scholarly journals The Effect of Recombinant Human TSH on Sclerostin and Other Selected Bone Markers in Patients after Total Thyroidectomy for Differentiated Thyroid Cancer

2021 ◽  
Vol 10 (21) ◽  
pp. 4905
Author(s):  
Arkadiusz Zygmunt ◽  
Kinga Krawczyk-Rusiecka ◽  
Elżbieta Skowrońska-Jóźwiak ◽  
Katarzyna Wojciechowska-Durczyńska ◽  
Ewa Głowacka ◽  
...  

The direct effect of TSH on bone metabolism in vivo is difficult to capture as the changes of its concentrations are followed by respective alterations of thyroid hormone levels. We evaluated the effect of recombinant human TSH (rhTSH) on sclerostin and other bone markers in 29 patients after total thyroidectomy for differentiated thyroid cancer (DTC), without any signs of disease recurrence, who received L-thyroxine, most at non-suppressive doses. For two consecutive days, the patients were administered a standard dose of 0.9 mg rhTSH, i.m. Concentrations of sclerostin, osteocalcin, β-CrossLaps, PTH, and some other parameters, were measured before and five days after the first rhTSH administration. The greater the increase in TSH concentration (∆TSH), the greater the decrease in: ∆sclerostin (r = −0.672; p < 0.001), ∆β-CrossLaps (r = −0.580; p < 0.001) and ∆osteocalcin (r = −0.405; p = 0.029) levels, were recorded. The degree of TSH increase depended on the baseline PTH (r = 0.651; p < 0.001), age, and creatinine concentrations. rhTSH strongly inhibited bone turnover, thus, TSH—independently of thyroid hormones—exerted a direct protective effect on bone metabolism. Baseline PTH affected the magnitude of TSH increase and the degree of lowering in sclerostin and β-CrossLaps that suggest factors affecting PTH may play a role in the effect of TSH on the bone.

Cancers ◽  
2021 ◽  
Vol 13 (14) ◽  
pp. 3487
Author(s):  
Yu-Ling Lu ◽  
Ming-Hsien Wu ◽  
Yi-Yin Lee ◽  
Ting-Chao Chou ◽  
Richard J. Wong ◽  
...  

Differentiated thyroid cancer (DTC) patients are usually known for their excellent prognoses. However, some patients with DTC develop refractory disease and require novel therapies with different therapeutic mechanisms. Targeting Wee1 with adavosertib has emerged as a novel strategy for cancer therapy. We determined the effects of adavosertib in four DTC cell lines. Adavosertib induces cell growth inhibition in a dose-dependent fashion. Cell cycle analyses revealed that cells were accumulated in the G2/M phase and apoptosis was induced by adavosertib in the four DTC tumor cell lines. The sensitivity of adavosertib correlated with baseline Wee1 expression. In vivo studies showed that adavosertib significantly inhibited the xenograft growth of papillary and follicular thyroid cancer tumor models. Adavosertib therapy, combined with dabrafenib and trametinib, had strong synergism in vitro, and revealed robust tumor growth suppression in vivo in a xenograft model of papillary thyroid cancer harboring mutant BRAFV600E, without appreciable toxicity. Furthermore, combination of adavosertib with lenvatinib was more effective than either agent alone in a xenograft model of follicular thyroid cancer. These results show that adavosertib has the potential in treating DTC.


2002 ◽  
Vol 56 (2) ◽  
pp. 247-252 ◽  
Author(s):  
Vitale Giovanni ◽  
Lupoli Gelsy Arianna ◽  
Ciccarelli Antonio ◽  
Fonderico Francesco ◽  
Klain Michele ◽  
...  

Surgery ◽  
2018 ◽  
Vol 164 (3) ◽  
pp. 504-510 ◽  
Author(s):  
Shih-Ping Cheng ◽  
Ming-Nan Chien ◽  
Tao-Yeuan Wang ◽  
Jie-Jen Lee ◽  
Chun-Chuan Lee ◽  
...  

2019 ◽  
Vol 8 (8) ◽  
pp. 1106 ◽  
Author(s):  
Young Ki Lee ◽  
Hokyou Lee ◽  
Seunghee Han ◽  
Hyein Jung ◽  
Dong Yeob Shin ◽  
...  

Less-intense TSH suppression strategies can be used for differentiated thyroid cancer (DTC) patients with a low recurrence risk, but their metabolic outcomes are not well known. We aimed to evaluate changes in the serum cholesterol levels and the risk of hypercholesterolemia according to postoperative TSH levels in 1092 female DTC patients receiving levothyroxine after total thyroidectomy. The preoperative-to-follow-up change in total cholesterol (TC) levels in the TSH level <0.03, 0.03–0.3, 0.3–2, and 2–5 mIU/L groups was −3.69 mg/dL (p = 0.006), +0.13 mg/dL (p = 0.926), +12.46 mg/dL (p < 0.001), and +16.46 mg/dL (p < 0.001), respectively. When compared with TSH levels of 0.03–0.3 mIU/L, those of 0.3–2 mIU/L were found to be associated with hypercholesterolemia (adjusted odds ratio (AOR) = 1.86 and 5.08 for TC 200–240 and ≥240 vs. <200 mg/dL) and hyper-low-density lipoprotein (LDL)-cholesterolemia (AOR = 2.76 for LDL-cholesterol ≥160 vs. <130 mg/dL). Additionally, TSH levels of 2–5 mIU/dL were associated with hypercholesterolemia (AOR = 2.85 and 6.95 for TC 200–240 and ≥240 vs. <200 mg/dL) and hyper-LDL-cholesterolemia (AOR = 2.08 and 4.17 for LDL-cholesterol 130–159 and ≥160 mg/dL vs. <130 mg/dL). In patients with normal TSH level maintenance following thyroidectomy, TC levels markedly increased, resulting in an increased hypercholesterolemia prevalence. Metabolic derangement risk due to insufficient levothyroxine replacement should be considered in the adoption of less-intense TSH suppression strategies, postoperatively, in DTC patients.


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