Several compounds of pharmaceutical importance from a variety of chemical families, for example chlorpromazine and clomipramine, have been found to form charge-transfer complexes with iodine. We have investigated the influence of dietary iodine on thyroid-gland dysfunction induced by clomipramine, chlorpromazine or 2-thiazoline-2-thiol. We suggest that iodine is partly diverted from its metabolic pathway by complexation with drugs, and so the urinary concentration of iodide is increased.

Both chlorpromazine and clomipramine, at doses which do not inhibit thyroperoxidase, enhanced urinary iodine excretion when dietary iodine was restricted (3.94 ± 0.96 μg/day for chlorpromazine-tested rats, 3.43 ± 1.33 μg/day for clomipramine-tested rats, compared with 2.34 ± 0.11 μg/day in control rats). Concurrently, these pharmaceutical compounds increased the level of free thyroid-stimulating hormone (TSH) in comparison with controls and induced histological modifications in, and enlargement of, the thyroid gland.

We have demonstrated that drug-induced loss of iodine in the urine was associated with antithyroid action when iodine intake was limited.

References

Benotti, J., Benotti, N. (1963) Protein-bound iodine, total iodine, and butanol-extractable iodine by partial automation. Clin. Chem. 4: 408–416.
Google Scholar
Capen, C. C. (1992) Pathophysiology of chemical injury of the thyroid gland. Toxicol. Lett. 64/65: 381–388.
Google Scholar
Carayanniotis, G., Rao, V. P. (1997) Searching for pathogenic epitopes in thyroglobulin: parameters and caveats. Immunol. Today 18: 83–88.
10.1016/S0167-5699(96)10073-6
PubMed Web of Science® Google Scholar
Comby, F., Lagorce, J. F., Buxeraud, J., Raby, C. (1994) Antithyroid action of ketoconazole: in-vitro studies and rat in-vivo studies. J. Pharm. Pharmacol. 46: 50–53.
10.1111/j.2042-7158.1994.tb03719.x
CAS PubMed Web of Science® Google Scholar
Distefano, J. J., Morris, W. L., Nguyen, T. T., Van Herle, A. J., Florsheim, W. (1993) Enterohepatic regulation and metabolism of 3,5,3′-triiodothyronine in hypothyroid rats. Endocrinology 132: 1665–1670.
10.1210/en.132.4.1665
CAS PubMed Web of Science® Google Scholar
Dunn, J. T., Crutchfield, H. E., Gutekunst, R., Dunn, A. D. (1993) Two simple methods for measuring iodine in urine. Thyroid 3: 119–123.
10.1089/thy.1993.3.119
PubMed Web of Science® Google Scholar
Gaitan, E. (1988) Goitrogens. Clin. Endocrinol. Metab. 2: 683–702.
Google Scholar
Gittoes, N. J. L., Franklyn, J. A. (1995) Drug-induced thyroid disorders. Pharmacoepidemiology 13: 46–55.
Google Scholar
Gökmen, I. G., Dagh, G. (1995) Determination of iodine concentration in human milk, cows' milk and infant formula and estimation of daily iodine intakes of infants. Analyst 120: 2005–2008.
CAS PubMed Web of Science® Google Scholar
Gutmann, F., Keyzer, H. (1967) Study of phenothiazine- and chlorpromazine -iodine complexes. J. Chem. Phys. 46: 1969–1974.
10.1063/1.1840961
CAS PubMed Web of Science® Google Scholar
Kelder, P. P., De Mol, N. J., Fischer, M. J. E., Janssen, L. H. M. (1994) Kinetic evaluation of the oxidation of phenothiazine derivatives by methemoglobin and horseradish peroxidase in the presence of hydrogen peroxide. Implications for the reaction mechanisms. Biochim. Biophys. Acta. 1205: 230–238.
10.1016/0167-4838(94)90238-0
CAS PubMed Web of Science® Google Scholar
Kennedy, J. A., Jarrett, D. B., Wellby, M. L. (1997) Influence of imipramine on the hypothalamic/pituitary/thyroid axis of the rat. Metabolism 46: 1429–1434.
Google Scholar
