Journal of Endocrinological Investigation

, Volume 9, Issue 5, pp 389–396 | Cite as

Increased serum thyroglobulin concentrations and impaired thyrotropin response to thyrotropin-releasing hormone in euthyroid subjects with endemic goiter in Sicily: their relation to goiter size and nodularity

  • F. Vermiglio
  • S. Benvenga
  • R. Melluso
  • S. Catalfamo
  • P. PrinciJr.
  • S. Battiato
  • F. Consolo
  • F. Trimarchi


Serum thyroglobulin (Tg), T4, T3, FT4, FT3, TSH concentrations and TSH response to iv TRH (ΔTSH) were measured in 56 consecutive patients with (multi) nodular goiter from a severily iodine-deficient endemic goiter area in Northeastern Sicily and in 11 non goitrous euthyroid individuals living in the same area. Serum Tg concentrations were sharply increased in goitrous subjects (453 ± 476 ng/ml) and related to thyroid size and the presence of nodules (χ2 = 43.5, p < 0.0005). Serum TSH levels measured in goitrous patients (2.1 ± 0.9 μU/ml) were significantly lower than those measured in nongoitrous iodine deficient subjects (3.1 ± 0.9 μU/ml, p <0.001) and decreased with increasing goiter size and nodularity (χ2 = 27.3, p<0.05). A similar pattern was shown by the analysis of the Δ TSH (χ2 = 43.1, p<0.0005). These results suggest that at least a part of the largest and multinodular goiters become autonomously functioning with duration and growing in size. In 13 goitrous patients with absent or impaired response to TRH, a significant direct relation was apparent between log-Tg and goiter size and nodularity (r = 0.64) with an inverse relationship between serum FT3 and Δ TSH (r = 0.73). A computed program analysis based on the combination of different independent variables (x) including age, thyroid size and nodularity, serum TSH, log-Tg and FT3, indicated the existence of a significant negative relationship between these variablesand the TSH response to TRH (r = 0.75, p = 0). This confirms the limited clinical significance of the impaired TSH response to TRH in patients with multinodular goiters and gives an explanation for the not infrequently observed ineffectiveness of suppressive treatment with thyroid hormones.


Thyroglobulin endemic goiter thyroid autonomy TSH response to TRH iodine deficiency 


