plasma cortisol in patients with adrenal nodule(s). Peptides. 2008;29(10):1767-1772. doi: 10.1016/j.peptides.2008.06.011

43. Lee S, Hwang R, Lee J, et al. Ectopic expression of vasopressin V1b and V2 receptors in the adrenal glands of familial ACTHindependent macronodular adrenal hyperplasia. Clin Endocrinol (Oxf ). 2005;63(6):625-630. doi: 10.1111/j.1365-2265.2005.02387.x

44. Gagliardi L, Hotu C, Casey G, et al. Familial vasopressin-sensitive ACTH-independent macronodular adrenal hyperplasia (VPs-AIMAH): clinical studies of three kindreds. Clin Endocrinol (Oxf ). 2009;70(6):883-891. doi: 10.1111/j.1365-2265.2008.03471.x

45. Vezzosi D, Carter D, Régnier C, et al. Familial adrenocorticotropinindependent macronodular adrenal hyperplasia with aberrant serotonin and vasopressin adrenal receptors. Eur J Endocrinol. 2007;156(1):21-31. doi: 10.1530/eje.1.02324

46. Arnaldi G, Gasc JM, De Keyzer Y, et al. Variable expression of the V1 vasopressin receptor modulates the phenotypic response of steroid-secreting adrenocortical tumors. J Clin Endocrinol Metab. 1998;83(6):2029-2035. doi: 10.1210/jc.83.6.2029

47. Mune T, Murase H, Yamakita N, et al. Eutopic overexpression of vasopressin V1a receptor in adrenocorticotropin-independent macronodular adrenal hyperplasia. J Clin Endocrinol Metab. 2002;87(12):5706-5713. doi: 10.1210/jc.2002-020067

48. Lacroix A, Tremblay J, Touyz RM, et al. Abnormal adrenal and vascular responses to vasopressin mediated by a V1-vasopressin receptor in a patient with adrenocorticotropin-independent macronodular adrenal hyperplasia, Cushing’s syndrome, and orthostatic hypotension. J Clin Endocrinol Metab. 1997;82(8):2414-2422. doi: 10.1210/jc.82.8.2414

49. Christopoulos S, Bourdeau I, Lacroix A. Aberrant expression of hormone receptors in adrenal Cushing’s syndrome. Pituitary. 2004;7(4):225-235. doi: 10.1007/s11102-005-1083-7

50. Hofland J, Hofland LJ, Van Koetsveld PM, et al. ACTH-independent macronodular adrenocortical hyperplasia reveals prevalent aberrant in vivo and in vitro responses to hormonal stimuli and coupling of arginine-vasopressin type 1a receptor to 11β-hydroxylase. Orphanet J Rare Dis. 2013;8(1):1-12. doi: 10.1186/1750-1172-8-142

51. Louiset E, Contesse V, Groussin L, et al. Expression of vasopressin receptors in ACTH-independent macronodular bilateral adrenal hyperplasia causing Cushing’s syndrome: Molecular, immunohistochemical and pharmacological correlates. J Endocrinol. 2008;196(1):1-9. doi: 10.1677/JOE-07-0413

52. El Ghorayeb N, Bourdeau I, Lacroix A. Multiple aberrant hormone receptors in Cushing’s syndrome. Eur J Endocrinol. 2015;173(4):M45-M60. doi: 10.1530/EJE-15-0200

53. Reznik Y, Allali-Zerah V, Chayvialle JA, et al. Food-dependent Cushing’s syndrome mediated by aberrant adrenal sensitivity to gastric inhibitory polypeptide. N Engl J Med. 1992;327(14):981-986. doi: 10.1056/NEJM199210013271403

54. Lacroix A, Bolté E, Tremblay J, et al. Gastric inhibitory polypeptide-dependent cortisol hypersecretion--a new cause of Cushing’s syndrome. N Engl J Med. 1992;327(14):974-980. doi: 10.1056/NEJM199210013271402

55. Lacroix A. Ectopic and abnormal hormone receptors in adrenal Cushing’s syndrome: Clinical consequences. Endocr Rev. 2001;22(1):75-110. doi: 10.1016/S1575-0922(03)74541-0

