Preliminary clinical analysis of direct renin inhibitor aliskiren in the treatment of severe coronavirus disease 2019 patients with hypertension / 中华内科杂志

Objective:To explore the feasibility of direct renin inhibitor aliskiren for the treatment of severe or critical coronavirus disease 2019 (COVID-19) patients with hypertension.Methods:The antihypertensive effects and safety of aliskiren was retrospectively analyzed in three severe and one critical COVID-19 patients with hypertension.Results:Four patients, two males and two females, with an average age of 78 years (66-87 years), were referred to hospital mainly because of respiratory symptoms. Three were diagnosed by positive novel coronavirus 2019 (2019-nCoV) nucleic acid or antibody, and the critical patient with cardiac insufficiency was clinically determined. Two patients were treated with calcium channel antagonist (CCB), one with angiotensin converting enzyme inhibitor (ACEI), and one with angiotensin Ⅱ receptor antagonist (ARB). After admission, ACEI and ARB were discontinued, one patient with heart failure was treated by aliskiren combined with diuretic.Three patients were treated with aliskiren combined with CCB among whom two withdrew CCB due to low blood pressure after 1 to 2 weeks. Based on comprehensive treatment including antiviral and oxygenation treatment, blood pressure was satisfactorily controlled by aliskiren after three to four weeks without serious adverse events. All patients were finally discharged.Conclusion:Our preliminary clinical data shows that antihypertensive effect of aliskiren is satisfactory and safe for severe COVID-19 patients complicated with hypertension.

New advances in pheochromocytoma and paraganglioma--the 5th international symposium on pheochromocytoma and paraganglioma / 中华内分泌代谢杂志

The 5th international symposium of pheochromocytoma and paraganglioma ( PPGL) has been held in September 2017 in Sydney. The conference included the new advances and progresses in the pathogenesis, diagnosis, and treatment of the PPGL. Comprehensive molecular characterization revealed that 95% of PPGL had single or combined germline mutations ( 27%), somatic mutations ( 39%), fusion gene ( 7%) or copy number alterations ( 89%). PPGL could be divided into kinase signaling subtype, pseudohypoxia subtype, Wnt-altered subtype and cortical admixture subtype. The sensitivity of 68Ga-dotatate-positron emission tomography/computed tomography (PET/CT) to detect the PPGL was quite high, which provided a basis for the treatment of PPGL by 177Lu-dota. The treatment of malignant PPGL included tyrosine kinase inhibitors, 131I-metaiodobenzylguanidine (MIBG ), and pembrolizumab. The ultratrace 131I-MIBG, was quite effective for the treatment of malignant PPGL. Although PPGL is a rare and complicated disease, multidisciplinary team and further research will bring more benefits to the early detection and appropriate treatment of PPGL patients.

Application of SDHB and SDHC immunohistochemistry in the differentiation of malignant and benign pheochromocytoma and paraganglioma / 中华内分泌代谢杂志

Objective To evaluate the expression profile of succinate dehydrogenase (SDH)B and SDHC in pheochromocytoma (PCC) and paraganglioma(PGL) (collectively abbreviated as PPGL), and their value in the early diagnosis of malignancy. Methods SDHB and SDHC immunohistochemistry were performed on 140 tumor specimens from 126 PPGL patients (PCC n＝62, PGL n＝61, PCC+PGL n＝3). Results (1) Germline mutation status of 67 patients were determined, of which, identifying 37(55.2%) patients with germline mutation: 2 (3.0%) SDHA, 18 ( 26. 9%) SDHB, 2 ( 3. 0%) SDHC, 5 ( 7. 5%) SDHD, 2 ( 3. 0%) VHL, 7 ( 10. 4%) RET, and 1(1.5%) NF1; and 30 (44.8%) individuals without known mutation. (2) Among 30 PPGLs from 27 patients with SDH-related (SDHx) mutations, 96.7%(29/30) stained negative for SDHB, 76.7%(23/30) stained negative for SDHC, while only 28.6%(14/49) and 18.4%(9/49) stained negative for SDHB and SDHC respectively in the 49 PPGLs without SDHx mutation (P<0.05). (3) The sensitivity of the SDH immunostaining in detecting the presence of germline SDHx mutation was 96.7%for SDHB and 76.7%for SDHC, while the specificity was 71.4%for SDHB and 81.6% for SDHC. ( 4 ) Among PPGLs without SDHB expression, 22. 9% were malignant. This percentage is significantly higher than that in PPGLs with preserved SDHB expression (3.8%, P<0.05). Conclusion SDHB and SDHC immunohistochemistry may serve as post-surgical screening tools to predict the presence of germline SDHx mutation in PPGLs. Negative SDHB expression calls for intense follow-up to rule out malignancy.

