Estudo prospectivo dos efeitos da amiodarona na função tiroidiana de pacientes chagásicos em área de deficiência de iodo

Barros, Maria Aparecida Enes de; Maciel, Rui Monteiro de Barros

doi:10.1590/S0037-86821994000300005

Resumos

Com o objetivo de avaliar a junção tiroidiana após uso crônico da amiodarona, em área de deficiência de iodo e endemia chagásica, 24 pacientes foram analisados antes e após três e nove meses de uso da droga. A avaliação constou de exame clínico, dosagem sérica de T4, T3, rT3, TSH, anticorpo antitiroglobulina e TSH 30 minutos após infusão venosa de uma ampola de 200µg de TRH. A captação do iodo radioativo 131 e a cintilografia datiróide foram realizadas antes e aos 9 meses após tratamento. Disfunção tiroidiana ocorreu em 20,8% dos pacientes sendo 12,5% de hipertiroidismo e 8,3% de hipotiroidismo, com anticorpos antitiroglobulina negativos. Captação do iodo radioativo 131 foi positiva em um paciente hipertiroideo com bócio. O diagnóstico de hipertiroidismo foi melhor evidenciado pela resposta reduzida ou bloqueada do TSH ao TRH e não pela concentração do T3 no soro e o de hipotiroidismo pela concentração elevada do TSH. O TSH elevado desde o início do tratamento pode predispor ao aparecimento de bócio. Concluímos que o uso da amiodarona em nossa região deve serjudiciosamente analisado, sendo a função tiroidiana cuidadosamente monitorizada antes e durante o tratamento.

Amiodarona; Função tiroidiana; Doença de Chagas; Deficiência de iodo

In order to evaluate the development of thyroid dysfunction during chronic amiodarone treatment in an area deficient in iodine and endemic for Chagas 'disease, a group of 24patients wasprospectively studied. Clinical examination and measurement of serum T4, T3, rT3, TSH and antithyroglobulin antibodies were performed before and at 3 and 9 months of use of amiodarone. A TSH response 30 minutes after IV injection of 200µg of TRH was also compared to TSH basal levels before and during amiodarone treatment. Thyroid radioative uptake and scan were obtained before and nine months after amiodarone was started. Elevated rT3 concentrations were unexpectedly found in two thirds of the patients before treatment. Thyroid dysfunction developed during amiodarone administration in 20,8% of the patients; 12,5% became hyperthyroid and 8,3%, hypothyroid (with negative antithyroglobulin antibodies). Positive RA1 uptake was seen in one patient with hyperthyroidism and diffuse goiter. Since T3 levels were not found to increase, the diagnosis of amiodarone-related hyperthyroidism was better evidenced by the reduced or blocked TSH response to TRH. Elevated TSH concentration was the best evidence of amiodarone- inducedhypothyroidism. Increase in TSH levels since the beginning of amiodarone therapy may predispose to the growth of a goiter. In conclusion, amiodarone treatment in an iodine deficient area as above should be judiciously decided and thyroidfunction carefully monitored before and during the use of the drug.

Amiodarone; Thyroidfunction; Chagas ' disease; Iodine deficiency

ARTIGOS

Estudo prospectivo dos efeitos da amiodarona na função tiroidiana de pacientes chagásicos em área de deficiência de iodo

Prospective study of amiodarone effects on thyroid function of chagasic patients in an iodine deficient area

Maria Aparecida Enes de Barros; Rui Monteiro de Barros Maciel

^{Endereço para correspondência} Endereço para correspondência: Prof a. Maria Aparecida Enes Barros. Depto. de Medicina, Endocrinologia/FMTM. Av. Getúlio Guarita s/n 38025-050 Uberaba, MG.

