This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints, Permissions and Rights Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Tonacchera, M. Articles by Chiovato, L. Search for Related Content PubMed PubMed Citation Articles by Tonacchera, M. Articles by Chiovato, L.

Thyroid Resistance to TSH Complicated by Autoimmune Thyroiditis

Dipartimento di Endocrinologia e Metabolismo, Ortopedia e Traumatologia, Medicina del Lavoro, Università di Pisa, 56124 Cisanello, Pisa, Italy

Address all correspondence and requests for reprints to: Dr. Massimo Tonacchera, Dipartimento di Endocrinologia, Università degli Studi di Pisa, Via Paradisa 2, 56124, Cisanello, Pisa, Italy.

Abstract

In this report we describe a 47-yr-old woman who was referred to our department for elevated serum TSH associated with normal free thyroid hormone levels, suggesting subclinical hypothyroidism. When first seen she was clinically euthyroid, and her thyroid gland was normal in size both at palpation and by ultrasound. The ultrasound of the thyroid showed a normoechogenic pattern. Serum thyroid hormone levels were confirmed to be within the normal range, whereas the serum TSH concentration was moderately elevated (13.4 µU/ml). Tests for antithyroperoxidase, antithyroglobulin, and anti-TSH receptor antibodies gave negative results. The only son of the proband, a clinically euthyroid 23-yr-old man, had a slightly elevated serum TSH concentration (5.2 µU/ml) with normal free thyroid hormone levels. The entire coding regions of the TSH receptor gene were sequenced in the proband, the son, and the father of the son. Genetic analysis in the proband showed a homozygous inactivating mutation of the TSH receptor. The mutation consisted of the substitution of an alanine in place of proline at position 162 in the extracellular portion of the receptor. The son was heterozygous for Pro¹⁶²Ala. Only the wild-type sequence was found in the father. Both the proband and her son were considered to have compensated TSH resistance and were not treated. After 2 yr of follow-up, new thyroid tests were performed in the proband and showed a marked increase in the serum TSH concentration (61 µU/ml) compared with the initially observed value; serum free T₄ and T₃ levels were in the low normal range. At that time, tests for antithyroglobulin and antithyroperoxidase antibodies gave positive results, and thyroid echography showed a gland of normal size, but with a diffuse hypoechogenic pattern. In conclusion, we describe the first case of compensated TSH resistance evolving to mild hypothyroidism due to the appearance of a chronic autoimmune thyroiditis.

This article has been cited by other articles:

				A. Nicoletti, M. Bal, G. De Marco, L. Baldazzi, P. Agretti, S. Menabo, E. Ballarini, A. Cicognani, M. Tonacchera, and A. Cassio Thyrotropin-Stimulating Hormone Receptor Gene Analysis in Pediatric Patients with Non-Autoimmune Subclinical Hypothyroidism J. Clin. Endocrinol. Metab., November 1, 2009; 94(11): 4187 - 4194. [Abstract] [Full Text] [PDF]

				B. Biondi and D. S. Cooper The Clinical Significance of Subclinical Thyroid Dysfunction Endocr. Rev., February 1, 2008; 29(1): 76 - 131. [Abstract] [Full Text] [PDF]

				D. Calebiro, T. de Filippis, S. Lucchi, C. Covino, S. Panigone, P. Beck-Peccoz, D. Dunlap, and L. Persani Intracellular entrapment of wild-type TSH receptor by oligomerization with mutants linked to dominant TSH resistance Hum. Mol. Genet., October 15, 2005; 14(20): 2991 - 3002. [Abstract] [Full Text] [PDF]

				S M Park and V K K Chatterjee Genetics of congenital hypothyroidism J. Med. Genet., May 1, 2005; 42(5): 379 - 389. [Abstract] [Full Text] [PDF]

				M. Tonacchera, A. Perri, G. De Marco, P. Agretti, M. E. Banco, C. Di Cosmo, L. Grasso, P. Vitti, L. Chiovato, and A. Pinchera Low Prevalence of Thyrotropin Receptor Mutations in a Large Series of Subjects with Sporadic and Familial Nonautoimmune Subclinical Hypothyroidism J. Clin. Endocrinol. Metab., November 1, 2004; 89(11): 5787 - 5793. [Abstract] [Full Text] [PDF]

				M. De Felice and R. Di Lauro Thyroid Development and Its Disorders: Genetics and Molecular Mechanisms Endocr. Rev., October 1, 2004; 25(5): 722 - 746. [Abstract] [Full Text] [PDF]

				N. Jordan, N. Williams, J. W. Gregory, C. Evans, M. Owen, and M. Ludgate The W546X Mutation of the Thyrotropin Receptor Gene: Potential Major Contributor to Thyroid Dysfunction in a Caucasian Population J. Clin. Endocrinol. Metab., March 1, 2003; 88(3): 1002 - 1005. [Abstract] [Full Text] [PDF]

				L. Alberti, M. C. Proverbio, S. Costagliola, R. Romoli, B. Boldrighini, M. C. Vigone, G. Weber, G. Chiumello, P. Beck-Peccoz, and L. Persani Germline Mutations of TSH Receptor Gene as Cause of Nonautoimmune Subclinical Hypothyroidism J. Clin. Endocrinol. Metab., June 1, 2002; 87(6): 2549 - 2555. [Abstract] [Full Text] [PDF]