Abstract
Leprosy is still an endemic disease, especially in Third World countries, and, because of migration, it still persists in Europe and the United States. The disease affects the peripheral nerves, skin, and multiple internal organs, making its clinical recognition difficult. In particular, the endocrine manifestations caused by leprosy have been underestimated, even by specialists. The endocrine changes present in leprosy include hypogonadism, sterility, and osteoporosis. In addition, the spectral immune nature of leprosy offers an attractive model to investigate the pathogenetic correlation between the patterns of inflammation in the poles of its spectrum and the hormonal disarrangements observed in this disease. It is important that those involved in leprosy management be aware of the potential endocrine changes and their treatment to address the disease in all of its aspects. In this article, we review the findings on endocrine dysfunction in leprosy, including a survey of the literature and of our own work.
Similar content being viewed by others
References
Gill AL, Bell DR, Gill GV, Wyatt GB, Beeching NJ (2005) Leprosy in Britain: 50 years experience in Liverpool. Q J Med 98:505–511
Ooi WW, Moschella SL (2001) Update on leprosy in immigrants in the United States: status in the year 2000. Clin Infect Dis 32:930–937. doi:10.1086/319357
Walker SL, Lockwood DNJ (2006) The clinical and immunological features of leprosy. Br Med Bull 77–78:103–121. doi:10.1093/bmb/ldl010
Britton WJ, Lockwood DNJ (2004) Leprosy. Lancet 363:1209–1219. doi:10.1016/S0140-6736(04)15952-7
Ridley DS, Jopling WH (1966) Classification of leprosy according to immunity. A five-group system. Int J Lepr Other Mycobact Dis 34:255–273
Powell CS, Swan LL (1955) Leprosy: pathologic changes observed in fifty consecutive necropsies. Am J Pathol 31:1131–1147
Desikan KV, Job CK (1968) A review of postmortem findings in 37 cases of leprosy. Int J Lepr Other Mycobact Dis 36:32–44
Bernard JC, Vazquez CAJ (1973) Visceral lesions in lepromatous leprosy. Study of sixty necropsies. Int J Lepr Other Mycobact Dis 41:94–101
Balybin ES, Nazarov KI (1983) Hydrocortisone production in lepromatous patients with insulin load. Int J Lepr Other Mycobact Dis 51:18–21
Durairaj V, Radhabai K, Alagappan R, Koteeswaran A, Venkataraman V, Kannan K (1984) Adrenal cortical function and reserve in lepromatous leprosy. Indian J Lepr 56:828–834
Saha K, Rao KN, Sehgal VN, Gadi S, Jain VK, Chakrabarty AK (1985) Radioimmunoassay of serum cortisol levels in leprosy patients with special reference to type I and type II reaction. Lepr Rev 56:117–125
Colak R, Ozkan Y, Onen SE, Saral Y, Halifeoglu I (2005) A comparison between the effects of low (1 μg) and standard dose (250 μg) ACTH stimulation tests on adrenal cortex functions with leprosy patients. Endocr Res 31:325–333. doi:10.1080/07435800500449478
Garg R, Agrawal JK, Bajpai HS, Singh G, Srivastava PK (1988) Adreno-cortical function in leprosy. Indian J Lepr 60:609–615
Goldgraber MB, Sulman FG (1969) Adrenal cortical dysfunction in leprosy. Int J Lepr Other Mycobact Dis 37:351–358
Leal AMO, Magalhães PKR, Souza CS, Foss NT (2003) Adrenocortical hormones and interleukin patterns in leprosy. Parasite Immunol 25:457–461. doi:10.1111/j.1365-3024.2003.00654.x WH
Leal AMO, Magalhães PKR, Martinez R, Moreira AC (2003) Adrenocortical hormones and interleukin patterns in paracoccidioidomycosis. J Infect Dis 187:124–127. doi:10.1086/345872
Bornstein SR, Chrousos GP (1999) Adrenocorticotropin (ACTH)- and non-ACTH-mediated regulation of the adrenal cortex: neural and immune inputs. J Clin Endocrinol Metab 84:1729–1736. doi:10.1210/jc.84.5.1729
