Characteristics of respiratory syncytial virus infections in children with severe acute respiratory tract infections in Huzhou City， Zhejiang Province from 2018 to 2022 / 上海预防医学

ObjectiveTo understand the prevalence of respiratory syncytial virus （RSV） infections among children hospitalized with severe acute respiratory infections （SARI） in Huzhou， Zhejiang Province， and to explore the epidemiological characteristics and influencing factors of RSV. MethodsNasopharyngeal swab samples from children under 15 years of age， newly admitted to the Huzhou First People's Hospital from 2018 to 2022 and who met the SARI surveillance definition， were collected for respiratory virus nucleic acid testing. SPSS 25.0 and Excel 2016 software were used for statistical analysis of the data. ResultsA total of 1 076 samples were tested for nucleic acids， with an overall positivity rate of 11.2%. The positivity rate of infants under 5 years old was relatively high （16.7%）. RSV infection showed a seasonal distribution， mainly concentrated in autumn and winter， with the highest positivity rate in December （22.3%）. A total of 23 cases of respiratory mixed infection were detected， with a mixed infection rate of 2.13%， among which 16 were RSV-related mixed infections. Logistic regression analysis indicated that season and age were risk factors for RSV infection. ConclusionFrom 2018 to 2022， RSV showed different epidemiological characteristics across different ages and seasons in SARI cases in Huzhou， with significant differences， providing a scientific basis for future prevention of RSV infections.

Clinical management of hyperthyroidism complicated with liver failure / 中华内分泌代谢杂志

Clinical data from 11 previously diagnosed and treated patients with hyperthyroidism(Graves′ disease) complicated by liver failure were collected. Among them, 4 cases were drug-induced liver injury leading to liver failure, 1 case had a history of schistosomal liver cirrhosis combined with hyperthyroidism, and 6 cases had hyperthyroidism-induced liver injury(HILI) leading to liver failure. During hospitalization, all patients received supportive therapy and symptomatic treatment with β-blockers. Nine patients were treated with glucocorticoids and artificial liver support therapy. Among the 11 patients, 2 died, 8 patients achieved normal thyroid and liver function within 1-12 months after treatment, and 1 patient with liver cirrhosis had stable liver function in the later stage. After improvement in liver function, 7 patients received isotope therapy, 1 patient underwent total thyroidectomy, and 1 patient received medication. These results indicate that the clinical characteristics differ for drug-induced liver injury and HILI-related liver failure. Early initiation of artificial liver support therapy, in addition to β-blockers and glucocorticoids, is important in alleviating thyroid toxicity and liver damage, thus creating an opportunity for subsequent radioactive iodine or surgical treatment.

Thyroid cancer has become a problem that gravely impacts public health / 中华内分泌代谢杂志

[Summary] The global incidence of thyroid cancer has been increasing in recent years,but the reasons for the increase are still not well established.Widely applied and improved diagnostic modalities,together with that people are more likely to concern their health status may contrilute to the increased incidence of thyroid microcarcinomas and incidental (asymptomatic) carcinomas.There might be an association between Hashimoto thyroiditis and thvroid cancer.Many environmental factors,such as exposure to ionizing radiation,may also be risk factors for thyroid cancer.

Advantages and disadvantages of lithium carbonate in the treatment of hyperthyroidism / 中华内分泌代谢杂志

[Summary] Lithium carbonate has been used as a psychiatric drug with some adverse effects such as hypothyroidism and leukocytosis.The adverse effects have been exploited for the treatment of hyperthyroid patients in particular conditions.It might be an alternative therapy for controlling hyperthyroidism in patients who can not tolerate or do not respond to thionamides or suffer from leukopenic condition.But it is important that monitoring serum lithium level,using smaller dose,and avoiding serious side-effects during the therapy of lithium carbonate should be carried out.

