Serum interleukin-6 in amiodarone-induced thyrotoxicosis.

Amiodarone, an iodine-rich cardiac drug, may induce thyrotoxicosis (AIT), which can occur in patients with preexisting thyroid abnormalities and in subjects with apparently normal thyroid glands. The pathogenesis of AIT is often due to iodine-induced excessive thyroid hormone synthesis, especially in patients with underlying thyroid disease. In some instances, however, AIT may be related to a destructive process due to amiodarone-induced thyroiditis, resulting in thyroid cell damage and thyroid hormone release into the circulation. Another thyroid inflammatory process, subacute thyroiditis, has been recently reported to be associated with markedly increased serum interleukin-6 (IL-6) levels. To investigate the significance of serum IL-6 levels in AIT, we evaluated in a cross-sectional study the following subjects: 27 AIT patients, 15 with no apparent thyroid abnormalities (AIT-) and 12 with nodular goiter and/or thyroid autoimmune disease (AIT+); 14 euthyroid patients receiving chronic amiodarone therapy; 10 patients with amiodarone-induced hypothyroidism; 56 patients with spontaneous hyperthyroidism due to Graves' disease (n = 35) or toxic adenoma/nodular goiter (n = 21); 20 subjects with nontoxic goiter; and 50 healthy controls. Serum free thyroid hormone concentrations did not differ in patients with amiodarone-induced or spontaneous hyperthyroidism. Mean (+/- SE) serum IL-6 values were as follows: AIT-, 573.5 +/- 78.7 fmol/L (range, 149.4-1145.1); AIT+, 152.7 +/- 46.3 fmol/L (range, < 25-505.6); euthyroid patients receiving chronic amiodarone therapy, 51.4 +/- 10.0 fmol/L (range, < 25-122.5); amiodarone-induced hypothyroidism, 43.8 +/- 8.4 fmol/L (range, < 25-84.3); Graves' disease, 108.2 +/- 18.2 fmol/L (range, < 25-250); toxic adenoma/nodular goiter, 97.6 +/- 10.3 fmol/L (range, < 25-168.9); nontoxic goiter, 47.3 +/- 7.1 fmol/L (range, < 25-106.6); and controls, 37.8 +/- 6.2 fmol/L (range, < 25-99.4). Serum IL-6 values in AIT- patients were markedly higher (P < 0.0001) than those in all other groups. Values in AIT+, although slightly higher, did not significantly differ from those in patients with spontaneous hyperthyroidism. AIT- patients had low 24-h thyroidal radioiodine uptake (RAIU), whereas AIT+ had inappropriately low normal to high (9-58%) RAIU values in the presence of excess iodine. The presence of markedly elevated serum IL-6 concentrations and low thyroidal RAIU values in patients with AIT without underlying thyroid disease suggests the presence of amiodarone-induced thyroiditis as the etiology of thyrotoxicosis. Treatment of 2 such patients with prednisone was associated with a dramatic reduction and prompt normalization of IL-6 and thyroid hormone values.(ABSTRACT TRUNCATED AT 400 WORDS)

[1]  L. Bartalena,et al.  Interleukin-6 inhibits corticosteroid-binding globulin synthesis by human hepatoblastoma-derived (Hep G2) cells. , 1993, Endocrinology.

[2]  L. Braverman,et al.  Thyrotoxicosis followed by hypothyroidism in patients treated with amiodarone. A possible consequence of a destructive process in the thyroid. , 1993, Archives of internal medicine.

[3]  G. Gavaruzzi,et al.  Effects of chronic iodine administration on thyroid status in euthyroid subjects previously treated with antithyroid drugs for Graves' hyperthyroidism. , 1993, Journal of Clinical Endocrinology and Metabolism.

[4]  L. Bartalena,et al.  Increased serum interleukin-6 concentration in patients with subacute thyroiditis: relationship with concomitant changes in serum T4-binding globulin concentration , 1993, Journal of endocrinological investigation.

[5]  G. Gavaruzzi,et al.  Iodine-induced subclinical hypothyroidism in euthyroid subjects with a previous episode of amiodarone-induced thyrotoxicosis. , 1992, The Journal of clinical endocrinology and metabolism.

[6]  C. Mestdagh,et al.  In vitro study of acute toxic effects of high iodide doses in human thyroid follicles. , 1992, Endocrinology.

[7]  L. Bartalena,et al.  Effects of interleukin-6 on the expression of thyroid hormone-binding protein genes in cultured human hepatoblastoma-derived (Hep G2) cells. , 1992, Molecular endocrinology.

[8]  G. Gavaruzzi,et al.  Impaired intrathyroidal iodine organification and iodine-induced hypothyroidism in euthyroid women with a previous episode of postpartum thyroiditis. , 1991, The Journal of clinical endocrinology and metabolism.

[9]  W. Wiersinga,et al.  Incidence, predictability, and pathogenesis of amiodarone-induced thyrotoxicosis and hypothyroidism. , 1991, The American journal of medicine.

