Abstract
Since Marine's observations some 50 years ago, it has been generally accepted that colloid goiters invariably result from colloid repletion of originally hyperplastic goiters after cessation of the goitrogenic stimulus. However, clinical observations suggest that many goiters never go through a stage of hyperplasia, but are colloid-rich from the beginning. We have injected rats and mice with thyrotropin (TSH), three times a day for 4 d, while the animals were kept on an iodine-rich diet (HID). Additional groups of animals were fed an iodine-poor diet (LID) or a diet containing 0.15% propylthiouracil (PTU) or 1% sodium perchlorate (ClO4). At intervals, thyroid weight, DNA, iodine and thyroglobulin content, thyroglobulin iodination, and intracellular droplet formation were measured. Histologic sections were also prepared and stained with periodic acid Schiff. Furthermore, thyroxine concentration was measured in the serum. Thyroglobulin content dropped by approximately 30% in HID animals but by 60% in all other groups 1 d after starting TSH. Thereafter, thyroglobulin reaccumulation occurred and droplet formation correspondingly decreased despite continuous heavy TSH stimulation. The largest amount of thyroglobulin was reaccumulated in HID animals followed by the PTU/LID groups, whereas no reaccumulation was observed in the ClO4 group. Reaccumulation of thyroglobulin only occurred if there was concomitant organification of at least some iodine. The subsequent phases of depletion and reaccumulation of thyroglobulin were mirrored by the morphology of the follicular lumina, the staining properties of the colloid and the serum T4 concentration. These observations suggest that endocytosis gradually becomes refractory to continuous TSH stimulation if a certain minimal amount of iodine is available for organic binding. Thus, primarily colloid-rich goiters may form in the presence of continuously higher than normal thyrotropin levels without a previous stage of follicular hyperplasia. The view should be revised that accumulation of colloid and intense thyrotropin stimulation are mutually exclusive events.
Full text
PDF









Images in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- BURTON K. A study of the conditions and mechanism of the diphenylamine reaction for the colorimetric estimation of deoxyribonucleic acid. Biochem J. 1956 Feb;62(2):315–323. doi: 10.1042/bj0620315. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Binswanger C., Studer H., Kohler H., Steiger J., Brun del Re R. Biological significance of a peculiar pattern of hormone release from iodine deficient rat goitres. Nature. 1968 Dec 28;220(5174):1328–1329. doi: 10.1038/2201328a0. [DOI] [PubMed] [Google Scholar]
- CLEMENTS F. W. Health significance of endemic goitre and related conditions. Monogr Ser World Health Organ. 1960;44:235–260. [PubMed] [Google Scholar]
- Dumont J. E. The action of thyrotropin on thyroid metabolism. Vitam Horm. 1971;29:287–412. doi: 10.1016/s0083-6729(08)60051-5. [DOI] [PubMed] [Google Scholar]
- FOLLIS R. H., Jr Experimental colloid goiter in the hamster. Proc Soc Exp Biol Med. 1959 Jan;100(1):203–206. doi: 10.3181/00379727-100-24573. [DOI] [PubMed] [Google Scholar]
- Field J. B., Dekker A., Titus G., Kerins M. E., Worden W., Frumess R. In vitro and in vivo refractoriness to thyrotropin stimulation of iodine organification and thyroid hormone secretion. J Clin Invest. 1979 Jul;64(1):265–271. doi: 10.1172/JCI109447. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Greer M. A., Studer H., Kendall J. W. Studies on the pathogenesis of colloid goiter. Endocrinology. 1967 Sep;81(3):623–632. doi: 10.1210/endo-81-3-623. [DOI] [PubMed] [Google Scholar]
- Haeberli A., Engler H., von Grünigen C., Kohler H., Studer H. Low molecular weight intracellular iodocompounds with long intrathyroidal half-life: remnants of thyroglobulin hydrolysis? Acta Endocrinol (Copenh) 1979 Sep;92(1):105–118. doi: 10.1530/acta.0.0920105. [DOI] [PubMed] [Google Scholar]
