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Role of colestipol in the treatment of hyperthyroidism

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Abstract

The enterohepatic circulation of thyroxine (T4) and triiodothyronine (T3) is higher in thyrotoxicosis. Bile-salt sequestrants bind iodothyronines and thereby increase their fecal excretion. We, therefore, evaluated the effect of colestipol-hydrochloride administration on clinical and biochemical indices of patients with hyperthyroidism. In a prospective, controlled trial, ninety-two adult volunteers with Graves’ disease, toxic autonomous nodule or toxic multinodular goiter were randomly assigned into the following treatment protocols: Group 1, 30 mg of methimazole (MMI) and 20 g of colestipol-hydrochloride (COL) daily; Group 2, 30 mg of MMI daily; and Group 3, 15 mg of MMI 20 g of COL daily. The patients were further classified into Group A, severe hyperthyroidism (baseline levels of total T3 (TT3) ≥5nmol/l) and Group B, mild to moderate thyrotoxicosis (baseline levels of TT3<5 nmol/l). Crook’s clinical index, serum free T4 (FT4), TT3 and thyroid stimulating hormone (TSH) levels were determined before (W0), following one week (W1) and two weeks (W2) of treatment. Serum TT3 level decreased (mean±SE) at W1 by 40.8±2.6% of W0 in Group 1 and by 29.2±2.4% in Group 2 (p<0.001), and down further to 47.8±3.0% at W2 in Group 1, and 40.6±2.8% in Group 2 (p=0.01). Serum FT4 level decreased (mean±SE) from W0 to W1 by 31.7±2.7% in Group 1 and by 16.2±3.1% in Group 2 (p=0.005), and down to 49.1±2.8% of W0 at W2 in Group 1 and to 38.7±3.5% in Group 2 (p=0.07). In sub groups B COL was not effective in reducing thyroid hormone levels nor in ameliorating the clinical status of the patients. However, in Group A3 COL lowered FT4 (p=0.001) and TT3 (p=0.05) levels as compared to group A2. At W2 the clinical hyperthyroidism score improved faster in Group A1 (p<0.001) and Group A3 (p=0.012) as compared to the control Group A2. In conclusion, COL is an effective and well tolerated adjunctive agent in the treatment of hyperthyroidism. Its main effect is in severe cases of thyrotoxicosis, and in the first phase of treatment. As adjunctive COL treatment in hyperthyroidism allows reducing MMI dosage it may decrease the rate of dose dependent MMI side effects.

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References

  1. Staffurth J.S., Gibberd M.C., Fui S.T. Arterial embolism in thyrotoxicosis with atrial fibrillation. BMJ 2: 688, 1997.

    Article  Google Scholar 

  2. Seely E.W., Williams G.H. The cardiovascular system and endocrine disease. In: Becker K.L. (Ed.), Principles and practice of endocrinology and metabolism. J.B. Lippincott, Philadelphia, 1990, p. 1496.

    Google Scholar 

  3. Burman K.D. Hyperthyroidism. In: Becker K.L. (Ed.), Principles and practice of endocrinology and metabolism. J.B. Lippincott, Philadelphia, 1990, p. 331.

    Google Scholar 

  4. Reinwein D., Benker G., Lazarus J.H., Alexander W.D. A prospective randomized trial of antithyroid drug dose in Graves’ disease therapy. European Multicenter Study Group on Antithyroid Drug Treatment. J. Clin. Endocrinol. Metab. 76: 1516, 1993.

    PubMed  CAS  Google Scholar 

  5. Bergman F., Heedman P.A., Van der Linden W. Influence of cholestyramine on absorption and excretion of thyroxine in Syrian hamster. Acta Endocrinol. (Copenh.) 53: 256, 1966.

    CAS  Google Scholar 

  6. Northcutt R.C., Stiel J.N., Hollifield J.W., Stant E.G. Jr. The influence of cholestyramine on thyroxine absorption. JAMA. 208: 1857, 1969.

    Article  PubMed  CAS  Google Scholar 

  7. Nicoloff J.T. Physiologic and pathophysiologic implications of hormone binding. In: Ingbar S.H., Braverman L. (Eds.), The Thyroid: a fundamental and clinical text. J.B. Lippincott, New York, 1986, p. 113.

    Google Scholar 

  8. Surks M.I., Stievert R. Drug therapy: drugs and thyroid function. N. Engl. J. Med. 333: 1688, 1995.

    Article  PubMed  CAS  Google Scholar 

  9. Phillips W.A., Schultz J.R., Stafford W.W. Effects of colestipol hydrochloride on drug absorption in rat: aspirin, L-thyroxine, phenobarbital, cortisone, and sulfa drugs. J. Pharm. Sci. 63: 1097, 1974.

    Article  PubMed  CAS  Google Scholar 

  10. Witztum J.L., Jacobs L.S., Schonfeld G. Thyroid hormone and thyrotropin levels in patients placed on colestipol hydrochloride. J. Clin. Endocrinol. Metab. 46: 838, 1978.

    Article  PubMed  CAS  Google Scholar 

  11. Harmon S.M., Seifert C.F. Levothyroxine-cholestyramine interaction reempha-sized. Ann. Intern. Med. 115: 658, 1991.

    Article  PubMed  CAS  Google Scholar 

  12. Shakir K.M.M., Michaels R.D., Hays J.H., Potter B.B. The use of bile acid sequestrants to lower serum thyroid hormones in iatrogenic hyperthyroidism. Ann. Intern. Med. 118: 112, 1993.