[10]  M. Iwamoto,et al.  Augumented interleukin 6 production by rat thyrocytes (FRTL5): Effect of interleukin 1β and thyroid-stimulating hormone , 1991 .

[11]  R. Bright-Thomas,et al.  Regulation of interleukin-6 release by human thyrocytes. , 1990, The Journal of endocrinology.

[12]  S. H. Wollman,et al.  Histologic changes in tissue components of the hyperplastic thyroid gland during its involution in the rat. , 1990, The American journal of anatomy.

[13]  L. Braverman,et al.  Iodine-induced hypothyroidism in euthyroid subjects with a previous episode of subacute thyroiditis. , 1990, The Journal of clinical endocrinology and metabolism.

[14]  L. Braverman,et al.  Thyroidectomy for amiodarone-induced thyrotoxicosis. , 1990, Journal of the American Medical Association (JAMA).

[15]  J V Castell,et al.  Interleukin-6 and the acute phase response. , 1990, The Biochemical journal.

[16]  S. Nussey,et al.  Cytotoxic effects of amiodarone and desethylamiodarone on human thyrocytes. , 1989, Biochemical pharmacology.

[17]  C. Lau,et al.  Amiodarone-induced thyroiditis. , 1989, American heart journal.

[18]  L. G. Thijs,et al.  Increased plasma levels of interleukin-6 in sepsis [see comments] , 1989 .

[19]  M. Feldmann,et al.  Analysis of intrathyroidal cytokine production in thyroid autoimmune disease: thyroid follicular cells produce interleukin-1 alpha and interleukin-6. , 1989, Clinical and experimental immunology.

[20]  L. Harrison,et al.  Evidence for IL-6 production by and effects on the pancreatic beta-cell. , 1989, Journal of Immunology.

[21]  M. Piga,et al.  Radioactive iodine thyroid uptake in patients with amiodarone-iodine-induced thyroid dysfunction. , 1988, Acta endocrinologica.

[22]  R. Zinkernagel,et al.  Production of B cell stimulatory factor-2 and interferon gamma in the central nervous system during viral meningitis and encephalitis. Evaluation in a murine model infection and in patients , 1988, The Journal of experimental medicine.

[23]  F. Houssiau,et al.  Interleukin-6 in synovial fluid and serum of patients with rheumatoid arthritis and other inflammatory arthritides. , 1988, Arthritis and rheumatism.

[24]  R. Harper,et al.  Amiodarone-induced hyperthyroidism: assessment of the predictive value of biochemical testing and response to combined therapy using propylthiouracil and potassium perchlorate. , 1988, Australian and New Zealand journal of medicine.

[25]  J. Dumont,et al.  Cell kinetics of thyroid epithelial cells during hyperplastic goitre involution. , 1987, The Journal of endocrinology.

[26]  S. Miaskiewicz,et al.  Amiodarone-associated thyrotoxicosis masquerading as painful thyroiditis. , 1987, Annals of internal medicine.

[27]  A. Pinchera,et al.  AMIODARONE IODINE‐INDUCED HYPOTHYROIDISM: RISK FACTORS AND FOLLOW‐UP IN 28 CASES , 1987, Clinical endocrinology.

[28]  A. Pinchera,et al.  Treatment of amiodarone associated thyrotoxicosis by simultaneous administration of potassium perchlorate and methimazole , 1986, Journal of endocrinological investigation.

[29]  A. Leger,et al.  Iodine‐induced thyrotoxicosis: analysis of eighty‐five consecutive cases , 1984, European journal of clinical investigation.

[30]  K. Nademanee,et al.  Amiodarone and thyroid function: clinical implications during antiarrhythmic therapy. , 1983, American heart journal.

[31]  M. Stäubli,et al.  Prednisone in amiodarone-induced thyrotoxicosis. , 1982, British medical journal.

[32]  M. Obregon,et al.  Effect of chronic iodide supplements on thyroid secretion: the role of lysosomes. , 1982, Endocrinology.

[33]  E. Prystowsky,et al.  Clinical efficacy and electrophysiology during long-term therapy for recurrent ventricular tachycardia or ventricular fibrillation. , 1981, The New England journal of medicine.

[34]  D. Becker,et al.  Necrosis of follicular cells and discharge of thyroidal iodine induced by administering iodide to iodine-deficient dogs. , 1973, The Journal of clinical endocrinology and metabolism.

[35]  R. H. Follis Thyroiditis Resulting from Administration of Excess Iodine to Hamsters with Hyperplastic Goiters.∗ , 1959, Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine.

[36]  P. Carmeliet,et al.  Production of interleukin-6 by folliculo-stellate cells of the anterior pituitary gland in a histiotypic cell aggregate culture system. , 1989, Neuroendocrinology.

[37]  A. Pinchera,et al.  Amiodarone: a common source of iodine-induced thyrotoxicosis. , 1987, Hormone research.