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  1. 1.
    Adams D.D., Kennedy T.H., Choufoer J.C., Querido A. Endemic goiter in Western New Guinea. III. Thyroid-stimulating activity of serum from severely iodine-deficient people. J. Clin. Endocrinol. Metab. 28: 685, 1968.PubMedCrossRefGoogle Scholar
  2. 2.
    Pisarev M.A., Utiger R.D., Salvaneschi J.P., Altschuler N., De Groot L.J. Serum TSH and thyroxine in goitrous subjects in Argentina. J. Clin. Endocrinol. Metab. 30: 680, 1970.CrossRefGoogle Scholar
  3. 3.
    Coble Y.D., Kohler P.O. Plasma TSH levels in endemic goiter subjects. J. Clin. Endocrinol. Metab. 31: 220, 1970.PubMedCrossRefGoogle Scholar
  4. 4.
    Whaner H.V., Mayberry W.E., Gaitan E., Gaitan J.E. Endemic goiter in the Cauca Valley III Role of serum TSH in goitrogenesis. J. Clin. Endocrinol. Metab. 32: 491, 1971.CrossRefGoogle Scholar
  5. 5.
    Delange F., Hershman J.M., Ermans A.M. Relationship between the serum thyrotropin level, the prevalence of goiter and the pattern of iodine metabolism in Idjwi Island. J. Clin. Endocrinol. Metab. 33: 261, 1971.PubMedCrossRefGoogle Scholar
  6. 6.
    Delange F., Camus M., Ermans A.M. Circulating thyroid hormones in endemic goiter. J. Clin. Endocrinol. Metab. 34: 891, 1972.PubMedCrossRefGoogle Scholar
  7. 7.
    Oghiara T., Yamamoto T., Fukuchi M., Oki K. Serum thyrotropin levels of natives in Sarawak, Borneo Island. J. Clin. Endocrinol. Metab. 35: 711, 1972.CrossRefGoogle Scholar
  8. 8.
    Beckers C., Maskens A., Cornette C. Thyrotropin response to synthetic thyrotropin-releasing hormone in normal subjects and in patients with nontoxic goitre. Eur. J. Clin. Invest. 2: 220, 1972.PubMedCrossRefGoogle Scholar
  9. 9.
    Vagenakis A.G., Koutras D.A., Burger A., Malamos B., Ingbar S.H., Braverman L.E. Studies of serum triiodothyronine, Thyroxine and thyrotropin concentrations in endemic goitre in Greece. J. Clin. Endocrinol. Metab. 37: 485, 1973.PubMedCrossRefGoogle Scholar
  10. 10.
    Patel Y.D., Pharaoh P.O.D., Homabrook R.W., Hetzel B.S. Serum triiodothyronine, thyroxine and thyroid stimulating hormone in endemic goitre: a comparison of goitrous and nongoitrous subjects in New Guinea. J. Clin. Endocrinol. Metab. 37: 783, 1973.PubMedCrossRefGoogle Scholar
  11. 11.
    Pharaoh P.O.D., Lawton N.F., Ellis S.M., Williams E.S., Ekins R.P. The role of triiodothyronine (T3) in the maintenance of euthyroidism in endemic goitre. Clin. Endocrinol. (Oxf.) 2: 193, 1973.CrossRefGoogle Scholar
  12. 12.
    Chopra I.J., Hershman J.M., Homabrook R.W. Serum thyroid hormone and thyrotropin levels in subjects from endemic goiter regions of New Guinea. J. Clin. Endocrinol. Metab. 40: 326, 1975.PubMedCrossRefGoogle Scholar
  13. 13.
    Hershman J.M., Due D.T., Sharp B., My L., Kent J.R., Binh L.N., Reed A.W., Phuc L.D., Van Herle A.J., Thai N.A., Trung T.X., Van N.V., Sugawara M., Pekary A.E. Endemic goiter in Vietnam. J. Clin. Endocrinol. Metab. 57: 243, 1983.PubMedCrossRefGoogle Scholar
  14. 14.
    Van Herle A.J., Chopra I.J., Hershman J.M., Homabrook R.W. Serum thyroglobulin in inhabitants of an endemic goiter Region in New Guinea. J. Clin. Endocrinol. Metab. 43: 512, 1976.PubMedCrossRefGoogle Scholar
  15. 15.
    Pezzino V., Vigneri R., Squatrito S., Filetti S., Camus M., Polosa P. Increased serum thyroglobulin levels in patients with nontoxic goiter. J. Clin. Endocrinol. Metab. 46: 653, 1978.PubMedCrossRefGoogle Scholar
  16. 16.
    Fenzi G.F., Ceccarelli C., Macchia E., Monzani F., Bartalena L., Giani C., Ceccarelli P., Lippi F., Baschieri L., Pinchera A. Reciprocal changes of serum thyroglobulin and TSH in residents of a moderate endemic goiter area. Clin. Endocrinol. (Oxf.) 23: 115, 1985.CrossRefGoogle Scholar
  17. 17.
    Studer H. A fresh look at an old thyroid disease: euthyroid and hyperthyroid nodular goiter. J. Endocrinol. Invest. 5: 57, 1982.PubMedCrossRefGoogle Scholar
  18. 18.
    Miller J.M., Block M.A. Functional autonomy in multinodular goitre. JAMA 214: 535, 1970.PubMedCrossRefGoogle Scholar
  19. 19.
    Gemsenjager E., Staub J.J., Girard J., Heitz P. Preclinical hyperthyroidism in multinodular goitre. J. Clin. Endocrinol. Metab. 43: 810, 1976.PubMedCrossRefGoogle Scholar
  20. 20.
    Emrich D., Bahre M. Autonomy in euthyroid goitre: maladaptation to iodine deficiency. Clin. Endocrinol. (Oxf.) 8: 257, 1978.CrossRefGoogle Scholar
