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Vol. 14. Issue 6.
Pages 613-620 (November - December 2010)
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Vol. 14. Issue 6.
Pages 613-620 (November - December 2010)
Review article
Open Access
Endocrine and metabolic disorders in HTLV-1 infected patients
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Cresio Alves1,
Corresponding author
cresio.alves@uol.com.br

Correspondence to: Pediatric Endocrinology Service, Hospital Universitário Professor Edgard Santos, Faculty of Medicine, Universidade Federal da Bahia Rua Plinio Moscoso, 222/601, 40157-190, Salvador, Bahia, Brazil.
, Luciano Dourado2
1 Chief of Pediatric Endocrinology, Hospital Universitário Prof. Edgard Santos, Faculty of Medicine, Universidade Federal da Bahia
2 Fellow in Pediatric Endocrinology, Pediatric Endocrinology Service, Hospital Universitário Professor Edgard Santos, Faculty of Medicine, Universidade Federal da Bahia
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Abstract

Human T-cell leukemia virus type 1 (HTLV-1) infection is endemic in Japan and several countries in South America, Caribbean and Africa. Endocrine and metabolic disorders have been variably reported to be associated with human T-cell leukemia virus type 1 (HTLV-1) infection. Therefore, the aim of this article was to critically evaluate the current knowledge of the endocrine and metabolic disorders associated with HTLV-1 infection. The literature search used PubMed, Web of Science, and LILACS databases in the past 10 years, utilizing, in various combinations, the following keywords: HTLV-1, adult T-cell leukemia, diabetes mellitus, GLUT-1, osteoporosis, hypercalcemia, autoimmune thyroid disorders, diabetes insipidus, inappropriate antidiuretic hormone secretion; pseudohypoparathyroidism; pseudopseudohypoparathyroidism. The proven endocrine manifestations of the HTLV-1 infection are calcium disorders which occur in some patients with acute HTLV-1/Adult T-cell leukemia/lymphoma. The few reports about thyroid, parathyroid, antidiuretic hormone and diabetes mellitus are insufficient to prove a causal association with HTLV-1 infection. The evidence for an association between endocrine disorders and HTLV-1 infection in general, and in asymptomatic patients is lacking. Given all these uncertainties, the endocrine expression of the HTLV-1 infection composes a promising research line for understanding the pathophysiology of this infection.

Keywords:
HTLV-1
adult T-cell leukemia
endocrine disorders
metabolic disorders
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References
[1.]
D. Schachter, L. Cartier, A. Borzutzky.
Osteoporosis in HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP).
Bone, 33 (2003), pp. 192-196
[2.]
P. Bagossi, P. Bander, B. Bozóki, J. Tözser.
Discovery and significance of new human T-lymphotropic viruses: HTLV-3 and HTLV- 4.
Expert Rev Anti Infect Ther, 7 (2009), pp. 1235-1249
[3.]
F.L.N. Santos, F.W.M. Lima.
Epidemiologia, fisiopatogenia e diagnóstico laboratorial da infecção pelo HTLV – I.
J Bras Patol Med Lab, 2 (2005), pp. 105-116
[4.]
C.M. Nakauchi, K. Maruyama, L.I. Kanzaki, et al.
Prevalence of HTLV-I antibody among two distinct ethnic groups inhabiting the Amazon region of Brazil.
Rev Inst Med Trop, 34 (1992), pp. 323-338
[5.]
R. Ishak, A.C.R. Vallinoto, V.N. Azevedo, M.O.G. Ishak.
Epidemiological aspects of retrovirus (HTLV) infection among Indian populations in the Amazon Region of Brazil.
Cad Saúde Pública (Rio de Janeiro), 19 (2003), pp. 901-914
[6.]
A.C.R. Vallinoto, G.S. Pontes, I.G.L. Lopes, et al.
Identification og human t-cell lymphotropic vírus infection in a semi-isolated Afro-Brazilian quilombo located in the Marajó Island (Pará, Brazil).
Mem Inst Oswaldo Cruz, 10 (2006), pp. 103-105
[7.]
A. Mota, C. Nunes, A. Melo, et al.
A case-control study of HTLV-infection among blood donors in Salvador, Bahia, Brazil - associated risk factors and trend towards declining prevalence.
Rev Bras Hematol Hemoter, 28 (2006), pp. 120-126
[8.]
