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The endocrinology of adrenal tuberculosis: The effects of tuberculosis on the hypothalamo-pituitary-adrenal axis and adrenocortical function

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Abstract

Tuberculosis may affect many of the endocrine glands including the hypothalamus, pituitary, thyroid and adrenals. The most commonly involved endocrine organ in tuberculosis is the adrenal gland. Adrenal glands may be directly or indirectly affected by tuberculosis. Tuberculous Addison’s disease is still an important cause of primary adrenocortical insufficiency particularly in the developing countries. Recent improvements in imaging techniques and modern endocrinological tests for the investigation of adrenal function have given us greater insight into the endocrinology of adrenal tuberculosis. Hypothalamo-pituitary-adrenal (HPA) axis is also involved in tuberculosis and recent findings revealed that HPA axis is activated rather than underactivated in active pulmonary tuberculosis. Activated HPA axis in tuberculosis causes increased cortisol secretion which results in a shift in the Th1/Th2 balance towards Th2. T cell dysfunction due to high cortisol and low DHEAS levels may be responsible for immunologically-mediated tissue damage in tuberculosis. In this review, recent findings concerning the adrenocortical function, radiological changes in adrenal glands and HPA axis involvement in tuberculosis are discussed.

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References

  1. Martin G, Lazarus A. Epidemiology and diagnosis of tuberculosis. Postgrad Med 2000, 108: 42–54.

    Article  CAS  PubMed  Google Scholar 

  2. Raviglione MC, Snider DE Jr, Kochi A. Global epidemiology of tuberculosis: morbidity and mortality of a worldwide epidemic. JAMA 1995, 273: 220–6.

    Article  CAS  PubMed  Google Scholar 

  3. WHO report. Global Tuberculosis Programme. Geneva. 1998.

  4. Kelestimur F, Güven M, Pasaoglu H, Özesmi M. Does tuberculosis really cause hypercalcemia? J Endocrinol Invest 1996, 19: 678–81.

    Article  CAS  PubMed  Google Scholar 

  5. Addison T. On the constitutional and local effects of disease of the supra-renal capsules. London: Highley. 1855.

    Google Scholar 

  6. Drury PL, Besser GM. Adrenal cortex. In: Hall R, Besser GM eds. Fundamentals of clinical endocrinology. Edinburgh: Churchill Livingstone. 1989, 153.

  7. Guttman PH. Addison’s disease: a statistical analysis of 566 cases and a study of the pathology. Arch Pathol 1930, 10: 742–85.

    Google Scholar 

  8. Sanford JP, Favour CB. The interrelationships between Addison’s disease and active tuberculosis: a review of 125 cases of Addison’s disease. Ann Intern Med 1956, 45: 56–72.

    Article  CAS  PubMed  Google Scholar 

  9. Stuart-Mason SA, Meade TW, Lee JAH, Morris JN. Epidemiological and clinical picture of Addison’s disease. Lancet 1968, 2: 744–7.

    Article  Google Scholar 

  10. De Rosa G, Corsello SM, Cecchini L, Della Casa S, Testa A. A clinical study of Addison’s disease. Exp Clin Endocrinol Diabetes 1987, 90: 232–42.

    Article  Google Scholar 

  11. Soule S. Addison’s disease in Africa — a teaching hospital experience. Clin Endocrinol (Oxf) 1999, 50: 115–20.

    Article  CAS  Google Scholar 

  12. Marie-France K, Jeffkoate W. Eighty-six cases of Addison’s disease. Clin Endocrinol (Oxf) 1994, 41: 757–61.

    Article  Google Scholar 

  13. Huebener KH, Treugut H. Adrenal cortex dysfunction: CT findings. Radiology 1984, 150: 195–9.

    CAS  PubMed  Google Scholar 

  14. Lam KY, Lo CY. A critical examination of adrenal tuberculosis and a 28-year autopsy experience of active tuberculosis. Clin Endocrinol (Oxf) 2001, 54: 633–9.

    Article  CAS  Google Scholar 

  15. Sun ZH, Nomura K, Toraya S, et al. Clinical significance of adrenal computed tomography in Addison’s disease. Endocrinol Jpn 1992, 39: 563–9.