Investigation on peripheral blood TSHR mRNA for differentiation of benign and malignant thyroid nodules / 中华内分泌代谢杂志

Objective To assess the value of peripheral blood thyroid stimulating hormone receptor(TSHR) mRNA determination in differential diagnosis of benign and malignant thyroid nodules.Methods Fine needle aspiration cytology (FNAC) and (or) postoperative histopathology as the gold standard were carried out,the expression of circulating TSHR mRNA was determined by RT-PCR in 33 patients with benign thyroid nodules,39 patients with thyroid cancer,and 20 normal controls.Results TSHR mRNA signals were not detected in normal controls,the positive rate of TSHR mRNA was higher in the group with malignant nodules than the group of benign nodules (91.2％ vs 48.5％,P＜0.01).TSHR mRNA level in the preoperative malignant group was significantly higher than that in the normal,benign,and postoperative cancer groups (all P ＜ 0.01).Using peripheral blood TSHR mRNA for differentiating benign or malignant of thyroid nodule had a sensitivity,specificity,and accuracy of 91.2％,51.5％ and 71.6％,respectively.The sensitivities of TSHR mRNA,FNAC,and these two methods combined in detecting malignant nodules were 91.3％,86.9％,and 100.0％ respectively,while diagnostic accuracies were respectively 84.0％,80.0％,and 92.0％.TSHR mRNA expression showed no significant relationship with sex,age,size,and number of nodule in these patients (all P ＞ 0.05),but it did exhibit significant difference between benign and malignant nodules(P＜0.01).Conclusion The peripheral blood TSHR mRNA could be used as a molecular marker for thyroid cancer,and it would help enhance the preoperative differentiation of benign and malignant thyroid nodules.

Risk factors analysis of microalbuminuria in patients newly diagnosed with type 2 diabetes mellitus / 中国综合临床

Objective To analyze the incidence and risk factors of microalbuminuria in newly diagnosed and hospitalized type 2 diabetes mellitus patients,and to provide the theoretical basis for therapy of diabetes and diabetic chronic complications.Methods The blood glucose,lipid profile,24h-urinaryalbumin,fasting and postprandial serum insulin and peptid C were measured in 286 newly diagnosed and hospitalized type 2 diabetic patients from Mar.2006 to Sep.2009.Microalbuminuria was defined as the 24h-urinary albumin between 30 to 300 mg twice.Insulin resistance index (HOMA-IR) was recorded and all the patients received fundus examination by ophthalmologists after expansion of the pupil to ensure whether there was retinopathy or not.Results (1)The incidence rate of microalbuminuria in this study was 19.58％ (56/286).(2)Normal albuminuria group and MA group combined DR were 19.57％ (45/230) and 33.93 ％ ( 19/56 ) respectively,and the difference was statistically significant( x2 =5.349,P =0.021 ).Compared with control,the FPG,HbA1c and HOMA-IR were significantly higher in microalbuminuria group ( FPG:[ 11.08 ± 1.76 ] mmol/L vs [9.24 ±1.65]mmol/L,t =-6.148,P ＜0.001;HbA1c:[11.54 ± 1.59]％ vs [9.39 ± 1.64]％,t =-7.533,P ＜0.001 ;HOMA-IR:[3.73 ±0.42] vs [3.50 ±0.30],t =-3.774,P ＜0.001 ).(3) Pearson correlation analysis revealed microalbuminuria was positively correlated with FPG( r =0.460),HbA1 c ( r =0.499),HOMA-IR( r =0.308)and combined DR(r =0.405)(P ＜0.01).(4)Stepwise multiple regression analysis revealed that FPG (ββ =- 0.804,P ＜ 0.01 ),HbA1 c (β =- 0.455,P ＜ 0.01 ) and combined DR (β =1.527,P ＜ 0.05 ) were independently risk factors of microalbuminuria.Conclusion The development of microalbuminuria in newly diagnosed and hospitalized type 2 diabetic patients is associated with FPG,HbA1c and HOMA-IR,and will be easier to merge diabetic retinopathy.

Influence of positive serum thyroid peroxidase antibody on pregnancy outcomes / 中华内分泌代谢杂志