I. Moxoto, N. Boa-Sorte, C. Nunes, et al.
Perfil sociodemográfico, epidemiológico e comportamental de mulheres infectadas pelo HTLV-I em Salvador-Bahia, uma área endêmica para o HTLV.
Rev Soc Bras Med Trop, 40 (2007), pp. 37-41
[9.]
M. Adachi, T. Shiomura, H. Shimada, et al.
Adult T-cell leukaemia with various abnormalities in endocrine and metabolic systems.
Br J Haematol, 87 (1994), pp. 853-855
[10.]
H. Akamine, N. Takasu, I. Komiya, et al.
Association of HTLV-1 with autoimmune thyroiditis in patients with adult T-cell leukaemia (ATL) and in HTLV-1 carriers.
Clin Endocrinol, 45 (1996), pp. 461-466
[11.]
M.F. Smikle, R. Wright-Pascoe, E.N. Barton, et al.
Autoantibodies, human T lymphotropic virus type I and type 1 diabetes mellitus in Jamaicans.
West Indian Med J, 5 (2002), pp. 153-156
[12.]
N. Machigashira, Y. Yoshida, S. Wang, M. Osame.
HTLV-I-associated myelopathy/tropical spastic paraparesis with pseudohypoparathyroidism.
Neurology, 56 (2001), pp. 104-106
[13.]
T. Kiyokawa, K. Yamaguchi, M. Takeya, et al.
Hypercalcemia and osteoclast proliferation in adult T-cell leukemia.
Cancer, 59 (1987), pp. 1187-1191
[14.]
Y. Sagara, Y. Inoue, Y. Sagara, S. Kashiwagi.
Involvement of molecular mimicry between human T-cell leukemia virus type 1 gp46 and osteoprotegerin in induction of hypercalcemia.
Cancer Sci, 100 (2009), pp. 490-496
[15.]
C. Nicot.
Current views in HTLV-I-associated adult T-cell leukemia/lymphoma.
Am J Hematol, 75 (2005), pp. 232-239
[16.]
C.M. Edwards, S.J.E. Edwards, R. Bhumbra, T.A. Chowdhury.
Severe refractory hypercalcaemia in HTLV-1 infection.
J R Soc Med, 96 (2003), pp. 126-127
[17.]
M.V.P. Nadella, S.T. Shu, W.P. Dirksen, et al.
Expression of parathyroid hormone-related protein during immortalization of human peripheral blood mononuclear cells by HTLV-I: implications for transformation.
Retrovirology, 5 (2008), pp. 46-58
[18.]
K. Nosaka, T. Miyamoto, T. Sakai, et al.
Mechanism of hypercalcemia in adult T-cell leukemia: overexpression of receptor activator of nuclear factor kappa B ligand on adult T-cell leukemia cells.
Blood, 99 (2002), pp. 634-640
[19.]
K. Hagler, J. Lynch.
Paraneoplastic manifestations of lymphoma.
Clin Lymphoma, 5 (2004), pp. 29-36
[20.]
V. Lyell, E. Khatamzas, T. Allain.
Severe hypercalcemia and lymphoma in a HTLV-I positive Jamaican woman: a case report.
J Med Case Reports, 1 (2007), pp. 56
[21.]
D. Shoback.
Update in osteoporosis and metabolic bone disorders.
J Clin Endocrinol Metab, 92 (2007), pp. 747-753
[22.]
A. Rogers, R. Eastell.
Circulating osteoprotegerin and receptor activator for nuclear factor kB ligand: clinical utility in metabolic bone disease assessment.
J Clin Endocrinol Metab, 90 (2005), pp. 6233-6331
[23.]
W.S. Simonet, D.L. Lacey, C.R. Dunstan, et al.
Osteoprotegerin: a novel secreted protein involved in the regulation of bone density.
Cell, 89 (1997), pp. 309-319
[24.]
N. Bucay, I. Sarosi, C.R. Dunstan, et al.
Osteoprotegerin-deficient mice develop early onset osteoporosis and arterial calcification.
Genes Dev, 12 (1998), pp. 1260-1268
[25.]
S. Fukumoto, T. Matsumoto, K. Ikeda, et al.
Clinical evaluation of calcium metabolism in adult T-cell leukemia/lymphoma.
