Abstract
Two different proliferation assays have been used to measure the proliferative potential of IgG-fractions from 57 patients with nontoxic goiter of an iodine-deficient area: primary human thyroid epithelial cells (TEC) and the thouroughly investigated FRTL-5 cell line. IgG-fractions from patients with nontoxic goiter (n = 30), nontoxic recurrent goiter (n = 8), toxicnodular goiter (n = 15) and carcinoma of the thyroid (n = 4) were highly purified on DEAE-Sepharose and additionaly Protein A-Sepharose in some cases. The two proliferation assays gave contradictory results: primary cultures of human thyroid epithelial cells (TEC) could not be stimulated by any of the patient’s IgG-fractions nor by bTSH. The FRTL-5 cells, however, were stimulated with 10 µU/ml bTSH by 326% ± 96% (range: 222% — 497%, p< 0.001). In one experimental series, 72% of all patients exceeded mean + 2 SD of normal controls, when the stimulation index was referred to the effect of bTSH (NTG: 77%, Rec. G.: 88%, Tox. G.: 53%, Ca. thyroid: 75%). With a different method of calculation — stimulation index referred to the basal value — the number of patients above mean + 2 SD of normal controls decreased to 30% (NTG: 33%, Rec. G.: 12,5%, Tox. G.: 33%, Ca. thyroid: 25%). Statistical analysis, however, of results of different patient groups compared to the normal control group failed to show any significance.
Similar content being viewed by others
Abbreviations
- AC-activity:
-
activity of the adenylate-cyclase
- bTSH:
-
bovine thyroidea stimulating hormone
- Ca.:
-
thyroid, Carcinoma of thyroid
- FRTL-5 cells:
-
Fischer’s rat thyroid cell line 5
- GD:
-
Graves’ disease
- 3H-TdR:
-
3H-Thymidine
- IBMX:
-
3-isobutyl-1-methyl-xanthine
- MAB:
-
microsomal antibody
- NTG:
-
non-toxic goitre
- PBS:
-
phosphate buffered saline
- Rec. goiter:
-
recurrent goiter
- SD:
-
standard deviation
- SI:
-
stimulation index
- TAB:
-
thyroglobulin antibody
- TBII:
-
TSH-binding inhibiting immunoglobulin
- TGI:
-
thyroid growth stimulating immunoglobulin
- Tox. goiter:
-
toxic goiter
- TSI:
-
thyroid stimulating immunoglobulin.
References
Drexhage H.A., Bottazzo G.F., Doniach D., Bitensky L., Chayen J. Evidence for Thyroid-Growth-Stimulating Immunoglobulins in some goitrous thyroid diseases. Lancet. 2: 287, 1980.
Valente W.A., Vitti P., Rotella C., Vaughan M., Aloj S., Grollman E., Ambesi-lmpiombato F., Kohn L. Antibodies that promote thyroid growth. N. Engl. J. Med. 309: 1028, 1983.
McMullan N.M., Smyth P.P.A. In vitro Generation of NADPH as an Index of Thyroid Stimulating Immunoglobulins (TGI) in Goitrous Disease. Clin. Endocrinol. (Oxf.) 20: 269, 1984.
Schatz H., Bär R., Müller F., Nickel J.A., Stracke H. Growth Promoting Effects of TSH and EGF in Isolated Porcine Thyroid Follicles and Occurrence of TGI in Euthyroid Goitre Patients from an Iodine-Deficient Endemic Goitre Area. In: Drexhage H.A., Wiersinga W.M. (Eds.), The thyroid and autoimmunity. Elsevier Science Publishers B.V, Amsterdam, 1986, p. 207.
Drexhage H.A., Hammond L.J., Bitensky L., Chayen J., Bottazzo G.F., Doniach D. The Involvement of the Pentose Shunt in Thyroid Metabolism after Stimulation with TSH or with Immungloblulins from Patients with Thyroid Disease. II. The Reoxidation of NADPH and Stimulation of Hormone Synthesis. Clin. Endocrinol. (Oxf.) 16: 57, 1982.
Chiovato L., Hammond L.J., Hanafusa T., Pujol-Borrell R., Doniach D., Bottazzo G.F. Detection of Thyroid Growth Immunogloblins (TGI) by (3H)-Thymidin Incorporation in Cultured Rat Thyroid Follicles. Clin. Endocrinol. (Oxf.) 19: 581, 1983.
Risdall J.E., Dahlberg P.A., Westermark B., Karlsson. Influence of thyroid autoantibodies on thyroid cellular in vitro. Mol. Cell. Endocrinol. 34: 215, 1984.