ObjectiveTo investigate the influence of positive serum thyroid peroxidase antibody (TPOAb) on pregnancy outcomes in biochemically euthyroid women during gestation.MethodsFrom July 2006 to December 2010,in the prenatal care unit all pregnant women,who had no medical and family history of thyroid diseases,underwent thyroid function screening.Serum TPOAb was tested among those pregnant women with euthyroidism.Pregnancy outcomes,including obstetric complications,neonate birth weight,and Apgar score,were compared between 185 TPOAb positive women and 1417 TPOAb negative women.ResultsCompared with TPOAb negative women,it was more frequent for TPOAb positive women to suffer from various obstetric complications.The prevalences of umbilical cord entanglement ( 18.9％ vs 12.9％,RR =1.47,95％ CI 1.06-2.03,P＜0.05 ),threatened premature delivery or abortion (3.8％ vs 1.0％,RR =3.83,95％ CI 1.57-9.37,P＜0.05 ),intrauterine growth retardation (5.4％ vs 0.8％,RR =6.96,95％ CI 3.00-16.17,P＜0.01 ),and neonatal pneumonia ( 4.9％ vs 1.3％,RR =3.83,95％ CI 1.75-8.40,P＜0.01 ) in the group of TPOAb positive women were higher than those in the group of TPOAb negative women.Apgar score of those newborns whose mothers had positive TPOAb was 9.27 ±1.13 at one minute and 9.44 ± 1.09 at five minutes,being lower than that of the TPOAb negative group (9.49 ±0.69 and 9.68 ±0.52,both P＜0.01 ).The rate of newborns with Apgar score at 7 or less by 5 min in group with positive TPOAb was higher than that of group with negative TPOAb ( 1.6％ vs 0.1％,RR =11.49,95 ％ CI 1.93-68.31,P＜ 0.05 ).ConclusionsThese results indicate that pregnant women with normal thyroid function but positive TPOAb may be liable to increase risk of serious pregnancy outcomes,such as threatened premature delivery or abortion,intrauterine growth retardation,and a lower Apgar score in neonatal.

Expression of iodothyronine deiodinases on human placenta in pregnant women with different thyroid disease / 中国综合临床

Objective To investigate the expression of type Ⅱ and type Ⅲ iodothyronine deiodinases (D2 and D3 ) of human placenta on pregnant women with different thyroid diseases and different autoimmunity.Methods Pregnant women with different thyroid diseases and autoimmunity were selected into the experiment group,and pregnant women who had no individual or family history of thyroid diseases with normal thyroid function and negative thyroid peroxidase antibody (TPOAb) were selected into the control group.Expression level of iodothyronine deiodinase( D2 and D3 )on placenta was measured by RT-PCR.Results D2 and D3 were both expressed on human placenta.D2 showed significantly higher expression level in hypothyroidism uncontrolled group than that in control group ( 0.916 ± 0.035 vs 0.833 ± 0.029,P ＜ 0.05 ),however,D3 showed a lower expression(0.766 ±0.038 vs 0.848 ±0.052),on placenta and the difference was not significant(P ＞ 0.05 ).In those who had history of hyperthyroidism or hypothyroidism but whose thyroid function become normal by effective treatment,D2 and D3 expression exhibited no difference from that of the control(P ＞ 0.05).In those pregnant women with normal thyroid function and TPOAb-positive,D2 and D3 expression was (0.842 ± 0.032 ) and ( 0.837 ± 0.053 ) respectively and there was also no difference from that of the control( P ＞ 0.05 ).Conclusion D2 and D3 were simultaneously expressed on human placenta.In those pregnant women with hypothyroidism,the level of D2 expression is high and the level of D3 expression is low.Those changes might be important and helpful for the stabilization of thyroid hormone transportation between mother and fetus.

Investigation onto thyroid dysfunction and autoantibody screening in second and third trimesters of pregnancy / 中华内分泌代谢杂志

Objective To investigate the prevalence of thyroid disorders and positive thyroid autoantibodies,and evaluate the necessity for universal thyroid screening during the second and third trimesters of pregnancy.Methods The pregnant women during the second and third trimesters who visited Shanghai Jiaotong University Affiliated First People's Hospital between June 2006 and February 2008 were chosen for thyroid screening by determining serum free triiodothyronine,free thyroxine,thyrotropin,thyroid peroxidase antibody (TPOAb),and thyrotropin receptor antibody.A personal and family history of thyroid disease and other autoimmune diseases was investigated by questionnaire.The pregnant women were divided into high risk or low risk groups for thyroid disease based on their personal or family histories.Results A total of 2 101 pregnant women were screened,712 ( 33.89％ ) of them were identified to suffer from thyroid disorders or with positive thyroid autoantibody.The prevalence of thyroid dysfunction was increased in high risk group.While in low risk group( n =1 983 ),the prevalence of clinical hypothyroidism was 2.27％ ( n =45 ),subclinical hypothyroidism 11.60％ ( n =230 ),clinical hyperthyroidism 0.20％ ( n =4 ),subclinical hyperthyroidism 1.06％ ( n =21 ),hypothyroxinemia 6.45％ ( n =128 ),and euthyroid with positive TPOAb 10.74％ ( n =213 ) in our study.Pregnant women with positive TPOAb were susceptible to thyroid dysfunction.It was shown that 79.74％ of pregnant women with thyroid disorders were diagnosed by universal thyroid screening.Conclusions 33.89％ of pregnant women in the second and third trimesters were identified to suffer from thyroid disorders or positive thyroid autoantibody by universal thyroid screening.Increased prevalence of thyroid dysfunction was found in pregnant women with positive TPOAb.79.74％ of pregnant women with thyroid disorders might be missed if screening was made only in the high risk cases.

