Objective To identify candidate regions of sporadic pheochromacytoma (PCC).Methods Totally 42 patients who were clinically diagnosed as sporadic PCC from 2011-9 to 2013-5 in PUMCH were enrolled .To extract whole genome DNA from their tumors as well as peripheral blood leukocytes and to exclude inherited cases by San-ger sequence mutation .Within 14 verified cases of sporadic PCC , we applyed single nucleotide polymorphism ( SNP) chip to detect whole genome DNA copy number variations ( CNV) and loss of heterozygosity ( LOH) to ini-tiallylocatethehotregions.FinallyapplyQ-PCRtoconfirmthehotregionsinleftcases.Results 38caseswere identified as sporadic PCC , and 4 as inherited cases .CNV were found in 14/14 tumors, of which deletions were more common.Missing regions occurred in 1p,3q,17p,22q,11p.On the other hand, of the 3 inherited cases, de-letion was also detected.The loss of parts of arm 1p is the most common, including chr1:74 957 006 ~86 132 879 , chr1:58 096 424~67 700 471 , and chr1:98 902 091~107 622 430 .The result of Q-PCR confirmed the above-mentioned three regions , and the three segments are final candidate regions .Conclusions Partially de-letion of 1p in most cases is the most striking phenomenon , we believe that the deletion of 1p may occur with PCC development , and there may be some tumor suppressor gene ( s) within these areas .

Cushing syndrome (CS) is a series of clinical symptoms and signs caused by long-term exposure to abnormally high levels of glucocorticoids.It is divided into two types of adrenocorticotropic hormone(ACTH) dependent and ACTH-independent CS.There are great differences in the target gland treatment of different causes of the disease, but the basic principle is to make a clear diagnosis.It is very important to treat primary lesions for ACTH-dependent CS.The adrenal gland will be resected when the treatment of primary lesions is not satisfied or the diagnosis is not clear.Adrenal sparing surgery is recommended for the definitive diagnosis adenomas of CS or subclinical CS.There is a lot of controversy about the treatment of ACTH-independent adrenal gland hyperplasia and primary pigmented nodular adrenal gland, and the individualized treatment scheme has been recognized.

Objective To evaluate the clinical application of retroperitoneal laparoscopic adrenal gland sparing adrenalectomy in the treatment of primary hyperaldosteronism with adrenal adenoma. Methods From 2001 to 2006, clinical data of 196 primary hyperaldosteronism with adrenal adenoma patients (78 males and 118 females with mean age of 41±12, ranging 16-69 years old) confirmed during operation were retrospectively analyzed. All cases were with preoperatively high plasma aldo-sterone, low plasma renin, hypokalemia and arterial hypertension. Results Retroperitoneal laparo-scopic adrenalectomy were successfully completed in all cases. No major complication occurred. of them, partial adrenaleetomies were performed in 51 cases and enucleationa of adrenal adenoma were performed in 145 cases. The operative time was ranged from 15 to 87 min (MD=33 min) and the esti-mated blood loss was ranged from 5 to 200 ml (MD=20 ml). There was no case accepted transfusion. The length of hospital stay was ranged from 2 to 5 d (mean 2.7±1.3 d). All the 196 cases were fol-lowed up with the range from 6 months to 3 years (mean, 1.8 years). Postoperatively, kalemia was normalized in all cases, blood pressure was normalized in 168 cases (85.7%). The abnormal blood pressure cases were under control with anti-hypertension drugs. The CT scan showed adrenal glands were normal. Serum test showed normal hormonal levels. The serum potassium levels were in normal range in all cases. One cases with abnormal post-operative blood pressure had accepted second surgery to remove the adrenal adenoma and the blood pressure turned to be in normal range afterwards. Con-clusion Retroperitoneal laparoscopic adrenal gland sparing adrenalectomy is a safe and feasible tech-nique and is the first choice in the management of primary hyperaldosteronism with adrenal adenoma.