Arch Intern Med, 148 (1988), pp. 921-925
[26.]
S. Fukumoto, T. Matsumoto, T. Watanabe, et al.
Secretion of parathyroid hormone-like activity from human T-cell lymphotropic virus type I-infected lymphocytes.
Cancer Res, 49 (1989), pp. 3849-3852
[27.]
T. Motokura, S. Fukumoto, S. Takahashi, et al.
Expression of parathyroid hormone-related protein in a human T cell lymphotrophic virus type I-infected T cell line.
Biochem Biophys Res Commun, 154 (1988), pp. 1182-1188
[28.]
T. Watanabe, K. Yamaguchi, K. Takatsuki, et al.
Constitutive expression of parathyroid hormone-related protein gene in human T cell leukemia virus type 1 (HTLV-1) carriers and adult T cell leukemia patients that can be trans-activated by HTLV-1 tax gene.
J Exp Med, 172 (1990), pp. 759-765
[29.]
V. Richard, M.D. Laimore, P.L. Green, et al.
Severe combined immnudeficiency/beige mouse model of adult T-cell lymphoma independent of human T-cell lymphotropic virus type-1 Tax expression.
Am J Pathol, 158 (2001), pp. 2219-2228
[30.]
Y. Okada, J. Tsukada, K. Nakano, et al.
Macrophage inflammatory protein-1alpha induces hypercalcemia in adult T-cell leukemia.
J Bone Miner Res, 19 (2004), pp. 1105-1111
[31.]
Q. Fu, R.L. Jilka, S.C. Manolagas, C.A. O’Brien.
Parathyroid hormone stimulates receptor activator of NFkB ligand and inhibited osteoprotegerin expression via protein kinase A activation of cAMP-response element-binding protein.
J Biol Chem, 277 (2002), pp. 48868-48875
[32.]
L. Gao, H. Deng, H. Zhao, et al.
HTLV-1 Tax transgenic mice develop spontaneous osteolytic bone metatastases prevented by osteoclastic inhibition.
Blood, 106 (2005), pp. 4294-4302
[33.]
Z. Zhou, S.S. Apte, R. Soinemen, et al.
Impaired endochondral ossification and angiogenesis in mice deficient in membrane-type matrix metalloproteinase 1.
Proc Natl Acad Sci (USA), 97 (2000), pp. 4052-4057
[34.]
A.W. Root, F.B. Diamond Jr..
Disorders of mineral homeostasis in the newborn, infant, child and adolescents.
Pediatric Endocrinology, edn 3, Saunders, (2008),
[35.]
Y. Yoshida, Y. Sakamoto, A. Yoshime, et al.
Three cases of juvenile onset HTLV-I-associated myeolopathy with pseudohypoparathyroidism.
J Neurol Sci, 111 (1993), pp. 145-149
[36.]
Y. Yoshida, N. Machigashira, S. Wang, M. Osame.
A patient with acute-onset HAM/TSP after blood transfusion complicated with pseudopseudohypoparathyroidism.
Intern Med, 41 (2002), pp. 899-900
[37.]
R. Fritzen.
HTLV-I associated myelopathy/tropical spastic paraparesis with pseudohypoparathyroidism.
Neurology, 57 (2001), pp. 1349-1350
[38.]
M.F. Prummel, T. Strieder, W.M. Wiersinga.
The environment and autoimmune thyroid diseases.
Eur J Endocrinol, 150 (2004), pp. 605-618
[39.]
Y. Tomer, A. Huber.
The etiology of autoimmune thyroid disease: A story of genes and environment.
J Autoimmun, 32 (2009), pp. 231-239
[40.]
M.F. Prummel, P. Laurberg.
Interferon-alpha and autoimmune thyroid disease.
Thyroid, 13 (2003), pp. 547-551
[41.]
N. Harii, C.J. Lewis, V. Vasko, et al.
Thyrocytes express a functional toll-like receptor 3: overexpression can be induced by viral infection and reversed by phenylmethimazole and is associated with Hashimoto's autoimmune thyroiditis.
Mol Endocrinol, 19 (2005), pp. 1231-1250
[42.]
S. Lagaye, P. Vexiau, V. Morozov, et al.
Detection of HTLV-I gag related sequences in leukocyte DNA from patients with polyendocrinopathies (Basedow-Graves’ disease and insulin-dependent diabetes).