Controlled or uncontrolled clinical and subclinical hypothyroidism in pregnant women and its effect on obstetrical and neonatal outcome / 中国医师杂志

ObjetiveTo investigate the obstetrical and neonatal outcomes of pregnant women with hypothyroidism or subclinical hypothyroidism.MethodsOne hundred and sixty-eight pregnant women with clinical or subclinical hypothyroidism during pregnancy,including 9 controlled hypothyroidism,29 uncontrolled hypothyroidism and 130 subclinical hypothyroidism,were enrolled in this study.The general clinical information,obstetrical complications and neonatal outcomes of these pregnant women were compared with that of 180 healthy pregnant women who delivered during the same period.ResultsCompared with control group,there were no significant differences in the levels of serum free triiodothyronine( FT3 ),free thyroxine ( FT4 ),thyrotropin-stimulating hormone (TSH) in the controlled hypothyroidism group in the third trimester [(3.68 ±1.11 ) pmol/L vs (3.19 ±0.33) pmol/L,(15.48 ±4.14) pmoL/L vs (13.95 ± 1.68) pmol/L,1.87 mU/L vs 1.76 mU/L,P ＞0.05].However,in the second and third trimester,the levels of FT3,FT4 in the uncontrolled hypothyroidism group were lower,while the levels of TSH were higher than in control group [(2.71 ±0.80) pmol/L vs (3.14 ± 0.34) pmoL/L,(10.94 ± 2.68) pmol/L vs (14.25 ±2.01) pmol/L,5.62 mU/L vs 2.28 mU/L,( 2.34 ± 0.70 ) pmol/L vs ( 3.19 ± 0.33 ) pmol/L,( 10.16 ± 1.65 ) pmol/L vs (13.95 ± 1.68) pmoL/L,7.13 mU/L vs 1.76 mU/L,t =2.754～9.15,P ＜0.01],the levels of TSH in the subclinical hypothyroidism were higher than in control group ( t =18.28,18.57,P ＜0.01 ).There was no adverse perinatal outcome of neonate happened in controlled hypothyroidism group.In contrast,the incidences of adverse perinatal outcomes and complications in the uncontrolled hypothyroidism group were higher than that in the control group ( 17.2％ vs 2.8％,37.9％ vs 5.6％,x2 =11.47,28.97,P ＜0.01 ).Compared with that of control group,the incidences of adverse obstetrical outcomes in pregnant women with subclinical hypothyroidism were increased (40.0％ vs 5.6％,x2 =52.97,P ＜ 0.01 ).ConclusionsThe rate of adverse obstetrical outcomes and complications is increased in women with clinical or subclinical hypothyroidism.But the incidence of adverse outcomes would decrease if hypothyroidism is controlled by treatment.

Analysis of bone strength and influencing factors in adults / 上海交通大学学报（医学版）

Objective To investigate bone strength in adults,and explore its influencing factors. Methods One hundred and ninety-one adults undergoing health examinations were selected.The questionnaires about milk intake and exercise conditions were performed,the body weight,fat mass,body mass index(BMI)and calcaneal bone strength were measured,and the relationship between each parameter and bone strength was analysed. Results Bone suength decreased with age increase,and was higher in males than that in females.Bone strength of overweight to obese adults was higher than that with normal body weight(P<0.05).Bone strength of adults with high milk intake was higher than that of those with low milk intake(P<0.05).Multivariate analysis revealed that age was negatively related to bone strength,females were more susceptible to bone strength decrease,and BMI and milk intake were positively related to bone strength. Conclusion Gender,age,BMI and milk intake are main influencing factors for bone strength.Bone strength decreases with age increase,and increase of BMI and milk intake will benefit bone strength,especially for females.

