The bilateral idiopathic aldosteronism (IHA) is the most common subtype of aldosteronism.Spironolactone is the primary preferred agent due to the pathophysiology of IHA and the long-standing clinical experience over years.If patients faced with severe side effects of spironolactone or poorly controlled blood pressure by this first-line treatment,additional treatment alternative to spironolactone,second antihypertensive,as well as adrenalectomy are suggested.In recent years,several new agents were developed to treat IHA,such as aldosterone synthase inhibitor and eplerenone.This review introduces these new kinds of medicine in the treatment of IHA.

ObjectiveTo investigate the effects of maternal thyroid dysfunction during pregnancy caused by iodine deficiency of different degrees on doublecortin ( DCX ) and synaptophysin ( p38 ) expressions in fetal brain.Methods Wistar female rats were randomly divided into four groups:adequate iodine ( AI),mild iodine deficiency ( MiID ),moderate iodine deficiency ( MoID ),and severe iodine deficiency ( SID ),according to the total daily iodine supply( fed on an iodine deficient diet with different dosages of KI added in drinking water).Three months later the rats were mated.Serum TSH and thyroid hormones were determined in maternal rats on gestational day 20 using chemiluminescent immunoassay.The iodine contents in urine and histological changes of thyroid gland were observed in pregnant rats.The mRNA and protein levels of DCX and synaptophysin ( p38 ) were analyzed in fetal brain by using real time quantitative RT-PCR and western blotting respectively.Results( 1 ) Iodine contents in urine of pregnant rats were reduced with the decrease of their iodine supply.Compared with group AI,serum TSH was significantly increased [ ( 2.95 ± 1.70 vs 1.31 ± 0.55 ) mU/L,P ＜ 0.05 ],and both TT4 and FT4 were significantly decreased [ ( 14.3±4.1 vs 28.4±19.3 ) nmol/L,P＜0.05 ] and [ ( 10.8±3.6 vs 20.2±8.0) pmol/L,P＜0.01 ] in pregnant rats of SID group.Whereas,a slight rise in TSH,and a mild decline in both TT4and FT4 were found in MoID and MiID groups.However,there were no significant changes in TT3 and FT3 levels among these four groups.( 2 )Histological characteristics of thyroid gland in pregnant rats showed a typical goiter with small follicular hyperplasia and lack of colloid in SID group,moderate follicular hyperplasia with decreased colloid in MoID group; but mild cellular hyperplasia without decrease in follicular size and colloid in MiID group.( 3 ) The mRNA levels of DCX were increased in fetal brains of three iodine deficiency groups compared with AI group,but a statistical significance was found in MoID group.The protein levels of DCX in all experiment groups were significantly increased.Both mRNA and protein expressions of synaptophysin ( p38 )were significantly down-regulated in three iodine deficiency groups.Conclusions Maternal thyroid dysfunction caused by iodine deficiency,even by mild or moderate iodine deficiency,may lead to retardation of fetal neuronal and synaptic growth.

Immunoprecipitation and Western-blot were performed to detect the expression of LGR8 in the testes in wild type (Wt) and Insl3-knockout ( KO ) mice.Testis were harvested from WT and KO mice on embryonic day 18 (E18) and on postnatal(P) 1,3,7,14,17,20,23,51,and 90 days.LGR8 staining in Leydig cells was stronger in all Wt mice than that in KO mice( all P＜0.05 ).LGR8 expression on spermatocytes varies with age.Strong stain on P1 Wt and postpubertal mice was concentrated in the developing and mature acrosome of spermatids

