Effect Of High Level Parathyroid Hormone On Thyroid Function Index FT4

BackgroundSecondary hyperparathyroidism is a common complication of end-stage renal disease.Hyperparathyroidism and elevated parathyroid hormone level are its main characteristics.Parathyroid gland and thyroid gland are adjacent organs.Previous studies focused on the impact of thyroid diseases on parathyroid function,while the impact of abnormal parathyroid function on thyroid was rarely reported.In addition,studies have shown that parathyroid hormone can affect the function of a variety of cells through apoptosis.This paper intends to explore the effect of high-level parathyroid hormone on thyroid function and its possible mechanism through clinical retrospective analysis and cell experiment.Part I Study on the correlation between parathyroid hormone level and thyroid function index FT4 levelObjectiveTo explore the effect of high-level parathyroid hormone on thyroid function by retrospectively analyzing the changes of serum PTH and FT4 levels in patients with secondary/primary hyperparathyroidism before and after operation.MethodThe clinical data of 308 patients with hyperparathyroidism in Henan Provincial People’s Hospital from September 2017 to December 2021 were retrospectively analyzed.They were divided into primary and secondary groups,including 205 patients in chronic kidney disease complicated with secondary hyperparathyroidism（SHPT）（including 124males and 81 females）,and 87 patients underwent total parathyroidectomy+abdominal wall transplantation;103 patients with primary hyperparathyroidism（PHPT）（including 61males and 42 females）underwent parathyroidectomy.The baseline data,the correlation between parathyroid hormone（PTH）,serum free thyroxine（FT4）and other clinical indexes were compared between SHPT group and PHPT group.Multivariate linear stepwise regression analysis was used to observe the changes of serum PTH and FT4 levels before and after operation.Result1.Compare the baseline data of patients in SHPT group and PHPT group.The levels of creatinine,urea nitrogen,serum PTH and serum phosphorus in SHPT group were higher than those in PHPT group,while the levels of hemoglobin,platelet,albumin,serum calcium,serum FT3 and serum FT4 in SHPT group were lower than those in PHPT group（P<0.05）.2.Comparison of baseline data at different PTH levels.In SHPT/PHPT group,the serum PTH concentration was divided into four subgroups from low to high by quartile method.With the gradual increase of PTH,the serum FT4 level gradually decreased（P<0.05）.3.Analysis of baseline serum PTH and various clinical indicators.The baseline PTH level in SHPT/PHPT group was negatively correlated with serum FT4（r<0,P<0.05）,and serum FT4 was an independent influencing factor of PTH in SHPT group（P<0.05）.4.Analysis of baseline serum FT4 and various clinical indicators.Serum PTH in SHPT/PHPT group was an independent influencing factor of FT4（P<0.05）.5.Changes of serum PTH and FT4 levels before/after operation.Serum PTH in SHPT/PHPT group decreased significantly 1 day after operation（P<0.001）.The level of serum FT4 in SHPT group increased significantly one day after operation,and decreased gradually four days and three months after operation.The difference between the groups was statistically significant（P<0.001）;There was no significant change in serum FT4level in PHPT group before operation and 1 day,4 days and 3 months after operation.There was no significant difference between the groups（P>0.05）.Part II Parathyroid hormone induces apoptosis of thyroid cellsObjectiveThrough cell experiment in vitro,human normal thyroid cells were stimulated with different concentrations of PTH,and the apoptosis was detected to explore the possible mechanism of parathyroid hormone affecting thyroid function.MethodIn vitro cell experiment,the research object is human normal thyroid cells（Nthy-ori3-1）.The experimental group takes 10^-1ng/ml,1 ng/ml,10 ng/ml and 10~2ng/ml as PTH concentration gradient,and the control group takes the same dose of 1×PBS stimulated thyroid cells for 48 hours.Cells were collected for the following tests:1.CCK8 was used to detect the cell proliferation of control group and experimental group.2.q RT-PCR was used to detect the m RNA levels of apoptosis related factors Bcl-2 and Bax in the control group and the experimental group.3.The protein expression of apoptosis related factors Bcl-2 and Bax in the control group and the experimental group were detected by Western blot.4.The apoptosis rate of control group and experimental group was detected by flow cytometry.Result1.1.The results of CCK8 showed that compared with the control group,the cell activity of the experimental group decreased gradually with the increase of PTH concentration,suggesting that PTH can inhibit the proliferation of thyroid cells.2.q RT-PCR results showed that compared with the control group,the level of apoptosis related factor Bax m RNA in the experimental group was positively correlated with the concentration of PTH stimulation,and the level of bcl-2 m RNA was negatively correlated with the concentration of PTH stimulation.3.The results of Western blot showed that compared with the control group,the level of Bax protein in the experimental group increased gradually with the increase of PTH concentration,and the level of Bcl-2 protein decreased gradually with the increase of PTH concentration.4.Annexin V-FITC flow cytometry showed that the increase of PTH level in the experimental group could increase the apoptosis rate of thyroid cells compared with the control group.Conclusion1.High level PTH is negatively correlated with thyroid function index FT4,and PTH is an independent influencing factor of FT4,which may be involved in affecting thyroid function.2.PTH stimulation can induce thyroid cell apoptosis in vitro.