Setting up a primary aldosteronism program:an Australian experience / 中华内分泌代谢杂志

The year after aldosterone was isolated and characterized, primary aldosteronism ( PA) was recognised as causing hypokalemia and hypertension, in response to hormone secretion inappropriate for sodium levels. This manuscript deals with three time periods since then: the first sixty five years, its current management in a very active clinic in Melbourne, Australia; and finally some suggestions as to improvements in recognition, diagnosis and management over the next five years. We will suggest improvements that endocrinologists, in China and elsewhere, might consider for what has emerged as a major public health issue.

Re-evaluation of screening and confirmatory tests in primary aldosteronism / 中华内分泌代谢杂志

Prevalence of primary aldosteronism (PA) ranges from 5%to 10%in hypertensive patients. The diagnostic process of PA includes screening, confirmation, and subtype classification. In this manuscript, the recently published data from China regarding to screening and confirmatory tests were summarized, and some important instructions of screening and confirmatory tests were emphasized for improving clinical practice.

The application of captopril challenge test in the diagnosis of primary aldosteronism / 中华内科杂志

Objective To evaluate the value of captopril challenge test (CCT) in the diagnosis of primary aldosteronism (PA).Methods A total of 674 patients [(45.0±13.7) years, men 341, women 333] admitted to Peking Union Medical College Hospital from 2000 to 2015 were analyzed.Among them, 222 subjects were with essential hypertension (EH), 28 were with pheochromocytoma (PHEO), 246 were with idiopathic hyperaldosteronism (IHA) and 178 were with aldosterone producing adenoma (APA).All patients received CCT.24 h urine sodium was measured in partial patients.Plasma renin activity (PRA), aldosterone (ALD) were detected.Results Compared with EH [PRA: before 0.5(0.2,0.9) μg·L-1·h-1, after 0.8(0.4,1.5) μg·L-1·h-1;ALD: before (393±122) pmol/L, after (360±97) pmol/L] and PHEO [PRA: before 0.3(0.1,0.9) μg·L-1·h-1, after 0.4(0.1,1.6) μg·L-1·h-1;ALD: before (396±108) pmol/L, after (374±114) pmol/L], lower levels of PRA and higher levels of ALD before and after CCT were observed in PA patients [PRA: before 0.1 (0.1,0.2) μg·L-1·h-1, after 0.1 (0.1,0.2) μg·L-1·h-1;ALD: before (468±216) pmol/L;after (457±199) pmol/L].After CCT, the suppression rate of ALD [2.8% (-8.8%,15.4%) vs 6.6% (-4.3%, 17.6%)] and increasing rate of PRA [0(0,50%) vs 50%(0, 200%)] in PA patients were lower than those in EH patients.The ALD/PRA ratio (ARR) were higher in PA than that in EH or PHEO patients.In the EH subjects, ALD levels of seated posture were higher than those of recumbent posture both before and after receiving captopril, but with no changes in ARR after CCT.No significant differences in ALD and ARR (before and after receiving captopril) were observed between seated and recumbent position in the PA group.The ARR after CCT tended to decrease in EH subjects with elevated urine-sodium compared with those with normal urine-sodium.No changes could be viewed in ALD and PRA levels between normal urine-sodium and elevated urine-sodium groups among APA, IHA and EH patients either before or after CCT.Among patients with APA, the ALD levels before CCT and the ARR after CCT were lower in the patients with AngiotensionⅡ(AngⅡ) reactive than those without.A ROC curve analysis suggested that the optimal cutoff value was 46.2 (ALD unit:ng/dl;PRA unit:μg·L-1·h-1) for ARR after challenge in diagnosing PA, with the sensitivity of 88.7% and specificity of 84.8%.Conclusions ARR after 25 mg captopril had high sensitivity and specificity in diagnosis of PA with the cutoff of 46.2.Seated CCT could replace recumbent CCT as a more confirmatory test.The PRA increasing rate should be taken into consideration when diagnosis of PA.