Objective To investigate the clinical-pathological feature and treatment of mvxoid adrenocortieal adenoma. Methods The clinical features of a Myxoid adrenocortical adenoma were re-viewed with its clinical manifestation,imaging,pathology and therapy.The patient was a 43-vear-old woman.The patient complained of recurrent headache,fatigue with hypertension and hypokalemia for 10 years.B-ultrasound examination revealed a 4.1 crux 3.4 cm hypoechoic solid mass in the left adre-nal gland. Relative literatures were reviewed. Results The patient was operated successfully by 1ap-aroscope.The section of tumor showed gray-like flour with yellow jelly-like substance.Hemorrhage was seen in some area. Under light microscope,the tumor cells were similar in size with boundary.There was no obvious heteromorphism and mitotic feature.There was full of mucoid substance.Im-munohitochemical staining showed that the tumor cells were positive for Vimentin,Melan-A and AB/ PAS staining,which confirmed the diagnosis of myxoid adrenocortical adenoraa. Blood pressure andbiochemical indicators returned to normal after surgery.There was no sign of recurrence after 6 month follow-up. Conclusions Myxoid adrenocortical adenoma is a rare adrenal tumor.Path010gy is the key to diagnosis.Surgical removal of tumor could be the preferred therapeutic choice.

Objective To evaluate the diagnosis and treatment of aldosterone producing adreral cortical neoplasms,and analyse the reason of misdiagnosis. Methods From 1998 to 2005,118 patients with aldosterone producing adrenal cortical neoplasms were diagnosed and treated.of these patients,age of onset was(37.3±8.4)years,age of diagnosis was(44.54-10.1)years.The age of 46 EH patients in the control group was(45.6±14.2)years.The information of the history,plasma/urine potassium,the ratio of night/day urine volume,PRA,PAC,ratio of erect position ALD/renin were recorded and analyzed.The diagnosis was all confirmed by surgery and pathological studies. Results It was found that plasma potassium(2.6±0.7)mmol/L;urine potassium(56.0±31.2)mmol/24 h,PRA(2.1±1.2)μg·L-1·h-1,PAC(840.5±527.1)pmol/L,ratio of erect position ALD/renin (254.24±153.4)in APA group.And plasma potassium concentration was(3.9±0.5)mmol/L,urine potassium(13.0±5.3)mmol/24 h,PRA(9.34±3.4)μg·L-1·h-1,PAC(393.94±216.4)pmol/L,ratio of erect position ALD/renin(23.94±15.5)in EH terms.There were significant differences between APA and EH groups(P<0.05).Average time of misdiagnosis in APA was(7.2±6.2)years,7 cases (6%)had complication before diagnosis.In all the patients,serum potassium level elevated to normalange within 1 month postoperatively.In 100 cases out of 118,the blood pressure dropped to normal range within three months after surgery.There were significant differences of the age of onset[(34.5 ±9.1)versus(48.5±12.1)years],persistence time of hypertension[(6.2±5.2)versus(8.85±6.6)years] and the ratio of night/day urine volume(0.9±0.7)versus(1.3±0.6),between normal and high postoperative blood pressure patients(P

Objective To study the clinical factors affecting the prognosis of adrenocortical car-cinoma (ACC) in order to guide the diagnosis and treatment of ACC. Methods The clinical data of 40 cases of ACC were retrospectively analyzed. The patients were diagnosed as ACC by histopatholo-gical examination after operation or biopsy, including 19 cases of nonfunctional ACC and 21 cases of functional ACC. The functional ACC included 14 cases of Cushing's syndrome, 4 cases of sexual ab-normality (3 cases of androphany and one case of male sexual precosity) and 3 cases of primary aldo-steronism. The clinical stage included 3 cases in stage Ⅰ , 10 cases in stage Ⅱ , 7 cases in stage Ⅲ, and 21 cases in stage Ⅳ. Eighteen cases underwent complete excision, 10 cases underwent palliative excision, 12 cases underwent expectant treatment (2 cases underwent arterial embolism). All patients were followed up for 2 to 121 months. The total life span and survival rate were calculated, and the dependability between life span and certain indices (tumor size, function, clinical stage and surgical treatment, etc) was compared. The results were statistically analyzed by utilizing the SPSS 11.5 soft-ware. Rank-sum test was used for the two independent samples, one-factor analysis of variance was used for multiple samples and Pearson correlation analysis was used for the correlation of two vari-ances. Results There were no statistical correlations between gender, age, sides and survival time (P>0.05). The survival time of nonfunctional ACC patients was 37.0 months, of which 11 dead ca-ses survived 11.0 months and 8 survival cases survived 73.5 months. The survival time of functional ACC patients was 11.5 months, of which 19 dead cases survived 12.2 months and 2 survival cases survived 4.8 months. The survival time of nonfunctional ACC was significantly longer than that of functional ACC (P<0. 05). The actual survival time was 66 months and 120 months in stage Ⅰ , of which both survived. The actual survival time was (44.9±40. 2) months in stage Ⅱ, of which 4 sur-vival cases survived 59.0 months. The actual survival time was(34. 5±29.8) months in stage Ⅲ, ofwhich 2 survival cases survived 42.0 months. The actual survival time was (7.1±6.7) months instage Ⅳ, of which 2 survival cases survived 8. 0 months. There was significant difference of the sur-vival time among different clinical stages(F=11. 078, P<0. 05). There was no significant difference of survival time between treatment methods[(10.04±0.0) vs (4.5±1.5) months, P>0. 05]. Con-clusions The most important influencing prognostic factors of ACC are function and clinical stage. For ACC in stage Ⅰ and Ⅱ , tumor resection is the most effective treatment, and second surgical oper-ation is recommended for local recurrence. For ACC in stage Ⅲ, radical or extensive surgical operation is recommended, and for ACC in stage Ⅳ, surgical operation has no effect on the prognosis.

