Persistent Graves' hyperthyroidism despite rapid negative conversion of thyroid-stimulating hormone-binding inhibitory immunoglobulin assay results: a case report.
BACKGROUND
Graves' disease is an autoimmune thyroid disorder characterized by hyperthyroidism, and patients exhibit thyroid-stimulating hormone receptor antibody. The major methods of measuring circulating thyroid-stimulating hormone receptor antibody include the thyroid-stimulating hormone-binding inhibitory immunoglobulin assays. Although the diagnostic accuracy of these assays has been improved, a minority of patients with Graves' disease test negative even on second-generation and third-generation thyroid-stimulating hormone-binding inhibitory immunoglobulins. We report a rare case of a thyroid-stimulating hormone-binding inhibitory immunoglobulin-positive patient with Graves' disease who showed rapid lowering of thyroid-stimulating hormone-binding inhibitory immunoglobulin levels following administration of the anti-thyroid drug thiamazole, but still experienced Graves' hyperthyroidism.


METHODS
A 45-year-old Japanese man presented with severe hyperthyroidism (serum free triiodothyronine >25.0 pg/mL; reference range 1.7 to 3.7 pg/mL) and tested weakly positive for thyroid-stimulating hormone-binding inhibitory immunoglobulins on second-generation tests (2.1 IU/L; reference range <1.0 IU/L). Within 9 months of treatment with oral thiamazole (30 mg/day), his thyroid-stimulating hormone-binding inhibitory immunoglobulin titers had normalized, but he experienced sustained hyperthyroidism for more than 8 years, requiring 15 mg/day of thiamazole to correct. During that period, he tested negative on all first-generation, second-generation, and third-generation thyroid-stimulating hormone-binding inhibitory immunoglobulin assays, but thyroid scintigraphy revealed diffuse and increased uptake, and thyroid ultrasound and color flow Doppler imaging showed typical findings of Graves' hyperthyroidism.


CONCLUSIONS
The possible explanations for serial changes in the thyroid-stimulating hormone-binding inhibitory immunoglobulin results in our patient include the presence of thyroid-stimulating hormone receptor antibody, which is bioactive but less reactive on thyroid-stimulating hormone-binding inhibitory immunoglobulin assays, or the effect of reduced levels of circulating thyroid-stimulating hormone receptor antibody upon improvement of thyroid autoimmunity with thiamazole treatment. Physicians should keep in mind that patients with Graves' disease may show thyroid-stimulating hormone-binding inhibitory immunoglobulin assay results that do not reflect the severity of Graves' disease or indicate the outcome of the disease, and that active Graves' disease may persist even after negative results on thyroid-stimulating hormone-binding inhibitory immunoglobulin assays. Timely performance of thyroid function tests in combination with sensitive imaging tests, including thyroid ultrasound and scintigraphy, are necessary to evaluate the severity of Graves' disease and treatment efficacy.
Department of Endocrinology and Metabolism, Nagaoka Red Cross Hospital, 2-297-1 Senshu, Nagaoka, Niigata, 940-2085, Japan. oharan@med.niigata-u.ac.jp.|Department of Endocrinology and Metabolism, Uonuma Institute of Community Medicine, Niigata University Medical and Dental Hospital, Niigata, Japan. oharan@med.niigata-u.ac.jp.
Nobumasa
N
Ohara
Department of Endocrinology and Metabolism, Nagaoka Red Cross Hospital, 2-297-1 Senshu, Nagaoka, Niigata, 940-2085, Japan.
Masanori
M
Kaneko
Department of Endocrinology and Metabolism, Nagaoka Red Cross Hospital, 2-297-1 Senshu, Nagaoka, Niigata, 940-2085, Japan.
Masaru
M
Kitazawa
Department of Endocrinology and Metabolism, Nagaoka Red Cross Hospital, 2-297-1 Senshu, Nagaoka, Niigata, 940-2085, Japan.
Yasuyuki
Y
Uemura
Department of Endocrinology and Metabolism, Nagaoka Red Cross Hospital, 2-297-1 Senshu, Nagaoka, Niigata, 940-2085, Japan.
Shinichi
S
Minagawa
Tsutsui Medical Clinic, Niigata, Japan.
Masashi
M
Miyakoshi
Department of Endocrinology and Metabolism, Nagaoka Red Cross Hospital, 2-297-1 Senshu, Nagaoka, Niigata, 940-2085, Japan.
Kenzo
K
Kaneko
Department of Internal Medicine, Ojiya General Hospital, Niigata, Japan.|Center of Diabetes, Endocrinology and Metabolism, Joetsu General Hospital, Niigata, Japan.
Kyuzi
K
Kamoi
D013956:Antithyroid Agents / Q000627:therapeutic use*; D001323:Autoantibodies / Q000097:blood; D006111:Graves Disease / Q000097:blood / Q000175:diagnosis* / Q000188:drug therapy / Q000276:immunology*; D006801:Humans; D018828:Immunoglobulins, Thyroid-Stimulating / Q000097:blood*; D008297:Male; D008713:Methimazole / Q000627:therapeutic use*; D008875:Middle Aged; D011877:Radionuclide Imaging; D011989:Receptors, Thyrotropin / Q000097:blood; D013960:Thyroid Function Tests; D013961:Thyroid Gland / Q000000981:diagnostic imaging / Q000503:physiopathology; D013974:Thyroxine / Q000627:therapeutic use; D016896:Treatment Outcome
D013956:Antithyroid Agents; D001323:Autoantibodies; D018828:Immunoglobulins, Thyroid-Stimulating; D011989:Receptors, Thyrotropin; C094372:thyrotropin-binding inhibitory immunoglobulin; D008713:Methimazole; D013974:Thyroxine
Graves’ disease; Human leukocyte antigen; Hyperthyroidism; Thiamazole; Thyroid scintigraphy; Thyroid-stimulating hormone-binding inhibitory immunoglobulin