**9. References**


[7] 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

Thyroid Hormone Excess: Graves' Disease 179

[24] Vitti P, Valente WA, Ambesi-Impiombato FS, et al: Graves' IgG stimulation of continuously cultured rat thyroid cells: a sensitive and potentially useful clinical assay. *J* 

[25] Rapoport B, Greenspan FS, Filetti S, et al: Clinical experience with a human thyroid cell bioassay for thyroid-stimulating immunoglobulin. *J Clin Endocrinol Metab* 1984; 58:332-

[26] Mariotti S, del Prete GF, Mastromauro C, et al: The autoimmune infiltrate of Basedow's disease: analysis of clonal level and comparison with Hashimoto's thyroiditis. *Exp Clin* 

[27] Watson PF, Pickerill AP, Davies R, et al: Analysis of cytokine gene expression in Graves' disease and multinodular goiter. *J Clin Endocrinol Metab* 1994; 79:355-360. [28] Leovey A, Nagy E, Balazs G, et al: Lymphocytes resided in the thyroid are the main source of TSH-receptor antibodies in Basedow's-Graves' disease?. *Exp Clin Endocrinol*

[29] Burch HB, Wartofsky L: Graves' ophthalmopathy: current concepts regarding

[30] Forbes G, Gorman CA, Brennan MD, et al: Ophthalmopathy of Graves' disease: computerized volume measurements of the orbital fat and muscle. *Am J Neuroradiol*

[31] Villadolid MC, Nagataki S, Uetani M, et al: Untreated Graves' disease patients without clinical ophthalmopathy demonstrate a high frequency of extraocular muscle (EOM)

[33] Burch HB, Lahiri S, Bahn R, et al: Superoxide radical production stimulates human retroocular fibroblast proliferation in Graves' ophthalmopathy. *Exp Eye Res* 1997;

[34] Vanderpump MP, Tunbridge WM, French JM, et al: The incidence of thyroid disorders in the community: A twenty-year follow-up of the Whickham survey. *Clin Endocrinol* 

[35] Perros P, Kendall-Taylor P: Pathogenetic mechanisms in thyroid-associated

[36] Fernandez-Sanchez JR, Vara-Thorbeck R, Garbin-Fuentes I, et al: Graves' ophthalmopathy after subtotal thyroidectomy and radioiodine therapy. *Br J Surg* 1993;

[37] Bartalena L, Pinchera A, Martino E, et al: Relation between therapy for hyperthyroidism

[38] Bartalena L, Marcocci C, Bogazzi F, et al: Use of corticosteroids to prevent progression of Graves' ophthalmopathy after radioiodine therapy for hyperthyroidism. *N Engl J* 

[39] Weetman AP, Wiersinga WM: Current management of thyroid-associated ophthalmopathy in Europe: results of an international survey. *Clin Endocrinol (Oxf)*

and the course of Graves' ophthalmopathy. *N Engl J Med* 1998; 338:73-78.

enlargement by magnetic resonance. *J Clin Endocrinol Metab* 1995; 80:2830-2833. [32] Metcalfe RA, Weetman AP: Stimulation of extraocular muscle fibroblasts by cytokines and hypoxia: possible role in thyroid-associated ophthalmopathy. *Clin Endocrinol (Oxf)*

pathogenesis and management. *Endocr Rev* 1993; 14:747-793.

*Endocrinol Invest* 1982; 5:179-182.

*Endocrinol* 1991; 97:139-146.

1992; 99:147-150.

1986; 7:651-656

1994; 40:67-72.

65:311-316.

80:1134-1136.

1998; 49:21-28.

*(Oxf)* 1995; 43:55-68.

*Med* 1989; 321:1349-1352..

ophthalmopathy. *J Intern Med* 1992; 231:205-211.

338.


[24] Vitti P, Valente WA, Ambesi-Impiombato FS, et al: Graves' IgG stimulation of continuously cultured rat thyroid cells: a sensitive and potentially useful clinical assay. *J Endocrinol Invest* 1982; 5:179-182.

178 Thyroid Hormone

84:561-566

1604.

289.

*Invest* 1993; 16:384-391.

*Otago Med Sch* 1956; 34:11-12.