  21. 21.
    Belfiore A., Sava L., Runello F., Tomaselli L., Vigneri R. Solitary autonomously functioning thyroid nodules and iodine deficiency. J. Clin. Endocrinol. Metab. 53: 283, 1983.CrossRefGoogle Scholar
  22. 22.
    Delange F., Vigneri R., Trimarchi F., Filetti S., Pezzino V., Squatrito S., Bordoux P., Ermans A.M. Etiological factors of endemic goiter in Northeastern Sicily. J. Endocrinol. Invest. 1: 137, 1978.PubMedCrossRefGoogle Scholar
  23. 23.
    Sava L., Delange F., Belfiore A., Purrello F., Vigneri R. Transient impairment of thyroid function in newborn from an area of endemic goiter. J. Clin. Endocrinol. Metab. 59: 90, 1984.PubMedCrossRefGoogle Scholar
  24. 24.
    Perez C., Scrimshaw N.S., Munoz J.A. Technique to endemic goitre surveys. In: Endemic goitre, Monograph Series no. 44. Geneva, World Health Organization, p. 369.Google Scholar
  25. 25.
    Querido A., Delange F., Dunn T., Fierro-Benitez R., Ibbertson H.K., Koutras D.A., Perinetti H. Definitions of endemic goiter and cretinism, classification of goiter size and severity endemias and survey techniques. In: Dunn J.T., Medeiros-Neto G.A. (Eds.), Endemic goiter and cretinism. Continuing threats to world health. PAHO Sci. Pub., no. 292, Washington, PAHO, p. 267.Google Scholar
  26. 26.
    Vigneri R., Lisi E., Catanuso A., Squatrito S. Abnormality of the thyroid function in newborns from an area of goiter endemia. Problems connected with screening for congenital hypothyroidism. In: Albertini A. (Ed.), Radioimmunoassay of hormones, proteins and enzymes. Excerpta Medica, Amsterdam, p. 159.Google Scholar
  27. 27.
    Barresi G., De Luca F., Galatioto S., Tuccari G., Trimarchi F. Su di un caso di gozzo congenito in area endemica: osservazioni istologiche, immunoistochimiche e ultrastrutturali. Pathologica 73: 501, 1981.PubMedGoogle Scholar
  28. 28.
    Squatrito S., Delange F., Trimarchi F., Lisi E., Vigneri R. Endemic cretinism in Sicily. J. Endocrinol. Invest. 4: 295, 1981.PubMedCrossRefGoogle Scholar
  29. 29.
    Trimarchi F., Vermiglio F., Benvenga S., Sobbrio G. An exceptionally monstrous goiter in Europe. J. Endocrinol. Invest. 7: 539, 1984.PubMedCrossRefGoogle Scholar
  30. 30.
    Rapaport B., Filetti S., Takai N., Seto P., Halverson G. Studies on the cyclic AMP response to thyroid stimulating immunoglobulin (TSI) and thyrotropin (TSH) in human thyroid cell monolayer. Metabolism 31: 1159, 1982.CrossRefGoogle Scholar
  31. 31.
    Rapaport B., Greenspan F.S., Filetti S., Pepitone M. Clinical experience with a human thyroid cell bioassay for thyroid stimulating immunoglobulins. J. Clin. Endocrinol. Metab. 58: 332, 1984.CrossRefGoogle Scholar
  32. 32.
    Snedecor G.W., Cochran W.G. Statistical methods, ed. 6. Iowa University Press, p. 91.Google Scholar
  33. 33.
    Pacini F., Pinchera A., Grasso L., Giani C., Doveri F., Baschieri L. Serum thyroglobulin in various thyroid disorders. Ann. Endocrinol. (Paris) 38: 51A, 1977.Google Scholar
  34. 34.
    Ceccarelli C., Giani C., Monzani F., Lippi F., Macchia E., Bartalena L., Ceccarelli P., Tedeschi D., Lari R., Fenzi G.F. Serum thyroglobulin in two villages of the same endemic area with different goiter prevalence. J. Endocrinol. Invest. 5(Suppl. 1): 74, 1982.Google Scholar
  35. 35.
    Mariano A., Carella C., Cipolla M., Pepe M., Cavalcanti A., Coppa A., Macchia V. Thyroid function and etiological factors in some areas of endemic goiter in South of Italy. J. Endocrinol. Invest. 6(Suppl. 1): 70, 1983.Google Scholar
  36. 36.
    Torrigiani C., Doniach D., Roitt I.M. Serum thyroglobulin levels in healthy subjects and in patients with thyroid disease. J. Clin. Endocrinol. Metab. 29: 305, 1969.PubMedCrossRefGoogle Scholar
  37. 37.
    Ermans A.M., Kinthaert J., Camus M. Defective intrathyroidal iodine metabolism in nontoxic goiter: inadequate iodination of thyroglobulin. J. Clin. Endocrinol. Metab. 28: 1307, 1968.PubMedCrossRefGoogle Scholar
  38. 38.
    Greer M.A., Grimm J., Studer H. Qualitative changes in the secretion of thyroid hormones induced by iodine deficiency. Endocrinology 83: 1193, 1968.PubMedCrossRefGoogle Scholar
  39. 39.
    Lamas L., Ingbar S.H. The effect of varying iodine content on the susceptibility of thyroglobulin to hydrolysis by thyroid acid protease. Endocrinology 102: 188, 1978.PubMedCrossRefGoogle Scholar
