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

Abstract

Intraindividual variation is smaller than the interindividual variation in serum TSH, free T(4), and free T(3) 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 T(4), and free T(3) 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 T(4), 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 T(4) and free T(3), 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.

Variation in thyroid function in subclinical hypothyroidism: importance of clinical follow-up and therapy

“…The intra-individual variation of thyroid function tests has been studied in individuals with normal thyroid function (28)(29)(30)(31)(32)(33)(34)(35)(36)(37). This has revealed both a considerable circadian rhythm and a small seasonal variation in TSH secretion, but over time TSH in an individual varies within a range of only half of a population-based reference range.…”

Genetic and environmental influence on thyroid gland volume and thickness of thyroid isthmus: a twin study

“…Previous twin studies confirmed the heritability of thyroid hormone levels (plasma TSH: 64%, fT4: 65% and fT3: 64%) too (23,24) and demonstrated that besides age, BMI, iodine intake, serum TSH concentration, parity and cigarette smoking played a small role in the thyroid size. Genetic loci associated with clinically overt euthyroid multinodular goiter were already mapped in linkage analyses, genome-wide association studies identified four genetic loci associated with thyroid volume and goiter risk (25).…”

“…In our study, no pregnant women participated, and thyroid hormone levels were not assessed. However, since thyroid hormone levels are heritable (23), large modifiable effect on our hereditary results (no heritability of thyroid lobe volumes) is not anticipatory. Iodine status did not seem to exert a significant influence on the changes in thyroid volume in a recent study, but changes in BMI levels seemed to be more important (27).…”

“…Hereditary factors were found to be important in the aetiology of the simple and nodular goitre, Basedow-Graves' disease, Hashimoto's thyroiditis and the regulation of the pituitary-thyroid axis (20)(21)(22)(23).…”

Does selenium supplementation affect thyroid function? Results from a randomized, controlled, double-blinded trial in a Danish population

“…However, the fact that thyroid function appears to be sensitive to selenium supplementation adds to the incentive for investigating its effects on multifactorially regulated traits, such as thyroid function (19,41), size (42,43), and autoimmunity (44) in autoimmune thyroid diseases, where selenoprotein biosynthesis may be impaired (18). A number of trials in Hashimoto's thyroiditis have thus far not clarified the role of selenium supplementation (39).…”