RESUMO

Com o objetivo de avaliar a junção tiroidiana após uso crônico da amiodarona, em área de deficiência de iodo e endemia chagásica, 24 pacientes foram analisados antes e após três e nove meses de uso da droga. A avaliação constou de exame clínico, dosagem sérica de T4, T3, rT3, TSH, anticorpo antitiroglobulina e TSH 30 minutos após infusão venosa de uma ampola de 200µg de TRH. A captação do iodo radioativo 131 e a cintilografia datiróide foram realizadas antes e aos 9 meses após tratamento. Disfunção tiroidiana ocorreu em 20,8% dos pacientes sendo 12,5% de hipertiroidismo e 8,3% de hipotiroidismo, com anticorpos antitiroglobulina negativos. Captação do iodo radioativo 131 foi positiva em um paciente hipertiroideo com bócio. O diagnóstico de hipertiroidismo foi melhor evidenciado pela resposta reduzida ou bloqueada do TSH ao TRH e não pela concentração do T3 no soro e o de hipotiroidismo pela concentração elevada do TSH. O TSH elevado desde o início do tratamento pode predispor ao aparecimento de bócio. Concluímos que o uso da amiodarona em nossa região deve serjudiciosamente analisado, sendo a função tiroidiana cuidadosamente monitorizada antes e durante o tratamento.

Palavras-chave: Amiodarona. Função tiroidiana. Doença de Chagas. Deficiência de iodo.

ABSTRACT

In order to evaluate the development of thyroid dysfunction during chronic amiodarone treatment in an area deficient in iodine and endemic for Chagas 'disease, a group of 24patients wasprospectively studied. Clinical examination and measurement of serum T4, T3, rT3, TSH and antithyroglobulin antibodies were performed before and at 3 and 9 months of use of amiodarone. A TSH response 30 minutes after IV injection of 200µg of TRH was also compared to TSH basal levels before and during amiodarone treatment. Thyroid radioative uptake and scan were obtained before and nine months after amiodarone was started. Elevated rT3 concentrations were unexpectedly found in two thirds of the patients before treatment. Thyroid dysfunction developed during amiodarone administration in 20,8% of the patients; 12,5% became hyperthyroid and 8,3%, hypothyroid (with negative antithyroglobulin antibodies). Positive RA1 uptake was seen in one patient with hyperthyroidism and diffuse goiter. Since T3 levels were not found to increase, the diagnosis of amiodarone-related hyperthyroidism was better evidenced by the reduced or blocked TSH response to TRH. Elevated TSH concentration was the best evidence of amiodarone- inducedhypothyroidism. Increase in TSH levels since the beginning of amiodarone therapy may predispose to the growth of a goiter. In conclusion, amiodarone treatment in an iodine deficient area as above should be judiciously decided and thyroidfunction carefully monitored before and during the use of the drug.

Keywords: Amiodarone. Thyroidfunction. Chagas ' disease. Iodine deficiency.

Texto completo disponível apenas em PDF.

Full text available only in PDF format.

Recebido para publicação em 28/02/94.

Curso de Pós-Graduação em Endocrinologia da Faculdade de Medicina da Escola Paulista de Medicina, São Paulo, SF e Faculdade de Medicina do Triângulo Mineiro, Uberaba, MG.