ObjectiveTo investigate the effect of rhPTH (1-34) and elcatonin on bone metabolism and serum secreted protein acidic and rich in cysteine ( SPARC ) in postmenopausal women with osteoporosis.Methods One hundred and twenty-four postmenopausal women with osteoporosis were randomly divided into 2 groups:One group was treated with recombinant human parathyroid hormone ( 1-34 ) [ rhPTH ( 1-34 ) ] 200 U/d by subcutaneous injection (PTH group,n =89 )and another group was treated with elcatonin 20 U/week by intramuscular injection (CT group,n =35 ) for 12 months.All patients received a basic therapy with oral calcium ( Ca 600 mg+ Vit D3125 U,q..d.).The bone mineral density ( BMD ) of lumbar spine( L2-4 ),the left femoral neck,greater trochanter,and Ward's triangle,serum calcium and phosphate were measured by baseline,6 months' and 12 months.Levels of serum bone-specific alkaline phosphatase( BSAP),serum secreted protein acidic and rich in cysteine (SPARC)were determined by an ELISA assay.ResultsBy 12 months,rhPTH ( 1-34 ) treatment significantly increased the lumbar spine L2-4 BMD 7.9％ (P＜0.05),serum calcium 8.3 ％ ( P＜ 0.05 ),serum BSAP 93.4％ ( P＜ 0.05 ),serum SPARC by 12.6％[ ( 195.68±59.57 vs 173.81 ±81.33 ) pμg/L,P＜0.05 ].Elcatonin therapy increased the lumbar spine L2-4 BMD by 3.2％ (P＜0.05) at the end of 12 months,but elcatonin did not influence serum calcium,BSAP and SPARC.The rhPTH( 1-34 ) increased lumbar spine L2-4 BMD more than elcatonin did at 12 months( P＜0.05 ).ConclusionrhPTH (1-34) could promote the bone anabolism more effectively than elcatonin did.Serum SPARC may play an important role in promoting osteogenesis by rhPTH.

ObjectiveTo explore the best measurement of waist circumference related with intra-abdominal fat volume evaluated by CT scan.MethodsHeight,weight,and hip circumference were measured among 147 subjects aged over 18 years old.Waist circumference was measured at 3 different levels:the upper brim of the iliac crest ( WC1 ),the midpoint between costal brim and iliac crest ( WC2 ),and the umbilicus ( WC3 ).The intra-abdominal fat volume was evaluated by CT scan.ResultsIntra-abdominal fat volume was significantly higher in men than in women [ ( 1 236.0±608.4 vs 931.0±665.0)cm3,P＜0.01 ].Correlation analysis showed that WC1 ( r =0.634),WC2( r=0.677),and WC3 (r =0.712)were positively correlated with intra-abdominal fat volume ( all P＜0.01 ).Partial correlation analysis adjusted by gender,weight,or body mass index showed that the correlation of intra-abdominal fat volume with WC3 ( r were 0.488 and 0.432) was better than that with WC1( r were 0.347 and 0.293 ) and WC2 ( r were 0.424 and 0.365 ).Multiple linear stepwise regression analysis demonstrated that WC2 and WC3 were independently associated with intra-abdominal fat volume and WC3 was the strongest impact factor (β =0.270,R2c =0.504,P＜0.01 ).ConclusionsWaist circumference is a simple anthropometric measurement parameter reflecting the degree of intraabdominal fat accumulation.All three different measurements of waist circumference may reflect intra-abdominal fat volume,while waist circumference at umbilical level is the best among them.