    Article  CAS  PubMed  Google Scholar 

  16. Vita JA, Silverberg SJ, Goland RS, Austin JHM, Knowlton AI. Clinical clues to the cause of Addison’s disease. Am J Med 1985, 78: 461–6.

    Article  CAS  PubMed  Google Scholar 

  17. Kelestimur F, Özbakir Ö, Saglam A, Öztürk F, Yücesoy M. Acute adrenocortical failure due to tuberculosis. J Endocrinol Invest 1993, 16: 281–4.

    Article  CAS  PubMed  Google Scholar 

  18. McMurry JF, Lond D, McClure R, Kotchen TA. Addison’s disease with adrenal enlargement on computed tomography scanning. Report of two cases of tuberculosis and review of the literature. Am J Med 1984, 77: 365–8.

    Article  PubMed  Google Scholar 

  19. Jayakar DV, Giuseppe C, DeSoto-LaPaix F, Plawker M, Farag A, Ghosh BC. Adrenal tuberculosis. Eur J Surg 1998, 164: 975–8.

    Article  CAS  PubMed  Google Scholar 

  20. Penrice J, Nussey SS. Recovery of adrenocortical function following treatment of tuberculous Addison’s disease. Postgrad Med J 1992, 68: 204–5.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  21. Kelestimur F. Recovery of adrenocortical function following treatment of tuberculous Addison’s disease. Postgrad Med J 1993, 69: 832.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  22. Villabona CM, Sahun M, Ricart W, et al. Tuberculous Addison’s disease. Utility of CT in diagnosis and follow-up. Eur J Radiol 1993, 17: 210–3.

    Article  CAS  PubMed  Google Scholar 

  23. Reznek RH, Armstrong P. The adrenal gland. Clin Endocrinol (Oxf) 1994, 40: 561–76.

    Article  CAS  Google Scholar 

  24. Oelkers W. Adrenal insufficiency. N Engl J Med 1996, 335: 1206–12.

    Article  CAS  PubMed  Google Scholar 

  25. Bhatia E, Jain SK, Grupta RK, Pandey R. Tuberculous Addison’s disease: Lack of normalization of adrenocortical function after anti-tuberculous chemotherapy. Clin Endocrinol (Oxf) 1998, 48: 355–9.

    Article  CAS  Google Scholar 

  26. Moss CN, England ML, Kowal J. Adrenal insufficiency (Addison’s disease) in the elderly. J Am Geriatr Soc 1985, 33: 63–8.

    CAS  PubMed  Google Scholar 

  27. Wilkins EGL, Hnizdo E, Cope A. Addisonian crisis induced by treatment with rifampicin. Tubercle 1989, 70: 69–73.

    Article  CAS  PubMed  Google Scholar 

  28. Elansary EH, Earis JE. Rifampicin and adrenal crisis. Br Med J 1983, 286: 1861–2.

    Article  CAS  Google Scholar 

  29. Kyriazopoulou V, Parparousi O, Vagenakis AG. Rifampicininduced adrenal crisis in Addisonian patients receiving corticosteroid replacement therapy. J Clin Endocrinol Metab 1984, 59: 1204–6.

    Article  CAS  PubMed  Google Scholar 

  30. Ünlühizarci K, Yildiz O, Aygen B, Bayram F, Kelestimur F. Rifampicin induced acute adrenal crisis in a patient with miliary tuberculosis. 5th European Congress of Endocrinology, Turin, 2001, p. 8 (abstract).

    Google Scholar 

  31. Kelestimur F, Ünlü Y, Özesmi M, Tolu I. A hormonal and radiological evaluation of adrenal gland in patients with acute or chronic pulmonary tuberculosis. Clin Endocrinol (Oxf) 1994, 41: 53–6.

    Article  CAS  Google Scholar 

  32. Ellis ME, Tayoub F. Adrenal functions in tuberculosis. Br J Dis Chest 1986, 80: 7–12.

    Article  CAS  PubMed  Google Scholar 

  33. Barnes DJ, Naragi S, Temu P, Turtle JR. Adrenal function in patients with active tuberculosis. Thorax 1989, 44: 422–4.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  34. Sarma GR, Immanuel C, Ramachandran G, Krishnamurthy PV, Kumaraswami V, Prabhakar R. Adrenocortical function in patients with pulmonary tuberculosis. Tubercle 1990, 71: 277–82.

