Giusti Massimo, Cecoli Francesca, Fazzuoli Laura, De Franchis Vincenzina, Ceresola Enrica, Ferone Diego, Mussap Michele, Minuto Francesco
UO Clinica Endocrinologica, Azienda Ospedaliera Universitaria San Martino, Genoa, Italy.
Metabolism. 2007 May;56(5):699-707. doi: 10.1016/j.metabol.2007.01.004.
Overt hyperthyroidism is associated with changes in bone metabolism, whereas the effect of levothyroxine (L-T4) load in patients with differentiated thyroid carcinoma (DTC) is controversial. The aim of our study was to evaluate osteoprotegerin (OPG) and soluble receptor activator of nuclear factor kappaB ligand (RANK-L) in patients with DTC with suppressed endogenous thyrotropin due to L-T4 regimen. A cohort of 80 subjects with DTC (68 women and 12 men; age range, 27-81 years) was studied. A cohort of 55 subjects with a history of partial or total surgery for nonmalignant thyroid pathology served as a control group. Groups were matched for sex, age, and body mass index. Per-week dosage of L-T4 was significantly higher in patients with DTC than in controls (P < .001). More elevated free T(4) concentrations (P < .001) and more suppressed thyrotropin and thyroglobulin levels (P < .001) were found in subjects with DTC than in controls. No difference in serum or urinary parameters related to bone metabolism or dual-energy x-ray absorptiometry was noted between the groups. Overall, OPG levels were similar in both groups but were significantly (P = .03) lower in postmenopausal women with DTC than in postmenopausal control women. Only control women showed lower OPG levels in premenopausal than in postmenopausal (P = .002) conditions. Overall, RANK-L levels were significantly higher (P = .03) in subjects with DTC than in controls. In both groups, OPG and RANK-L levels were unrelated to each other. A significant positive correlation was seen between OPG levels and age in both subjects with DTC (P < .001) and controls (P < .001). Serum RANK-L correlated negatively with age in subjects with DTC (P = .05). Although there were several differences in L-T4 dosages, OPG and RANK-L levels were similar in patients with a history of DTC and those with a history of nonmalignant thyroid diseases. The correlation between circulating OPG and RANK-L levels was not significant. The increase in OPG with age indicates its protective role in bone loss. The cause of bone loss after long-term L-T4 load will be more extensively studied.
显性甲状腺功能亢进与骨代谢变化有关,而左甲状腺素(L-T4)负荷对分化型甲状腺癌(DTC)患者的影响存在争议。我们研究的目的是评估因L-T4治疗导致内源性促甲状腺激素受抑制的DTC患者的骨保护素(OPG)和可溶性核因子κB受体活化因子配体(RANK-L)。研究了一组80例DTC患者(68名女性和12名男性;年龄范围27 - 81岁)。一组55例有非恶性甲状腺疾病部分或全部手术史的患者作为对照组。两组在性别、年龄和体重指数方面相匹配。DTC患者的每周L-T4剂量显著高于对照组(P <.001)。与对照组相比,DTC患者的游离T4浓度更高(P <.001),促甲状腺激素和甲状腺球蛋白水平受抑制更明显(P <.001)。两组之间在与骨代谢相关的血清或尿液参数或双能X线吸收法方面未发现差异。总体而言,两组的OPG水平相似,但DTC绝经后女性的OPG水平显著低于绝经后对照女性(P =.03)。只有对照女性在绝经前的OPG水平低于绝经后(P =.002)。总体而言,DTC患者的RANK-L水平显著高于对照组(P =.03)。在两组中,OPG和RANK-L水平相互无关。DTC患者(P <.001)和对照组(P <.001)的OPG水平与年龄均呈显著正相关。DTC患者的血清RANK-L与年龄呈负相关(P =.05)。尽管L-T4剂量存在一些差异,但有DTC病史的患者和有非恶性甲状腺疾病病史的患者的OPG和RANK-L水平相似。循环中OPG和RANK-L水平之间的相关性不显著。OPG随年龄增加表明其在骨质流失中起保护作用。长期L-T4负荷后骨质流失的原因将得到更广泛的研究。