Cushing's Adenoma Research Articles

WNT-4mRNA Expression in Human Adrenocortical Tumors and Cultured Adrenal Cells

The members of the Wnt glycoprotein family are important in embryogenesis and adult tissue homeostasis, and deletion of WNT-4 gene in mice leads to improper development of many organs including the adrenals. The objective of this study was to investigate the expression of WNT-4 gene in human adrenals and adrenocortical tumors. The WNT-4 mRNA expression (analyzed by quantitative real-time RT-PCR) was significantly higher in Conn's adenomas (p<0.01) and lower in Cushing's adenomas, virilizing carcinomas and fetal adrenals (p<0.05) compared with normal adult adrenals. WNT-4 mRNA expression was clearly upregulated by ACTH and 8-bromo-cAMP (8-BrcAMP) in primary cultures of normal adult adrenocortical cells, but downregulated by 8-BrcAMP and 12- O-tetradecanoylphorbol-13-acetate (TPA) in human NCI-H295R adrenocortical carcinoma cells. Angiotensin II tended to increase WNT-4 mRNA expression at 24 hours and decreased it at 48 hours time point in both cell culture types. The abundant WNT-4 mRNA expression in Conn's adenomas and its hormonal regulation in adrenocortical cells suggest a role for WNT-4 in human adrenocortical function.

Evolución de la cirugía laparoscópica adrenal en un servicio de cirugía general

To evaluate the reproducibility, safety and short-term results of laparoscopic adrenal surgery during the first few years after its introduction in our department. A prospective analysis of data of all patients who underwent laparoscopic adrenalectomy in our endocrine surgical unit over a 4-year period. Demographic data, medical history, diagnosis, adrenal and tumour size, technique, conversions, complications and hospital stay were re-viewed. All patients were treated with a laparoscopic transperitoneal lateral approach. Twenty-four laparoscopic adrenalectomies were performed on 23 consecutive patients (one underwent bilateral adrenalectomy). There were 15 females and 8 males; the mean age was 49.6 years (range, 20-72). There were obesity and vascular hypertension in half of the patients. The indications for surgery were: 8 incidentalomas, 6 aldosterone-producing adenomas, 5 Cushing's adenomas, 3 phaeochromocytoma and 2 metastasis. Right adrenalectomy was performed on 11 patients, left on 11 and one was bilateral. Three cases required open conversion. Respiratory tract infection and hypertensive crisis were the postoperative complications. There was no mortality. The mean operative time was 125 minutes (range, 70-265). The mean size of adrenals excised was 6.5 cm (range, 4-14). The mean size of tumours excised was 4.6 cm (range, 1.5-12). The mean hospital stay was 3.5 days (range, 2-11). Laparoscopic adrenalectomy is a safe, reproducible and effective procedure with low complication rates, and well tolerated by the patients. The operating time and the length of hospital stay have decreased with the confidence of the technique.

Flank approach versus anterior sub-mesocolic access in left laparoscopic adrenalectomy: a prospective randomized study

Laparoscopy is commonly recognized as the gold standard in adrenal surgery. The most used surgical access is at present the so-called flank approach. The aim of this study was to compare the flank approach and the anterior sub-mesocolic access carrying out left laparoscopic adrenalectomy (LA). From January 2003 to January 2006 50 eligible left LAs were randomized to the flank (n = 25, group A) or sub-mesocolic transperitoneal approach (n = 25, group B). The two groups were similar concerning patient and lesion features. Comparing the two approaches, the main parameters analyzed, adjusted for tumor size and histology, were operating time (OpT), complication rate, and hospital stay. There were no converted procedures. Mean overall OpT was 76.4 min (54-96 min) versus 65.6 min (45-95 min) in group A and B, respectively (p = 0.001), while the OpT required to tie the adrenal vein was 42.8 min (26-55 min) and 24.5 min (16-41 min) (p = 0.000). Oral feeding resumed within 12-24 h in both groups. Mean hospital stay was 3 and 2.4 days in groups A and B, respectively (p = 0.04). Mean tumor size was similar in group A and B: 3.6 cm (1.5-6.5 cm) and 3.8 cm (2-6 cm), respectively. Definitive histology in groups A and B were: Cushing adenoma (6 and 4), Conn adenoma (5 and 6), pheochromocytoma (4 and 9), and incidentaloma (8 and 5, respectively). A myelolipoma and an adrenogenital adenoma were observed in group A and one carcinoma was observed in group B. Sub-mesocolic approach provides a statistically significant shorter OpT and hospital stay. Identification and early closure of the adrenal vein by means of a really minimal dissection and no-touch gland technique resulted in the main benefits of this approach.