The value of X-ray guided desmopressin stimulated bilateral inferior petrosal sinus sampling in diagnosing the recurrence of ACTH dependent Cushing disease or ineffectiveness of surgery or radiotherapy / 中华放射学杂志

Objective To investigate the value of X-ray guided desmopressin (DDAVP) stimulated bilateral inferior petrosal sinus sampling (IPSS) in diagnosing the recurrence of ACTH dependent Cushing disease or ineffectiveness after surgery or radiotherapy. Methods Retrospective analyses of patients with recurrent ACTH dependent Cushing disease (31 cases) or ineffective (3 cases) treatment after surgery or radiotherapy from January 2013 to October 2014 in our hospital was conducted. Bilateral inferior petrosal sinus angiography showed the same side of the cavernous sinus to prove successful intubation. The cases with discontinuous of the inferior petrosal sinus and cavernous sinus were excluded by this study. Finally, there were 34 cases of the patients in this study. Diagnosis was based on the ratio of ACTH level in IPS to peripheral vein after desmopressin test.The gradient≥2 at baseline or gradient≥3 after desmopressin test suggested the sources were in the pituitary. Diagnosis was confirmed by gold standard to investigate the value of X-ray guided desmopressin (DDAVP) stimulated bilateral IPSS. Results The IPS gradient≥2 at baseline or gradient≥3 after desmopressin test suggested the sources were in the pituitary in 30 patients. A total of 22 (22/30) patients underwent surgery with a final diagnosis of ACTH adenoma. The symptoms were obviously relieved in 8 (8/30) cases after sellar area gamma knife treatment and lesions were confirmed in the pituitary. IPS gradient<2 at baseline or gradient<3 after desmopressin test was found in 4 cases. One case (1/4) was found to have for ACTH adenoma after pituitary surgery. The other 3 cases (3/4) were confirmed to have lung carcinoid and clinical symptom alleviated after surgery. The sensitivity of desmopressin stimulated IPSS was 96.8%, the specificity was 100%, and the accuracy was 97.1%. Conclusion Desmopressin stimulated IPSS is an effective diagnostic procedure in diagnosing ACTH dependent Cushing disease recurrence or ineffectiveness after surgery or radiotherapy.

Clinical efficacy of 131I-MIBG therapy in malignant pheochromocytoma/malignant paraganglioma / 中华泌尿外科杂志

Objective To evaluate the efficacy and safety of 131I-metaiodobenzylguanidine (131 I-MIBG) in treatment of malignant pheochromocytoma/malignant paraganglioma (MPHEO/MPGL).Methods The clinical data of 96 cases of MPHEO/MPGL (60/36) treated with 131I-MIBG between December 1998 and April 2014 were retrospectively reviewed.Among them,the malignant pheochromocytoma was found in 60 cases and malignant paraganglioma was found in 36 cases.Seventy-eight patients (81.2％)presented initially with hypertension,whereas 18 patients (18.8％) presented adrenal incidentaloma.Before 131I-MIBG treatment,24 h urinary norepinephrine was (409.5± 127.2) nmol,24 h urinary dopamine was (99.3±41.1) nmol,24 h urine adrenaline was (1 409.9±336.0) nmol.Before treatment,the compound iodine solution was given to each one.Then,all patients were given an initial course of 131I-MIBG therapy (5.55,7.40 GBq).Subsequent 131I-MIBG treatment (5.55,7.40 GBq) was undertaken every three to six months.The patients got symptomatic,hormonal or radiological response underwent sbsequent 131I-MIBG therapy (3.70,5.55 GBq) every year.All patients underwent clinical symptoms (headache,palpitate,sweating,hypertension),biochemical (24 h urine catecholamin) and radiological evaluation (CT/MRI) within 6 months to evaluate the efficacy and safety of 131I-MIBG treatment.Results After one to eleven sessions of 131 I-MIBG treatment,in total,266 doses of 131 I-MIBG were administered,average dose was 6.49 GBq.22.9％ of patients demonstrated radiological partial response (≥ 50％ reduction in tumor size) after first or repeated 131 I-MIBG treatment.Eleven cases (11.5％) achieved clinical complete response,41 cases (42.7％) achieved clinical partial response and 23 cases (24.0％) maintained the stable clinic symptoms.After treatment,24 h urinary norepinephrine (164.3±71.6) nmol and dopamine (49.7±24.7) nmol showed significantly decline,compared with those before treatment (P＜ 0.05).While,24 h urinary epinephrine (1 354.7±433.4) nmol had no obvious change (P＞0.05).No life-threatening adverse events were reported,but 2 MPGL patients developed transient leucopenia or thrombocytopenia after four and five times 131 I-MIBG treatment,respectively.Conclusions Treatment with repeated low dose 131I-MIBG is well tolerated and effective in controlling the progression and alleviating the clinical symptoms.The 131I-MIBG therapy is an effective and safe treatment modality for MPHEO/MPGL.