Referências bibliográficas

1. Aguini-Lombardi F, Martino E, Lenziardi M, Grasso L, Pacchiarotti A, Capellini Q, Odoguardi L, Fenzi E, Baschieri L, Pinchera A. Hipertiroidismo iodo- indotto da amiodarone. Medicina 76:431-436, 1985.
2. Albert GS, Larry EA, Edward PR. Thyroid dysfunction during chronic amiodarone therapy. Journal of the American College of Cardiology 9:175-183, 1987.
3. Amino N, Hagen SR, Yamada N, Refetoff S. Measurement of circulating thyroid microssomal antibodies by the tanned red cell haemaglutination technique: its usefulness in the diagnosis of autoimmune diseases. Clinical Endocrinology 5:115- 125, 1976.
4. Barros MA, Barros AJ, Lopes ER, Vasconcelos JLM, Teodoro CS. Ocorrência das patologias tiroidianas, com especial referêcia às neoplasias, na região do Triângulo Mineiro. Arquivos Brasileiros de Endocrinologia e Metabologia 25:95-98, 1981.
5. Burger A, Dinichert D, Nicot P, Jenny M, Lemarchand-Beraud T, Vallotton MB. Effect of amiodarone on serum triiodothyronine, reverse triiodothyronine, thyroxine and thyrotropin. Journal of Clinical Investigation 58:255-259,1976.
6. Burger AG. Effects of certain pharmacologic agents on the peripheral metabolism of thyroxine. In: Ingbar SH, Braverman LE (eds) Werner's-The Thyroid. 5 edition. Lippincott, Philadelfia p.351- 360, 1986.
7. Chopra IJ, Solomon DH, Hepner GW, Morgenstein AA, Misleading LY. Low free thyroxine index and usefulness of reverse triiodothyronine measurement in non thyroidal illness. Annals of Internal Medicine 90:905-912, 1979.
8. Fradkin JE, Wolff J. Iodine-induced thyrotoxicosis. Medicine 62:1-20, 1983.
9. HegerJJ, PrystowskyEN, Jackamn WM, Naccarelli GW, Warfel KA, Rinkenberger RL, Zipes DP: Amiodarone: clinical efficacy and electrophysiology during long-term therapy for recurrent ventricular tachycardia or ventricular fibrillation. New England Journal of Medicine 305:539, 1981.
10. Heger JJ, Prystowsky EN, Zipes DP. Clinical efficacy of amiodarone in treatment of recurrent ventricular tachycardia and ventricular fibrillation. American Heart Journal 106:887, 1983.
11. Jonckheer MH, Blockx P, Broeckertl, Comette C, Beckers C. "Low T3 syndrome" in patients chronically treated with an iodine-containing drug, amiodarone. ClinicalEndocrinology 9:27-35,1978.
12. Jorge PT, Enzimaimunoensaio para detecção de anticorpos anti-tiroglobulina no soro. Desenvolvimento metodológico e implicações diagnosticas. Tese de Doutorado, Escola Paulista de Medicina, São Paulo,SP, 1986.
13. Lambert MJ, Burger AG, Galeazzi RL, Engler D. Are selective increases in serum thyroxine due to iodinated inhibitors of T4 monodeiodination indicative of hiperthyroidism? Journal of Clinical Endocrinology and Metabolism 55:1058-1065, 1982.
14. Lombardi A, Martino A, Braverman LE. Amiodarone and the thyroid. Thyroid Today 2:1- 7, 1990.
15. Lopes ER, Moraes CA, Chapadeiro E, Mineo JR, Leite LC, Guimarães AHB, Rocha A, Gava M. Prevalência da infecção chagásica em necrópsias no Triângulo Mineiro. Revista de Medicina Tropical de São Paulo 26:125-129, 1984.
16. Maciel RMB, Russo EMK, Furlaneto PP. Testes de função tiroideana. In: Guimarães RX, Guerra CCC (eds) Clinica e Laboratório. 3 edition, Sarvier São Paulo pjll5-126, 1983.
17. Martino E, Macchia E, Lombardi F, Antonelli A, Lenziaríii M, Concetti R, Fenzi GF, Baschieri H, Pincherá A. Is humoral thyroid auto immunity relevant in amiödarone iodine-induced thyrotoxicosis? Clinical Endocrinology 24:627-633, 1986a.