Päth G, Scherbaum WA, Bornstein SR (2000) The role of interleukin-6 in the human adrenal gland. Eur J Clin Invest 30:91–95. doi:10.1046/j.1365-2362.2000.0300s3091.x
Päth G, Bornstein SR, Ehrhardt-Bornstein M, Scherbaum WA (1997) Interleukin-6 and the interleukin-6 receptor in the human adrenal gland: expression and effects on steroidogenesis. J Clin Endocrinol Metab 82:2343–2349. doi:10.1210/jc.82.7.2343
Parker LN, Levin ER, Lifrak ET (1985) Evidence for adrenocortical adaptation to severe illness. J Clin Endocrinol Metab 60:947–952
Daynes RA, Dudley DJ, Araneo BA (1990) Regulation of murine lymphokine production in vivo. II. Dehydroepiandrosterone is a natural enhancer of interleukin 2 synthesis by helper T cells. Eur J Immunol 20:793–802. doi:10.1002/eji.1830200413
Suzuki T, Suzuki N, Daynes RA, Engleman EG (1991) Dehydroepiandrosterone enhances IL2 production and cytotoxic effector function of human T cells. Clin Immunol Immunopathol 61:202–211. doi:10.1016/S0090-1229(05)80024-8
Padgett DA, Loria RM (1994) In vitro potentiation of lymphocyte activation by dehydroepiandrosterone, androstenediol, and androstenetriol. J Immunol 153:1544–1552
Rook GAW, Baker R (1999) Cortisol metabolism, cortisol sensitivity and the pathogenesis of leprosy reactions. Trop Med Int Health 4:493–498. doi:10.1046/j.1365-3156.1999.00432.x
Andersson AK, Atkinson SE, Khanolkar-Young S, Chaduvula M, Jain S, Suneetha L, Suneetha S, Lockwood DN (2007) Alteration of the cortisol–cortisone shuttle in leprosy type 1 reactions in leprosy patients in Hyderabad, India. Immunol Lett 109:72–75. doi:10.1016/j.imlet.2007.01.004
Baptista L (1937) A gynecomastia na lepra. Rev Brasil Leprol 5:53–66
Rée GH, Martin F, Myles K, Peluso I (1981) Hormonal changes in human leprosy. Lepr Rev 52:121–126
Levis WR, Lanza AP, Swersie S, Meeker HC, Schuller-Levis GB, Bardin CW (1989) Testicular dysfunction in leprosy: relationships of FSH, LH and testosterone to disease classification, activity and duration. Lepr Rev 60:94–101
Grabstald H, Swan LL (1952) Genitourinary lesions in leprosy, with special reference to the problem of atrophy of the testes. JAMA 119:1287–1291
Job CK (1961) Gynecomastia and leprous orchitis. A preliminary study. Int J Lepr Other Mycobact Dis 29:423–441
Ibrahiem AA, Awad HA, Metawi BA, Hamada TAY (1979) Pathologic changes in testis and epididymis of infertile leprotic males. Int J Lepr Other Mycobact Dis 47:44–49
Saporta L, Yuksel A (1994) Androgenic status in patients with lepromatous leprosy. Br J Urol 74:221–224
Kannan V, Vijaya G (1984) Endocrine testicular functions in leprosy. Horm Metab Res 16:146–150
Akhtar M, Ali MA, Mackey DM (1980) Lepromatous leprosy presenting as orchitis. Am J Clin Pathol 73:712–715
Job CK, Macaden VP (1963) Leprous orchitis in reactional borderline cases. Int J Lepr Other Mycobact Dis 31:273–279
Singh N, Arora VK, Jain A, Bhattacharya SN, Bhatia A (2002) Cytology of testicular changes in leprosy. Acta Cytol 46:659–663
Neena K, Ammini AC, Singh M, Pandhi RK (2003) Ovarian function in female patients with multibacillary leprosy. Int J Lepr Other Mycobact Dis 71:101–105. doi:10.1489/1544-581X(2003)071<0101:OFIFPW>2.0.CO;2
Rea TH (1988) A comparative study of testicular involvement in lepromatous and borderline lepromatous leprosy. Int J Lepr Other Mycobact Dis 56:383–388
Dash RJ, Kumar B, Sialy R, Rastogi GK (1979) LH, FSH responses to GnRH in lepromatous leprosy. Horm Metab Res 11:413–414
Shilo S, Livshin Y, Sheskin J, Spitz IM (1981) Gonadal function in lepromatous leprosy. Lepr Rev 52:127–134
Morley JE, Distiller LA, Sagel J, Kok SH, Kay G, Carr P, Katz M (1977) Hormonal changes associated with testicular atrophy and gynaecomastia in patients with leprosy. Clin Endocrinol (Oxf) 6:299–303. doi:10.1111/j.1365-2265.1977.tb02015.x