56. Lecoq A, Bouligand J, Kamenický P, et al. Adrenal GIPR expression and chromosome 19q13 microduplications in GIP-dependent Cushing’s syndrome Find the latest version : Adrenal GIPR expression and chromosome 19q13 microduplications in GIP-dependent Cushing’s syndrome. 2017;2(18):e92184. doi: 10.1172/jci.insight.92184

57. Regazzo D, Barbot M, Scaroni C, et al. The pathogenic role of the GIP/GIPR axis in human endocrine tumors: emerging clinical mechanisms beyond diabetes. Rev Endocr Metab Disord. 2020;21(1):165-183. doi:10.1007/s11154-019-09536-6

58. Lampron A, Bourdeau I, Oble S, et al. Regulation of aldosterone secretion by several aberrant receptors including for glucosedependent insulinotropic peptide in a patient with an aldosteronoma. J Clin Endocrinol Metab. 2009;94(3):750-756. doi: 10.1210/jc.2008-1340

59. Albiger NM, Occhi G, Mariniello B, et al. Food-dependent Cushing’s syndrome: From molecular characterization to therapeutical results. Eur J Endocrinol. 2007;157(6):771-778. doi:10.1530/EJE-07-0253

60. Messidoro C, Elte JWF, Castro Cabezas M, et al. Food-dependent Cushing’s syndrome. Neth J Med. 2009;67(5):187-190.

61. Chabre O, Liakos P, Vivier J, et al. Cushing’s syndrome due to a gastric inhibitory polypeptide-dependent adrenal adenoma: Insights into hormonal control of adrenocortical tumorigenesis. J Clin Endocrinol Metab. 1998;83(9):3134-3143. doi: 10.1210/jc.83.9.3134

62. N’Diaye N, Hamet P, Tremblay J, et al. Asynchronous development of bilateral nodular adrenal hyperplasia in gastric inhibitory polypeptide-dependent Cushing’s syndrome. J Clin Endocrinol Metab. 1999;84(8):2616-2622. doi: 10.1210/jc.84.8.2616

63. Groussin L, Perlemoine K, Contesse V, et al. The ectopic expression of the gastric inhibitory polypeptide receptor is frequent in adrenocorticotropin-independent bilateral macronodular adrenal hyperplasia, but rare in unilateral tumors. J Clin Endocrinol Metab. 2002;87(5):1980-1985. doi: 10.1210/jcem.87.5.8458

64. Mircescu H, Jilwan J, N’Diaye N, et al. Are ectopic or abnormal membrane hormone receptors frequently present in adrenal Cushing’s syndrome? J Clin Endocrinol Metab. 2015;85(10):3531-3536. doi: 10.1210/jcem.85.10.6865

65. Imai T, Sarkar D, Shibata A, et al. Expression of adrenocorticotropin receptor gene in adrenocortical adenomas from patients with Cushing syndrome: Possible contribution for the autonomous production of cortisol. Ann Surg. 2001;234(1):85-91. doi: 10.1097/00000658-200107000-00013

66. Beuschlein F, Fassnacht M, Klink A, et al. ACTH-receptor expression, regulation and role in adrenocortical tumor formation. Eur J Endocrinol. 2001;144(3):199-206. doi: 10.1530/eje.0.1440199

67. Lefebvre H, Duparc C, Prévost G, et al. Cell-to-cell communication in bilateral macronodular adrenal hyperplasia causing hypercortisolism. Front Endocrinol (Lausanne). 2015;6:11-13. doi: 10.3389/fendo.2015.00034

68. Louiset E, Duparc C, Young J, et al. Intraadrenal corticotropin in bilateral macronodular adrenal hyperplasia. N Engl J Med. 2013;369(22):2115-2125. doi: 10.1056/NEJMoa1215245

69. Lacroix A, Hamet P BJ. Leuprolide acetate therapy in luteinizing hormone-dependent Cushing’s syndrome. N Engl J Med. 1999;341(21):1577-1581. doi: 10.1056/NEJM199911183412104

70. Bourdeau I, Amour PD, Hamet P, Boutin J. Discovered Bilateral Macronodular Adrenal Hyperplasia with Subclinical Cushing’s Syndrome. J Clin Endocrinol Metab. 2001;86(11):5534-5540. doi: 10.1210/jcem.86.11.8062

