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The TRHR Gene Is Associated with Hypothalamo-Pituitary Sensitivity to Levothyroxine.

ABSTRACT: BACKGROUND:Thyroidectomized patients need variable doses of levothyroxine (LT4) to obtain target thyroid-stimulating hormone (TSH) levels. Individual feedback set-points have been hypothesized and the influence of several genes in the regulation of the pituitary-thyroid axis has been demonstrated. OBJECTIVES:We hypothesized that genetic variants of the TRHR gene could be associated with a different hypothalamo-pituitary sensitivity to thyroid hormone feedback. METHODS:We retrospectively analyzed 84 thyroidectomized patients with no residual thyroid function and undetectable thyroglobulin levels. Patients were evaluated under LT4 resulting in TSH levels detectable but <0.5 ?IU/ml. The two SNPs rs3134105 and rs3110040 were identified as informative markers of the TRHR gene. Genotyping was performed using high-resolution melting technology. Genotype distribution was compared between the patients and 99 euthyroid controls. RESULTS:The selected SNPs were in linkage disequilibrium and only rs3134105 was further considered. A significant difference between the three possible genotypes for rs3134105 was found for TSH (p = 0.04) and free thyroxine (fT4)/TSH ratio (p = 0.02). Moreover, despite similar serum concentrations of free triiodothyronine (fT3) and fT4, carriers of at least one A allele of rs3134105 had significantly lower serum TSH levels (p = 0.01) as well as higher fT3/TSH (p = 0.01) and fT4/TSH ratios (p < 0.01). CONCLUSIONS:We demonstrated an association between serum TSH levels and discrete alleles of the TRHR gene in totally thyroidectomized patients under LT4 therapy. Therefore, the TRHR gene seems to be a determinant of hypothalamo-pituitary sensitivity to LT4.

SUBMITTER: Brigante G

PROVIDER: S-EPMC4109513 | biostudies-literature | 2014 Jun

REPOSITORIES: biostudies-literature

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The TRHR Gene Is Associated with Hypothalamo-Pituitary Sensitivity to Levothyroxine.

Brigante Giulia G Spaggiari Giorgia G Santi Daniele D Cioni Katia K Gnarini Valentina V Diazzi Chiara C Pignatti Elisa E Casarini Livio L Marino Marco M Tüttelmann Frank F Carani Cesare C Simoni Manuela M

European thyroid journal 20140607 2

<h4>Background</h4>Thyroidectomized patients need variable doses of levothyroxine (LT4) to obtain target thyroid-stimulating hormone (TSH) levels. Individual feedback set-points have been hypothesized and the influence of several genes in the regulation of the pituitary-thyroid axis has been demonstrated.<h4>Objectives</h4>We hypothesized that genetic variants of the TRHR gene could be associated with a different hypothalamo-pituitary sensitivity to thyroid hormone feedback.<h4>Methods</h4>We re ...[more]

PMID: 25114873

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The TRHR Gene Is Associated with Hypothalamo-Pituitary Sensitivity to Levothyroxine.

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The TRHR Gene Is Associated with Hypothalamo-Pituitary Sensitivity to Levothyroxine.

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