Kirkegaard, C., Bjoerum, C. N., Cohn, D., Faber, J., Lauridsen, U. B., Nekup, J. (1977) Studies of the influence of biogenic amines and psychoactive drugs on the prognostic value of the TRH stimulation test in endogenous depression. Psychoneuroendocrinology 2: 131–136.
10.1016/0306-4530(77)90018-X
PubMed Web of Science® Google Scholar
Lagorce, J. F., Fatimi, J., Chabernaud, M. L., Marion, S., Buxeraud, J., Raby, C. (1995) Thirame: example of the thyroid toxicity of an agrochemical with strong electrondonor property. Int. J. Environ. Stud. 48: 221–229.
Google Scholar
Lombardi, G., Panza, N., Cei, S., Cosimato, F., Minozzi, M. (1978) Radioimmunoassay of thyrotropin-releasing hormone (TRH) in normal subjects, in abnormal thyroid states and under catecholaminergic influences. Acta Endocrinol. 87: 70–79.
Google Scholar
May, S. L., May, W. A., Bourdoux, P. P., Pino, S., Sullivan, K. M., Maberly, G. F. (1997) Validation of a simple, manual urinary iodine method for estimating the prevalence of iodine-deficiency disorders, and interlaboratory comparison with other methods. Am. J. Clin. Nutr. 65: 1441–1445.
CAS PubMed Web of Science® Google Scholar
Meller, B., Lauer, I., Bahre, M., Richter, E. (1998) Influence of radioiodine therapy on urinary iodine excretion. Nuklearmedizin 37: 107–112.
Google Scholar
Okamura, K., Taurog, A., Krulich, L. (1981) Elevation of serum 3,5,3′-triiodothyronine and thyroxine levels in rats fed Remington diets: opposing effects of nutritional deficiency and iodine deficiency. Endocrinology 108: 1247–1256.
10.1210/endo-108-4-1247
CAS PubMed Web of Science® Google Scholar
Raby, C., Lagorce, J. F., Jambut-Absil, A. C., Buxeraud, J., Catanzano, G. (1990) The mechanism of action of synthetic antithyroid drugs: iodine complexation during oxidation of iodide. Endocrinology 126: 1683–1691.
10.1210/endo-126-3-1683
CAS PubMed Web of Science® Google Scholar
Saito, K., Yamamoto, K., Takai, T., Yoshida, S. (1983) Inhibition of iodide accumulation by perchlorate and thiocyanate in a model of the thyroid iodide transport system. Acta Endocrinol. 104: 456–461.
CAS PubMed Web of Science® Google Scholar
Sanchez-Franco, F., Cacicedo, L., de Escobar, Morreale G., del Rey, Escobar F. (1983) Nutrition and iodine versus genetic factors in endemic goitre. J. Endocrinol. Invest. 6: 185–188.
Google Scholar
Sandell, E. B., Kolthoff, I. M. (1937) Microdetermination of iodine by catalytic method. Microchim. Acta. 1: 9–25.
10.1007/BF01476194
CAS Google Scholar
Sundick, R. S., Bagchi, N., Brown, T. R. (1992) The role of iodine in thyroid autoimmunity: from chickens to humans: a review. Autoimmunity 13: 61–68.
10.3109/08916939209014636
CAS PubMed Web of Science® Google Scholar
Taurog, A. (1991) Thyroid hormone synthesis. In: L. E. Braverman, R. D. Utiger (eds) Wener's The Thyroid, 6th edn, J. B. Lippincott, Philadelphia, pp 51–97.
Google Scholar
Thomes, J. C., Comby, F., Lagorce, J. F., Buxeraud, J., Raby, C. (1992) Sites of action of 2-thiazoline-2-thiol on biogenesis of thyroid. Jpn J. Pharmacol. 58: 201–207.
Google Scholar
Visser, T. J. (1996) Pathways of thyroid hormone metabolism. Acta Med. Austriaca 23: 10–16.
CAS PubMed Web of Science® Google Scholar

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Volume51, Issue6

June 1999

Pages 745-750

Influence of Dietary Iodine on Drug-induced Hypothyroidism in the Rat

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Influence of Dietary Iodine on Drug-induced Hypothyroidism in the Rat

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