High Serum Circulating Telopeptide Type I in Multinodular Goiter

Abstract

Recently, concentrations of serum carboxy-terminal-1-telopeptide (ICTP), a marker of bone collagen resorption, were found to be more sensitive than sex hormone-binding globulin (SHBG) in identifying peripheral overexposure to thyroid hormones in exogenous subclinical hyperthyroidism. The aim of the present study was to assess serum ICTP and SHBG in multinodular goiter with (pretoxic goiter) or without biochemical evidence of endogenous subclinical hyperthyroidism. Forty-five women affected by multinodular goiter were enrolled in this study. They were subdivided into two groups: group 1, consisting of 27 patients affected by pretoxic goiter; group 2, consisting of 18 patients affected by non toxic goiter; group 3, consisting of thirty-six euthyroid women matched with the other groups for age and lifestyle. In group 1, serum ICTP (mean ± SD: 5.8 ± 2.9 µg/l) concentrations were significantly higher when compared either to group 2 (3.6 ± 1.2 µg/l; p < 0.02) or controls (2.7 ± 0.7 µg/l; p < 0.0001); serum ICTP concentrations were also slightly but significantly higher in patients of group 2 compared to controls (p < 0.003). In contrast, mean serum SHBG concentrations did not show any difference among the three groups. No significant correlation was found between serum TSH and ICTP concentrations, while a weak positive correlation (p < 0.05) was only found between serum FT₃ and ICTP concentrations when data from the two patient groups were analyzed together. Moreover, when we subdivided patients into pre- and postmenopausal patients, we observed that SHBG but not ICTP serum concentrations were influenced by estrogenic status. In summary, the measurement of serum ICTP seems to be more suitable than SHBG for identifying those with a higher degree of peripheral thyroid hormone exposure in women affected by endogenous subclinical hyperthyroidism.