The clinical implication of left ventricular hypertrophy in patients with pheochromocytoma and paraganglioma / 中华心血管病杂志

<p><b>OBJECTIVE</b>To explore the clinical implications of left ventricular hypertrophy (LVH) in patients with pheochromocytoma and paraganglioma (PH/PGL).</p><p><b>METHODS</b>Seventy-eight PH/PGL patients receiving medical attention at Peking Union Medical College Hospital from October 2010 to April 2013 were included in the study.Forty-six healthy people who had no hypertension, pathoglycemia, dyslipidemia history, and with normal chest X-ray, electrocardiogram and echocardiography results served as control group. Clinical symptoms and signs, levels of 24-hour urinary catecholamine, electrocardiogram and echocardiography of participants were recorded and analyzed.</p><p><b>RESULTS</b>(1)Left ventricular ejection fraction, cardiac output index, left ventricular mass index (LVMI), left atrial volume index (LAVI) and mitral E/E' were all significantly higher while mitral annulus lateral E' velocity was significantly lower in PH/PGL group than in control group (all P < 0.05). (2) LVH was associated with more prevalent acute left-sided heart failure episodes (12% (3/25) vs. 0, P = 0.030), sustained LVEF depression (12% (3/25) vs. 0, P = 0.030) and ECG ST-T segment alterations (60% (15/25) vs. 21% (11/53) , P = 0.001) in PH/PGL patients. LAVI ((30.2 ± 8.8) ml/m(2) vs. (23.8 ± 4.7) ml/m(2), P = 0.007) and mitral E/E' (11.2 ± 6.0 vs. 7.2 ± 1.4, P = 0.003) were significantly higher in patients with LVH than in patients without LVH. Mitral annulus septal ((7.8 ± 2.6) cm/s vs. (10.4 ± 3.2) cm/s, P = 0.001) and lateral ((9.3 ± 3.3) cm/s vs. (12.9 ± 2.9) cm/s, P < 0.001) E' velocity, averaged S' velocity((7.9 ± 1.6) cm/s vs. (8.8 ± 1.7) cm/s, P = 0.036) were significantly lower in LVH patients comparing to patients without LVH. (3) According to multiple linear regression analysis, age (t = 3.491, P = 0.001), gender (t = 2.899, P = 0.005), heart rate (t = 2.255, P = 0.027), and 24-hour urinary norepinephrine level (t = 3.369, P = 0.001) were independent factors affecting LVMI of PH/PGL patients.</p><p><b>CONCLUSION</b>Left ventricular hypertrophy is associated with acute left-sided heart failure, left ventricular diastolic dysfunction and elevated left ventricular filling pressure in PH/PGL patients.</p>

The advances of research on adrenal diseases from 2010 to 2012 / 中华内分泌代谢杂志

This article reviews the major advances of basal and clinical research on the adrenal diseases at home and abroad from 2010 to 2012.There are many advances including the diagnostic value of steroidogenic factor-1 in adrenal tumors,the pathogenesis and new diagnostic methods of aldosterone-producing adenoma,the treatment for severe ACTH-dependent Cushing's syndrome,approach to the patient with an adrenal incidentaloma and subclinical hypercortisolism,screening test for subclinical hypercortisolism in the patients with diabetes or osteoporosis,the characterization of macronodular adrenocortical hyperplasia of the zona reticularis,as well as genetic testing for pheochromocytoma and paragangliomas,etc.