    Article  CAS  PubMed  Google Scholar 

  35. Hawken MP, Ojoo JCO, Morris JS, et al. No increased prevalence of adrenocortical insufficiency in human immunodeficiency virus-associated tuberculosis. Tuber Lung Dis 1996, 77: 444–8.

    Article  CAS  PubMed  Google Scholar 

  36. May EE, Carey RM. Rapid adrenocorticotropic hormone test in practice. Am J Med 1985, 79: 679–84.

    Article  CAS  PubMed  Google Scholar 

  37. Kelestimur F, Akgün A, Günay O. A comparison between short synacthen test and depot synacthen test in the evaluation of cortisol reserve of adrenal gland in normal subjects. J Endocrinol Invest 1995, 18: 823–6.

    Article  CAS  PubMed  Google Scholar 

  38. Mayenknecht J, Diederich S, Bahr V, Plockinger U, Oelkers W. Comparison of low and high dose corticotropin stimulation tests in patients with pituitary disease. J Clin Endocrinol Metab 1998, 83: 1558–62.

    Article  CAS  PubMed  Google Scholar 

  39. Kelestimur F. Adrenocortical function in active pulmonary tuberculosis. Int J Tuberc Lung Dis 1998, 2: 172–4.

    CAS  PubMed  Google Scholar 

  40. Kukreja SC, Williams GA. Corticotropin stimulation test: inverse correlation between basal serum cortisol and its response to corticotropin. Acta Endocrinol (Copenh) 1981, 97: 522–4.

    CAS  Google Scholar 

  41. Post FA, Soule SG, Willcox PA, Lewitt NS. The spectrum of endocrine dysfunction in active pulmonary tuberculosis. Clin Endocrinol (Oxf) 1994, 40: 367–71.

    Article  CAS  Google Scholar 

  42. Rasmuson S, Olsson T, Hagg E. A low dose ACTH test to assess the function of the hypothalamic-pituitary-adrenal axis. Clin Endocrinol (Oxf) 1996, 44: 151–6.

    Article  CAS  Google Scholar 

  43. Dökmetas HS, Çolak R, Kelestimur F, Selçuklu A, Ünlühizarci K, Bayram F. A comparison between the 1μg adrenocorticotropin (ACTH) test, the short ACTH (250 μg) test, and the insulin tolerance test in the assessment of hypothalamopituitary- adrenal axis immediately after pituitary surgery. J Clin Endocrinol Metab 2000, 85: 3713–9.

    PubMed  Google Scholar 

  44. Dickstein G, Shechner C, Nicholson WE, et al. Adrenocorticotropin stimulation test: effects of basal cortisol level, time of day, and suggested new sensitive low dose test. J Clin Endocrinol Metab 1991, 72: 773–8.

    Article  CAS  PubMed  Google Scholar 

  45. Kelestimur F, Göktas Z, Gülmez I, et al. Low dose (1 μg) adrenocorticotropin stimulation test in the evaluation of the hypothalamo-pituitary-adrenal axis in patients with active pulmonary tuberculosis. J Endocrinol Invest 2000, 23: 235–9.

    Article  CAS  PubMed  Google Scholar 

  46. York EL, Enarson DA, Nobert EJ, Fanning A, Sproule BJ. Adrenocortical function in patients investigated for active tuberculosis. Chest 1992, 101: 1338–41.

    Article  CAS  PubMed  Google Scholar 

  47. Gülmez S, Kelestimur F, Durak AC, Özesmi M. Changes in the size of adrenal glands in acute pulmonary tuberculosis with therapy. Endocr J 1996, 43: 573–6.

    Article  PubMed  Google Scholar 

  48. Hernandez-Pando R, Orozco H, Honour J, Silva P, Leyva R, Rook GA. Adrenal changes in murine pulmonary tuberculosis: a clue to pathogenesis ? FEMS Immunol Med Microbiol 1995, 12: 63–72.

    Article  CAS  PubMed  Google Scholar 

  49. Gaillard R.C. Neuroendocrine-immune system interactions: the immune-hypothalamo-pituitary-adrenal axis. Trends Endocrinol Metab 1994, 5: 303–9.