[7] 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;

[8] Bülow Pedersen I, Laurberg P, Knudsen N, et al: Increase in incidence of hyperthyroidism predominantly occurs in young people after iodine fortification of salt

[9] Chiovato L, Lapi P, Fiore E, et al: Thyroid autoimmunity and female gender. *J Endocrinol* 

[10] Amino N, Tada H, Hidaka Y: Postpartum autoimmune thyroid syndrome: a model of

[12] Holm IA, Manson JE, Michels KB, et al: Smoking and other lifestyle factors and the risk

[13] Adams DD, Purves HD: Abnormal responses in the assay of thyrotropin. *Proc Univ* 

[14] McKenzie JM, Zakarija M: Fetal and neonatal hyperthyroidism and hypothyroidism

[15] McLachlan SM, Dickinson AM, Malcolm A, et al: Thyroid autoantibody synthesis by cultures of thyroid and peripheral blood lymphocytes. I: Lymphocyte markers and

[16] Okuda J, Akamizu T, Sugawa H, et al: Preparation and characterization of monoclonal antithyrotropin receptor antibodies obtained from peripheral lymphocytes of hypothyroid patients with primary myxedema. *J Clin Endocrinol Metab* 1994; 79:1600-

[17] Bolton J,Sanders J,Oda Y,et al.Measurment of thyroid stimulating hormone receptor

[18] CostagliolaS,Morgenthaler NG,Hoermann R,et al.Second generation assay for thyrotropin receptor antibodies has superior diagnostic sensitivity for Graves disease.J

[19] Pinchera A, Liberti P, Martino E, et al: Effects of antithyroid therapy on the long-acting thyroid stimulator and the antithyroglobulin antibodies. *J Clin Endocrinol* 1969; 29:231-

[20] Fenzi GF, Hashizume K, Roudeboush CP, et al: Changes in thyroid-stimulating immunoglobulins during antithyroid therapy. *J Clin Endocrinol Metab* 1979; 48:572-576. [21] Costagliola S, Morgenthaler NG, Hoermann R, et al: Second generation assay for thyrotropin receptor antibodies has superior diagnostic sensitivity for Graves' disease. *J* 

[22] Schott M, Scherbaum WA, Morgenthaler NG: Thyrotropin receptor autoantibodies in

[23] Ludgate M, Perret J, Parmentier M, et al: Use of the recombinant human thyrotropin receptor (TSH-R) expressed in mammalian cell lines to assay TSH-R autoantibodies. *Mol* 

in Denmark. *J Clin Endocrinol Metab* 2006; 91:3830-3834,2006.

aggravation of autoimmune disease. *Thyroid* 1999; 9:705-713.

[11] Bartalena L: Smoking and Graves' disease. *J Endocrinol Invest* 2002; 25:402.

of Graves' hyperthyroidism. *Arch Intern Med* 2005; 165:1606-1611.

due to maternal TSH receptor antibodies. *Thyroid* 1992; 2:155-159.

response to pokeweed mitogen. *Isr J Med Sci* 1983; 52:45-53.

autoantibodies by ELISA.Clin Chem 1999;45:2285-2287.

Graves' disease. *Trends Endocrinol Metab* 2005; 16:243-248.

Clin Endocrinol Metab 1999;84:90-97.

*Clin Endocrinol Metab* 1999; 84:90-97.

*Cell Endocrinol* 1990; 73:R13-R18.


[40] Aniszewski JP, Valyasevi RW, Bahn RS: Relationship between disease duration and predominant orbital T cell subset in Graves' ophthalmopathy. *J Clin Endocrinol Metab* 2000; 85:776-780.

**Section 4** 

**Thyroid Hormone Deficiency** 


**Thyroid Hormone Deficiency** 

180 Thyroid Hormone

2000; 85:776-780.

17:939-994.

80:468-472.

Metab 1998;83:3777-3781.

Sep; 90(9):5234-5240.

*Endocrinol (Copenh)* 1989; 120:689-701.

Protocol.Nucl Med Commun 2004;25:675-682.

and perspectives. *Endocr Rev* 2000; 21:168-199.

perspectives. *J Endocrinol Invest* 2004; 27:295-301.

thyroid diseases. *J Clin Endocrinol Metab* 1990; 71:661-669.

thyroid peroxidase autoantibodies?. *Thyroid* 2004; 14:510-520.

[40] Aniszewski JP, Valyasevi RW, Bahn RS: Relationship between disease duration and predominant orbital T cell subset in Graves' ophthalmopathy. *J Clin Endocrinol Metab*

[41] Bartalena L, Pinchera A, Marcocci C: Management of Graves' ophthalmopathy: reality

[42] Bartalena L, Wiersinga WM, Pinchera A: Graves' ophthalmopathy: state of the art and

[43] Mariotti S, Caturegli P, Piccolo P, et al: Antithyroid peroxidase autoantibodies in

[44] McLachlan SM, Rapoport B: Thyroid peroxidase as an autoantigen. *Thyroid* 2007;

[45] McLachlan SM, Rapoport B: Why measure thyroglobulin autoantibodies rather than