Differences of blood plasma renin activity, angiotensin Ⅱ and aldosterone levels in essential or secondary hypertension / 中华内科杂志

Objective To study on the difference of plasma renin activity ( PRA),angiotensin Ⅱ (Ang Ⅱ ),and aldosterone levels in patients with essential hypertension (EH) or primary aldosteronism (PA) or pheochromocytoma (PHEO),and to analyze the sensitivity and specificity on the diagnosis of PA among patients with hypertension with aldosterone/PRA ratio (ARR).Methods The plasma aldosterone,Ang Ⅱ and PRA concentrations in supine and upright positions were measured by radioimmunoassay from 413 patients including idiopathic hyperaldosteronism (IHA,n =111 ),aldosterone-producing adenoma (APA,n=l18),PHEO (n=98) and EH (n=86).ARR was calculated.Results Plasma aldosterone concentrations in both of supine and upright positions in PHEO group [ 374 (294,465 ) pmol/L and 629 (449,997) pmol/L] and PA group [471 (346,632) pmol/L and 673(499,825) pmol/L] were higher than those in EH group [ 277 (224,332) pmol/L and 427 (341,501 ) pmol/L ] (P ＜ 0.01 ).They were also higher in APA group [576 (416,731 ) pmol/L and 726 (554,906 )pmol/L ] than those in IHA group [399(313,504) pmol/L and 609(485,776)pmol/L ] (P ＜0.01).Ang Ⅱ levels in both positions were lower in PA group [43.2(26.4,74.4) ng/L and 60.1(38.5,103.6) ng/L] than in EH group [56.7 (43.3,78.9) ng/L and 84.3(61.3,108.4) ng/L] or PHEO group [54.3(29.9,101.5) ng/L and 102.8 (49.9,167.0) ng/L] (all P values ＜ 0.01 ),and there was no difference between IHA and APA group (P ＞ 0.05 ).The PRA level in both positions of each group were PHEO group [ 0.3 (0.2,1.0) μg ·L-1 · h-1 and 1.4(0.6,3.4) μg · L-1 · h-1] ＞EH group [0.2(0.1,0.4)μg · L-1 · h-1 and 0.6(0.4,1.0)μg· L-1 ·h-1] (P＜0.01) ＞PAgroup [0.1(0.1,0.1)μg· L-1 · h-1 and 0.2(0.1,0.3)μg·L-1 · h-1] (P＜0.01),and APA group [0.1(0.1,0.1)μg · L-1 · h-1 and0.1(0.1,0.3)μg · L-1 ·h - 1 ] ＜ IHA group [ 0.1 ( 0.1,0.2 ) μg · L - 1 · h - 1 and 0.2 (0.1,0.3 ) μg · L-1 · h - 1 ] ( supine P ＜0.01 ; upright P ＜ 0.05 ).APA was divided into 2 types with renin-Ang Ⅱ -responsive APA ( n =26) and unresponsive APA (n =92).The plasma aldosterone concentration was lower in supine position but higher in upright position in renin-Ang Ⅱ-responsive APA than in unresponsive APA patients.ARR in upright was higher in PA group ( P ＜ 0.01 ) but lower in PHEO group ( P ＜ 0.05 ) compared with EH.ARR was higher in APA than in IHA (P ＜0.01 ).The sensitivity and specificity of ARR as 40 (aldosterone unit:ng/dl;PRA unit:μg · L-1 · h-1; its value should multiply 27.7 when transferred to pmol/L,simili) were 93％ and 76％,respectively.Conclusion The levels of PRA,Ang Ⅱ and aldosterone from patients with EH,PA and PHEO are significant different.ARR as 40 in upright position could be used for PA screening cutoff point.

Epigenetic aspects in pheochromocytoma / 中华内分泌代谢杂志

Although the mutations in RET,VHL,NF1,SDHB,and SDHD genes have been identified to be　responsible for familial pheochromocytomas, the pathogenesis of most pheochromocytomas remains unknown.Inadequate methods to distinguish malignant from benign tumors and a lack of effective treatments for the malignancy　are critical problems that require further resolution.Indeed,epigenetic changes are now recognized to be at least as　common as genetic changes in cancer.In recent years,research has been initiated to shed light on epigenetic aspects　such as DNA methylation and microRNA in pheochromocytomas,to explore the molecular mechanism,and might　provide a diagnostic tool and a target for future therapies.