ObjectiveTo detect mRNA and protein expression of steroidogenic factor-1 ( SF-1 ) and DAX-1 in human adrenocortical tumors and normal adrenal cortex,and to investigate the effect of SF-1 and DAX-1 on the steroidogenesis and development of adrenocortical tumors.Methods Total RNA and protein was extracted from angiotensin Ⅱ unresponsive aldoterone-producing adenomas ( A Ⅱ -U-APA,n =12 ),angiotensin Ⅱ responsive aldoterone-producing adenomas ( AⅡ -R-APA,n =5 ),cortisol-producing adenomas ( CPA,n =10 ),adrenal nonfunctional adenomas ( NFA,n =10 ),aldosterone-producing carcinoma ( APC,n =2 ) and normal adrenal cortex ( NAC,n =8).To analyze gene expression of SF-1,DAX-1,ACTH receptor(ACTHR),and β-actin by real-time quantitative PCR in different tissues.The protein expression of SF-1,DAX-1,and β-actin in the same tissues by Western blot.To study the relationship of ACTHR,SF-1,and DAX-1 with clinical data in adrenocortical tumors.ResultsThe expression of SF-1,DAX-1 mRNA and protein was different in NAC,AⅡ -U-APA,A Ⅱ -R- APA,APC,CPA,and NFA tissues [ relative expression of SF-1 mRNA:24.58±2.45,23.89±3.17,21.59±3.00,(38.75,44.16),14.17±2.80,and 36.38±3.50; DAX-1 mRNA:0.57±0.06,0.37±0.05,0.43±0.05,( 1.52,1.21 ),0.39 ±0.04,and 0.83 ±0.08 ; SF-1 protein:0.76 ±0.11,0.76 ±0.10,0.73 ±0.07,(1.24,1.40),0.55±0.04,and0.98±0.10; DAX-1 protein:0.65±0.14,0.39±0.13,0.43±0.14,(1.18,1.02),0.56±0.04,and 1.03±0.13 ; all P＜0.05 or P＜0.01 ].There was negative correlation by higher SF-1/DAX-1 ratio and tumor size in AⅡ -U-APA tissues.The mRNA and protein expression of SF-1 was lower in CPA and there was the positive correlation with tumor size.Conclusion SF-1 and DAX-1 might play a key role in the development of the adrenocortical tumorigenesis and steroidogenic tissues.

A 31-year-old male normotensive patient with aldosterone-producmg adenoma complained of thirst,polydipsia,polyuria,and periodical paraplegia.The diagnosis is raised by signs of hypokalemia.Despite the lack of hypertension,primary aldosteronism was confirmed by persistent hypokalemia,increased urinary potassium,increased urinary and plasma aldosterone levels and suppressed plasma rennin activity (PRA).The blood pressure profile was studied by ambulatory monitoring,and the mean blood pressure of 24h was normal and the circadian rhythm remained normal. Surgical removal of the histologically typical aldosterone-producing adenomas normalized the kalemia.The patient had a marked fall in blood pressure with mean values of 21/17 mm Hg ( diurnal and nocturnal blood pressure were 19/17 and 22/17 mm Hg respectively)and recovery of normal urinary and plasma aldosterone levels and PRA 6 weeks after surgery.This suggests that excess serum aldosterone induced relative hypertension in those patients whose blood pressure was spontaneously very low.Our observations call for primary hyperaldosteronism assay in patients with hypokalemia and renal potassium leakage.

3T3-L1 adipocytes were cultured and differentiated into mature adipocytes in vitro. The adipocytes were intervened by ACAT inhibitor( 2 μg/ml) and ox-LDL with various concentrations (0,25,50,75,and 100 μg/ml)for 48 h,ACAT inhibitor( 2 μg/ml) and ox-LDL( 50 μg/ml) at the 0,6,18,36,and 48 h,or ACAT inhibitor( 2 μg/ml),ox-LDL( 50 μg/ml),and TUDCA with various concentrations(0,100,200,and 400 μ mol/L)for 48 h,respectively.The levels of visfatin in supernatant were examined by ELISA and the expressions of protein GRP78 and CHOP in adipocytes were detected by Western blot.After the adipocytes were treated with ACAT inhibitor and ox-LDL at different concentrations for 48 h,the cholesterol concentration and the expressions of GRP78 and CHOP protein in adipocytes and the visfatin levels in the supernatant fluid were increased with the increase of the ox-LDL concentration.The differences had statistical significance in the experimental groups compared with blank control group( all P＜0.05 ).After the intervention with ACAT inhibitor and ox-LDL for different durations,the expressions of GRP78 and CHOP protein in adipocytes and the visfatin levels in the supernatant fluid were up-regulated in a timedependent manner.The differences between experimental groups and blank control had statistical significance( all P＜0.05 ).After the intervention with ACAT inhibitor,ox-LDL,and different concentrations of TUDCA for 48 hours,the expressions of GRP78 and CHOP protein in adipocytes and visfatin levels in the supernatant fluid were down-regulated in a dose-dependent manner and as compared with blank control group the difference were statistically significant( all P＜ 0.05 ).The increase of cholesterol load in adipocyte may promote the visfatin secretion,denoting that the mechanism might be due to the enhancement of endoplasmic reticulum stress in aidpocytes.