18. Martino E, Safran M, Aguini-Lombardi F, Rajatanáven R, Lenziardi M, Fay M, Pacchiarotti A, Aronin N, Macchia H, Haffajee C, AdoguardiL, Love J, Bigalli A, Bascuieri L, Pinchera A, Braveraan L. Environmental iodine intake and thyroid dysfunction during chronic amiodarone therapy; Annals of Internal Medicine 101:28-34, 1984.
19. Massin JP, Thomopoulos P, Karan J, Savoie JC. Le risque thyroidien d'un nouveau coronariodilatateur iodé; l'amiodarone (Cordarone). Annales Endocrinologie 32:438-448, 1971.
20. Medeiros-Neto GA, Lobo LCG, Nicolau W. Endemic goiter in Brazil. In: Pan American Health Organization (ed) "Endemic Goiter". World Health Organization John B.Stanbury, New York p. 179- 182, 1969.
21. Pellon AB, Silva W, Borges P, Gualberto V. Áreas bocigenas no Brasil. Div Org Sanit, Ministério da Saúde, Brasil, 1956. In: Freire-Maia A, Freire- Maia DV (eds) Endemic Goiter and Genetics. Revista Brasileira de Pesquisas Médicas e Biológicas 3:53-58, 1970.
22. PeterT, Hamer A, Mandel W, Weiss D. Evaluation of amiòdarone therapy in the treatment of drug- resistant cardiac arrhythmias: Long-term follow- up. American Heart Journal 106:943, 1983.
23. Pritchard DA, Singh BN, Hurley PJ. Effect of amiodarone on thyroid function in patients with ischaemic heart disease. British HeartJournal37:856- 860, 1975.
24. Rabinowe DL, Laesen PR, Antman EM George KL, Friedman PL, Jackson RA, Eisenbarth GS. Amiodarone therapy and autoimmune thyroid disease. Increase in a new monoclonal antibody defined Tcell subset. American Joumalof Medicine 81:53-57, 1986.
25. Russo EMK, Vieira JGH, Maciel RMB, Fonseca RMG. Desenvolvimento e caracterização de métodos de radioimunoensaio para dosagem de iodotironinas. Arquivos Brasileiros de Endocrinologia e Metabologia 26:23-28,1982.
26. Safran M, Fang SL, Bambini G, Pinchera A, Martino E, Braverman L. Effects of amiodarone and desethylamiodarone on pituitary deiodinase actity and thyrotropin secretion in the rat. American J ournal of theMedical Sciences 292:136-141,1986.
27. Sanmarti A, Permanyer GM, Castellanos JM, Foz- Sala M, Galard PM, Soler-Soler J. Chronic administration of amiodarone and thyroid function: a follow-up study. American Heart Journal 108:1262- 1268, 1984.
28. Siegel S. Estatística não paramétrica. McGraw-Hill, São Paulo, 1975.
29. Silva JE, Larsen PR. Pituitary nuclear 3,5,3'- triiodothyronine and thuyrotropin secretion: an explanation for the effect of thyroxine. Science 198:617-622, 1977.
30. Silva JE, Leonard JL. Regulation of rat cerebrocortical and adenohypophyseal type II 5'- deiodinase by thyroxine, triidothyronine and reverse triiodothyronine. Endocrinology 116:1627-1635, 1985.
31. Singh BN, Nademanee K. Amiodarone and thyroid function: Clinical implications during antiarrhythmic therapy. American Heart Journal 106:857, 1983.
32. Smirk TC, Goellner JZ, Brennan MD, Carney JA. Pathology of the thyroid in amiodarone associated thyrotoxicosis. American Journal of Surgical Pathology 11:197-209, 1987.
33. Vagenakis AG, Wang C, Burger A, Maloof F, Braverman LE, Ingbar SH. Iodine - induced thyrotoxicosis in Boston. New England Journal of Medicine 287:523-527, 1972.
34. Ward DE, Camm AJ, Spurrel RAJ. Clinical antiarrhythmic effects of amiodarone in patients with resistant paroxysmal tachycardias. British Heart Journal 44:82, 1980.
35. Wiersinga WM, Touber JL, Trip M, Van-Royen EA. Uninhibited thyroidal uptake of radioiodine despite iodine excess in amiodarone induced hypothyroidism. Journal Clinical of Endocrinology and Metabolism 63:485-491, 1986.