Expression of steroidogenic factor-1 and DAX-1 in human adrenocortical tumours / 中华内分泌代谢杂志

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.

An analysis of hyperinsulinemia in Bartter syndrome / 中华内科杂志

Objective To analys hyperinsulinemia in Bartter syndrome. Methods Twenty-three cases of Bartter syndrome [age (27 ±9) years;fasting serum potassium(2. 8 ±0. 5)mmol/L], 20 patients of aldosterone-producing adenoma [APA, age (45 ± 11 ) years, fasting serum potassium ( 3.0 ± 0. 4 ) mmol/L], 20 patients of idiopathic hyperaldosteronism [IHA, age (51 ± 11 ) years, fasting serum potassium (3.4 ±0. 2)mmol/L] were diagnosed in Peking Union Medical College Hospital from September 2003 to May 2008. All patients underwent 3-hours oral glucose tolerance test(3hOGTT), postural stimulation test and calculated HOMA-insulin resistance ( HOMA-IR ) and HOMA-insulin sensitivity ( HOMA-IS ) by Homeostasis model.Results The insulin area under curve-(229.0±162.4)mIU·L-1·h] was singnificantly higher than APA group [(227.7±158.6)mIU·-1·h].But HOMA-IR in Bartter group were similar to APA group( 1.96 ± 1.14 vs 1.41 ± 0. 91 ), and HOMA-IR in APA group was lower than IHA group ( 1.96 ± 1.14 vs 2.40 ± 1.60, P ＜ 0. 05 ). There was no deference in HOMA-IS among three groups,but APA group had lower level. In all three groups, the peak of insulin secretion was delayed. Conclusion Bartter syndrome patients commonly present with hyperinsulinemia.

Carry out epigenetic research in endocrine and metabolic diseases and adrenal tumors / 中华内分泌代谢杂志

This editorial introduces the definition and development of epigenetics, and its theory in the pathogenesis of many diseases, including endocrine and metabolic diseases. The difference between genetics and epigenetics in explaining neoplastic pathogenesis is compared in detail with illustration. It emphasizes the importance of environmental factors as well as the interaction of genetical and environmental factors in causing the diseases. The article calls for more epigenetic research in endocrine neoplasm, especially in pheochromocytoma and neuroblastoma.

Methylation of p16 gene promoter in human pheochromocytomas and paragangliomas / 中华内分泌代谢杂志

Objective To elucidate gene mutation and promoter methylation changes of p16 gene in pheochromocytomas (PHEO) and paragangliomas (PGL) and to assess its relation with tumor clinical characters. Methods A total of 34 tumors (20 PHEO, 14 PG L, 15 benign, 19 malignant) were collected.Direct sequencing of p16 gene after PCR was performed to analyze genetic alterations. Hypermethylation of p16 gene promoter CpG island was analyzed by methylation specific PCR(MSP). In addition, mRNA expression was detected by RT-PCR. Results Homozygous deletion and gene mutation were not observed in 34 PHEO and PGL. Aberrant methylation of p16 gene promoter CpG island was found in 35.3% (12 of 34 tumors, 3 PHEO, 9 PGL). The p16 promoter hypermethylation in PGL was significantly higher than PHEO (P=0. 005). The higher p16 promoter hypermethylation was associated with malignant behavior, tumor number, and younger age at presentation, but no statistical significance, due to the limited number of cases. The p16 mRNA expression in malignant cases was lower than in benign tumors(0.83±0.65 vs 1.12±0.81 ,P=0.278). Conclusion p16 gene homozygous deletion and mutation were not frequent in PHEO and PGL. The promoter hypermethylation is mainly attributed to inactivation of the p16 gene.