Sultan Sheriff D (1984) Endocrine profile and seminal plasma composition in Hansen’s disease. Trans R Soc Trop Med Hyg 78:311–313. doi:10.1016/0035-9203(84)90103-2
Rolston R, Mathews M, Taylor PM, Koshy TS (1981) Hormone profile in lepromatous leprosy. A preliminary study. Int J Lepr Other Mycobact Dis 49:31–36
Leal AMO, Magalhães PKR, Souza CS, Foss NT (2006) Pituitary-gonadal hormones and interleukin patterns in leprosy. Trop Med Int Health 11:1416–1421. doi:10.1111/j.1365-3156.2006.01692.x
Garg R, Agarwal JK, Singh G, Bajpai HS (1989) Hormone profile in leprosy. Indian J Lepr 61:428–431
Dass J, Murugesan K, Laumas KR, Deo MG, Kandhari KC, Bhutani LK (1976) Androgenic status of lepromatous leprosy patients with gynecomastia. Int J Lepr Other Mycobact Dis 44:469–474
Kinnear AA, Davison AR (1957) Hormone excretion and liver function in the gynecomastia of leprosy. Int J Lepr Other Mycobact Dis 25:110–118
Abraham A, Sharma VK, Kaur S (1990) Assessment of testicular volume in bacilliferous leprosy: correlation with clinical parameters. Indian J Lepr 62:310–315
Kumar A, Bagghi CS, Indrayan A (1973) Impact of lepromatous leprosy on fecundity. Fertil Steril 24:324–325
Faulstich ME (1985) Behavioral analysis of sexual dysfunction in Hansen’s disease. Percept Mot Skills 60:115–118
El-Shiemy S, El-Hefnawi H, Abdel-Fattah A, El-Okbi M, Farid A (1976) Testicular and epididymal involvement in leprosy patients, with special reference to gynecomastia. Int J Dermatol 15:52–58. doi:10.1111/j.1365-4362.1976.tb05097.x
Martin FIR, Maddocks I, Brown JB, Hudson B (1968) Leprous endocrinopathy. Lancet 2:1320–1321. doi:10.1016/S0140-6736(68)91817-5
Iyer C, Languillon J, Ramanujam G, Tarabini-Castellani G, De las Aguas JT, Bechelli LM, Uemura K, Martinez Dominguez V, Sundaresan T (1971) WHO co-ordinated short-term double-blind trial with thalidomide in the treatment of acute lepra reactions in male lepromatous patients. Bull World Health Organ 45:719–732
Brand PW (1959) Temperature variation and leprosy deformity. Int J Lepr Other Mycobact Dis 27:1–7
Wall JR, Wright DJM (1974) Antibodies against testicular germinal cells in lepromatous leprosy. Clin Exp Immunol 17:51–59
Saha K, Gupta I (1977) Immunologic aspects of leprosy with special reference to the circulating antispermatozoal antibodies. Int J Lepr Other Mycobact Dis 45:28–37
Wall JR, Walters BAJ (1981) Immunoreactivity in vitro to human testis in patients with lepromatous leprosy. Aust N Z J Med 11:375–379
Mealy K, Robinson B, Millette CF, Majzoub J, Wilmore DW (1990) The testicular effects of tumor necrosis factor. Ann Surg 211:470–475. doi:10.1097/00000658-199004000-00014
Lin T, Wang TL, Nagpal ML, Calkins JH, Chang WW, Chi R (1991) Interleukin-1 inhibits cholesterol side-chain cleavage cytochrome P450 expression in primary cultures of Leydig cells. Endocrinology 129:1305–1311
Mauduit C, Hartmann DJ, Chauvin MA, Revol A, Morera AM, Benahmed M (1991) Tumor necrosis factor alpha inhibits gonadotropin action in cultured porcine Leydig cells: site(s) of action. Endocrinology 129:2933–2940
Hales DB, Xiong Y, Tur-Kaspa I (1992) The role of cytokines in the regulation of Leydig cell P450c17 gene expression. J Steroid Biochem Mol Biol 43:907–914. doi:10.1016/0960-0760(92)90318-D
Hales DB (2002) Testicular macrophage modulation of Leydig cell steroidogenesis. J Reprod Immunol 57:3–18. doi:10.1016/S0165-0378(02)00020-7
Hedger MP, Meinhardt A (2003) Cytokines and the immune-testicular axis. J Reprod Immunol 58:1–26. doi:10.1016/S0165-0378(02)00060-8