Threshold prediction in adults with normal hearing using ASSR, Tb-ABR and c-ABR: a within-subject comparison / 临床耳鼻咽喉头颈外科杂志

OBJECTIVE@#To evaluate the accuracy with which auditory steady-state response (ASSR), tone burst auditory brain stem response (Tb-ABR) and click-evoked auditory brainstem response (c-ABR) thresholds predict behavioral thresholds, using a within-subjects design.@*METHOD@#ASSR, Tb-ABR and c-ABR thresholds were recorded in a group of adults with normal hearing (58 ears). Evoked-potential thresholds were recorded and compared with behavioral, pure-tone thresholds.@*RESULT@#The results suggested both ASSR and Tb-ABR thresholds had high correlations to pure-tone thresholds. Tb-ABR thresholds were recorded much closer to behavioral threshold than ASSR thresholds. There was a linear relation between c-ABR thresholds and average thresholds of 2 kHz, 4 kHz pure tone audiometry.@*CONCLUSION@#Both the ABR and the ASSR provided reasonably accurate predictions of multifrequencies behavioral threshold. Tb-ABR combined with c-ABR may take the accuracy predicted behavioral threshold.

Effect of pentoxifylline on Fas and FasL expressions in pancreas and spleen of NOD mice / 中华内分泌代谢杂志

NOD mice were treated with pentoxifylline (FTX) to investigate the incidence of cyclophosphamide-accelerated diabetes, the apoptosis and the insulin expression of β-cells and expressions of Fas or FasL mRNA in both pancreas and spleen. The results showed that incidence of diabetes in PTX group was significantly lower compared with control group (P<0.05). The apoptosis of β-cells was decreased in PTX group with higher insulin expression level in islet cells. The expression of FasL mRNA in pancreas of PTX group was lower than that of control group (P<0.05), and there was no significant difference in Fas mRNA expression between two groups. Both Fas and FasL mRNA levels in spleen of PTX group were much higher than those of control group (P<0.05 or P<0.01).

Analysis on clinical and pathological features of 127 thyroid carcinomas / 中国实用内科杂志

Objective To study the clinical features of thyroid carcinoma and to explore the approach of early diagnosis for the disease.Methods The data of patients with thyroid carcinoma confirmed by pathology during January of 1999 to January of 2005 in the First Hospital affiliated to Shanghai Jiao Tong University were retrospectively reviewed,including clinical appearance,thyroid ultrasonography and radioisotope scanning.Results One hundred and twenty-seven consecutive patients,30 males and 97 females,mean age(48.9?13.6)years,were diagnosed with thyroid carcinoma by surgery and pathology.A total of 127 cases of thyroid carcinoma were included,which were 105 papillary thyroid carcinomas,14 follicular thyroid carcinomas,2 undifferentiated thyroid carcinomas and 6 medullary thyroid carcinomas.Thyroid ultrasonography findings showed the majority(85.1%)thyroid nodules were low echo nodules and the proportions of solid and mixed nodules were 81.8%and 17.4%,respectively.The proportion of cold nodules was 88.9% by radioisotope scanning.Mean values of serum triiodothyronine,thyroxine and thyrotropin were all within the normal range.Conclusion In the present study the thyroid carcinomas are predominant in females and the incidence of papillary thyroid carcinomas is very high.The diagnosis of thyroid carcinoma can not just depend on findings of ultrasonography,radioisotope scanning and serum thyroid hormone.

Effect of treatment and change of islet function by adding insulin glargine on patients with second failure of sulfonylureas / 中国实用内科杂志

Objective To investigate the effect of insulin glaring(IG)and neutral protamine hagedorn(NPH)on metabolic control and islet cell function in type 2 diabetic patients who secondly failed to sulfonylureas(SU)treatment.Methods Fifty-two diabetic patients with second SU failure were studied in our hospital during May,2004 to Nov,2004,and they were divided into two groups:twenty treated with glipizide extended release tablets(GERT)plus IG injection,while thirty-two with GERT plus NPH.Fasting and postprandial blood glucose,HbA_1c,fasting and postprandial C-peptide were determined in all patients at different following points.Results Blood glucose decreased obviously and similarly in two groups;however,hypoglycemia occurred less in IG group.Interestingly,fasting and postprandial C-peptide significantly increased in IG group,but didn't change in NPH group.Conclusion Combination treatment with IG or NPH has good effect on metabolic control in second SU failure patients;and moreover,IG improves B-cell function.