Subclinical Hyperthyroidism - Nodular Goiter - Telopeptide

References

• 1 Parle J V, Maisonneuve P, Sheppard M C, Boyle P, Franklyn J A. Prediction of all-cause and cardiovascular mortality in elderly people from one low serum thyrotropin result: a 10-year cohort study.  Lancet. 2001;  358 861-865
• 2 Fatourechi V. Adverse effects of subclinical hyperthyroidism.  Lancet. 2001;  358 856-857
• 3 Toft A D. Clinical practice. Subclinical hyperthyroidism.  N Engl J Med. 2001;  345 512-516
• 4 Cooper D S. Subclinical thyroid disease: a clinician's perspective.  Ann Intern Med. 1998;  129 135-138
• 5 Bauer D C, Ettinger B, Nevitt M C, Stone K L. Group FtSoOFR . Risk for Fracture in Women with Low Serum Levels of Thyroid-Stimulatin Hormone.  Ann Intern Med. 2001;  134 561-568
• 6 Sawin C T, Geller A, Wolf P A. et al . Low serum thyrotropin concentrations as a risk factor for atrial fibrillation in older persons.  N Engl J Med. 1994;  331 1249-1252
• 7 Biondi B, Palmieri E A, Fazio S. et al . Endogenous subclinical hyperthyroidism affects quality of life and cardiac morphology and function in young and middle-aged patients.  J Clin Endocrinol Metab. 2000;  85 4701-4705
• 8 Ross D S, Ardisson L J, Meskell M J. Measurement of thyrotropin in clinical and subclinical hyperthyroidism using a new chemiluminescent assay.  J Clin Endocrinol Metab. 1989;  69 684-688
• 9 Kasagi K, Kousaka T, Misaki T, Iwata M, Alam M S, Konishi J. Comparison of serum thyrotrophin concentrations determined by a third generation assay in patients with various types of overt and subclinical thyrotoxicosis [In Process Citation].  Clin Endocrinol (Oxf). 1999;  50 185-189
• 10 Franklyn J A, Black E G, Betteridge J, Sheppard M C. Comparison of second and third generation methods for measurement of serum thyrotropin in patients with overt hyperthyroidism, patients receiving thyroxine therapy, and those with non-thyroidal illness.  J Clin Endocrinol Metab. 1994;  78 1368-1371
• 11 Meier C A, Maisey M N, Lowry A, Muller J, Smith M A. Interindividual differences in the pituitary-thyroid axis influence the interpretation of thyroid function tests.  Clin Endocrinol (Oxf). 1993;  39 101-107
• 12 Spencer C A, LoPresti J S, Patel A. et al . Applications of a new chemiluminometric thyrotropin assay to subnormal measurement.  J Clin Endocrinol Metab. 1990;  70 453-460
• 13 Lecomte P, Lecureuil N, Osorio-Salazar C, Lecureuil M, Valat C. Effects of suppressive doses of levothyroxine treatment on sex-hormone- binding globulin and bone metabolism.  Thyroid. 1995;  5 19-23
• 14 Roti E, Minelli R, Gardini E, Braverman L E. The use and misuse of thyroid hormone.  Endocr Rev. 1993;  14 401-423
• 15 de Rosa G, Testa A, Maussier M L, Calla C, Astazi P, Albanese C. A slightly suppressive dose of L-thyroxine does not affect bone turnover and bone mineral density in pre- and postmenopausal women with non-toxic goiter.  Horm Metab Res. 1995;  27 503-507
• 16 Faber J, Perrild H, Johansen J S. Bone Gla protein and sex hormone-binding globulin in non-toxic goiter: parameters for metabolic status at the tissue level.  J Clin Endocrinol Metab. 1990;  70 49-55
• 17 Faber J, Gam A, Siersbaek-Nielsen K. Improved sensitivity of serum thyrotropin measurements. Studies on serum sex hormone-binding globulin in patients with reduced serum thyrotropin.  Acta Endocrinol (Copenhagen). 1990;  123 535-540
• 18 Foldes J, Lakatos P, Zsadanyi J, Horvath C. Decreased serum IGF-I and dehydroepiandrosterone sulphate may be risk factors for the development of reduced bone mass in postmenopausal women with endogenous subclinical hyperthyroidism.  Eur J Endocrinol. 1997;  136 277-281
• 19 Giagulli V A, Vermeulen A. Increased plasma 5 alpha-androstane-3 alpha, 17 beta-diol glucuronide concentration in clinically euthyroid women with suppressed plasma thyrotropin levels: further evidence for generalized tissue overexposure to thyroid hormones in these subjects.  J Clin Endocrinol Metab. 1992;  74 1465-1467
• 20 Tenerz A, Forberg R, Jansson R. Is a more active attitude warranted in patients with subclinical thyrotoxicosis?.  J Intern Med. 1990;  228 229-233
• 21 Persani L, Preziati D, Matthews C H, Sartorio A, Chatterjee V K, Beck-Peccoz P. Serum levels of carboxyterminal cross-linked telopeptide of type I collagen (ICTP) in the differential diagnosis of the syndromes of inappropriate secretion of TSH.  Clin Endocrinol (Oxf). 1997;  47 207-214
• 22 Engler H, Oettli R E, Riesen W F. Biochemical markers of bone turnover in patients with thyroid dysfunctions and in euthyroid controls: a cross-sectional study.  Clin Chim Acta. 1999;  289 159-172
• 23 Miyakawa M, Tsushima T, Demura H. Carboxy-terminal propeptide of type 1 procollagen (P1CP) and carboxy-terminal telopeptide of type 1 collagen (1CTP) as sensitive markers of bone metabolism in thyroid disease.  Endocr J. 1996;  43 701-708
