Exp. Clin. Endocrino!. Vol. 97, No. 2/3, 1991, pp. 303-307
J. A. Barth, Leipzig
Department of Nuc!ear Medicine and Internal Medicine*), Kyoto University, School of Medicine, Shogoin, Sakyo-ku, Kyoto 606, Japan
TSH-Receptor Antibodies in Hypothyroid Graves' Disease J. Koisrn, K. KASAGI, A. HIDAKA, R. Txnucm, Y. JIDA and With 3 Figures
Introduction Euthyroid or hypothyroid Graves' disease describes Graves' ophthalmopathy that develops in either euthyroid or hypothyroid subjects, respectively. It has been reported that TSH-receptor antibodies (TRAb) such as TSH-binding inhibitor immunoglobulins (TBII) and thyroid stimulating antibodies (TSAb), especially the latter, are detected in a majority of patients with euthyroid Graves' disease (Kasagi et al., 1988), suggesting a close relationship between TRAb and Graves' ophthalmopathy. We have recently experienced six cases of hypothyroid Graves' disease. In the present paper, we report the clinical features and the results from TBII and TSAb measurements in these patients.
Methods and Patients TBII were assayed by using a commercially available kit with a minor modification (Konishi et al., 1987). Solubilized porcine thyroid membranes were used as receptor fractions. Resu!ts were expressed as follows: (1-a/b) x 100%, where a is specific 1251-TSH binding in the presence of a test samp!e, and b is specific 1251-TSH binding in the presence of a norma! pool sample. The norma! range
was 11.9 to 11.0%. TSAb and TSBAb (thyroid-stimulation blocking antibodies) were assayed by measuring cAMP production in FRTL-5 thyroid cells or cultured porcine thyroid cells (case 2 only) as an index of stimulation. The cells were incubated with crude immunoglobulin (1g) fraction precipitated with polyethylene
glycol in the presence or absence of 100 tU/ml bovine TSH under hypotonic conditions. TSAb activities were expressed as percent of cAMP compared with the mean of the values for normal samples. The normal range was 55.0-145.0%. TSBAb were calculated and expressed as follows: (1 -(a-b)/(cd))x 100%, where "a" is cAMP generated in the presence of test 1g and TSH, "b" is cAMP generated in the presence of test, "c" is cAMP generated in the presence of 1g from a pool of normal serum and TSH, and "d" is cAMP generated in the presence of 1g from a pool of normal serum. The normal range was 40.0 to 40.0% - Serum samples containing high concentrations of TSH (>30 i.tU/ml) were pretreated with anti-TSH antibodies before 1g preparation, so that TSH contamination of the crude ¡g would not cause cAMP stimulation. The diagnosis of hypothyroid Graves' disease was made on the basis of Graves' ophthalmopathy and either permanent or transient hypothyroidism without a history of hyperthyr'bi4 Graves' disease.
Downloaded by: University of Pittsburgh. Copyrighted material.
H. NAKAMIJRA*)
304
Exp. Clin. Endocrino!. 97 (1991) 2/
Case 1: A 51-year-old woman presented to the hospital in December 1979. She has had exophthalmos and anterior neck swelling for 4to 5 years. She had gained weight by 6 kg for the last 6 months. She also had noticed general malaise for 6 months; periorbital edema, lacrimation and chemosis for 3 months; hoarseness, oppressive feeling in the anterior neck, puffiness of her face and extremities for 2 months. Her height was 146 cm, weight was 83 kg. She had proptosis (24mm for the right eye and 26mm for the left eye by exophthalmometry) with Graefe sign. On physical examination, her skin was dry, and a diffusely enlarged firm goiter with a transverse diameter of 10.5 cm was palpable. Laboratory findings revealed that she was hypothyroid with serum TSH concentration of 254 tU/ml (Fig. 1). mTc thyroid uptake after i.v. injection of mTc pertechnetate was 1.8% (normal: 0.4-3.0). Histological findings obtained by needle biopsy revealed destruction of follicular cells with marked fibrosis. She was treated with 150 g/day T4, and has been euthyroid (Fig. 1). Case 2: This case had been reported previously (Kasagi
hypothyroidism such as tiredness, cold intolerance and weight gain, and slight exophthalmos (17mm right eye, 17 mm left eye). The diagnosis of primary hypothyroidism was confirmed by a serum total T4 value of 0.7 ng/dl (normal: 6-13), a serum total T3 value of 40 ng/dl (normal: 90-190) and a TSH value of 155 l.U/ml (normal:
J. A. Barth, Leipzig
Department of Nuc!ear Medicine and Internal Medicine*), Kyoto University, School of Medicine, Shogoin, Sakyo-ku, Kyoto 606, Japan
TSH-Receptor Antibodies in Hypothyroid Graves' Disease J. Koisrn, K. KASAGI, A. HIDAKA, R. Txnucm, Y. JIDA and With 3 Figures
Introduction Euthyroid or hypothyroid Graves' disease describes Graves' ophthalmopathy that develops in either euthyroid or hypothyroid subjects, respectively. It has been reported that TSH-receptor antibodies (TRAb) such as TSH-binding inhibitor immunoglobulins (TBII) and thyroid stimulating antibodies (TSAb), especially the latter, are detected in a majority of patients with euthyroid Graves' disease (Kasagi et al., 1988), suggesting a close relationship between TRAb and Graves' ophthalmopathy. We have recently experienced six cases of hypothyroid Graves' disease. In the present paper, we report the clinical features and the results from TBII and TSAb measurements in these patients.