Endereço para correspondência:

Prof

^a. Maria Aparecida Enes Barros.

Depto. de Medicina, Endocrinologia/FMTM.

Av. Getúlio Guarita s/n

38025-050

Uberaba, MG.

Datas de Publicação

Publicação nesta coleção
12 Abr 2013
Data do Fascículo
Set 1994

Histórico

Recebido
28 Fev 1994
Aceito
28 Fev 1994

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

[1] 1. Aguini-Lombardi F, Martino E, Lenziardi M, Grasso L, Pacchiarotti A, Capellini Q, Odoguardi L, Fenzi E, Baschieri L, Pinchera A. Hipertiroidismo iodo- indotto da amiodarone. Medicina 76:431-436, 1985.

[2] 2. Albert GS, Larry EA, Edward PR. Thyroid dysfunction during chronic amiodarone therapy. Journal of the American College of Cardiology 9:175-183, 1987.

[3] 3. Amino N, Hagen SR, Yamada N, Refetoff S. Measurement of circulating thyroid microssomal antibodies by the tanned red cell haemaglutination technique: its usefulness in the diagnosis of autoimmune diseases. Clinical Endocrinology 5:115- 125, 1976.

[4] 4. Barros MA, Barros AJ, Lopes ER, Vasconcelos JLM, Teodoro CS. Ocorrência das patologias tiroidianas, com especial referêcia às neoplasias, na região do Triângulo Mineiro. Arquivos Brasileiros de Endocrinologia e Metabologia 25:95-98, 1981.

[5] 5. Burger A, Dinichert D, Nicot P, Jenny M, Lemarchand-Beraud T, Vallotton MB. Effect of amiodarone on serum triiodothyronine, reverse triiodothyronine, thyroxine and thyrotropin. Journal of Clinical Investigation 58:255-259,1976.

[6] 6. Burger AG. Effects of certain pharmacologic agents on the peripheral metabolism of thyroxine. In: Ingbar SH, Braverman LE (eds) Werner's-The Thyroid. 5 edition. Lippincott, Philadelfia p.351- 360, 1986.

[7] 7. Chopra IJ, Solomon DH, Hepner GW, Morgenstein AA, Misleading LY. Low free thyroxine index and usefulness of reverse triiodothyronine measurement in non thyroidal illness. Annals of Internal Medicine 90:905-912, 1979.

[8] 8. Fradkin JE, Wolff J. Iodine-induced thyrotoxicosis. Medicine 62:1-20, 1983.

[9] 9. HegerJJ, PrystowskyEN, Jackamn WM, Naccarelli GW, Warfel KA, Rinkenberger RL, Zipes DP: Amiodarone: clinical efficacy and electrophysiology during long-term therapy for recurrent ventricular tachycardia or ventricular fibrillation. New England Journal of Medicine 305:539, 1981.

[10] 10. Heger JJ, Prystowsky EN, Zipes DP. Clinical efficacy of amiodarone in treatment of recurrent ventricular tachycardia and ventricular fibrillation. American Heart Journal 106:887, 1983.

[11] 11. Jonckheer MH, Blockx P, Broeckertl, Comette C, Beckers C. "Low T3 syndrome" in patients chronically treated with an iodine-containing drug, amiodarone. ClinicalEndocrinology 9:27-35,1978.

[12] 12. Jorge PT, Enzimaimunoensaio para detecção de anticorpos anti-tiroglobulina no soro. Desenvolvimento metodológico e implicações diagnosticas. Tese de Doutorado, Escola Paulista de Medicina, São Paulo,SP, 1986.

[13] 13. Lambert MJ, Burger AG, Galeazzi RL, Engler D. Are selective increases in serum thyroxine due to iodinated inhibitors of T4 monodeiodination indicative of hiperthyroidism? Journal of Clinical Endocrinology and Metabolism 55:1058-1065, 1982.

[14] 14. Lombardi A, Martino A, Braverman LE. Amiodarone and the thyroid. Thyroid Today 2:1- 7, 1990.

[15] 15. Lopes ER, Moraes CA, Chapadeiro E, Mineo JR, Leite LC, Guimarães AHB, Rocha A, Gava M. Prevalência da infecção chagásica em necrópsias no Triângulo Mineiro. Revista de Medicina Tropical de São Paulo 26:125-129, 1984.

[16] 16. Maciel RMB, Russo EMK, Furlaneto PP. Testes de função tiroideana. In: Guimarães RX, Guerra CCC (eds) Clinica e Laboratório. 3 edition, Sarvier São Paulo pjll5-126, 1983.

[17] 17. Martino E, Macchia E, Lombardi F, Antonelli A, Lenziaríii M, Concetti R, Fenzi GF, Baschieri H, Pincherá A. Is humoral thyroid auto immunity relevant in amiödarone iodine-induced thyrotoxicosis? Clinical Endocrinology 24:627-633, 1986a.

[18] 18. Martino E, Safran M, Aguini-Lombardi F, Rajatanáven R, Lenziardi M, Fay M, Pacchiarotti A, Aronin N, Macchia H, Haffajee C, AdoguardiL, Love J, Bigalli A, Bascuieri L, Pinchera A, Braveraan L. Environmental iodine intake and thyroid dysfunction during chronic amiodarone therapy; Annals of Internal Medicine 101:28-34, 1984.

