This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Purchase Article View Shopping Cart 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 Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Hansen, P. S. Articles by Hegedüs, L. Search for Related Content PubMed PubMed Citation Articles by Hansen, P. S. Articles by Hegedüs, L.

Major Genetic Influence on the Regulation of the Pituitary-Thyroid Axis: A Study of Healthy Danish Twins

Department of Endocrinology M (P.S.H., T.H.B., L.H.), Odense University Hospital, and The Danish Twin Registry (P.S.H., K.O.K.), Epidemiology, Institute of Public Health, University of Southern Denmark, DK-5000 Odense C, Denmark; and Danish Epidemiology Science Centre (T.I.A.S.), Institute of Preventive Medicine, Copenhagen University Hospital, DK-1399 Copenhagen K, Denmark

Address all correspondence and requests for reprints to: Pia Skov Hansen, The Danish Twin Registry, Epidemiology, Institute of Public Health, University of Southern Denmark, Odense, Sdr. Boulevard 23A, DK-5000 Odense C, Denmark. E-mail: piaskovhansen{at}dadlnet.dk.

Intraindividual variation is smaller than the interindividual variation in serum TSH, free T₄, and free T₃ concentrations. This suggests that each individual may have a genetically determined thyroid function set-point.

A representative sample of self-reported healthy twin pairs was identified through the Danish Twin Registry. A total of 284 monozygotic (MZ), 286 dizygotic same-sex (DZ), and 120 opposite-sex (OS) twin pairs were investigated. A classical twin study was performed. After adjustment for age, sex, and other covariates, the intraclass correlations of serum TSH, free T₄, and free T₃ were calculated. To elucidate the relative importance of hereditary and environmental factors on the variation of these hormone levels, quantitative genetic modeling was used.

The intraclass correlations were consistently higher for MZ twin pairs than for DZ twin pairs. Regression analysis suggested that iodine intake played a small but significant role for the concentration of serum TSH and free T₄, whereas cigarette smoking was without influence. In quantitative genetic modeling, the heritability (with 95% confidence intervals) accounted for 64% (57–70%) of the variation in serum TSH concentration and 65% (58–71%) and 64% (57–70%), for the concentrations of free T₄ and free T₃, respectively.

Genetic factors play a substantial role in controlling the pituitary-thyroid axis, indicating that each individual has a genetically determined thyroid function set-point. Whether this is of importance when treating individuals in whom pituitary-thyroid function has been disrupted by, e.g. hypo- or hyperthyroidism, remains to be clarified.

This work was supported by grants from the Foundation of 17-12-1981, the Agnes and Knut Mørks Foundation, the Novo Nordisk Foundation, the Foundation of Medical Research in the County of Funen, Else Poulsens Mindelegat, the Foundation of Direktør Jacob Madsen and Hustru Olga Madsen, the Foundation of Johan Boserup and Lise Boserup, the A. P. Møller and Hustru Chastine McKinney Møllers Foundation, and the Clinical Research Institute, Odense University. Perkin-Elmer/Wallac, Turku, Finland, kindly provided the kits for determination of serum TSH, freeT₄, freeT₃, TgAb, and TPOAb.

Abbreviations: A, Additive component; AIC, Akaike’s information criterion; BMI, body mass index; C, shared/common environmental component; CV, coefficient(s) of variation; D, dominant genetic component; DZ, dizygotic same-sex; E, unique environmental component; lnTSH, the natural logarithm of the serum TSH level; MZ, monozygotic; OS, opposite-sex; TgAb, thyroglobulin antibody; TPOAb, thyroid peroxidase antibody.

This article has been cited by other articles:

				W. M. van der Deure, P. S. Hansen, R. P. Peeters, K. O. Kyvik, E. C. H. Friesema, L. Hegedus, and T. J. Visser Thyroid Hormone Transport and Metabolism by Organic Anion Transporter 1C1 and Consequences of Genetic Variation Endocrinology, October 1, 2008; 149(10): 5307 - 5314. [Abstract] [Full Text] [PDF]

				V. Panicker, S. G. Wilson, T. D. Spector, S. J. Brown, B. S. Kato, P. W. Reed, M. Falchi, J. B. Richards, G. L. Surdulescu, E. M. Lim, et al. Genetic Loci Linked to Pituitary-Thyroid Axis Set Points: A Genome-Wide Scan of a Large Twin Cohort J. Clin. Endocrinol. Metab., September 1, 2008; 93(9): 3519 - 3523. [Abstract] [Full Text] [PDF]

				V. Panicker, C. Cluett, B. Shields, A. Murray, K. S. Parnell, J. R. B. Perry, M. N. Weedon, A. Singleton, D. Hernandez, J. Evans, et al. A Common Variation in Deiodinase 1 Gene DIO1 Is Associated with the Relative Levels of Free Thyroxine and Triiodothyronine J. Clin. Endocrinol. Metab., August 1, 2008; 93(8): 3075 - 3081. [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]

				P. S. Hansen, T. H. Brix, I. Iachine, T. I. A. Sorensen, K. O. Kyvik, and L. Hegedus Genetic and environmental interrelations between measurements of thyroid function in a healthy Danish twin population Am J Physiol Endocrinol Metab, March 1, 2007; 292(3): E765 - E770. [Abstract] [Full Text] [PDF]

				F. J. de Jong, R. P. Peeters, T. den Heijer, W. M. van der Deure, A. Hofman, A. G. Uitterlinden, T. J. Visser, and M. M. B. Breteler The Association of Polymorphisms in the Type 1 and 2 Deiodinase Genes with Circulating Thyroid Hormone Parameters and Atrophy of the Medial Temporal Lobe J. Clin. Endocrinol. Metab., February 1, 2007; 92(2): 636 - 640. [Abstract] [Full Text] [PDF]

				R. P Peeters, W. M van der Deure, and T. J Visser Genetic variation in thyroid hormone pathway genes; polymorphisms in the TSH receptor and the iodothyronine deiodinases. Eur. J. Endocrinol., November 1, 2006; 155(5): 655 - 662. [Abstract] [Full Text] [PDF]

				G Brabant, P Beck-Peccoz, B Jarzab, P Laurberg, J Orgiazzi, I Szabolcs, A P Weetman, and W M Wiersinga Is there a need to redefine the upper normal limit of TSH? Eur. J. Endocrinol., May 1, 2006; 154(5): 633 - 637. [Abstract] [Full Text] [PDF]

				O. Gumieniak, S. Hurwitz, T. S. Perlstein, U. C. Ngumezi, P. N. Hopkins, X. Jeunemaitre, and G. H. Williams Aggregation of High-Normal Thyroid-Stimulating Hormone in Hypertensive Families J. Clin. Endocrinol. Metab., November 1, 2005; 90(11): 5985 - 5990. [Abstract] [Full Text] [PDF]

				N. Knudsen, P. Laurberg, L. B. Rasmussen, I. Bulow, H. Perrild, L. Ovesen, and T. Jorgensen Small Differences in Thyroid Function May Be Important for Body Mass Index and the Occurrence of Obesity in the Population J. Clin. Endocrinol. Metab., July 1, 2005; 90(7): 4019 - 4024. [Abstract] [Full Text] [PDF]

				P. S. Hansen, T. H. Brix, F. N. Bennedbaek, S. J. Bonnema, K. O. Kyvik, and L. Hegedus Genetic and Environmental Causes of Individual Differences in Thyroid Size: A Study of Healthy Danish Twins J. Clin. Endocrinol. Metab., May 1, 2004; 89(5): 2071 - 2077. [Abstract] [Full Text] [PDF]