C R Acad Sci III, 312 (1991), pp. 309-315
[43.]
H. Kawai, T. Inui, S. Kashiwagi, et al.
HTLV-1 infection in patients with autoimmune thyroiditis (Hashimoto's thyroiditis).
J Med Virol, 38 (1992), pp. 138-141
[44.]
T. Mizokami, K. Okamura, H. Ikenoue, et al.
High prevalence of human T-lymphotropic vitus type I carriers in patients with antithyroid antibodies.
Thyroid, 4 (1994), pp. 415-419
[45.]
H. Mine, H. Kawai, K. Yokoi, M. Akaike, S. Saito.
High frequencies of human T lymphotropic virus type 1 (HTLV-1) proviral DNA in blood donors with anti-thyroid antibodies.
J Molecular Med, 74 (1996), pp. 471-477
[46.]
H. Kawai, T. Mitsui, K. Yokoi, et al.
Demonstration of viral protein of HTLV-I and its messenger RNA in thyroid tissue of HTLV-I carriers with Hashimoto's thyroiditis.
J Clin Exp Med (Tokyo), 169 (1994), pp. 965-966
[47.]
H. Kawai, T. Mitsui, K. Yokoi, et al.
Evidence of HTLV-I in thyroid tissue in an HTLV-I carrier with Hashimoto's thyroiditis.
J Mol Med, 74 (1996), pp. 275-278
[48.]
R.AC. Filho, M. Vaisman, E.A.G. Vilar, E.C. Fonseca.
Expressão das proteínas p19(gag) e gp 21(env) do HTLV-I no tecido tireoidiano de pacientes com doença autoimune da tireóide e no tecido tireoidiano normal.
Arq Bras Endocrinol Metab, 44 (2000), pp. 417-424
[49.]
T. Matsuda, M. Tomita, J.N. Uchihara, et al.
Human T cell leukemia virus type I-infected patients with Hashimoto's thyreoiditis and Grave's disease.
J Clin Endocrinol Metab, 90 (2005), pp. 5704-5710
[50.]
Y. Tomer, D.A. Greenberg, G. Barbesino, E. Concepcion, T.F. Davies.
CTLA-4 and not CD28 is a susceptibility gene for thyroid autoantibody production.
J Clin Endocrinol Metab, 86 (2001), pp. 1687-1693
[51.]
T. Tomoyose, I. Komiya, M. Takara, et al.
Cytotoxic T-lymphotrophic virus-1 infection: their associations with Hashimoto's thyroiditis in Japanese patients.
Thyroid, 12 (2002), pp. 673-677
[52.]
K. Yamaguchi, M. Mochizuki, T. Watanabe, et al.
Human T lymphotropic virus type 1 uveitis after Graves disease.
Br. J Ophthalmol, 78 (1994), pp. 163-166
[53.]
H. Kawai, K. Yokoi, M. Akaike, et al.
Graves disease in HTLV-I carriers.
J Mol Med, 73 (1995), pp. 85-88
[54.]
U. Oh, C. Grant, C. Griffith, et al.
Reduced Foxp3 protein expression is associated with inflammatory disease during human t lymphotropic virus type 1 Infection.
J Infect Dis, 193 (2006), pp. 1557-1566
[55.]
A. Marabelle, M. Meyer, F. Demeocq, A. Lachaux.
From Ipex to foxp3: a new contribution of pediatrics to the understanding of the immune system.
Arch Pediatr, 15 (2008), pp. 55-63
[56.]
B. Conrad, R.N. Weissmahr, J. Boni, et al.
A human endogenous retroviral superantigen as candidate autoimmune in type 1 diabetes.
Cell, 90 (1997), pp. 303-313
[57.]
K. Badenhoop, H. Donner, J. Neumann, et al.
IDDM patients neither show humoral reactivities against endogenous retroviral envelop protein nor do they differ in retroviral mRNA expression from healthy relatives or normal individuals.
Diabetes, 48 (1999), pp. 215-218
[58.]
E. Jaeckel, S. Heringlake, D. Berger, et al.
No evidence for association between IDDMK1,222 a novel isolated retrovirus and IDDM.
Diabetes, 48 (1999), pp. 200-214
[59.]
