Bone Abstracts

Introduction: Resistance to thyroid hormone (RTH) is a rare disease, characterized by elevated thyroid hormone and not suppressed TSH concentrations. In 85% of cases it is related to TRβ gene mutations.

Objectives: To evaluate biochemical and densitometric features of 14 patients with RTH (RTHG: 7 females (4 children) and seven males (2 children)) in comparison to 24 control subjects (CG, 14 females (8 children) and 10 males (4 children)).

Methods: Serum levels of total calcium (TCa), albumin, inorganic phosphorus (iP), creatinine, alkaline phosphatase, osteocalcin, parathyroid hormone, 25-hydroxyvitamin D, fibroblast growth factor-23 (FGF-23) and cross-linked C-telopeptide and urinary measurement of calcium, phosphorus, and creatinine were measured. Renal threshold phosphate concentration (TmP/GFR) was estimated. Bone densitometry with focus on whole body, lumbar spine, total hip, femoral neck and forearm was obtained. Nonparametric tests were applied.

Results: The RTH patients exhibited higher concentrations of TCa (P=0.04) and corrected serum levels of calcium for albumin concentrations (CG=9.3±0.5; RTHG=9.8±0.4 mg/dl; P=0.01), lower concentrations of iP (CG=4.5±1.2; RTHG=3.7±0.9; P=0.04) and lower TmP/GFR (CG=4.3±1.4; RTHG=3.4±1.2; P=0.03) than the CG. The FGF-23 concentrations were higher in children with RTH than in CG (CG=32.2±13.6; RTHG=43.1±12.2; P=0.04). The bone mass was lower among adults in RTHG, in whole body (CG=1.15±0.07; RTHG=1.07±0.08; P=0.02), lumbar spine (CG=1.04±0.12; RTHG=0.94±0.11; P=0.05), and femoral neck (CG=0.91±0.11; RTHG=0.76±0.16; P=0.05) than in the corresponding CG. The z-scores were lower in the RTHG than in CG in total hip (P=0.04) and femoral neck (P=0.05).

Conclusions: These data indicate alterations in bone mineral metabolism in RTHG. The higher concentrations of calcium and lower bone mass in RTHG than in CG associated with the results of studies using animal models with mutant mice suggest that RTHG may exhibit thyrotoxic bone phenotype. However, it was not possible to point out a single pathophysiological mechanism that justifies simultaneously all changes observed.