Impaired Intestinal Absorption of Thyroid Hormone in a Case of Hashimoto's Disease with Anti-T3 and Anti-T4 Antibody Yutaka SUZUKI Department of Inter

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1 Impaired Intestinal Absorption of Thyroid Hormone in a Case of Hashimoto's Disease with Anti-T3 and Anti-T4 Antibody Yutaka SUZUKI Department of Internal Medicine Saitama Chuo Hospital Saitama Eiko TAKESHITA and Shojiro KANO Department of Laboratory Medicine School of Medicine, Keio University Tokyo Shiro HIRATA and Seiya SATO Kitazato Biochemical Laboratories Kanagawa A 28 year old woman with Hashimoto's and triiodothyronine (T3). She improved steadily during the first 2 to 3 months and thyroidal function disease was treated with desiccated thyroid tests turned to normal. Then, in spite of continuing treatment, her serum T4 level decreased gradually and she became fatigued. A serum T3 radioimmunoassay manifested an interference pattern suggested anti-t3 antibody in her serum. Ethanol-extracted serum T3 and T4 levels were low in spite of ingestion of desiccated thyroid or synthetic T3 and T4, suggesting intestinal malabsorption of T3 and T4. Antibodies against T3 and T4 were identified in her serum; affinity constants were 1.16 X 1010 and 8.73 X 108k/mol respectively. After treatment with synthetic T3 and/or T4 for 20 months, the titer of anti-t3 and anti-t4 antibodies decreased, and impaired intestinal absorption of thyroid hormone improved. Then, after desiccated thyroid treatment was reinstituted, the anti-t3

2 antibody titer again increased and intestinal absorption of thyroid hormone decreased. These results suggest the oral immunization against thyroid hormones. There was associated impairment in intestinal absorption of thyroid hormone presumably secondary to the anti- T3 and anti-t4 antibodies.

3 Fig. 1. Clinical course : After the treatment with desiccated thyroid and synthetic T3, her serum T4 level turned up to 8.2g/dl. However, in spite of continuing treatment, her serum T4 level decreased gradually. June 1977: When she came to our hospital again, her serum thyroid hormone levels by RIA were undetectable or very low, suggesting the assay interference by antibodies in her serum. June 1977 April 1979: The data suggest the impaired absorption of thyroid hormone from the intestine. August.1979: After the treatment with synthetic T3 and/or T4 in 20 months, the titer of antibodies decreased and impaired intestinal absorption of thyroid hormone improved. August 1979 April 1980: After desiccated thyroid treatment was reinstituted, the anti-t3 antibody titer again increased and intestinal absorption of thyroid hormone decreased. Table 1. Laboratory examination.

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5 Fig. 2. Microscopic examination of the thyroid gland obtained by open biopsy showed lymphocytic infiltration and advanced fibrosis. Fig. 3. The correlation between T3 results in ethanol extracts and in unextracted sera.

6 Fig. 4. Binding of T3 in serum. Fig. 5. Scatchard analysis for anti-t3 and anti-; antibody from patient serum (March, 1977).

7 Fig. 6. Radioautography of '25 I-T3 binding. In normal serum the radioactivity is seen only at the TBG fraction, but in patient serum the radioactivity is seen at the gamma globulin fraction, too. Fig. 7. Column chromatographic profil of 125I-T3 incubated with patient serum, rabbit anti-t3 serum or control serum in presence of ANS.

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10 1) Anderson, A.F. and Schloss, 0.M.: Allergy to cow's milk in infants with nutritional disorders. Amer. J. Dis. Child., 26: , ) Bauer, J.: Ober den Nachweis der pracipitablen Substanz der Kuhmilch im Blute atrophischer Sauglinge. Berl. Klin. Wchnschr., 43: , ) Becker, K.L., J.L. Titus, L.B. Woolner microscopy of intestinal ferritin absorption. Observations in sensitized and nonsensitized hamsters. Anat. Rec., 155: , ) Buckley, R.H. and S.C. Dees: Correlation of milk precipitins with IGA deficiency. New Engl. J. Med., 281: , ) Chopra, I.J., J.C. Nelson, D.H. Solomon and G.N. Beall: Production of antibodies specifically binding triiodothyronine and thyroxine. J. Clin. Endocrinol. Metab., 32: , ) Chopra, I.J., D.H. Solomon and G.N. Beall: Radioimmunoassay for measurement of triiodothyronine in human serum. J. Clin. Invest., 50: , ) Gyorgy, P., E. Moro and E. Witebsky: Milchantikorper im Serum von Saunglinger. Klin. Wchnschr., 10: , ) Heiner, D.C., J.W. Sears and W.T. Kniker: Multiple precipitins to cow's milk in chronic respiratory disease. Amer. J. Dis. Child., 103: , ) Ikekubo, K., J. Konishi, K. Nakajima, K. Endo, T. Mori and K. Torizuka: Low serum thyroxine due to

11 anti-thyroxine antibody. Endocrinol. Japon., 25: , ) Karlsson, F.A., L. Wibell and L. Wide: Hypothyroidism due to thyroid-hormone-binding antibodies. New Engl. J. Med., 296: , ) Lippard, V.W., O.M. Schloss and P.A. Johnson: Immune reaction induced in infants by intestinal absorption of incompletely digested cow's milk protein. Amer. J. Dis. Child., 51: , ) Moro, E.: Kuhmilchprazipitin im Blute eines 41/2 Monate alten Atrophikers. MUnch. Med. Wchnschr., 5: 214, ) Ochi, Y., K. Shiomi, T. Hachiya, M. Yoshimura and T. Miyazaki: Immunological analysis of abnormal binding of thyroid hormone in the gamma-globulin. J. Clin. Endocrinol. Metab., 35: , ) Premachandra, B.N. and H.T. Blumenthal: Abnormal binding of thyroid hormone in sera from patients with Hashimoto's disease. J. Clin. Endocrinol. Metab., 27: , ) Robbins, J., J.E. Rall and R.W. Rawson: An unusual instance of thyroxine-binding by human serum gamma globulin. J. Clin. Endocrinol. Metab., 16: , ) Rothberg, R.M. and R.S. Farr: Anti-bovine serum albumin and anti-alpha lactalbumin in the serum of children and adults. Pediatrics, 35: , ) Staeheli, V., M.B. Vallotton and A. Burger: Detection of human anti-triiodothyronine antibodies in different thyroid conditions. J. Clin. Endocrinol. Metab., 41: , ) Walker, W.A., K.J. Isselbacher and K.J. Bloch: Intestinal uptake of macromolecules: Effect of oral immunization. Science, 177: , ) Wu, S.Y. and W.L. Green: Triiodothyronine (T3 )-binding immunoglobulins in a euthyroid woman: Effects on measurement of T3(RIA) and on T3 turnover. J. Clin. Endocrinol. Metab., 42: 642

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