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Thyroid Hormone Independent Associations between serum TSH levels and Indicators of Bone Turnover in Cured Patients with Differentiated Thyroid Carcinoma

K Heemstra, Endocrinology and Metabolism, Leiden University Medical Centre, Leiden, 2300 RC, Netherlands
W van der Deure, Internal Medicine, Erasmus Medical Centre, Rotterdam, Netherlands
R Peeters, Internal Medicine, Erasmus Medical Centre, Rotterdam, Netherlands
N Hamdy, Endocrinology and metabolic diseases, Leiden University Medical Centre, Leiden, Netherlands
M Stokkel, Nuclear Medicine, Leiden University Medical Centre, Leiden, Netherlands
E Corssmit, Department of Endocrinology C4R, Leiden University Medical Center, Leiden, Netherlands
J Romijn, Department of Endocrinology, C4-R, Leiden University Medical Center, Leiden, Netherlands
T Visser, Internal Medicine, Erasmus Medical Centre, Leiden, Netherlands
J Smit, Endocrinology, Leiden University Medical Center, Leiden, Netherlands

Correspondence: Karen Heemstra, Email: K.A.Heemstra{at}LUMC.nl

Abstract

Objective: It has been proposed that thyrotropin (TSH) has thyroid hormone independent effects on bone mineral density (BMD) and bone metabolism. This concept is still controversial and has not been studied in human subjects in detail. We addressed this question by studying relationships between serum TSH concentration and indicators of bone turnover, after controlling for T3, FT4 and non-thyroid factors relevant to BMD and bone metabolism. We also studied the contribution of the TSHR-Asp727Glu polymorphism to these relationships.

Design: We performed a cross-sectional study with 148 patients, who had been thyroidectomized for differentiated thyroid carcinoma.

Methods: We measured BMD of the Femoral Neck and Lumbar Spine. FT4, T3, TSH, Bone Specific Alkaline Phosphatase, procollagen type 1 aminoterminal propeptide levels, C-crosslinking Terminal Telopeptide of Type I collagen and Urinary N-Telopeptide of Collagen Cross-links were measured. Genotypes of the TSHR-Asp727Glu polymorphism were determined by Taqman assay.

Results: We found a significant, inverse correlation between serum TSH levels and indicators of bone turnover that was independent of serum FT4 and T3 levels as well as other parameters influencing bone metabolism. We found that carriers of the TSHR-Asp727Glu polymorphism had an 8.1% higher femoral neck BMD, which was however no longer significant after adjusting for body mass index.

Conclusion: We conclude that in this group of patients, serum TSH was related to indicators of bone remodeling independently of thyroid hormone levels. This may point to a functional role of the TSHR in bone in humans. Further research into this mechanism needs to be performed.