Drexhage H.A., Van der Gaag R.D. Thyroid Growth Stimulating Immunoglobulins (TGI) and Goitre. In: Drexhage H.A., Wiersinga W.M. (Eds.): The thyroid and autoimmunity. Elsevier Science Publishers B.V., Amsterdam, 1986, p. 173.
Smyth P.P.A, Grubeck-Loebenstein B, McKenna T.J. Possible Significance of IgG Thyroid Stimulator in Nontoxic Goitre. In: Drexhage H.A., Wiersinga W.M. (Eds.), The thyroid and auto-immunity. Elsevier Science Publishers B.V., Amsterdam, 1986, p. 196.
Rotella C.M., Mavilia C., Kohn L.D., Toccafondi R. Thyroid Growth Promoting Antibody in Patients with non Toxic Goiter. In: Drexhage H.A., Wiersinga W.M. (Eds.), The thyroid and auto-immunity. Elsevier Science Publishers B.V., Amsterdam, 1986, p. 198.
Halpern A., Medeiros-Neto G., Kohn L.D. Thyroid Growth Promoting Activity in Endemic Goiter. In: Drexhage H.A., Wiersinga W.M. (Eds.), The thyroid and auto-immunity. Elsevier Science Publishers B.V., Amsterdam, 1986, p. 209.
Gärtner R., Greil W., Tzavella C., Witte A., Pickardt C.R. What is Thyroid Growth Promoting Activity (“TGI”)? In: Drexhage H.A., Wiersinga W.M. (Eds.), The thyroid and auto-immunity. Elsevier Science Publishers B.V., Amsterdam, 1986, p. 191.
Goretzki P.E. West M., Koob R., Koller Ch., Joseph K, Röher H-D. Adenylate cyclase stimulation and (3H) thymidine incorporation in human thyroid tissues and thyrocyte cultures: The effect of IgG preparation from patients with different thyroid disorders. In: Wenzel B.E., Bottazzo G.F. (Eds.), Advances in Thyroidology. Acta Endocrinol. (Copenh.) (Suppl.) 281: 281, 1987.
Valente W.A., Vitti P., Kohn L., Brandi M., Rotella C., Toccafondi R., Tramontano D., Aloj C., Ambesi-Impiombato F. The relationship of growth and adenylate cyclase activity in cultured thyroid cells: Separate bioeffects of Thyrotropin. Endocrinology 112: 71, 1983.
Ambesi-lmpiombato F.S., Villone G. The FRTL-5 thyroid cell strain as a model for studies on thyroid cell growth. In: Wenzel B.E., Bottazzo G.F. (Eds.), Advances in Thyroidology. Acta Endocrinol. (Copenh.) (Suppl.) 281: 242, 1987.
Vitti P., Rotella C.M., Valente W.A., Cohen J., Aloj S.M., Laccetti P., Ambesi-lmpiombato F.S., Grollman E.F., Pinchera A., Toccafondi R., Kohn L.D. Characterization of the Optimal Stimulatory Effects of Graves’ Monoclonal and Serum Immunoglobulin G on Adenosine 3′, 5′-Monophospate Production in FRTL-5 Thyroid Cells: A Potential Clical Assay. J. Clin. Endocrinol. Metab., 57 782, 1983.
Reuse S., Roger P., Lamy F., Foureau F., Gerard C., Dumont J.E. Control of thyroid cell proliferation: The example of the dog thyrocyte. In: Wenzel B.E., Bottazzo G.F. (Eds.), Advances in Thyroidology. Acta Endocrinol. (Copenh.) (Suppl.) 215, 1987.
Eggo M.C., Bachrach L.K., Burrow G. Role of non-TSH factors in thyroid cell growth. In: Wenzel B.E., Bottazzo G.F. (Eds.), Advances in Thyroidology. Acta Endocrinol. (Copenh.) (Suppl.) 281: 231, 1987.
Gärtner R., Tsavella C., Bechtner G., Greil W. Evidence that thyroid growth promoting activity of immunoglobulin preparations is due to a contamination with EGF. In: Wenzel B.E., Bottazzo G.F. (Eds.), Adavances in Thyroidology. Acta Endocrinol. (Copenh.) (Suppl.) 281: 256, 1987.
Isozaki O., Santisteban P., Chan J., Grollmann E., Kohn L. Insulin and insulin-like growth factor-l (IGF-I) regulate differentiation as well as growth in FRTL-5 cells. In: Wenzel B.E., Bottazzo G.F. (Eds.), Advances in Thyroidology. Acta Endocrinol. (Copenh.) (Suppl.) 281: 288, 1987.
Marcocci C., Fenzi G.F., Grollman E.F. Role of the adenylate cyclase-cAMP system on TSH-stimulated thyroid cell growth. Acta Endocrinol. (Copenh.) (Suppl.) 281: 246, 1987.