71. Cartier D, Lihrmann I, Parmentier F, et al. Overexpression of serotonin4 receptors in cisapride-responsive adrenocorticotropinindependent bilateral macronodular adrenal hyperplasia causing Cushing’s syndrome. J Clin Endocrinol Metab. 2003;88(1):248-254. doi:10.1210/jc.2002-021107

72. Mannelli M, Ferruzzi P, Luciani P, et al. Cushing’s syndrome in a patient with bilateral macronodular adrenal hyperplasia responding to Cisapride: an in vivo and in vitro study. J Clin Endocrinol Metab. 2003;88(10):4616-4622. doi: 10.1210/jc.2002-021949

73. Lefebvre H, Duparc C, Prévost G, et al. Paracrine control of steroidogenesis by serotonin in adrenocortical neoplasms. Mol Cell Endocrinol. 2015;408:198-204. doi: 10.1016/j.mce.2014.11.013

74. Louiset E, Contesse V, Groussin L, et al. Expression of serotonin 7 receptor and coupling of ectopic receptors to protein kinase A and ionic currents in adrenocorticotropin- independent macronodular adrenal hyperplasia causing Cushing’s syndrome. J Clin Endocrinol Metab. 2006;91(11):4578-4586. doi: 10.1210/jc.2006-0538

75. Roels H. The the effect and adrenal of some cortex pituitary in hormones nuclei on of volume content of cell hypophysectomized- castrated. Exp Cell Res. 1963;31:407-415. doi: 10.1016/0014-4827(63)90017-x

76. Mikolajczyk H, Pawlikowski T. Histologic changes in the adrenal cortex of hypophysectomized-gonadectomized rats treated with gonadotrophins or adrenocorticotrophin. Endokrynol Pol. 1965;16(4):359-69.

77. Rilianawati, Paukku T, Kero J, et al. Direct luteinizing hormone action triggers adrenocortical tumorigenesis in castrated mice transgenic for the murine inhibin α-subunit promoter/simian virus 40 t-antigen fusion gene. Mol Endocrinol. 1998;12(6):801-809. doi: 10.1210/mend.12.6.0117

78. Bertagna X, Groussin L, Luton JP, Bertherat J. Aberrant receptormediated Cushing’s syndrome. Horm Res. 2003;59(1):99-103. doi: 10.1159/000067832

79. Pabon JE, Li X, Lei ZM, Sanfilippo JS, et al. Novel presence of luteinizing hormone/chorionic gonadotropin receptors in human adrenal glands. J Clin Endocrinol Metab. 1996;81(6):2397-2400. doi: 10.1210/jc.81.6.2397

80. Korol P, Jaranowska M, Pawlikowski M. Immunohistochemical demonstration of LH/CG receptors in non-neoplastic human adrenal cortex and adrenocortical tumors. Folia Histochem Cytobiol. 2019;57(1):23-27. doi: 10.5603/FHC.a2019.0003

81. Feelders RA, Lamberts SWJ, Hofland LJ, et al. Luteinizing hormone (LH)-responsive cushing’s syndrome: The demonstration of LH receptor messenger ribonucleic acid in hyperplastic adrenal cells, which respond to chorionic gonadotropin and serotonin agonists in vitro. J Clin Endocrinol Metab. 2003;88(1):230-237. doi: 10.1210/jc.2002-020621


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Шевэ А., Селиванова Л.С., Кузнецов Н.С., Деркач Д.А., Юкина М.Ю., Бельцевич Д.Г. Иммуногистохимическое исследование экспрессии аберрантных/эутопических рецепторов у пациентов с макронодулярной гиперплазией надпочечников. Проблемы Эндокринологии. 0;. https://doi.org/10.14341/probl12516

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Chevais A., Selivanova L.S., Kuznetzov N.S., Derkatch D.А., Yukina M.Y., Beltsevich D.G. Immunohistochemical study on the expression/hyperexpression of aberrant/ eutopic receptors in patients with bilateral macronodular adrenal hyperplasia. Problems of Endocrinology. 0;. (In Russ.) https://doi.org/10.14341/probl12516

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