- Haeberli A., Studer H., Kohler H., Bürgi H., Engler H. Autoradiographic localization of slow turnover iodocompounds within the follicular cells of the rat thyroid gland. Endocrinology. 1975 Oct;97(4):978–984. doi: 10.1210/endo-97-4-978. [DOI] [PubMed] [Google Scholar]
- IINO S., YAMADA T., GREER M. A. Effect of graded doses of propylthiouracil on biosynthesis of thyroid hormones. Endocrinology. 1961 Apr;68:582–588. doi: 10.1210/endo-68-4-582. [DOI] [PubMed] [Google Scholar]
- Lauber K. Iodine determination in biological material. Kinetic measurement of the catalytic activity of iodide. Anal Chem. 1975 Apr;47(4):769–771. doi: 10.1021/ac60354a023. [DOI] [PubMed] [Google Scholar]
- Rapoport B., West M. N., Ingbar S. H. Inhibitory effect of dietary iodine on the thyroid adenylate cyclase response to thyrotropin in the hypophysectomized rat. J Clin Invest. 1975 Aug;56(2):516–519. doi: 10.1172/JCI108119. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rousset B., Orgiazzi J., Mornex R. Perchlorate ion enhances mouse thyroid responsiveness to thyrotropin, human chorionic gonadotropin and long acting thyroid stimulator. Endocrinology. 1977 Jun;100(6):1628–1635. doi: 10.1210/endo-100-6-1628. [DOI] [PubMed] [Google Scholar]
- Saddok C., Gafni M., Gross J. Effect of iodide on the adenyl cyclase system of the mouse thyroid in vivo. Acta Endocrinol (Copenh) 1978 Jul;88(3):517–527. doi: 10.1530/acta.0.0880517. [DOI] [PubMed] [Google Scholar]
- Schmid M., Schulthess C., Bürgi H., Studer H. Jodmangel ist in der Schweiz noch immer endemisch. Schweiz Med Wochenschr. 1980 Sep 6;110(36):1290–1295. [PubMed] [Google Scholar]
- Sherwin J. R., Tong W. Thyroidal autoregulation. Iodide-induced suppression of thyrotropin-stimulated cyclic AMP production and iodinating activity in thyroid cells. Biochim Biophys Acta. 1975 Sep 8;404(1):30–39. [PubMed] [Google Scholar]
- Shishiba Y., Solomon D. H., Beall G. N. Comparison of early effects of thyrotropin and long-acting thyroid stimulator on thyroid secretion. Endocrinology. 1967 May;80(5):957–961. doi: 10.1210/endo-80-5-957. [DOI] [PubMed] [Google Scholar]
- Studer H., Forster R., Conti A., Kohler H., Haeberli A., Engler H. Transformation of normal follicles into thyrotropin-refractory "cold" follicles in the aging mouse thyroid gland. Endocrinology. 1978 May;102(5):1576–1586. doi: 10.1210/endo-102-5-1576. [DOI] [PubMed] [Google Scholar]
- Studer H., Hunziker H. R., Ruchti C. Morphologic and functional substrate of thyrotoxicosis caused by nodular goiters. Am J Med. 1978 Aug;65(2):227–234. doi: 10.1016/0002-9343(78)90813-6. [DOI] [PubMed] [Google Scholar]
- Studer H., Kohler H., Bürgi H., Binswanger C., Steiger J. Possible importance of thyroidal iodine compartments in the adaptation of thyroid hormone secretion to antithyroid drugs. Endocrinology. 1972 Nov;91(5):1154–1159. doi: 10.1210/endo-91-5-1154. [DOI] [PubMed] [Google Scholar]
- Van Sande J., Dumont J. E. Effects of thyrotropin, prostaglandin E1 and iodide on cyclic 3',5'-AMP concentration in dog thyroid slices. Biochim Biophys Acta. 1973 Jul 28;313(2):320–328. doi: 10.1016/0304-4165(73)90031-7. [DOI] [PubMed] [Google Scholar]
- Wolff J., Williams J. A. The role of microtubles and microfilaments in thyroid secretion. Recent Prog Horm Res. 1973;29:229–285. doi: 10.1016/b978-0-12-571129-6.50010-5. [DOI] [PubMed] [Google Scholar]
- van den Hove-Vandenbroucke M. F., Couvreur-Eppe M., De Visscher M. Defective thyroglobulin endocytosis and hydrolysis in thyroid cold nodules. Eur J Clin Invest. 1975 Jun 12;5(3):229–234. doi: 10.1111/j.1365-2362.1975.tb00449.x. [DOI] [PubMed] [Google Scholar]
- van den Hove-Vandenbroucke M. F., De Visscher M., Couvreur-Eppe M. Secretory activity of isolated thyroid adenomas. J Clin Endocrinol Metab. 1976 Jul;43(1):178–181. doi: 10.1210/jcem-43-1-178. [DOI] [PubMed] [Google Scholar]