[19] 19. Massin JP, Thomopoulos P, Karan J, Savoie JC. Le risque thyroidien d'un nouveau coronariodilatateur iodé; l'amiodarone (Cordarone). Annales Endocrinologie 32:438-448, 1971.

[20] 20. Medeiros-Neto GA, Lobo LCG, Nicolau W. Endemic goiter in Brazil. In: Pan American Health Organization (ed) "Endemic Goiter". World Health Organization John B.Stanbury, New York p. 179- 182, 1969.

[21] 21. Pellon AB, Silva W, Borges P, Gualberto V. Áreas bocigenas no Brasil. Div Org Sanit, Ministério da Saúde, Brasil, 1956. In: Freire-Maia A, Freire- Maia DV (eds) Endemic Goiter and Genetics. Revista Brasileira de Pesquisas Médicas e Biológicas 3:53-58, 1970.

[22] 22. PeterT, Hamer A, Mandel W, Weiss D. Evaluation of amiòdarone therapy in the treatment of drug- resistant cardiac arrhythmias: Long-term follow- up. American Heart Journal 106:943, 1983.

[23] 23. Pritchard DA, Singh BN, Hurley PJ. Effect of amiodarone on thyroid function in patients with ischaemic heart disease. British HeartJournal37:856- 860, 1975.

[24] 24. Rabinowe DL, Laesen PR, Antman EM George KL, Friedman PL, Jackson RA, Eisenbarth GS. Amiodarone therapy and autoimmune thyroid disease. Increase in a new monoclonal antibody defined Tcell subset. American Joumalof Medicine 81:53-57, 1986.

[25] 25. Russo EMK, Vieira JGH, Maciel RMB, Fonseca RMG. Desenvolvimento e caracterização de métodos de radioimunoensaio para dosagem de iodotironinas. Arquivos Brasileiros de Endocrinologia e Metabologia 26:23-28,1982.

[26] 26. Safran M, Fang SL, Bambini G, Pinchera A, Martino E, Braverman L. Effects of amiodarone and desethylamiodarone on pituitary deiodinase actity and thyrotropin secretion in the rat. American J ournal of theMedical Sciences 292:136-141,1986.

[27] 27. Sanmarti A, Permanyer GM, Castellanos JM, Foz- Sala M, Galard PM, Soler-Soler J. Chronic administration of amiodarone and thyroid function: a follow-up study. American Heart Journal 108:1262- 1268, 1984.

[28] 28. Siegel S. Estatística não paramétrica. McGraw-Hill, São Paulo, 1975.

[29] 29. Silva JE, Larsen PR. Pituitary nuclear 3,5,3'- triiodothyronine and thuyrotropin secretion: an explanation for the effect of thyroxine. Science 198:617-622, 1977.

[30] 30. Silva JE, Leonard JL. Regulation of rat cerebrocortical and adenohypophyseal type II 5'- deiodinase by thyroxine, triidothyronine and reverse triiodothyronine. Endocrinology 116:1627-1635, 1985.

[31] 31. Singh BN, Nademanee K. Amiodarone and thyroid function: Clinical implications during antiarrhythmic therapy. American Heart Journal 106:857, 1983.

[32] 32. Smirk TC, Goellner JZ, Brennan MD, Carney JA. Pathology of the thyroid in amiodarone associated thyrotoxicosis. American Journal of Surgical Pathology 11:197-209, 1987.

[33] 33. Vagenakis AG, Wang C, Burger A, Maloof F, Braverman LE, Ingbar SH. Iodine - induced thyrotoxicosis in Boston. New England Journal of Medicine 287:523-527, 1972.

[34] 34. Ward DE, Camm AJ, Spurrel RAJ. Clinical antiarrhythmic effects of amiodarone in patients with resistant paroxysmal tachycardias. British Heart Journal 44:82, 1980.

[35] 35. Wiersinga WM, Touber JL, Trip M, Van-Royen EA. Uninhibited thyroidal uptake of radioiodine despite iodine excess in amiodarone induced hypothyroidism. Journal Clinical of Endocrinology and Metabolism 63:485-491, 1986.