A. Muir, Q. Ruan, M.P. Marron, J. She.
The IDDDMK1,222 retrovirus is not detectable in either mRNA or genomic DNA from patients with type 1 diabetes.
Diabetes, 48 (1999), pp. 219-222
[60.]
S. Marguerat, W.Y.S. Yang, J.A. Todd, B. Conrad.
Association of human endogenous retrovirus K-18 polymorphisms with type 1 diabetes.
Diabetes, 53 (2004), pp. 852-854
[61.]
L. Swainson, S. Kinet, N. Manel, et al.
Glucose transporter 1 expression identifies a population of cycling CD4+ CD8+ human thymocytes with high CXCR4-induced chemotaxis.
PNAS, 102 (2005), pp. 12867-12872
[62.]
N. Manel, N.S. Kim, N. Kinet, et al.
The ubiquitous glucose transporter GLUT-1 is a receptor for HTLV.
Cell, 115 (2003), pp. 449-459
[63.]
A.K. Coskun, R.E. Sutton.
Expression of glucose transporter 1 confers susceptibility to human T-cell leukemia virus envelope-mediated fusion.
[64.]
G.C. Costa, R. Azevedo, S.R. Gadelha, et al.
Polymorphisms at GLUT1 gene are not associated with the development of TSP/HAM in Brazilian HTLV-1 infected individuals and the discovery of a new polymorphism at GLUT1 gene.
J Med Virol, 81 (2009), pp. 552-557
[65.]
M. Katsuno, E. Uchida, K. Goto, et al.
Adult T-cell leukaemia presenting with pancytopenia followed by diabetes insipidus.
Rinsho Ketsueki, 28 (1987), pp. 730-737
[66.]
M. Ishii, K. Kubota, Y. Matsuoka, K. Yamaguchi, K. Takatsuki.
Chronic adult T-cell leukemia with T4 and T8 positive leukaemic cells associated with central diabetes insipidus.
Rinsho Ketsueki, 28 (1987), pp. 578-582
[67.]
C. Kawasaki, S. Hayashi, T. Shibuya, et al.
Syndrome of inappropriate secretion of antidiuretic hormone in the central nervous system involvement of adult T-cell leukaemia.
Rinsho Ketsueki, 29 (1988), pp. 1482-1487
[68.]
T. Teshima, Y. Nakahara, Y. Hirata, et al.
Adult T-cell leukaemia with brain mass complicated with inappropriate secretion of ADH.
Rinsho Ketsueki, 29 (1988), pp. 2307-2311
[69.]
S. Morony, K. Warmington, S. Adamu, et al.
The inhibition of RANKL causes supression of bone resorption and hypercalcemia compared with biphosphonates in two models of humoral hypercalcemia of malignancy.
Endocrinology, 146 (2005), pp. 3235-3243
[70.]
G. Mazziotti, G. Amato, F. Sorvillo, et al.
Increased serum osteoprotegerin values in long-lived subjects: different effects of inflammation and bone metabolism.
Eu J Endocrinol, 154 (2006), pp. 373-377
[71.]
P. Szulc, L.C. Hofbauer, A.E. Heufelder, S. Roth, P.D. Delmas.
Osteoprotegerin serum levels in men: correlation with age, estrogen and testosterone status.
J Clin Endocrinol Metab, 86 (2001), pp. 3162-3165
[72.]
P.J. Bekker, D. Holloway, A. Nakanishi, et al.
The effect of a single dose of osteoprotegerin in postmenopausal women.
J Bone Miner Res, 16 (2001), pp. 348-360
[73.]
M.R. McClung, E.M. Lewiecki, S.B. Cohen, AMG 162 Bone Loss Study Group, et al.
Denosumab in postmenopausal women with low bone mineral density.
N Engl J Med, 354 (2006), pp. 821-831
[74.]
E. Onuma, K. Sato, H. Saito, et al.
Generation of a humanized monoclonal antibody against human parathyroid hormone-related protein and its efficacy against humoral hypercalcemia of malignancy.
Anticancer Res, 24 (2004), pp. 2665-2674
[75.]
C. Ishikawa, T. Matsuta, T. Okudaira, et al.
Biphosphonate incadronate inhibits growth of human T-cell leukemia vírus type 1-infected T-cell lines and primary adult T-cell leukemia cells by interfering with the mevalonate pathway.
Br J Haematol, 136 (2007), pp. 424-432
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