  40. 40.
    Uller P., VanHerle A.J., Chopra I.J. Thyroidal response to graded doses of bovine thyrotropin. J. Clin. Endocrinol. Metab. 45: 312, 1977.PubMedCrossRefGoogle Scholar
  41. 41.
    Uller P., VanHerle A.J., Chopra I.J. Comparison of alterations in circulating thyroglobulin, triiodothyronine and thyroxine in response to exogenous (bovine) and endogenous (human) thyrotropin. J. Clin. Endocrinol. Metab. 37: 741, 1973.PubMedCrossRefGoogle Scholar
  42. 42.
    Belfiore A., Runello F., Sava L., La Rosa G., Vigneri R. Thyroglobulin release after graded endogenous thyrotropin stimulation in man: lack of correlation with thyroid hormone response. J. Clin. Endocrinol. Metab. 59: 974, 1984.PubMedCrossRefGoogle Scholar
  43. 43.
    Bray G.A. Increased sensivity of the thyroid in iodine — depleted rats to the goitrogenic effects of thyrotropin. J. Clin. Invest. 47: 1640, 1968.PubMedCentralPubMedCrossRefGoogle Scholar
  44. 44.
    Gebel F., Ramelli E., Burgi U., Ingold U., Studer H., Winand R. The site of leakage of intrafollicular thyroglobulin into the blood stream in simple human goiter. J. Clin. Endocrinol. Metab. 57: 915, 1983.PubMedCrossRefGoogle Scholar
  45. 45.
    Haigler E.D. jr., Pittman J.A., Bangh C.M. Direct evaluation of pituitary thyrotropin reserve utilizing synthetic thyrotropin releasing hormone. J. Clin. Endocrinol. Metab. 33: 573, 1971.PubMedCrossRefGoogle Scholar
  46. 46.
    Snyder P.J., Utiger R.D. Response to thyrotropin releasing hormone (TRH) in normal man. J. Clin. Endocrinol. Metab. 34: 380, 1972.PubMedCrossRefGoogle Scholar
  47. 47.
    Snyder P.J., Utiger R.D. Inhibition of thyrotropin response to thyrotropin releasing hormone by small quantities of thyroid hormones. J. Clin. Invest. 51: 2077, 1972.PubMedCentralPubMedCrossRefGoogle Scholar
  48. 48.
    Vagenakis A.G., Rapaport B., Azizi F., Portnay G.I., Braverman L.E., Ingbar S.H. Hyperresponse to thyrotropin releasing hormone accompanying small decreases in serum thyroid hormone concentration. J. Clin. Invest. 54: 913, 1974.PubMedCentralPubMedCrossRefGoogle Scholar
  49. 49.
    Saberi M., Utiger R.D. Augmentation of thyrotropin response to thyrotropin releasing hormone following small decreases in serum thyroid hormone concentration. J. Clin. Endocrinol. Metab. 40: 435, 1975.PubMedCrossRefGoogle Scholar
  50. 50.
    Drexhage H.A., Bottazzo G.F., Doniach D., Bitensky L., Chayen L. Evidence for thyroid growth stimulating immunoglobulins in some goitrous thyroid diseases. Lancet 2: 287, 1980.CrossRefGoogle Scholar
  51. 51.
    Schatz H., Floren M., Beckmann F.H. Thyroid growth stimulating immunoglobulins in patients of an iodine-deficient goiter region estimated by 3H-thymidine incorporation into isolated porcine thyroid follicles. Ann. Endocrinol. (Paris) 45: 43A, 1984.Google Scholar
  52. 52.
    Smyth P.P.A., Neylan D., O’Donovan D.K. Association of thyroid stimulating immunoglobulins and thyrotropin-releasing hormone responsiveness in women with endemic goiter. J. Clin. Endocrinol. Metab. 57: 1001, 1983.PubMedCrossRefGoogle Scholar
  53. 53.
    Tanabe T., Izumi M., Yamashita S., Ohtakara S., Morita S., Okamoto S., Nagataki S. Serum thyroglobulin as a good indicator of thyroid suppressibility. J. Steroid Biochem. 20: 1440, 1984.CrossRefGoogle Scholar
  54. 54.
    Ermans A.M., Camus M. Modifications of thyroid function induced by chronic administration of iodide in the presence of “autonomous” thyroid tissue. Acta Endocrinol. (Kbh.) 70: 463, 1972.Google Scholar
  55. 55.
    Peter H., Gerber H., Studer H. Autonomous and TSH dependent growth patterns of human nodular goiter tissue transplanted to thymus dysgenetic nude mice. Ann. Endocrinol. (Kbh.) 45: 81A, 1984.Google Scholar

Copyright information

© Italian Society of Endocrinology (SIE) 1986

Authors and Affiliations

  • F. Vermiglio
    • 1
    • 2
  • S. Benvenga
    • 1
  • R. Melluso
    • 1
  • S. Catalfamo
    • 1
  • P. PrinciJr.
    • 1
  • S. Battiato
    • 1
  • F. Consolo
    • 1
  • F. Trimarchi
    • 1
  1. 1.Istituto di Clinica Medica e Terapia Medica Generale e SpecialeUniversity of MessinaMessinaItaly
  2. 2.Istituto di Clinica MedicaPoliclinico UniversitarioMessinaItaly

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