Objective To review the diagnosis and surgical therapeutic methods of adrenocorti-cal hyperplasia disease. Methods One hundred and eighty adrenocortical hyperplasia patients (74 males and 106 females with a mean age of 40 years) were retrospectively analyzed. The patients were divided into hypereortisolism (n=152) and aldosteronism (n=28) according to secretion. Data of clinical characteristic, endocrine and image examination were collected. All patients were treated by operation. Results Of these patients, 107 had Cushing disease (CD), 28 had adrenocorticotropin independent macronodular adrenal hyperplasia (AIMAH), 19 had ectopic adrenocorticotropin adrenal hyperplasia (EAAH), 4 had primary pigmented nodular adrenocortical hyperplasia (PPNAH), 28 had DOI: 10.3760/cma.j.issn. 1000-6702.2009.05.002idiopathic hyperaldosteronism (IHA). 24 h urinay free cortisol (24hUFC) excretion of CD, AIMAH, EAAH and PPNAH were 95.2-535.7 μg (mean, 287.6 μg), 24.8-808.2 μg (mean, 307.9 μg), 102.5-3127.0 μg (mean, 852.5 μg), 243.8-1124.6 μg (mean. 564.3 μg). The proportion loss of the serum cortisol circadian rhythm were 99% (102/103), 92% (11/12), 100% (17/17), 100% (4/ 4), respectively. Low- and high-dose dexamethasone suppression tests (DDST) failed to suppress cor-tisol secretion in AIMAH, PPNAH and EAAH groups, but HDDST was suppressed in CD group. Of the 28 IHA cases, 17 had hypokalemia and 15 had high urine kalium (>30 mmol/24 h). The results of plasma renin activity and serum aldosterone accorded with the diagnosis. Unilateral adrenalectomy were operated in 102 hypercortisolism cases, and 24hUFC of CD, AIMAH, EAAH and PPNAH were 56.2-233.5 μg (mean, 157.4 μg), 22.5-418.5 μg (mean, 117.9 μg), 116.5-1137.0 μg (mean, 756.7 μg), 124.6-422.6 μg (mean, 164.3 μg) 1 week after operation. The blood pressure was nor-mal in 8 paitents and droped in 13 patients for IHA after unilateral adrenalectomy. 24hUFC were nor-mal in 55 patients after bilateral adrenalectomy for hypercortisolism. One hundred and six patients were followed up for 4-158 months, the Cushing syndrome ameliorated and blood pressure dropped. Conclusions Unilateral adrenalectomy is the first choice for adrenocortical hyperplasia disease which needs operation. The operation mode of the contralateral adrenal gland is based on the hyperplasia types and clinical observation.

Objective To investigate the clinical characteristics and diagnostic methods of multiple endocrine neoplasia ( MEN) 2B. Methods The clinical data collected from 4 cases with multiple endo-crine neoplasia type 2B, who had been diagnosed and treated from July .1980 to Jan.2012, were retrospec-tively analyzed.Of the 4 patients, 3 males were diagnosed at the age of 14, 24, 21, respectively, and 1 fe-male was diagnosed at age of 23.Two cases had the first diagnosis of thyroid mass during the physical exami-nation, and the adrenal tumors and hypertension were first diagnosed in other two cases , respectively.All four cases had multiple mucosal neuromata .Of whom, three cases had medullary thyroid carcinoma and pheochromocytoma , two cases had Marfan syndrome figure , and one case had pheochromocytoma and Marfan syndrome.Two cases were accompanied by paroxysmal hypertension , and the highest systolic blood pressure was over 200 mmHg (1 mmHg=0.133 KPa).Two cases of pheochromocytoma were found during follow up . Three cases had bilateral adrenal tumors .The thyroid mass was diagnosed by ultrasonography , and the pheo-chromocytoma was confirmed by ultrasonography , CT and 24-hour urine catecholamine test .Adrenalectomy and thyroidectomy were carried out during the treatment process .To clarify the RET mutation status , exons and adjacent introns from 10th to 16th of RET proto-oncogene were sequenced in two patients . Results Gene analysis of two cases confirmed the activating mutation at the sites of 918 in exon 16 of RET proto-on-cogene in which methionine was replaced by threonine ( ATG-ACG) .Among the 3 cases with medullary thy-roid carcinoma , two patients were treated by total thyroidectomy and neck lymphadenectomy , one was opera-ted by subtotal thyroidectomy .For the treatment of pheochromocytoma , adrenal tumor resection was carried out in 3 cases, but not in the other one .Patients were followed up for 2 to 15 years postoperatively , 1 case without tumor recurrence and metastasis , 2 cases with multiple metastases . Conclusions The diagnosis of multiple endocrine neoplasia type 2B mainly depends on endocrine tests , ultrasonography and CT .Surgery is the primary treatment .When pheochromocytoma coexists with other tumors , pheochromocytoma should be re-moved first .