Methods and Patients TBII were assayed by using a commercially available kit with a minor modification (Konishi et al., 1987). Solubilized porcine thyroid membranes were used as receptor fractions. Resu!ts were expressed as follows: (1-a/b) x 100%, where a is specific 1251-TSH binding in the presence of a test samp!e, and b is specific 1251-TSH binding in the presence of a norma! pool sample. The norma! range
was 11.9 to 11.0%. TSAb and TSBAb (thyroid-stimulation blocking antibodies) were assayed by measuring cAMP production in FRTL-5 thyroid cells or cultured porcine thyroid cells (case 2 only) as an index of stimulation. The cells were incubated with crude immunoglobulin (1g) fraction precipitated with polyethylene
glycol in the presence or absence of 100 tU/ml bovine TSH under hypotonic conditions. TSAb activities were expressed as percent of cAMP compared with the mean of the values for normal samples. The normal range was 55.0-145.0%. TSBAb were calculated and expressed as follows: (1 -(a-b)/(cd))x 100%, where "a" is cAMP generated in the presence of test 1g and TSH, "b" is cAMP generated in the presence of test, "c" is cAMP generated in the presence of 1g from a pool of normal serum and TSH, and "d" is cAMP generated in the presence of 1g from a pool of normal serum. The normal range was 40.0 to 40.0% - Serum samples containing high concentrations of TSH (>30 i.tU/ml) were pretreated with anti-TSH antibodies before 1g preparation, so that TSH contamination of the crude ¡g would not cause cAMP stimulation. The diagnosis of hypothyroid Graves' disease was made on the basis of Graves' ophthalmopathy and either permanent or transient hypothyroidism without a history of hyperthyr'bi4 Graves' disease.
Downloaded by: University of Pittsburgh. Copyrighted material.
H. NAKAMIJRA*)
304
Exp. Clin. Endocrino!. 97 (1991) 2/
Case 1: A 51-year-old woman presented to the hospital in December 1979. She has had exophthalmos and anterior neck swelling for 4to 5 years. She had gained weight by 6 kg for the last 6 months. She also had noticed general malaise for 6 months; periorbital edema, lacrimation and chemosis for 3 months; hoarseness, oppressive feeling in the anterior neck, puffiness of her face and extremities for 2 months. Her height was 146 cm, weight was 83 kg. She had proptosis (24mm for the right eye and 26mm for the left eye by exophthalmometry) with Graefe sign. On physical examination, her skin was dry, and a diffusely enlarged firm goiter with a transverse diameter of 10.5 cm was palpable. Laboratory findings revealed that she was hypothyroid with serum TSH concentration of 254 tU/ml (Fig. 1). mTc thyroid uptake after i.v. injection of mTc pertechnetate was 1.8% (normal: 0.4-3.0). Histological findings obtained by needle biopsy revealed destruction of follicular cells with marked fibrosis. She was treated with 150 g/day T4, and has been euthyroid (Fig. 1). Case 2: This case had been reported previously (Kasagi
hypothyroidism such as tiredness, cold intolerance and weight gain, and slight exophthalmos (17mm right eye, 17 mm left eye). The diagnosis of primary hypothyroidism was confirmed by a serum total T4 value of 0.7 ng/dl (normal: 6-13), a serum total T3 value of 40 ng/dl (normal: 90-190) and a TSH value of 155 l.U/ml (normal:
