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Clinical And Basic Research On Serum Adipokines In Patients With Acromegaly And Molecular Detection Of Serum Macroprolactin In Patients With Hyperprolactinemia

Posted on:2022-03-07Degree:MasterType:Thesis
Country:ChinaCandidate:X A KeFull Text:PDF
GTID:2514306353458694Subject:Endocrine and metabolic diseases
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ObjectivesAsprosin is a novel identified adipokine secreted mainly by white adipose tissue,which is elevated in metabolic related diseases such as diabetes,obesity,and polycystic ovary syndrome.Acromegaly refers to a syndrome mostly caused by pituitary growth hormone cell adenoma with excessive GH secretion.Patients with acromegaly mainly manifested as acromegaly,abnormal facial appearance,and abnormal structure or function of multiple systems,such as respiratory system,cardiovascular system,and bone and joint system etc.Acromegaly patients often have abnormal glucose and lipid metabolism.Serum adipocytokines levels may be involved in abnormal glycolipid metabolism in acromegaly patients.This study aims to investigate serum asprosin levels in patients with acromegaly and its correlation with high GH levels and glucolipid metabolic parameters.MethodsA retrospective case-control study was conducted.68 acromegaly patients visited the pituitary multi-disciplinary team(MDT)of Peking Union Medical College Hospital and 121 controls matched with gender,age,and BMI were included in this study.Clinical information and laboratory examinations of all subjects were collected and serum asprosin levels were measured by commercial ELISA kits.ResultsSerum asprosin levels in acromegaly patients were significantly lower than controls(2.18±0.86 vs 2.71±0.86 ng/ml,P<0.001).Serum asprosin levels in patients with the course of acromegaly?5 years(compared with<5 years),high area under curve of growth hormone(GH-AUC)after 75g oral glucose tolerance test(compared with low GHAUC group),and high IGF-1 SDS group(compared with low IGF-1 SDS group)were significantly reduced(all P<0.05).Serum asprosin levels in acromegaly patients were negatively correlated with the course of acromegaly(r=-0.273,P=0.026),IGF-1 SDS(r=-0.295,P=0.016),nadir growth hormone value(GH Nadir,r=-0.249,P=0.046),and GH-AUC(r=-0.285,P=0.021)after 75g oral glucose tolerance test(75g OGTT).Multiple stepwise linear regression analysis indicated that acromegaly was one of the independent influencing factors of serum asprosin levels.In addition,serum asprosin levels were higher in females than that of males in both acromegaly group and the control group(acromegaly:2.56 ± 0.69 vs 1.66 ± 0.80 ng/ml;controls:3.15±0.54 vs 1.87 ± 0.71 ng/ml,P<0.01)?ConclusionsThe levels of serum asprosin in patients with acromegaly are lower,suggesting the reduced serum asprosin levels in patients with acromegaly are closely related to the reduction of fat content and increased blood glucose caused by long-term high GH levels,and the causal relationship between high growth hormone levels and serum asprosin levels needs further mechanism research.ObjectivesHyperprolactinemia is a common clinical endocrine condition,often manifested as menstrual disorders,infertility,or found after physical examination.Recent studies have shown that macroprolactinemia is one of the common causes of hyperprolactinemia with an average incidence of 18.9%,which can easily be misdiagnosed and overtreatment.The determination methods of serum macroprolactin mainly include gel filtration chromatography(GFC),polyethylene glycol(PEG)precipitation and ultrafiltration(UF).Each of the three methods has advantages and disadvantages.This study aims to compare the diagnostic value of PEG precipitation and ultrafiltration for macroprolactinemia in patients with hyperprolactinemia using the gel filtration chromatography as a standard.Methods71 patients with hyperprolactinemia(more than 13.1 ng/ml in men;more than 30 ng/ml in women)in Peking Union Medical College Hospital(PUMCH)during February 2019 to December 2020 were included with 17 patients clinically suspected as macroprolactinemia.The serum samples,medical records,and laboratory and examines'results of all subjects were collected.After separation for macroprolactin in gel filtration chromatography,PEG precipitation method and ultrafiltration,chemiluminescence method(Beckman system)was used to determine the prolactin levels of all serum samples.ResultsThe methodologies of gel filtration chromatography(GFC),PEG precipitation and ultrafiltration had been established through exploration different factors.The reproducible results of different levels of prolactin by PEG precipitation and ultrafiltration were relatively reliable(CV<20%).Gel filtration chromatography,PEG precipitation and ultrafiltration were used to detect macroprolactin in 71 patients with hyperprolactinemia.The recoveries of monomeric prolactin were 74.1 7±14.62%(GFC),76.74±16.08%(PEG),and 73.49±13.30%(UF),respectively.Besides,there were 7(GFC),5(PEG),and 4(UF)cases of macroprolactinemia found,respectively.The recoveries of monomeric prolactin after PEG precipitation or ultrafiltration both had a significantly linear correlation(correlation of coefficient:0.732 vs 0.276)with that of gel filtration chromatography.The Bland-Altman diagram showed that the recoveries of monomeric prolactin by both PEG precipitation and ultrafiltration were consistent with that of gel filtration chromatography method(average difference-2.57%and 0.679%).However,the recoveries of monomeric prolactin varied greatly(95%CI:-32.32?33.67%)in ultrafiltration.In addition,the PEG precipitation method used for diagnosis of macroprolactinemia had a better consistency with gel filtration chromatography than ultrafiltration(Cohen's Kappa coefficient=0.818 vs 0.401).In our study,the incidence of macroprolactinemia in hyperprolactinemia and in clinically suspected macroprolactinemia patients was 9.9%(7/71)and 29.4%(7/17),respectively.All the patients with macroprolactinemia showed insignificant clinical manifestations,mild to moderate increase in prolactin levels,and the imaging manifestations were mainly negative or pituitary microadenoma.The levels of monomeric prolactin decreased significantly after determination in three methods.ConclusionThe incidence of macroprolactinemia in patients with hyperprolactinemia was 9.9%(7/71)by gel filtration chromatography.With gel filtration chromatography as the gold standard,PEG precipitation method is still the best method for the detection of macroprolactinemia at present.However,the feasibility of ultrafiltration for the detection of macroprolactinemia from patients with hyperprolactinemia remains to be further explored.Considering for the existing determination methods,it's recommended to carry out the determination only in patients clinically suspected as macroprolactinemia.
Keywords/Search Tags:Acromegaly, Adipocytokines, Asprosin, Growth hormone, Glucolipid metabolism, Hyperprolactinemia, Macroprolactinemia, PEG precipitation, Ultrafiltration, Gel filtration chromatography
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