[46] Mariotti S, Barbesino G, Caturegli P, et al: Assay of thyroglobulin in serum with thyroglobulin autoantibodies: an unobtainable goal?. *J Clin Endocrinol Metab* 1995;

[47] Davis TF.Thyroid stimulating antibodies predict hyperthyroidism.J Clin Endocrinol

[48] Hedley AJ, Young RE, Jones SJ, et al: Antithyroid drugs in the treatment of hyperthyroidism of Graves' disease: long-term follow-up of 434 patients. Scottish

[50] Vitti P, Rago T, Chiovato L, et al: Clinical features of patients with Graves' disease undergoing remission after antithyroid drug treatment. *Thyroid* 1997; 7:369-375. [51] Razvi S,Basu A,McIntyre EA,et al.Low failure rate of fixed administered activity of 400 MBq of I131 with pre-treatment with carbimazole for thyrotoxicosis:the Gateshead

[52] Franklyn JA, Daykin J, Drolc Z, et al: Long-term follow-up of treatment of thyrotoxicosis by three different methods. *Clin Endocrinol (Oxf)* 1991; 34:71-76. [53] Dobyns BM, Sheline GE, Workman JB, et al: Malignant and benign neoplasms of the thyroid in patients treated for hyperthyroidism: a report of the Cooperative Thyrotoxicosis Therapy Follow-Up Study. *J Clin Endocrinol Metab* 1974; 38:976-998. [54] Kahaly GJ, Pitz S, Hommel G, et al: Randomized, single blind trial of intravenous versus oral steroid monotherapy in Graves' orbitopathy. *J Clin Endocrinol Metab* 2005

[55] Prummel MF, Mourits MP, Berghout A, et al: Prednisone and cyclosporine in the treatment of severe Graves' ophthalmopathy. *N Engl J Med* 1989; 321:1353-1359.

Automated Follow-Up Register Group. *Clin Endocrinol (Oxf)* 1989; 31:209-218. [49] Schleusener H, Schwander J, Fischer C, et al: Prospective multicentre study on the prediction of relapse after antithyroid drug treatment in patients with Graves' disease [published erratum appears in Acta Endocrinol (Copenh) 1989 Aug;121(2):304]. *Acta* 

**Chapter 7** 

© 2012 Monzani et al., licensee InTech. This is an open access chapter distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

© 2012 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution,

**Mild Thyroid Deficiency in the Elderly** 

Subclinical hypothyroidism (sHT) is defined as serum thyrotropin-stimulating hormone (TSH) concentration above the statistically defined upper limit of the reference range in the face of serum free T4 (FT4) and free T3 (FT3) concentrations within the normal range (Ross, 2004). sHT is a frequent condition among the general population, especially middle-aged and elderly women (Canaris et al., 2000). Depending on the degree of TSH elevation, sHT has been associated with hyperlipidemia, intermediary metabolism alterations, arterial hypertension and cardiovascular disease (CVD) as well as neuropsychiatric features, including cognitive impairment (Ashizawa et al., 2010; Biondi & Cooper., 2008; Cappola et al., 2006; Ceresini et al., 2010; Mitrou et al., 2011; Monzani et al., 2006; Rodondi et al., 2010; Tan et al., 2008; Tappy, 1987). Interestingly, the analysis of variation in thyroid function tests in healthy volunteers has shown that the physiological individual reference ranges for test results are narrow compared with laboratory references (Andersen et al., 2002). This finding suggests that a test result within laboratory reference limits is not necessarily normal for an individual. Giving that serum TSH responds with logarithmically amplified degree to minor changes in serum T4 and T3, abnormal serum TSH may indicate that T4 and T3 are not normal for an individual although still within the laboratory references. These data point out that the distinction between subclinical and overt thyroid failure (elevated serum TSH and low T4 and/or T3) is somewhat arbitrary. Indeed, for the same degree of thyroid function abnormality, the diagnosis depends to a considerable extent on the position of the patient's

Because sHT is mainly detected as a biochemical TSH abnormality, the definition of the TSH reference range represents a critical point, especially in the elderly (Baloch et al., 2003; Olsen, 1978; Dayan et al., 2001). In the past, the upper normal limit of TSH was considered about 10 mIU/L with the first-generation TSH RIA assay while, the current normal reference range of serum TSH concentration is around 0.45 to 4.5 mIU/L (Biondi & Cooper, 2008; Surks et al.,

and reproduction in any medium, provided the original work is properly cited.

Giuseppe Pasqualetti, Angela Dardano, Sara Tognini,

normal set point for T4 and T3 within the laboratory reference range.

Antonio Polini and Fabio Monzani

http://dx.doi.org/10.5772/48805

**1. Introduction** 

Additional information is available at the end of the chapter
