Endocrine Abstracts (2007) 13 P328

T3 rather than TSH mediates the effects of altered thyroid status on bone turnover in man

Elaine Murphy & Graham Richard Williams


Imperial College, London, United Kingdom.


Recent controversial studies in mice imply that TSH inhibits bone remodelling, suggesting TSH-deficiency rather than thyroid hormone excess causes bone loss in thyrotoxicosis. Measurement of the TRH-stimulated rise in TSH following three days administration of graded doses of T3 is the gold-standard for determining resistance to thyroid hormone (RTH). During this test, T3 excess coupled with suppressed TSH should induce high bone turnover, whilst administration of TRH causes a rapid rise in circulating TSH. Thus, we hypothesised that if TSH inhibits bone remodelling this would result in suppression of bone turnover. Following ethical approval, TSH, osteocalcin and type I collagen C-terminal telopeptide (CTX) responses to TRH were determined during the graded T3-suppression test in eight volunteers (6 male, 2 female, 26–44 years) and two subjects with RTH: (1) female aged 60, T3 receptor β mutation TRβF455L, (2) male, 54, TRβG332Q. Following TRH-stimulation, mean peak TSH (mU/L) in volunteers was 8.39±3.13 at baseline, 1.21±0.40 following 50 μg T3, 0.23±0.16 following 100 μg T3 and 0.06±0.06 following 200 μg T3. In subjects 1 and 2, TSH levels rose to 8.43 and 104.8 (baseline), 5.41 and 77.21 (50 μg T3) and 2.83 and 35.23 (100 μg T3), respectively, and to 13.18 mU/L following 200 μg T3 in subject 2. In volunteers, osteocalcin (ng/mL) increased significantly (P<0.01) following each dose of T3; 19.9±1.8 (baseline), 23.9±1.8 (50 μg T3), 27.3±2.1 (100 μg T3) and 29.7±1.4 (200 μg T3). In contrast, baseline osteocalcin levels were lower (P<0.01) in RTH subjects [(1) 16.3±4.5; (2) 11.8±1.4] and were unaffected by T3. TRH-stimulated rises in TSH did not alter osteocalcin in volunteers or RTH subjects up to 48 hours following TRH. Similarly, normal diurnal variations in CTX levels were unaffected by TRH-stimulated rises in TSH in both volunteers and RTH subjects. These data indicate that T3 rather than TSH is the physiological regulator of bone turnover in man.

Article tools

My recent searches

No recent searches.