Stracke H., Bär R., Müller F., Schatz H. Stimulation of thyroid cell growth by thyrotropin and epidermal growth factor in isolated porcine thyroid follicles. In: Wenzel B.E., Bottazzo G.F., (Eds.), Advaces in Thyroidology. Acta Endocrinol. (Copenh.) (Suppl.) 281: 270, 1987.
Westermark K., Karlsson F.A., Westermark B. Epidermal Growth Factor Modulates Thyroid Growth and Function in Culture. Endocrinology 112: 1680, 1983.
Gärtner R., Greil W., Tzavella C., Witte A., Pickardt C.R. What is Thyroid Growth Promoting Activity (TGI)? In: Drexhage H.A., Wiersings W.M. (Eds.), The thyroid and autoimmunity. Elsevier Science Publishers B.V, Amsterdam, 1986, p. 191
Wenzel B.E., Dwenger M., Mansky T., Engel U., Bay V., Scriba P.C. Thyrotrophin and growth promoting immunoglobulin (TGI) of FRTL-5 cells have no growth stimulating activity on human thyroid epithelial cell cultures. In: Pinchera A., Ingbar S.H., McKenzie J.M., Fenzi G.F. (Eds.), Thyroid Autoimmunity. Plenum Publishing Corporation, New York, 1987, p. 379
Ambesi-lmpiombato F.S., Parks L.A.M., Coon H.G. Culture of hormone dependent functional cells from rat thyroids. Proc. Natl. Acad. Sci., USA 77: 3455, 1980.
Dumont J.E., Roger P., Ludgate M. Autoimmunity and Thyroid Growth: Methods, Concepts and Misconceptions. In: Wenzel B.E., Bottazzo G.F. (Eds.), Advances in Thyroidology. Acta Endocrinol. (Copenh.) (Suppl.) 281: 299, 1987.
Gutekunst R., Smolarek H., Hasenpusch U., Stubbe P., Friedrich H.-J., Wood W.G, Scriba P.C. Goitre epidemiology: thyroid volume, iodine excretion, thyroglobulin and thyrotropin in Germany and Sweden Acta Endocrinol. (Copenh.) 112: 494, 1986.
Wenzel B.E., Gutekunst R., Grammerstorf S., Scriba P.C. An in vitro model for thyroid autoimmunity. In: Pinchera A., Ingbar S.H., McKenzie J.M. and Fenzi G.F. (Eds.), Thyroid autoimmunity. Plenum Publishing Corporation, New York, 1987, p. 145.
Bidey S.P., Marshall N.J. Ekins R.P. Characterisation of the cyclic cAMP response to thyrotropin in monolayer cultures of normal human thyroid cells. Acta Endocrinol. (Copenh.) 98: 370, 1981.
Bidey S.P., Marshall N.J., Ekins R.P. Bioassay of Thyroid-Stimulating Immunoglobulins Using Human Thyroid Cell Cultures: Optimization and Clinical Assessment. Clin. Endocrinol. (Oxf.) 18: 193, 1983.
Bidey S.P., Emmerson J.M., Marshall N.J., Ekins R.P. Characterization of Thyroid-Stimulating Immunoglobulin-induced Cyclic AMP Accumulation in the Rat Thyroid Cell Strain FRTL-5: Potentiation by Forskolin and Calibration against Reference Preparations of Thyrotrophin. J. Endocrinol. 105: 7, 1985.
Tankersley D.L., Preston M.S., Finlayson J.S. Immunoglobulin G Dimer: an Idiotype-anti-ldiotype Complex. Mol. Immunol. 25: 41, 1988.
Westermark B., Karlsson F.A., Walinder O. Thyrotropin is not a growth factor for human thyroid cells in culture. Proc. Natl. Acad. Sci. USA 76: 2022, 1979. au35._Westermark K., Lundquist M., Hacker G., Karlsson A., Westermark B. Growth factor receptors in thyroid follicle cells. In: Wenzel B.E., Bottazzo G.F. (Eds.) Advances in Thyroidology. Acta Endocrinol. (Copenh.) (Suppl.) 281: 252, 1987.
Roger P., Taton M., Van Sande J., Dumont J. Mitogenic Effects of Thyrotropin and Adenosine 3′, 5′-Monophosphate in Differentiated Normal Human Thyroid Cells in Vitro. J. Clin. Endocrinol. Metab. 66: 1158, 1988.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Oethinger, M.D., Wenzel, B.E. & Scriba, P.C. Thyroid growth stimulating activity in highly purified IgG-fractions of patients with nonimmune thyroid diseases. J Endocrinol Invest 12, 631–642 (1989). https://doi.org/10.1007/BF03350024
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/BF03350024