Цель. Осветить причины, патогенез, клиническую картину, диагностику и лечение хронической надпочечниковой недостаточности (НН). Материалы и методы. Рассмотрены данные 23 научных источников, опубликованных в российской и зарубежной печати в 1985–2017 гг. Результаты. Несмотря на то, что НН относится к числу редких заболеваний эндокринной системы, в клинической практике очень важны своевременные диагностика и лечение НН, поскольку без своевременной терапии это угрожающее жизни пациента состояние. В зависимости от уровня поражения гипоталамо-гипофизарно-надпочечниковой системы выделяют первичную (ПНН), вторичную (ВНН) и третичную НН. Основной причиной ПНН (80–90%) является аутоиммунная деструкция коры надпочечников (аутоиммунный адреналит): изолированное поражение или компонент аутоиммунного полигландулярного синдрома. Поражение надпочечников также может развиваться в результате воздействия различных факторов: инфекционное (туберкулез, грибковые и цитомегаловирусные инфекции), опухолевое (опухоли, метастазы рака), адреналэктомия, адренолейкодистрофия. Наиболее частые причины ВНН – терапия глюкокортикоидами в фармакологических дозах, опухолевые и деструктивные процессы в гипоталамо-гипофизарной области с уменьшением или подавлением секреции адренокортикотропного гормона. Клинические проявления не являются строго специфическим критерием диагностики хронической НН и требуют лабораторного подтверждения. Проявления НН обычно усиливаются на фоне стрессовых ситуаций, интеркуррентных заболеваний, высокой температуры, оперативных вмешательств. Пациент, страдающий хронической ПНН, нуждается в постоянной заместительной терапии глюкокортикоидами и, в большинстве случаев, минералокортикоидами. Заключение. Знание клинических признаков НН, методов современной диагностики позволит своевременно диагностировать заболевание и назначить заместительную терапию.
Aim. To present causes, pathogenesis, clinical presentation, diagnostics and treatment of chronic adrenal insufficiency. Materials and methods. Data from 23 scientific sources published in Russia and abroad in years 1985–2017 are presented. Results. Although adrenal insufficiency is a rare endocrine system disorder, early diagnostics and treatment of adrenal insufficiency (AI) is of great importance in clinical practice because this is a life-threatening disorder when not treated. Depending on the level of hypothalamic–pituitary–adrenal system damage, primary (PAI), secondary (SAI) and tertiary adrenal insufficiency are distinguished. The main cause of PAI (80–90%) is an autoimmune destruction of adrenal cortex (autoimmune adrenalitis): isolated damage or a part of autoimmune polyglandular syndrome. Adrenal glands damage can also develop as a result of various factors: infections (tuberculosis, fungous and cytomegalovirus infections), tumors (malignant tumors or metastases), adrenalectomy, and adrenoleukodystrophy. The most frequent cause of SAI is glucocorticoids therapy in pharmacological doses, timorous and destructive processes in pituitary-hypothalamic area that result in ACTH production decrease and suppression. Clinical presentation is not a highly specific criterion of CAI diagnostics and requires confirmation with laboratory results. AI clinical manifestations aggravate in association with stressful situations, intercurrent diseases, high fever, and surgical interventions. A patient with chronic primary adrenal insufficiency needs constant replacement therapy with glucocorticoids and, in most cases with mineralocorticoids. Conclusion. Awareness of AI clinical presentation and modern diagnostic methods will allow diagnosing the disease on time and prescribing replacement therapy.
1. Bleicken B, Hahner S, Ventz M, Quinkler M. Delayed diagnosis of adrenal insufficiency is common: a cross-sectional study in 216 patients. Am J Med Sci 2010; 339: 525–31.
2. Husebye ES, Allolio B, Arlt W et al. Consensus statement on the diagnosis, treatment and follow-up of patients with primary adrenal insufficiency. J Intern Med 2014; 275: 104–15.
3. Pazderska A, Pearce SHS. Adrenal insufficiency – recognition and management. Clin Med 2017; 17 (3): 258–62.
4. Betterle C, Scalici C, Presotto F et al. The natural history of adrenal function in autoimmune patients with adrenal autoantibodies. J Endocrinol 1988; 117 (3): 467–75.
5. Клиническая эндокринология: рук. 3-е изд. Под ред. Н.Т Старковой. СПб: Питер, 2002; с. 305–12.
