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.

To standardize the diagnosis and treatment of primary aldosteronism (primary aldosteronism syndrome),and to enhance the knowledge and clinical management the disease,six orgnizations,including the American Endocrine Society,the International Endocrine Society,the International Society of Hypertension,European Endocrine Society,European Society of Hypertension,Japan Endocrine Society,and the Japanese Society of Hypertension,established the "Detection,diagnosis and treatment of patients with primary aldosteronism:Endocrine Society Clinical Practice Guidelines" ,and this is the first international clinical guideline ever made by multiple international societies from allover the world for a individual disease.This paper,based on the authors' experience,introduces the diagnosis,screening,diagnosis test,complications and treatment of primary aldosteronism.

Pheochromocytoma is the catecholamine-secreting tumor arising from the adrenal medulla and extra-adrenal chromaffin cells and the important cause of endocrine hypertension, which leads to serious complications of the heart, brain and renal vascular events. The prevalence of phochromocytoma accounts for approximately 1.9% in the population with hypertension. The detection, diagnosis and treatment of pheochro-mocytoma at early stage are of uppermost importance. More efforts should be made to study the pathogenesis and management of pheochromocytoma.

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.

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.

Objective To study the circadian changes of blood pressure and urinary catecholamine excretion in patients with pheochromocytoma before and after tumor removal. Methods Twenty-seven patients with pheochromocytoma were examined by 24h ambulatory blood pressure monitoring before tumor removal, and 12 of them were examined by ambulatory blood pressure monitoring both before and after operation, meanwhile, their urinary norepinephrine (NE), epinephrine (E) and dopamine (DA) excretions of 10 time-segmental portions of urine at the same day were determined by HPLC method. The circadian changes were analyzed by Cosinor method. Results The circadian changes of catecholamine excretion were observed, and the peak excretion time of E and DA were shifted to 14:00-16:00. The circadian changes of systolic and diastolic blood pressure disappeared in patients with sustained hypertension and existed in patients with paroxysmal hypertension. The circadian changes of blood pressure and urinary catecholamine excretion were returned to normal after surgery. The circadian change of heart rate was observed both before and after operation. Analysis of data from 12 cases with pheochromocytoma showed strongly positive correlationsbetween24hmeansystolicanddiastolic blood pressure and mean urinary NE excretion (r=0.83, 0.91, P

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.

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.

Objective To review and discuss the changes of diagnostic techniques and therapeutic modalities of pheochromocytoma during the past fifty years. Methods The clinical data of 362 patients (196 men and 166 women; age range,7-75 years;mean age,38 years) with pheochromocytoma from January 1955 to July 2004 were retrospectively analyzed.The disease course ranged from 20 d to 20 years with a mean of 3.9 years.According to the premedication,the past 50-year period was divided into 3 stages;and the diagnostic techniques,premedication, anesthetic skills,surgical procedures and perioperative death rate were compared among the 3 stages. Results There were 60 patients in the first stage (1955-1975) and their diagnoses were made on urine VMA and retroperitoneal air-contrast imaging.They had no premedication except for tranquilizers.The therapeutic modality was open surgery of resecting tumors under peridural anesthesia.The perioperative mortality was 8.3% (5/60).The second stage (1976-1994) included 105 patients and they were diagnosed mainly by 24-h urine catecholamine, ultrasonography and CT.Phenoxybenzamine was taken as the regular premedication and open surgery general anesthesia was used; the mortality decreased significantly to 1.0% (1/105).The third stage (1995-2004) consisted of 197 cases.In addition to 24-h urine catecholamine,ultrasonography and CT, 131I-MIBG scan was used as the specific diagnostic technique for pheochromocytoma widely.The premedication was phenoxybenzamine and urapidil.The microcirculation imaging analysis was used to judge the volume expansion preparation. Laparoscopic resection of the tumor under general anesthesia was adopted as the regular means.The perioperative mortality was 0.5% (1/197). Conclusions The diagnostic techniques for pheochromocytoma have become enriched and mature.The premedication has been standardized and included more medicines.The microinvasive surgery has become the current method for resecting tumors,and the perioperative mortality has become significantly decreased.

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.