Objective To discuss the value of unilateral adrenalectomy(UA)for the treatment of refractory or recurrent Cushing disease(RRCD).Methods From January 2003 to July 2011,10 patients with RRCD underwent UA.The preoperative symptoms,preoperative treatments,intra-and post-operative complications and follow-up in patients were reviewed.All the 10 patients presented with hypercortisolemia symptoms.Transsphenoidal surgery had been performed in 9 patients as initial therapy.Of the 10 patients,8 received radiation therapy before adrenalectomy.All the 10 cases accepted a right UA.Results No perioperative complications occurred.The 10 patients were followed up for 1-8 years.Eight patients with radiation therapy before adrenalectomy got remission.Two bilateral adrenalectomies were eventually performed because the symptoms could not be controlled.Of the 8 patients who got remission,none of them developed Nelson syndrome and none need lifelong mineralocorticoid and glucocorticoid replacement therapy.Conclusions UA could be an option for RRCD.For patients with RRCD receiving radiation therapy,UA may effectively relief hypercortisolemia.Compared with bilateral adrenalectomies,UA could avert permanent adrenal insufficiency,which leads to a lifelong glucocorticoid and mineralocorticoid replacement therapies,and a life-threatening adrenal crisis.

Objective To report a case of multiple endocrine neoplasia type 2B (MEN 2B) combined with analogous Marfan's syndrome with the related literature review,in order to improve the knowledge of this disease.Methods A case of MEN 2B combined with analogous Marfan's syndrome was admitted in Peking Union Medical College Hospital in Nov 2011.The patient was a 21-year-old male with the chief complaint of tongue thick for 13 years,found a tumor in right adrenal gland for 3 months.The patient underwent radical thyroidectomy and lymph node dissection in April 2011 because of thyroid tumor,and postoperative pathology confirmed the diagnosis of medullary thyroid carcinoma(T2N1bM0).The patient had normal blood pressure without fluctuation.Physical examination indicated that the patient had thin limbs,long fingers and long toes.Carpal syndrome and finger syndrome were positive.There were multiple tumor like nodules in the tip of the tongue,lips,inner canthus of eyelids,and laryngoscopy showed multiple nodulars in bilateral vocal cord and bilateral tip splitting.Enhanced CT showed a tumor of 2.9 cm×3.4 cm×3.8 cm in the right adrenal gland.Endocrine examination revealed high catecholamines:norepinephrine 159.3 nmol,epinephrine 13.3 nmol,and DA 918.2 nmol.131I-MIBG was positive for pheochromocytoma.The clinical manifestation was in stationary state.Preoperative diagnosis was MEN 2B,right adrenal pheochromocytoma,medullary thyroid carcinoma (T2N1bM0)after operation,multilple mucosa neurofibroma and analogous Marfan's syndrome.Results The pheochromocytoma in right adrenal gland was removed by laparoscopy under general anesthesia successfully on Dec 12,2011.The postoperative pathology confirmed the diagnosis of pheochromocytoma.And gene mutation was found in exon 16 of RET gene.MEN 2B with analogous Marfan's syndrome was diagnosed.During the follow-up period for 28 months,the patient had normal blood pressure and heart rate without tumor recurrence or metastasis.Conclusions MEN 2B combined with analogous Marfan's syndrome is extremely rare.For patients with medullary thyroid carcinoma,pheochromocytoma should be considered before operation.For patients with analogous Marfan's appearance,Marfan's syndrome should be differentially diagnosed.