[Klinicheskaia endokrinologiia: ruk. 3-e izd. Pod red. N.T Starkovoi. Saint Petersburg: Piter, 2002; p. 305–12 (in Russian).]
6. Arlt W, Allolio B. Adrenal insufficiency. Lancet 2003; 361: 1881–93.
7. Laureti S, Vecchi L, Santeusanio F, Falorni A. Is the prevalence of Addison’s disease underestimated? J Clin Endocrinol Metab 1999; 84 (5): 1762.
8. Kong MF, Jeffocoate W. Eighty-six cases of Addison’s disease. Clin Endocrinol (Oxf) 1994; 41 (6): 757–61.
9. Regal M, Páramo C, Sierra SM, Garcia-Mayor RV. Prevalence and incidence of hypopituitarism in an adult Caucasian population in northwestern Spain. Clin Endocrinol 2001; 55: 735–40.
10. Husebye ES, Løvås K. Immunology of Addison's disease and premature ovarian failure. Endocrinol Metab Clin North Am 2009; 38: 389.
11. Bleicken B, Hahner S, Ventz M, Quinkler M. Delayed diagnosis of adrenal insufficiency is common: a cross-sectional study in 216 patients. Am J Med Sci 2010; 339 (6): 525–31.
12. Eisenbarth GS, Gottlieb PA. Autoimmune polyendocrine syndromes. N Engl J Med 2004; 350: 2068–79.
13. Winqvist O, Karlsson FA, Kampe O. 21-Hydroxylase, a major autoantigen in idiopathic Addison’s disease. Lancet 1992; 339: 1559–62.
14. Eledrisi MS, Verghese AC. Adrenal insufficiency in HIV Infection: A review and recommendations. Am J Med Sci 2001; 321 (2): 137–44.
15. Engelen M, Kemp S, de Visser M et al. X-linked adrenoleukodystrophy (X-ALD): clinical presentation and guidelines for diagnosis, follow-up and management. Orphanet J Dis 2012; 7: 51–8.
16. Борисова Е.О. Побочные эффекты системной глюкокортикостероидной терапии. Пульмонология и аллергология. 2004; 3: 14–8.
[Borisova E.O. Pobochnye effekty sistemnoi gliukokortikosteroidnoi terapii. Pul'monologiia i allergologiia. 2004; 3: 14–8 (in Russian).]
17. Gilchrist FJ, Cox KJ, Rowe R et al. Itraconazole and inhaled fluti-casone causing hypothalamic-pituitary-adrenal axis suppression in adults with cystic fibrosis. J Cyst Fibros 2013; 12: 399–402.
18. Préville-Ratelle S, Coriati A, Ménard A. Adrenal Insufficiency in Cystic Fibrosis: A Rare Phenomenon? Can Resp J 2018; Article ID 3629031. https://doi.org/10.1155/2018/3629031
19. Løvås K, Husebye ES. Addison's disease. Lancet 2005; 365: 2058–61.
20. Husebye E, Løvås K. Pathogenesis of primary adrenal insufficiency. Best Pract Res Clin Endocrinol Metab 2009; 23: 147–57.
21. Husebye ES, Allolio B, Arlt W et al. Consensus statement on the diagnosis, treatment and follow-up of patients with primary adrenal insufficiency. J Intern Med 2014; 275: 104–15.
22. Stryker TD, Molitch ME. Reversible hyperthyrotropinemia, hyperthyroxinemia, and hyperprolactinemia due to adrenalinsufficiency. Am J Med 1985; 79: 271–6.
23. Bornstein SR, Allolio B, Arlt W. Diagnosis and Treatment of Primary Adrenal Insufficiency: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab 2016; 101 (2): 364–89.
________________________________________________
1. Bleicken B, Hahner S, Ventz M, Quinkler M. Delayed diagnosis of adrenal insufficiency is common: a cross-sectional study in 216 patients. Am J Med Sci 2010; 339: 525–31.
2. Husebye ES, Allolio B, Arlt W et al. Consensus statement on the diagnosis, treatment and follow-up of patients with primary adrenal insufficiency. J Intern Med 2014; 275: 104–15.
3. Pazderska A, Pearce SHS. Adrenal insufficiency – recognition and management. Clin Med 2017; 17 (3): 258–62.
4. Betterle C, Scalici C, Presotto F et al. The natural history of adrenal function in autoimmune patients with adrenal autoantibodies. J Endocrinol 1988; 117 (3): 467–75.
