Bone metabolism in patients with differentiated thyroid carcinoma receiving suppressive levothyroxine treatment

Patients with differentiated thyroid carcinoma (DTC) must receive suppressive levothyroxine (LT(4)) therapy for the rest of their lives. The literature, however, presents conflicting results on how this affects bone metabolism. The aim of this study was to assess the influence of the estrogen status and LT(4) therapy, in particular LT(4) dosage in micrograms per kilograms (microg/kg), on bone metabolism in female patients with DTC.

Three markers of bone metabolism (C-terminal telopeptide of type I collagen in serum [SCTx]; N-terminal telopeptide of type I collagen in urine [U-NTx]; and osteocalcin [OC]) were investigated in four groups: group REF (healthy premenopausal female controls), group DTC-ES (premenopausal women with DTC and normal estrogen levels), group DTC-ED (postmenopausal women with DTC and estrogen deficiency), and group DTC-HRT (postmenopausal women with DTC undergoing hormone replacement therapy [HRT]). All patients with DTC were on a well-adjusted suppressive LT(4) therapy with TSH levels 0.1 mU/L or less.

In group DTC-ES bone turnover was comparable to group REF, whereas in group DTC-ED, all three markers were significantly increased as compared to groups REF and DTC-ES. In group DTC-HRT, the HRT normalized U-NTx and OC. However, in this group S-CTx was not completely normalized by HRT in all patients, although also significantly lowered compared to group DTC-ED. The analysis of LT(4 )dosage per kilogram showed that premenopausal DTC-patients had increased markers of bone metabolism if LT(4) dosage exceeded 2.6 microg/kg. Estrogen-deficient patients with DTC, however, had a much lower critical LT(4) dosage, above which increased markers of bone metabolism were seen.

A well-adjusted suppressive LT(4) therapy of less than 2.6 microg/kg and normal estrogen levels do not seem to increase bone metabolism in estrogen-sufficient patients with DTC. The normalization of an estrogen deficiency by HRT or other antiresorptive therapies and minimal suppressive dosages of LT(4) are attempts to optimize the care of patients with DTC. In postmenopausal patients with DTC and patients with DTC who require LT(4) dosages in excess of 2.6 microg/kg, the information provided by markers of bone metabolism may help to prevent bone damage.