Morales V, Santana P, Diáz R, Tabraue C, Gallardo G, López Blanco F, Hernández I, Fanjul LF, Ruiz de Galarreta CM (2003) Intratesticular delivery of tumor necrosis factor-alpha and ceramide directly abrogates steroidogenic acute regulatory protein expression and Leydig cell steroidogenesis in adult rats. Endocrinology 144:4763–4772. doi:10.1210/en.2003-0569
Olsen NJ, Kovacs WJ (1996) Gonadal steroids and immunity. Endocr Rev 17:369–384. doi:10.1210/er.17.4.369
Cutolo M, Seriolo B, Villaggio B, Pizzorni C, Craviotto C, Sulli A (2002) Androgens and estrogens modulate the immune and inflammatory responses in rheumatoid arthritis. Ann N Y Acad Sci 966:131–142
Zofková I, Kancheva RL, Hampl R (1995) A decreasing CD4+/CD8+ ratio after one month of treatment with stanazolol in postmenopausal women. Steroids 60:430–433. doi:10.1016/0039-128X(94)00036-C
Cutolo M, Balleari E, Giusti M, Intra E, Accardo S (1991) Androgen replacement therapy in male patients with rheumatoid arthritis. Arthritis Rheum 34:1–5. doi:10.1002/art.1780340102
Couri CEB, Foss NT, Dos Santos CS, de Paula FJA (2004) Hypercalcemia secondary to leprosy. Am J Med Sci 328:357–359
Ryzen E, Rea TH, Singer FR (1988) Hypercalcemia and abnormal 1,25-dihydroxyvitamin D concentrations in leprosy. Am J Med 84:325–329. doi:10.1016/0002-9343(88)90434-2
Rao KN, Saha K (1986) Undernutrition in lepromatous leprosy, Part II. Altered levels of serum elements. Their association with the disease and not with food deprivation. Lepr Rev 57:311–316
Hoffman VN, Korzeniowski OM (1986) Leprosy, hypercalcemia, and elevated serum calcitriol levels. Ann Intern Med 105:890–891
Vidal MC, Botasso OA, Lehrer A, Puche RC (1993) Altered calcium-binding ability of plasma proteins as the cause of hypocalcemia in lepromatous leprosy. Int J Lepr Other Mycobact Dis 61:586–591
Mautalen CA, Vaquero NL, Zeni SN, Mendez MA, Gonzalez DC, Bagur AC, Casco CA, Ladizesky MG (1994) Calcium metabolism and its regulating hormones in patients with leprosy. Int J Lepr Other Mycobact Dis 62:580–585
Ryzen E, Singer FR (1985) Hypercalcemia in leprosy. Arch Intern Med 145:1305–1306. doi:10.1001/archinte.145.7.1305
Barbour GL, Coburn JW, Slatopolsky E, Norman AW, Horst RL (1991) Hypercalcemia in an anephric patient with sarcoidosis: evidence for extrarenal generation of 1,25-dihydroxyvitamin D. N Engl J Med 305:440–443
Parker MS, Dokoh S, Woolfenden JM, Buchsbaum HW (1984) Hypercalcemia in coccidioidomycosis. Am J Med 76:341–344. doi:10.1016/0002-9343(84)90799-X
Abbasi AA, Chemplavil JK, Farah S, Muller BF, Arnstein AR (1979) Hypercalcemia in active pulmonary tuberculosis. Ann Intern Med 90:324–328
Bell NH, Stern PH, Pantzer E, Sinha TK, Deluca HF (1979) Evidence that increased circulating 1α,25-dihydroxyvitamin D is the probable cause for abnormal calcium metabolism in sarcoidosis. J Clin Invest 64:218–225. doi:10.1172/JCI109442
Adams JS, Sharma OP, Gacad MA, Singer FR (1983) Metabolism of 25-hydroxyvitamin D3 by cultured pulmonary alveolar macrophages in sarcoidosis. J Clin Invest 72:1856–1860. doi:10.1172/JCI111147
Mason RS, Frankel T, Chan YL, Lissner D, Posen S (1984) Vitamin D conversion by sarcoid lymph node homogenate. Ann Intern Med 100:59–61
Lips P (2006) Vitamin D physiology. Prog Biophys Mol Biol 92:4–8. doi:10.1016/j.pbiomolbio.2006.02.016
Paterson DE, Rad M (1961) Bone changes in leprosy, their incidence, progress, prevention and arrest. Int J Lepr Other Mycobact Dis 29:393–422
Thappa DM, Sharma VK, Kaur S, Suri S (1992) Radiological changes in hands and feet in disabled leprosy patients: a clinico-radiological correlation. Indian J Lepr 62:58–66
Choudhuri H, Thappa DM, Kumar RH, Elangovan S (1999) Bone changes in leprosy patients with disabilities/deformities (a clinico-radiological correlation). Indian J Lepr 71:203–215
Ishikawa S, Ishikawa A, Yoh K, Tanaka H, Fujiwara M (1999) Osteoporosis in male and female leprosy patients. Calcif Tissue Int 64:144–147. doi:10.1007/s002239900593