5. Klinicheskaia endokrinologiia: ruk. 3-e izd. Pod red. N.T Starkovoi. Saint Petersburg: Piter, 2002; p. 305–12 (in Russian).
6. Arlt W, Allolio B. Adrenal insufficiency. Lancet 2003; 361: 1881–93.
7. Laureti S, Vecchi L, Santeusanio F, Falorni A. Is the prevalence of Addison’s disease underestimated? J Clin Endocrinol Metab 1999; 84 (5): 1762.
8. Kong MF, Jeffocoate W. Eighty-six cases of Addison’s disease. Clin Endocrinol (Oxf) 1994; 41 (6): 757–61.
9. Regal M, Páramo C, Sierra SM, Garcia-Mayor RV. Prevalence and incidence of hypopituitarism in an adult Caucasian population in northwestern Spain. Clin Endocrinol 2001; 55: 735–40.
10. Husebye ES, Løvås K. Immunology of Addison's disease and premature ovarian failure. Endocrinol Metab Clin North Am 2009; 38: 389.
11. Bleicken B, Hahner S, Ventz M, Quinkler M. Delayed diagnosis of adrenal insufficiency is common: a cross-sectional study in 216 patients. Am J Med Sci 2010; 339 (6): 525–31.
12. Eisenbarth GS, Gottlieb PA. Autoimmune polyendocrine syndromes. N Engl J Med 2004; 350: 2068–79.
13. Winqvist O, Karlsson FA, Kampe O. 21-Hydroxylase, a major autoantigen in idiopathic Addison’s disease. Lancet 1992; 339: 1559–62.
14. Eledrisi MS, Verghese AC. Adrenal insufficiency in HIV Infection: A review and recommendations. Am J Med Sci 2001; 321 (2): 137–44.
15. Engelen M, Kemp S, de Visser M et al. X-linked adrenoleukodystrophy (X-ALD): clinical presentation and guidelines for diagnosis, follow-up and management. Orphanet J Dis 2012; 7: 51–8.
16. Borisova E.O. Pobochnye effekty sistemnoi gliukokortikosteroidnoi terapii. Pul'monologiia i allergologiia. 2004; 3: 14–8 (in Russian).
17. Gilchrist FJ, Cox KJ, Rowe R et al. Itraconazole and inhaled fluti-casone causing hypothalamic-pituitary-adrenal axis suppression in adults with cystic fibrosis. J Cyst Fibros 2013; 12: 399–402.
18. Préville-Ratelle S, Coriati A, Ménard A. Adrenal Insufficiency in Cystic Fibrosis: A Rare Phenomenon? Can Resp J 2018; Article ID 3629031. https://doi.org/10.1155/2018/3629031
19. Løvås K, Husebye ES. Addison's disease. Lancet 2005; 365: 2058–61.
20. Husebye E, Løvås K. Pathogenesis of primary adrenal insufficiency. Best Pract Res Clin Endocrinol Metab 2009; 23: 147–57.
21. Husebye ES, Allolio B, Arlt W et al. Consensus statement on the diagnosis, treatment and follow-up of patients with primary adrenal insufficiency. J Intern Med 2014; 275: 104–15.
22. Stryker TD, Molitch ME. Reversible hyperthyrotropinemia, hyperthyroxinemia, and hyperprolactinemia due to adrenalinsufficiency. Am J Med 1985; 79: 271–6.
23. Bornstein SR, Allolio B, Arlt W. Diagnosis and Treatment of Primary Adrenal Insufficiency: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab 2016; 101 (2): 364–89.
Авторы
Е.В.Бирюкова*1,2, Е.С.Ганенкова1, М.Д.Лованова1
1 ФГБОУ ВО «Московский государственный медико-стоматологический университет им. А.И.Евдокимова» Минздрава России, Москва, Россия;
2 ГБУЗ «Московский клинический научно-практический центр им. А.С.Логинова» Департамента здравоохранения г. Москвы, Москва, Россия
*lena@obsudim.ru
________________________________________________
Elena V. Biryukova*1,2, Ekaterina S. Ganenkova1, Marina D. Lovanova1
1 A.I.Evdokimov Moscow State University of Medicine and Dentistry, Moscow, Russia;
2 A.S.Loginov Moscow Clinical Scientific Practical Center, Moscow, Russia
*lena@obsudim.ru