1. Analysis Of The Clinical Characteristics Of Primary Hyperparathyroidism In Children/adolescents And Screening Of Pathogenic Genes 2. The Characteristics Of Bone Microstructure Detected By HR-pQCT In Patients With Primary Hyperparathyroidism

Context and Objective:Primary hyperparathyroidism(PHPT)in children is thought to be extremely rare.Our study aimed to summarize the clinical characterization and molecular genetics in this rare condition in Chinese population.Methods:A total of 67 pediatric patients(onset age<18yrs)of PHPT admitted in our hospital during 1977 to 2017 were retrospectively analysed.And 134 patients of adult-onset patients with PHPT during the same period were randomly selected to compare clinical characterization between pediatric PHPT and adult-onset PHPT.Germline mutation analysis of MEN1,CDC73,RET,CDKN1B or CaSR gene were performed in 32 pediatric PHPT patients.Results:Sixty-seven pediatric patients with PHPT(3 8 females and 29 males)with a mean onset age of 14.1 ±2.8 years(range:5-18 years)were included.Only two patient(3%)was asymptomatic.Bone involvement,urolithiasis,acute pancreatitis and hypercalcemic crisis were presented in 82.1%,41.8%,7.5%and 13.4%of cases,respectively.Short stature was found in 20.7%of cases at diagnosis.Pediatric PHPT presented with more common rickets/osteomalacia,less common urolithiasis,lower rate of hypophosphatemia,and higher rate of hypercalciuria when compared with adult-onset PHPT.Sixty-three child-onset patients underwent surgeries.Adenomas,hyperplasia and atypical adenoma and carcinoma occurred in 77.8%,9.5%,4.8%and 7.9%of cases,respectively.The remission and recurrence rate were 93.7%and 9.5%,respectively.There were no significant differences between the adult and pediatric groups in terms of recurrence rates and recurrence timeframe.Among the 32 pediatric patients screened for gene mutation,three cases were found to carry MEN-1 mutations and seven were found to carry CDC73 mutations,with a total mutation rate of 31.2%.Conclusion:Different from adult-onset PHPT patients,most children and adolescents with PHPT were still symptomatic.Rickets/osteomalacia were more common than their adult counterparts.The most common pathology of children and adolescents with PHPT was adenomas.These patients can be successfully treated surgically like adults.Mutations of MEN1 and CDC73 genes were recommended for a relative high mutation rate.Context and Objective:Bone is the most common target organ damage of primary hyperparathyroidism(PHPT).High resolution peripheral quantitative CT(HR-pQCT)is a new imaging technique that can separately assess trabecular and cortical bone microstructure of the radius and tibia in vivo.A few studies have evaluated bone involvement of PHPT by HR-pQCT and found that both cortical and trabecular bone were significantly impaired by PTH excess.But current HR-pQCT data on PHPT were limited to Caucasian females.Using HR-pQCT,we aimed to evaluate the bone structural features of PHPT patients in a Chinese population,and reveal the similarities and differences of bone structural features in multiple endocrine neoplasia type 1 related PHPT(MHPT)and sporadic PHPT(SHPT).Methods:In 58 patients with PHPT and 58 sex-and age-matched healthy controls,the distal radius and tibia were imaged using HR-pQCT.Clinical data including areal bone mineral density(aBMD)assessed by Dual-energy X-ray absorptiometry(DXA)were collected.Results:1.Compared with controls,PHPT patients had reduced total bone,trabecular and cortical volumetric BMD(all p<0.001)in both radius and tibia.Reduced cortical thickness and area(all p<0.001),as well as reduced trabecular thickness and number,and increased trabecular separation(p=0.01,p<0.001 and p<0.001,respectively)were found in the radius compartment.And reduced cortical thickness and trabecular number(p=0.009 and p<0.001,respectively),along with increased trabecular area,and trabecular separation(p=0.021and p<0.001,respectively)were found in the tibia compartment.2.The HR-pQCT data of female and male patients were compared with age-matched controls separately.In the male groups,PHPT patients had significantly reduced Tt.vBMD,Tb.vBMD and Ct.vBMD in the radius,and reduced Ct.vBMD in the tibia,when compared with controls.For the female groups,PHPT patients had significantly reduced Tt.vBMD,Tb.vBMD and Ct.vBMD in both radius and tibia,when compared with controls.When comparing male and female patients,Tb.Ar in the radius was reduced in male patients(-13.1%),but increased in female patients(+2.9%)compared with controls.The decrease in Ct.Th and Ct.Po.Dm were more significant in male patients than that in female patients(21.4%vs.8.3%,P=0.024 and 18.2%vs.9.7%,P=0.011,respectively).No significant differences were found in other HR-pQCT parameters between male and female patients.3.The MHPT patients(n=11)had lower aBMD Z-scores in lumbar spine,trochanteric region and total hip than SHPT patients(n=47),whereas no differences were found in structural indices measured by HR-pQCTbetween the two groups.4.In the multiple linear regression model,Tb.Th at tibia and Ct.Po at radius were positively correlated with PTH levels(?=-1.908e-5 and ?=-5.859e-5,respectively;all P<0.01).Ct.Ar at radius and Tt.vBMD?Tb.vBMD at tibia were positively correlated with ALP levels(? =0.019,P<0.05;?=0.075,P<0.05 and ?=0.066,P<0.01,respectively).Ct.Po at radius and BV/TV at tibia were also positively correlated with ALP levels,but the regression coefficients were extremely low(? =4.554e-5 and ?=9.185e-5,respectively;all P<0.01).Conclusion:PHPT affects bone microstructure in both cortical and trabecular bone in Chinese patients.Significant differences still existed when comparing data of both female and male patients with age-matched controls separately.MHPT patients had reduced aBMD assessed by DXA in lumbar spine and hip compared with SHPT patients,but HR-pQCT indices did not differ.