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Endocrine Abstracts (2015) 37 EP253 | DOI: 10.1530/endoabs.37.EP253

ECE2015 Eposter Presentations Calcium and Vitamin D metabolism (96 abstracts)

TSH and free-T3 correlate negatively and independently with bone mineral density in adults with subclinical hypothyroidism

Anna de Lloyd 1 , Ilaria Muller 1 , Alan Dodd 2 , Hilary Durrant 2 , Rebecca Pettit 3 , Sarah Darlington 3 , Lei Zhang 1 , Carol Evans 2 , Aled Rees 1 & Marian Ludgate 1

1Thyroid Research Group, IMEM, Cardiff University, Cardiff, Wales, UK; 2Department of Medical Biochemistry and Immunology, University Hospital of Wales, Cardiff, Wales, UK; 3Department of Medical Physics, University Hospital of Wales, Cardiff, Wales, UK.

The role of the thyrotropin receptor (TSHR) in bone is unclear. TSHR-deficient mice have low bone mineral density (BMD) and focal osteosclerosis despite normal thyroid hormones (suggesting TSHR function, in bone, is important). Subclinical hypothyroidism (SH) has various aetiologies including thyroid autoimmunity (TA) and inactivating TSHR mutations (TSHR-M). In TSHR-deficiency & TSH-M elevated TSH compensates for reduced TSHR function, whereas in TA it compensates for reduced thyroid synthetic responsiveness (inflammation mediated). We hypothesised differential bone effects in SH relating to these causes.

Aims: i) To establish whether free-T4, free-T3 or TSH are associated with BMD and bone turnover (BT) in SH. ii) To explore whether SH aetiology influences BMD and BT.

Methods: 208 adults with primary untreated SH (TSH≧5 mU/l) and free of known bone disease were recruited. A medical/lifestyle history, anthropometric data and blood samples were collected (free-T3, free-T4, TSH, anti-TPO antibodies, BT markers (CTX, P1NP)). Mutational screening of the entire TSHR coding region was undertaken by dHPLC and confirmed by direct sequencing. A DXA bone scan (lumbar spine (LS) and hip) generated Z-scores (relative to age/sex-matched normals (BMD-Z)) which were evaluated alongside thyroid parameters in stepwise multivariate regression analyses.

Results: 50% of the cohort were TPO+ and 6% had TSHR-Ms. After adjustment for potential confounders, TSH associated negatively with BMD-Z at the LS (R=−1.7, P<0.001) whereas free-T3 associated negatively with BMD-Z at both sites (hip: R=−0.35, P=0.005; LS: R=−0.5, P=0.002) and free-T4 showed no independent associations. Stratification by SH aetiology showed no influence of TSHR-M on BMD-Z (despite lower free-T3 relative to TSH (R=−0.34, P=0.01) but TPO+ associated negatively with BMD-Z at the LS (R=−0.65, P<0.001). Male gender associated negatively with BMD-Z at all sites (R=−0.8, P=0.001). BT markers did not associate with thyroid function or BMD.

Conclusions: In adults with SH, BMD is associated negatively with free-T3, TSH, male gender and TPO antibody positivity.

Disclosure: Society for endocrinology grant

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