Autoimmune and Malignant Thyroid Diseases

Within the last decade much knowledge has been gained in our understanding of the etiology and the pathogenesis of autoimmune and malignant thyroid diseases. Based on that, many new diagnostic tools as well as treatment options have occurred, which have now already been applied to patients either on a routine or an experimental level. For this Special Issue of Hormone and Metabolic Research, we requested leading scientists in the thyroid field to contribute research articles within their area of expertise, thereby covering a broad field of thyroid research.

Dr. A. Weetman from Sheffield contributed a well-composed review article on the genetics of autoimmune thyroid diseases. He summarizes recent advances in our understanding of different gene loci including the HLA-D region, the cytotoxic T lymphocyte antigen-4 (CTLA-4) locus, and others on the development of autoimmune thyroid diseases [1]. The importance of the CTLA-4 gene is strengthened by the group of Dr. G. Kahaly from Mainz, Germany who demonstrated that a polymorphism of this gene is associated with the occurrence of a polyglandular autoimmune syndrome [2]. In this context, the group of Dr. A. Eckstein from the University of Essen, Germany, describes a new association between a polymorphism of the GNAS1 gene encoding the α-subunit of the G protein and the course of hyperthyroidism of Graves’ disease [3].

The interaction between environments and the occurrence of autoimmune thyroid diseases is discussed by Dr. L. Bartalena and co-workers from Varese, Italy. They describe clear connections between smoking, stress, drugs, trace elements such as iodine and selenium and other environmental factors, and the modulation of the immune system towards a Th1/Th2 immune response [4]. A more detailed insight into to role of selenium in AITD is given by Dr. L. Duntas, one of the leading experts in this field. Selenium and selenoproteins exert multiple actions, including antioxidant and immunomodulatory effects [5]. He describes the large progress, which has been made in our understanding of the role of this trace element in the physiology and pathophysiology of the thyroid gland. Promising clinical trials have been initiated to study the usefulness of seleno compounds for treatment of patients with AITD.

We also very much appreciate the brilliant contribution from the group of Dr. B. Rees Smith from Cardiff on TSH receptor – autoantibody interactions [6]. Two years ago, this group was the first to describe the crystal structure of the TSH receptor in complex with a thyroid-stimulating autoantibody [7]. In the present paper, the group summarizes the features of two monoclonal antibodies with stimulating and blocking characteristics, which were isolated from a single blood sample of a patient with hypothyroidism who previously presented with hyperthyroidism. Using an elegant technique, this is a clear proof that a patient can produce blocking and stimulating TRAbs at the same time. The authors also show that both antibodies recognize the N-terminal region of the TSH receptor and not two independent regions, as has been suggested by some previous studies.

This Special Issue also focuses on some recent developments on thyroid cancer research. The most prevalent thyroid cancer is that of papillary origin. The T1799A (V600E) BRAF mutation is the most common genetic alteration the pathogenesis of papillary thyroid cancer (PTC). It leads to a constitutive activation of the MAPK pathway. In a large series of PTC patients, the group of Dr. K. W. Schmid from Essen could demonstrate that BRAF has no regulatory influence on the expression of distinct microRNAs [8]. Nonetheless, this study confirms the diagnostic utility of a distinct set of miRNAs to detect PTC irrespective of its histological variant. Importantly, in another paper the same group demonstrates that the use of two different sets of miRNA may represent useful tools to distinguish poorly differentiated thyroid cancer from “pure” PTC [9].

Within the last couple of years important progress has been made in the establishment of new mouse models for thyroid cancer. These mouse models are valuable tools in elucidating molecular genetic changes underlying thyroid carcinogenesis and in identifying potential molecular targets for therapeutic intervention. The review by Dr. Cheng and co-worker gives an excellent overview on mouse models of papillary, follicular, and medullary thyroid carcinomas. In particular, they focus on models for follicular thyroid carcinomas [10], which is in line with their original description of a mouse model for follicular thyroid cancer [11] [12].

Finally, this Special Issue also deals with innovative therapy options for the treatment of thyroid cancer. Dr. C. Spitzweg and colleagues are well known for their work on gene therapy encoding the sodium-iodide-symporter for the treatment of poorly differentiated thyroid cancer and other malignancies. She reviews now the progress which has been made in the field of corrective gene therapy, cytoreductive gene therapy, and immunomodulatory gene therapy [13].

It is our pleasure to present this excellent collection of exper-tise to you, and we are confident that you will enjoy reading the articles.

References

• 1 Weetman AP. The genetics of autoimmune thyroid disease.  Horm Metab Res. 2009;  41 421-425
• 2 Dultz G, Matheis N, Dittmar M, Bender K, Kahaly GJ. CTLA-4 CT60 polymorphism in thyroid and polyglandular autoimmunity.  Horm Metab Res. 2009;  41 426-429
• 3 Glowacka D, Loesch C, Johnson KTM, Mann K, Esser J, Morgenthaler NG, Siffert W, Schmid KW, Eckstein AK. The T393C polymorphism of the Gαs gene (GNAS1) is associated with the course of Graves’ disease.  Horm Metab Res. 2009;  41 430-435
• 4 Tanda ML, Piantanida E, Lai A, Lombardi V, Dalle Mule I, Liparulo L, Pariani N, Bartalena L. Thyroid autoimmunity and environment.  Horm Metab Res. 2009;  41 436-442
• 5 Duntas LH. Selenium and inflammation: underlying anti-inflammatory mechanisms.  Horm Metab Res. 2009;  41 443-447
• 6 Rees Smith B, Sanders J, Evans M, Tagami T, Furmaniak J. TSH receptor – autoantibody interactions.  Horm Metab Res. 2009;  41 448-455
• 7 Sanders J, Chirgadze DY, Sanders P, Baker S, Sullivan A, Bhardwaja A, Bolton J, Reeve M, Nakatake N, Evans M, Richards T, Powell M, Núñez Miguel R, Blundell TL, Furmaniak J, Rees Smith B. Crystal structure of the TSH receptor in complex with a thyroid-stimulating autoantibody.  Thyroid. 2007;  17 395-410
• 8 Sheu SY, Grabellus F, Schwertheim S, Handke S, Worm K, Schmid KW. Lack of correlation between BRAF V600E mutational status and the expression profile of a distinct set of miRNAs in papillary thyroid carcinoma.  Horm Metab Res. 2009;  41 482-487
• 9 Schwertheim S, Sheu SY, Worm K, Grabellus F, Schmid KW. Analysis of deregulated miRNAs is helpful to distinguish poorly differentiated thyroid carcinoma from papillary thyroid carcinoma.  Horm Metab Res. 2009;  41 475-481
• 10 Zhu XG, Cheng SY. Modeling thyroid cancer in the mouse.  Horm Metab Res. 2009;  41 488-499
• 11 Suzuki H, Willingham MC, Cheng SY. Mice with a mutation in the thyroid hormone receptor beta gene spontaneously develop thyroid carcinoma: a mouse model of thyroid carcinogenesis.  Thyroid. 2002;  12 963-969
• 12 Ying H, Suzuki H, Zhao L, Willingham MC, Meltzer P, Cheng SY. Mutant thyroid hormone receptor beta represses the expression and transcriptional activity of peroxisome proliferator-activated receptor gamma during thyroid carcinogenesis.  Cancer Res. 2003;  63 5274-5280
• 13 Spitzweg C. Gene therapy in thyroid cancer.  Horm Metab Res. 2009;  41 500-509

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