Investigation on translating relationship of hemoglobin A_1C and average glucose / 中国实用内科杂志

HbA1c measures chronic glycemia and is widely used to judge the adequacy of diabetic treatment and adjust therapy.According to ADAG study,the relationship between HbA1c and the calculated AG can be expressed as the linear regression:eAG(mg/dL)=28.7?HbA1c-46.7.ADA has adopted this equation on its website.In the same unit of measurement as used in self-monitoring blood glucose,eAG would facilitate the doctors to communicate with patients in the daily glucose control.

Effect of pentoxifylline on caspases expression in islet beta-cells of NOD mice / 中国病理生理杂志

AIM: To investigate the intervention effect of pentoxifylline(PTX) on type 1 diabetes mellitus in non-obese diabetic(NOD)mice and explore its possible mechanism.METHODS: Eight-week-old NOD mice were treated with PTX to investigate the incidence of cyclophosphamide accelerating diabetes.The apoptosis of beta-cells was detected by TUNEL,the expressions of caspase-3 in islet of the NOD mice was checked by immunohistochemistry and the expressions of caspase-8 was determined by RT-PCR.RESULTS: The incidence of diabetes in PTX group was 40.63%,which was obviously lower than 69.70% in the control group(P

Comparison of clinic characters among patients with latent autoimmune diabetes in adults and type 1 or type 2 diabetes / 中国糖尿病杂志

Objective To study the clinic characters of patients with latent autoimmune diabetes in adults (LADA). Methods We evaluated the prevalence of acute and chronic complications in the LADA patients with serum antibodies to glutamic acid decarboxylase (GADA) or to islet cell cytoplasmic antigens (ICA). The prevalence of acute and chronic complications were further compared with that in patients with acute onset type 1 or type 2 diabetes. Results The mean age, BMI, fasting and postprandial C peptide levels of the LADA patients were higher than those of type 1 diabetes and lower than those of type 2 diabetes. Of the LADA patients, 29.3% had ketosis. Although the frequency of repeated attack of ketosis in the LADA patients was similar to that in type 1 diabetes, the duration from diabetic onset to first ketosis in the LADA patients was much longer. The prevalence of retinopathy in the LADA patients was 19.5%, which was similar to that in type 1 diabetes. The prevalence of cataract in the LADA patients was 48.8%, which was similar to that in type 2 diabetes. Less LADA patients had microalbuminuria, compared with the other groups. There was no difference in the prevalence of overt nephropathy, neuropathy and hyperlipidemia among the three groups. The prevalence of coronary heart disease in the LADA patients was similar to that in type 2 diabetes. The prevalence of hypertension in the LADA patients was higher than that in type 1 but lower than that in type 2 diabetes. Conclusion The clinic characters as well as acute and chronic complications in LADA patients are different from those in type 1 and type 2 diabetes.

Effect of combined treatment of glargine and gllpizide GITS on metabolic control and ?-cell function / 中华内分泌代谢杂志

Diabetic patients with secondary sulfonylureas failure were shifted to glipizide plus glargine ( n = 20) or neutral protamine hagedorn (n =32). Sixteen weeks later, blood glucose and HbAIC were decreased and serum C peptide level increased in both groups. Hypoglycemia occurred less frequently and?-cell function was improved in glargine group.

THE THERAPEUTIC EFFECT OF PROPRANOLOL COMBINED WITH METHIMAZOLE IN HYPERTHYROIDISM / 中华内分泌代谢杂志

Ninty-nine initial but untreated patients with hyperthyroidism were divided at random into three groups :propranolol, methimazole, and combined groups. Determination of serum T4, T3, rT3 and TSH levels together with STI and ICG were performed before and during treatment among these groups. The results showed that in the combined group, the fall of mean T3 levels to normal was the earliest and fastest, there was a better normalization of cardiac parameters, and the clinical manifestations could be brought under control rapidly. The combined therapy of propranolol with methimazole was especially advantageous to cases of mild and moderate hyperthyroidism.