    Article  PubMed  CAS  Google Scholar 

  13. Solomon B.L., Wartofsky L., Burman K.D. Adjunctive cholestyramine therapy for thyrotoxicosis. Clin. Endocrinol. (Oxf.) 38: 39, 1993.

    Article  CAS  Google Scholar 

  14. Mercado M., Mendoza-Zubieta V., Bautista-Osorio R., Espinoza de los Monteros A.L. Treatment of hyperthyroidism with a combination of methimazole and cholestyramine. J. Clin. Endocrinol. Metab. 81: 3191, 1996.

    PubMed  CAS  Google Scholar 

  15. Benker G., Vitti P., Kahaly G., Raue F., Tegler L., Hirche H., Reinwein D., the European Multicenter Study Group. Response to methimazole in Graves’ disease. Clin. Endocrinol. (Oxf.) 43: 257, 1995.

    Article  CAS  Google Scholar 

  16. Dahlberg P.A., Karlsson F.A., Lindstrom B., Wide L. Studies of thyroid hormone and methimazole levels in patients with Graves’ disease on a standardized anti-thyroid drug regimen. Clin. Endocrinol. (Oxf.) 14: 555, 1981.

    Article  CAS  Google Scholar 

  17. Artzenius A.B., Elte J.W.F., Frolich M., Haak A. The significance of the initial FT4-index for the management of single daily dose methimazole treatment of hyperthyroidism. Clin. Endocrinol. (Oxf.) 29: 239, 1988.

    Article  Google Scholar 

  18. Nygaard B., Faber J., Hegedüs L., Hansen J.M. 131I treatment of nodular non-toxic goitre. Eur. J. Endocrinol. 134: 15, 1996.

    Article  PubMed  CAS  Google Scholar 

  19. Shiroozu A., Okamura K., Ikenove H., Sato K., Nakashima T., Yoshinari M., Fujishima M., Yoshizumi T. Treatment of hyperthyroidism with a small single daily dose of methimazole. J. Clin. Endocrinol. Metab. 63: 125, 1986.

    Article  PubMed  CAS  Google Scholar 

  20. Hillier A.P. Autoregulation of thyroxine secretion into bile. J. Physiol. 221: 471, 1972.

    PubMed Central  PubMed  CAS  Google Scholar 

  21. Barnes H.V., Bledsoe T. A simple test for selecting the thionamide schedule in thyrotoxicosis. J. Clin. Endocrinol. Metab. 35: 250, 1972.

    Article  PubMed  CAS  Google Scholar 

  22. Bouma D.J., Kammer H. A single daily dose methimazole treatment of hyperthyroidism. West. J. Med. 132: 13, 1980.

    PubMed Central  PubMed  CAS  Google Scholar 

  23. McCruden D.C., Hilditch T.E., Connel J.M.C., Alexander W.D. Kinetics of 123-iodine uptake and discharge by Perchlorate in studies of inhibition of iodide binding by antithyroid drugs. Acta Endocrinol (Copenh.) 110: 499, 1985.

    CAS  Google Scholar 

  24. Glinoer D., Hesch D., Lagasse R., Laurberg P. The management of hyperthyroidism due to Graves’ disease in Europe in 1986. Results of an international survey. Acta Endocrinol. (Copenh.) 185 (Suppl.): 9, 1987.

    Google Scholar 

  25. Meyer-Gessner M., Benker G., Lederbogen S., Olbricht T.H., Reinwein D. Antithyroid drug-induced agranulocytosis: Clinical experience with ten patients treated at one institution and review of the literature. J. Endocrinol. Invest. 17: 29, 1994.

    Article  PubMed  CAS  Google Scholar 

  26. Al-Meshal M.A., El-Sayed Y.M., Al-Balla S.R., Gouda M.W. The effect of colestipol and cholestyramine on ibuprofen bioavailability in man. Biopharm. Drug Dispos. 15: 463, 1994.

    Article  PubMed  CAS  Google Scholar 

  27. Al-Balla S.R., El-Sayed Y.M., Al-Meshal M.A., Gouda M.W. The effect of cholestyramine and colestipol on the absorption of diclofenac in man. Int. J. Clin. Pharmacol. Ther. 32: 441, 1994.

    PubMed  CAS  Google Scholar 

  28. Kivisto K.T., Neuvonen P.J. The effect of cholestyramine and activated charcoal on glipizide absorption. Br. J. Clin. Pharmacol. 30: 733, 1990.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  29. Forland S.C., Feng Y., Cutler R.E. Apparent reduced absorption of gemfibrozil when given with colestipol. J. Clin. Pharmacol. 30: 29, 1990.

    Article  PubMed  CAS  Google Scholar 

  30. Superko H.R., Greenland P., Manchester R.A., Andreadis N.A., Schectman G., Hendriksen West N., Hunninghake D., Haskell W.L., Probstfield J.L. Effectiveness of low-dose colestipol therapy in patients with moderate hypercholesterolemia. Am. J. Cardiol. 70: 135, 1992.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Assaf Harofeh Medical Centre, Endocrine Institute, P.O. Box Beer Yaakov, Zerifin, 70300, Israel

    Philippe Hagag

  2. Biochemistry Wing, Assaf Harofeh Medical Centre, Zerifin, Israel

    H. Nissenbaum

  3. Sackler Faculty of Medicine, Tel Aviv University, Zerifin, Israel

    M. Weiss

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  1. Philippe Hagag
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  2. H. Nissenbaum
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  3. M. Weiss
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Hagag, P., Nissenbaum, H. & Weiss, M. Role of colestipol in the treatment of hyperthyroidism. J Endocrinol Invest 21, 725–731 (1998). https://doi.org/10.1007/BF03348036

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