• 24 Isaia G C, Roggia C, Gola D. et al . Bone turnover in hyperthyroidism before and after thyrostatic management.  J Endocrinol Invest. 2000;  23 727-731
• 25 Toivonen J, Tahtela R, Laitinen K, Risteli J, Valimaki M J. Markers of bone turnover in patients with differentiated thyroid cancer with and following withdrawal of thyroxine suppressive therapy.  Eur J Endocrinol. 1998;  138 667-673
• 26 Jodar Gimeno E, Munoz-Torres M, Escobar-Jimenez F, Quesada C harneco, Luna del Castillo J D, Olea N. Identification of metabolic bone disease in patients with endogenous hyperthyroidism: role of biological markers of bone turnover.  Calcif Tissue Int. 1997;  61 370-376
• 27 Loviselli A, Mastinu R, Rizzolo E. et al . Circulating telopeptide type I is a peripheral marker of thyroid hormone action in hyperthyroidism and during levothyroxine suppressive therapy.  Thyroid. 1997;  7 561-566
• 28 Martino E, Loviselli A, Velluzzi F. et al . Endemic goiter and thyroid function in central-southern Sardinia. Report on an extensive epidemiological survey.  J Endocrinol Invest. 1994;  17 653-657
• 29 Surks M I, Ocampo E. Subclinical thyroid disease.  Am J Med. 1996;  100 217-223
• 30 Sallis J F, Haskell W L, Wood P D. et al . Physical activity assessment methodology in the Five-City Project.  Am J Epidemiol. 1985;  121 91-106
• 31 Aghini-Lombardi F, Antonangeli L, Martino E. et al . The spectrum of thyroid disorders in an iodine-deficient community: the Pescopagano survey.  J Clin Endocrinol Metab. 1999;  84 561-566
• 32 Gurlek A, Gedik O. Effect of endogenous subclinical hyperthyroidism on bone metabolism and bone mineral density in premenopausal women.  Thyroid. 1999;  9 539-543
• 33 Garnero P, Vassy V, Bertholin A, Riou J P, Delmas P D. Markers of bone turnover in hyperthyroidism and the effects of treatment.  J Clin Endocrinol Metab. 1994;  78 955-999
• 34 Langdahl B L, Loft A G, Moller N. et al . Skeletal responsiveness to thyroid hormone is not altered at menopause.  Bone. 1996;  19 557-564
• 35 Bartalena L, Martino E, Velluzzi F. et al . The lack of nocturnal serum thyrotropin surge in patients with nontoxic nodular goiter may predict the subsequent occurrence of hyperthyroidism.  J Clin Endocrinol Metab. 1991;  73 604-608
• 36 Berghout A, Wiersinga W M, Smits N J, Touber J L. Interrelationships between age, thyroid volume, thyroid nodularity, and thyroid function in patients with sporadic nontoxic goiter.  Am J Med. 1990;  89 602-608
• 37 Bregengard C, Kirkegaard C, Faber J. et al . Relationships between serum thyrotropin, serum free thyroxine (T4), and 3,5,3'-triiodothyronine (T3) and the daily T4 and T3 production rates in euthyroid patients with multinodular goiter.  J Clin Endocrinol Metab. 1987;  65 258-261
• 38 Dremier S, Coppee F, Delange F, Vassart G, Dumont J E, van Sande J. Clinical review 84: Thyroid autonomy: mechanism and clinical effects.  J Clin Endocrinol Metab. 1996;  81 4187-4193
• 39 Kirkegaard C, Bregengard C. Assessment of the clinically significant TSH response to TRH in patients with nodular goitre.  Horm Metab Res. 1988;  20 357-359
• 40 Romaldini J H, Farah C S, Werner R S, Dall'Antonia Junior R P, Camargo R S. ‘In vitro' study on release of cyclic AMP and thyroid hormone in autonomously functioning thyroid nodules.  Horm Metab Res. 1988;  20 510-512
• 41 Hoshino H, Kushida K, Takahashi M. et al . Characteristics of biochemical markers in patients with metabolic bone disorders.  Endocr Res. 1998;  24 55-64
• 42 Takahashi M, Kushida K, Kawana K, Hoshino H, Inoue T. Discrimination ability of pyridinoline crosslinks related markers for bone resorption in postmenopause and osteoporosis.  Endocr Res. 1997;  23 105-117
• 43 Takahashi M, Kushida K, Hoshino H, Ohishi T, Inoue T. Evaluation of bone turnover in postmenopause, vertebral fracture, and hip fracture using biochemical markers for bone formation and resorption.  J Endocrinol Invest. 1997;  20 112-117
• 44 Yasumizu T, Hoshi K, Iijima S, Asaka A. Serum concentration of the pyridinoline cross-linked carboxyterminal telopeptide of type I collagen (ICTP) is a useful indicator of decline and recovery of bone mineral density in lumbar spine: analysis in Japanese postmenopausal women with or without hormone replacement.  Endocr J. 1998;  45 45-51
• 45 Brenta G, Schnitman M, Gurfinkiel M. et al . Variations of sex hormone-binding globulin in thyroid dysfunction [In Process Citation].  Thyroid. 1999;  9 273-277
• 46 Hammond G L, Langley M S, Robinson P A. A liquid-phase immunoradiometric assay (IRMA) for human sex hormone binding globulin (SHBG).  J Steroid Biochem. 1985;  23 451-460
• 47 Pasquali R, Vicennati V, Bertazzo D. et al . Determinants of sex hormone-binding globulin blood concentrations in premenopausal and postmenopausal women with different estrogen status. Virgilio-Menopause-Health Group.  Metabolism. 1997;  46 5-9