Diagnosis and treatment of subclinical pheochromocytoma / 基础医学与临床

Objective To analyze the clinical features of patients with subclinical pheochromocytoma(PHEO).Methods Review of clinical features of 22 patients with subclinical PHEO treated in PUMC hospital from 1997 to 2007.Results All patients were asymptomatic.24hr-urinary catecholamine excretion was detected normal in 10 of 22 cases,while increased in the others.Sixteen patients were prepared with ?-receptor blocker before operation.During the operation,BPmax(maximal blood pressure) before tumor resection,BPmin(minimal blood pressure) after resection and ?BP(BPmax-BPmin) were(163?34)/(86?20)mmHg,(105?12)/(61?10)mmHg and(58?37)/(25?21)mmHg,Respectively,in the prepared group.They were(169?36)/(104?20)mmHg,(97?18)/(56?13)mmHg and(71?48)/(48?29)mmHg in the other 6 cases without ?-blocker preparation.DBPmax and ?DBP in the prepared group were significantly lower than the unprepared group.Conclusion Most patients with subclinical PHEO have increased catecholamine secretion.Blood pressure is fluctuant greatly during operation in some patients.Patients should be treated with ?-receptor blocker preoperatively in order to decreasethe operation risk.

Urotensin Ⅱ promotes proliferation of pheochromocytoma cells in vitro / 基础医学与临床

Objective To investigate the effects of Urotensin Ⅱ(UⅡ)on proliferation of rat pheochromocytoma cell line(PC12) and primary cultured human pheochromocytoma cells.Methods We observed the effects of UⅡ on the proliferation of rat PC12 cells and human pheochromocytoma cells in vitro by MTT method.Results 1.UⅡ had no obvious effect on the proliferation of rat PC12 cells.2.UⅡ(at 10-7 and 10-6mol/L) promoted the proliferation of primary cultured human pheochromocytoma cells. Conclusion UⅡ stimulates the proliferation of human pheochromocytoma cells and probably plays a role in the pathogenesis of pheochromocytoma.

Comparison of effects between the combined and classic dexamethasone suppression test on diagnosis of Cushing's syndrome / 中国实用内科杂志

Objective To evaluate effects of the combined and classic dexamethasone suppression test(DST)on the diagnosis of Cushing's syndrome.Methods Retrospective analysis was made about the results of DST from 152 patients of Cushing syndrome with surgically confirmed causes in recent 10 years.Results The diagnosis accuracy of overnight low dose DST,classic low dose DST and of combined low dose DST was 97.5%,96.1%and 97.6% respectively for determining diagnosis of Cushing's syndrome.No obvious difference was found in three groups(P=0.86).The diagnosis accuracy of 31 cases of classic and 17 cases of combined high dose DST was 80.6%(25/31)and 76.4% respectively without obvious difference(P =0.73)for locating diagnosis of Cushing's disease.The diagnosis accuracy of classic and combined high dose DST was 94.2% and 95.5% respectively without obvious difference(P =0.83)for locating diagnosis of ACTH independent Cushing's syndrome.Sensitivity and specificity for Cushing's disease were 81.5% and 92.5% in classic low dose and high dose DST and 77.8% and 95.5% in combined low dose and high dose DST.Conclusion Compared to the classic DST,combined DST has the advantages of double controls,simplicity and saving time.Because diagnosis accuracy of combined DST is in accordance with the classic DST,it is recommended to be a routine for diagnosing Cushing's syndrome.

Characteristics of growth and secretion in primarily cultured human pheochromocytoma cells / 中国康复理论与实践

@#ObjectiveTo investigate the characteristics of growth and secretion in primarily cultured human pheochromocytoma cells.MethodsThe human pheochromocytoma tissues were digested successively,and the tumor cells were cultured.The growth curves of three tumors were plotted by cell count.At the same time,the catecholomine in the medium was measured with high performance liquid chromatography.ResultsThe number of primarily cultured human pheochromocytoma cells increased gradually from first to sixth day after plating,and then the cell number began to decrease from seventh day.The levels of norepinephrine(NE) and epinephrine(E) in the medium of cultured cells significantly decreased on first and second day,and the levels of NE and E had no significant difference on the second to eighth day.The levels of dopamine in the medium had no significant difference on the first to eighth day.ConclusionThe primarily cultured pheochromocytoma cells differentiate obviously after plating,but have no significant proliferation.The levels of catecholomine in the medium are decreased significantly on the first and second day.