ObjectiveTo explore the prevalence of thyroid nodules and metabolic syndrome,and to analyze the correlation between thyroid nodules and the components of metabolic syndrome.MethodsThis cross-sectional study included 8 217 people in our hospital health check-up center.Height,body weight,blood pressure,blood glucose,lipid profile,and liver function were measured and ultrasonic scanning of thyroid was performed.Metabolic syndrome was diagnosed according to criteria of CDS/2004.Results ( 1 ) The prevalence of thyroid nodules was 42.1％.The prevalence in women (49.6％) was significantly higher than that in men( 38.4％,P＜0.01.),and it was progressively increased with aging in both sexes.(2) The overall prevalence of metabolic syndrome was 21.7％.The prevalence in men( 28.5％ ) was significantly higher than that in women( 12.8％,P＜0.01 ),and was increased with age until 70 years old.( 3 ) Body mass index,systolic pressure,diastolic pressure,blood glucose,triglyceride in subject with thyroid nodules (TN) were higher than those in subjects without ( non-TN,P＜0.05 ).No difference in the levels of HDL-C was found between cases with TN and non-TN ( P＞0.05 ).(4) Logistic regression analysis revealed that the existence of thyroid nodules was significantly associated with overweight/obesity ( OR =1.263,95 ％ CI 1.134-1.407 ) after adjusting age and sex.Conclusion( 1 ) The prevalences of thyroid nodules and metabolic syndrome are high,and both prevalence increase with advancing age.(2) Obesity or overweight might be a risk factor for the development of thyroid nodules.

Objective To improve the diagnosis and treatment of ACTH-independent macronodular adrenal hyperplasia(AIMAH).Methods A 51-year-old female patient with Cushing's syndrome caused by AIMAH was reported.Elevated early morning plasma cortisol levels,increased 24 h urinary free cortisol excretion,and loss of the normal circadian rhythm in cortisol secretion were presented.There was no suppression of cortisol secretion by administration of low-and high-dose overnight dexamethasone suppression test.Cardio-pulmonary function was very bad with the highest blood pressure reaching 300/120 mm Hg( 1 mm Hg=0.133 kPa).Initially,she was treated with mitotane(60 mg/d),but was not effective.After taking ketoconazole (800 mg/d)for 5 days,cardio-pulmonary function was not effectively improved with blood pressure only descending to 180/120 mm Hg.Orthopnoea appeared and Spo2fell once to 75％.The patient had to undergo right total adrenalectomy immediately.ResultsThe mass resected was 10 cm× 10 cm in size and weighted 67.5 g.Histological examination of the removed adrenal revealed nonpigmented macronodular cortical hyperplasia.The patient continued to take ketoconazole (400-800 mg/d)from the 6th day of the operation without steroid replacement therapy in that period.With normal cortisol levels( plasma cortisol at 8:00 was 18.65 μg/dl,24 h urinary free cortisol was 78.75 μmol),she left hospital after the general condition had been improved.During the following updated 10 months follow up,the indexes of her laboratory examination were maintained normal.ConclusionIndividualized therapy should be adopted for the patient with AIMAH.The medication is useful to suppress the adrenal gland cortisol production for those with progression of symptoms,very high blood pressure,hypokalemia and hypoproteinemia.Once the cardio-pulmonary function improves,the target organ should be resected as soon as possible.The supplement of cortisol is not appropriate during the perioperative period.The unilateral adrenalectomy is an effective treatment for AIMAH.