Ishikawa A, Tanaka H, Mizushima M, Hashizume H, Ishida Y, Inoue H (1997) Osteoporosis due to testicular atrophy in male leprosy patients. Acta Med Okayama 51:279–283
Ishikawa S, Mizushima M, Furuta M, Ishikawa A, Kawamura K (2000) Leydig cell hyperplasia and the maintenance of bone volume: bone histomorphometry and testicular histopathology in 29 male leprosy autopsy cases. Int J Lepr Other Mycobact Dis 68:258–266
Ishikawa A, Ishikawa S, Hirakawa M (2001) Osteoporosis, bone turnover and hypogonadism in elderly men with treated leprosy. Lepr Rev 72:322–329
Walker SL, Waters MFR, Lockwood DNJ (2007) The role of thalidomide in the management of erythema nodosum leprosum. Lepr Rev 78:197–215
Ribeiro FB, Pereira F de A, Muller E, Foss NT, de Paula FJ (2007) Evaluation of bone and mineral metabolism in patients recently diagnosed with leprosy. Am J Med Sci 334:322–326
Clowes JA, Riggs BL, Khosla S (2005) The role of the immune system in the pathophysiology of osteoporosis. Immunol Rev 208:207–227. doi:10.1111/j.0105-2896.2005.00334.x
Kanaji A, Higashi M, Namisato M, Ando K, Nakagawa M, Yato Y, Ichinose H, Sakamaki T, Yamada H (2005) Trochanteric hip fracture in an elderly patient with leprosy during osteoporosis treatment with risedronate and alfacalcidol. J Bone Miner Metab 23:90–94. doi:10.1007/s00774-004-0546-7
Kanaji A, Higashi M, Namisato M, Nishio M, Ando K, Yamada H (2006) Effects of risedronate on lumbar bone mineral density, bone resorption, and incidence of vertebral fracture in elderly male patients with leprosy. Lepr Rev 77:147–153
Yumnam IS, Kaur S, Kumar B, Rastogi GK (1977) Evaluation of thyroid functions in leprosy. I. Thyroid function tests. Lepr India 49:485–491
Garg R, Agarwal JK, Singh G, Bajpai HS (1990) Thyroid function in leprosy. Indian J Lepr 62:215–218
Kheir MM, Ahmed AM, Elsarrag AA (2001) Thyroid functional status in leprosy patients in Sudan. East Mediterr Health J 7:79–83
Larsen PR, Davies TF, Schlumberger M-J, Hay ID (2002) Thyroid physiology and diagnostic evaluation of patients with thyroid disorders. In: Larsen PR, Kronenberg HM, Melmed S, Polonsky KS, Wilson JD, Foster DW (eds) Williams textbook of endocrinology, 10th edn. Saunders, Philadelphia, PA
Bonomo L, Dammacco F, Pinto L, Babieri G (1963) Thyroglobulin antibodies in leprosy. Lancet 2:807–809. doi:10.1016/S0140-6736(63)90501-4
Shwe T (1972) Clinical significance of autoimmune antibodies in leprosy. Trans R Soc Trop Med Hyg 66:749–753. doi:10.1016/0035-9203(72)90089-2
Pradhan V, Badakere SS, Shankar Kumar U (2004) Increased incidence of cytoplasmic ANCA (cANCA) and other autoantibodies in leprosy patients from western India. Lepr Rev 75:50–56
Badros AF, Siegel E, Bodenner D, Zangari M, Zeldis J, Barlogie B, Tricot G (2002) Hypothyroidism in patients with multiple myeloma following treatment with thalidomide. Am J Med 112:412–413. doi:10.1016/S0002-9343(01)01137-8
Nigam P, Dayal SG, Srivastava P, Joshi LD, Goyal BM, Dutt B, Gupta MC (1979) Diabetic status in leprosy. Hansenol Int 4:7–14
Garg R, Agrawal JK, Bajpai HS, Singh G, Srivastava PK (1990) Glucose tolerance test in leprosy. Indian J Lepr 62:50–54
Marik PE, Rahavan M (2004) Stress-hyperglycemia, insulin and immunomodulation in sepsis. Intensive Care Med 30:748–756. doi:10.1007/s00134-004-2167-y
Sugumaran DS (1998) Leprosy reactions—complications of steroid therapy. Int J Lepr Other Mycobact Dis 66:10–15
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Leal, Â.M.O., Foss, N.T. Endocrine dysfunction in leprosy. Eur J Clin Microbiol Infect Dis 28, 1–7 (2009). https://doi.org/10.1007/s10096-008-0576-5
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10096-008-0576-5