Recombinant human thyroid stimulating hormone does not acutely change serum osteoprotegerin and soluble receptor activator of nuclear factor-?? ligand in patients under evaluation for differentiated thyroid carcinoma*

Abstract

ObJEctIVE: some extra-thyroid actions of thyroid stimulating hormone (tsH), such as an in vitro action on bone, have been described. Our aim was to evaluate in vivo the acute effect of a recombinant human tsH (rhtsH)-induced tsH surge on Osteoprotegerin (OPG) and receptor activator of the nuclear factor-κb (rANK-L) levels in patients under levo-thyroxine (L-t4) therapy. DEsIGN: 24 patients with differentiated thyroid carcinoma (Dtc) were studied. standard rhtsH testing was performed. OPG, rANK-L, tsH, thyroid hormones, thyroglobulin and several parameters of bone metabolism were evaluated. rEsuLts: baseline OPG and rANK-L levels were in the range of our reference population. An inverse correlation between OPG and spinal Z-score (p=0.029) and between rANK-L and age (p=0.018) or urinary calcium/creatinine ratio (p=0.011) was detected. After rhtsH administration, a significant (p<0.001) increase in tsH was found. No significant increase in OPG or rANK-L levels after rhtsH was observed. No correlation was detected between tsH peak value after rhtsH and maximal percentage change in OPG or rANK-L. A slight increase in urinary cross-links after rhtsH was found. cONcLusIONs: In a small group of subjects with a history of Dtc on Lt4 regimen, our study did not support an acute direct effect of tsH on OPG and rANK-L.

The skeletal consequences of thyrotoxicosis

“…As these patients had previously undergone total thyroidectomy, the rhTSH treatment did not affect T 4 and T 3 concentrations but increased serum TSH concentrations to O100 mU/l. rhTSh was found to have no effect on bone formation or resorption markers in pre-menopausal women (Mazziotti et al 2005, Giusti et al 2007, Martini et al 2008. Results in postmenopausal women have been contradictory: two of four studies reported increased bone formation markers and reduced bone resorption markers in response to hTSH, whereas two studies showed no effect (Mazziotti et al 2005, Giusti et al 2007, Martini et al 2008, Karga et al 2010.…”

“…rhTSh was found to have no effect on bone formation or resorption markers in pre-menopausal women (Mazziotti et al 2005, Giusti et al 2007, Martini et al 2008. Results in postmenopausal women have been contradictory: two of four studies reported increased bone formation markers and reduced bone resorption markers in response to hTSH, whereas two studies showed no effect (Mazziotti et al 2005, Giusti et al 2007, Martini et al 2008, Karga et al 2010. Finally, a study of two siblings with isolated TSH deficiency, who had received T 4 replacement from birth, reported that BMD and bone turnover markers were normal despite the absence of TSH (Papadimitriou et al 2007).…”

Ten-year estimated risk of bone fracture in women with differentiated thyroid cancer under TSH-suppressive levo-thyroxine therapy

“…While this increased risk seems to be age-related, we cannot exclude the possibility that other factors are involved. These include: 1) lower compliance with ART; 2) disputed TSH action on bone [15], in that its direct positive effect may decline; and 3) changes in age-related cytokine agents which remodel the skeletal characteristics of DTC patients [16]. Moreover, we cannot exclude the possibility that the L-T4 dosage at the first evaluation may be influenced by the manipulations necessary in the initial phases of therapy and staging (RAI, rhTSH-test).…”

RANKL/Osteoprotegerin System and Bone Turnover in Hashimoto Thyroiditis

“…Giusti et al showed that OPG and RANKL levels were similar in patients with different LT4 doses and thyroid hormone levels [11]. Another study showed that recombinant TSH did not affect OPG and RANKL levels in DTC [21]. All of the aforementioned studies included patients from both sexes, women with both pre-and postmenopausal status and hypothyroidism due to both autoimmune and non-autoimmune etiologies and the aim in most of those studies were not evaluating RANKL/OPG in the context of bone turnover.…”