    Article  CAS  PubMed  Google Scholar 

  50. Fukata J, Imura H, Nakao K. Cytokines as mediators in the regulation of the hypothalamic-pituitary-adrenocortical function. J Endocrinol Invest 1993, 16: 141–55.

    Google Scholar 

  51. Egdahl R, Melby JC, Spink WW. Adrenal cortical and body temperature responses to repeated endotoxin administration. Proc Soc Exp Biol Med 1959, 101: 369–72

    Article  CAS  PubMed  Google Scholar 

  52. Pozzoli G, Costa A, Grimaldi M, et al. Lipopolysaccharide modulation of eicosanoid and corticotrophin-releasing hormone release from rat hypothalamic explants and astrocyte cultures in vitro: evidence for the involvement of prostaglandin E2 but not prostaglandin F2a and lack of effect of nerve growth factor. J Endocrinol 1994, 140: 103–9.

    Article  CAS  PubMed  Google Scholar 

  53. Perlstein RS, Whitnall MH, Abrams JS, Mougey EH, Neta R. Synergistic roles of interleukin-6, interleukin-1, and tumor necrosis factor in the adrenocorticotropin response to bacterial lipopolysaccharide in vivo. Endocrinology 1993, 132: 949–52.

    Google Scholar 

  54. Mandrup-Poulsen T, Nerup J, Reimers JI, et al. Cytokines and the endocrine system. I. The immunoendocrine network. Eur J Endocrinol 1995, 133: 660–71.

    Article  CAS  PubMed  Google Scholar 

  55. Zhang Y, Doerfler M, Lee TC, Guillemir B, Rom WN. Mechanisms of stimulation of interleukin-1 beta and tumor necrosis factor-alpha by mycobacterium tuberculosis components. J Clin Invest 1993, 91: 2076–83.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  56. Barnes PF, Abrams JS, Lu S, Sieling PA, Rea TH, Modlin R. Patterns of cytokine production by mycobacteriumreactive human T-cell clones. Infect Immun 1993, 61: 197–203.

    CAS  PubMed Central  PubMed  Google Scholar 

  57. Rook GAW, Hernandez-Pando R. Immunological and endocrinological characteristics of tuberculosis that provide opportunities for immunotherapeutic intervention. In: Genetics and tuberculosis. Novartis Foundation Symposium. Chichester: Wiley. 1988, 73.

  58. Rook GAW, Hernandez-Pando R, Lightman SL. Hormones, peripherally activated prohormones and regulation of the Th1/Th2 balance. Immunol Today 1994, 15: 301–3.

    Article  CAS  PubMed  Google Scholar 

  59. Blauer KL, Poth M, Rogers WM, Bernton EW. Dehydroepiandrosterone antagonises the suppressive effects of dexamethasone on lymphocyte proliferation. Endocrinology 1991, 129: 3174–9.

    Article  CAS  PubMed  Google Scholar 

  60. Orentreich N, Brind JL, Rizer RL, Vogelman JH. Age changes and sex differences in serum dehydroepiandrosterone sulfate concentrations throughout adulthood. J Clin Endocrinol Metab 1984, 59: 551–5.

    Article  CAS  PubMed  Google Scholar 

  61. Donald PR, Beyers N, Rook GAW. Adolescent tuberculosis. S Afr Med J 1996, 86: 231–3.

    CAS  PubMed  Google Scholar 

  62. Keven K, Uysal AR, Erdogan G. Adrenal function during tuberculous infection and effects of antituberculosis treatment on endogenous and exogenous steroids. Int J Tuberc Lung Dis 1998, 2: 419–24.

    CAS  PubMed  Google Scholar 

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  1. Division of Endocrinology, Department of Medical Sciences, University of Erciyes, 38039, Kayseri, Turkey

    F. Kelestimur M.D.

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  1. F. Kelestimur M.D.
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Kelestimur, F. The endocrinology of adrenal tuberculosis: The effects of tuberculosis on the hypothalamo-pituitary-adrenal axis and adrenocortical function. J Endocrinol Invest 27, 380–386 (2004). https://doi.org/10.1007/BF03351067

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