Vasopressin responders have a high prevalence of hypertension and insulin resistance in spite of a lower secretion of cortisol in subclinical Cushing's syndrome

The hyper-responsiveness of plasma cortisol to vasopressin has been reported in patients with ACTH-independent bilateral macronodular adrenocortical hyperplasia (AIMAH) and in certain cases of Cushing's adenomas with overexpression of V1a receptors in the adrenal gland. We previously reported a high prevalence of the adrenal hyper-responsiveness of plasma cortisol to vasopressin (vasopressin responders) in Japanese patients with Cushing's syndrome (CS), in which vasopressin responders had low autonomous cortisol secretion and were diagnosed as having subclinical CS. In the present study, we aimed to evaluate the pathophysiological significance of vasopressin responsiveness in patients with subclinical CS in terms of hormonal secretion and metabolic abnormalities. We compared 14 vasopressin responders and 13 non-responders with subclinical CS, admitted to Chiba University Hospital between 1999 and 2007. Among these patients, the vasopressin responders were found to have lower plasma cortisol levels than non-responders at midnight (P<0.05) and in the morning following overnight dexamethasone suppression at 1 mg (P<0.05). On the other hand, they showed a significantly higher frequency of hypertensive complications than non-responders. In addition, according to 75g-OGTT the vasopressin responders had significantly higher levels of plasma insulin at 60 min than the non-responders, and their cortisol response to vasopressin had a significantly positive association with HOMA-IR (r=0.671, P<0.05). A high expression level of V1a receptor mRNAs was observed in the resected adrenal glands of vasopressin responders with AIMAH and unilateral adenomas. Though vasopressin responders with subclinical CS had lower autonomous cortisol secretion, they had a high prevalence of hypertension, in which insulin resistance was closely correlated with cortisol response to vasopressin.

Laparoscopic Adrenalectomy Using Needlescopic Instruments for Adrenal Tumors Less Than 5 cm in 112 Cases

ObjectiveTo examine the safety and efficacy of laparoscopic adrenalectomy with needlescopic instruments for most adrenal tumors less than 5cm. MethodsTransperitoneal laparoscopic adrenalectomy with needlescopic instruments for 112 patients with presumptively benign adrenal tumors < 5cm were enrolled from July 2000 to February 2005. Operative time, blood loss, conversion and complication rates, and postoperative data were analyzed by appropriate statistical methods. ResultsAll 112 operations were completed without any mortality or reoperation. Mean operative time was 151min and mean blood loss was 30ml. Only one patient required a blood transfusion and application of a hand-assisted device. Conversion to conventional laparoscopic instruments was necessary in another five patients (4.5%). The operative time of the latter 100 cases (147±5.1min, mean±standard error of mean) was significantly shorter than that of the initial 12 cases (183±8.8min, p=0.001). Larger tumors, previous abdominal surgery, and pheochromocytoma group were independent risk factors of a longer operative time. Except for one leiomyosarcoma, all other tumors were benign adrenal pathologies (57 aldosterone-producing adenomas, 23 Cushing's adenomas, 12 pheochromocytomas, and 20 incidentalomas). ConclusionThe safety and effectiveness of laparoscopic adrenalectomy employing needlescopic instruments for most adrenal tumors less than 5cm was feasible with acceptable operative time. Pheochromocytomas can also be managed with a longer operative time. Patients with previous upper midline or ipsilateral upper quadrant open surgery might not be suitable candidates for such a technique.

Perioperative results of 214 laparoscopic adrenalectomies by anterior transperitoneal approach

The present study attempts to evaluate the perioperative results of the anterior approached laparoscopic adrenalectomy (LA) in a large cohort of patients, and report the advantages and disadvantages of this route. 204 patients, 125 female and 79 male with a mean age 52.8 years (range, 19-75 years), underwent LA by the anterior transperitoneal approach from 1994 to 2005 in our institution. There were 100 right and 114 left LAs. Ten patients underwent bilateral LA. Associated surgical procedures were performed in 17 cases. During the same period 47 LAs had been performed by different approaches (flank and submesocolic). Mean operative time was 80 minutes for right (40-150), 109 minutes for left (64-300) and 194 minutes for bilateral adrenalectomy. Intraoperative major complications were observed in six patients. Mortality occurred in one diabetic patient who was converted to open surgery because of a colonic perforation and subsequently developed a Candida sepsis in the postoperative course. The mean size of lesion removed was 6.2 cm (1.5-12 cm). Oral intake started within 24 hours and the mean hospital stay was 2.5 days (1-8 days). Histology results were as follows: nonsecreting adenoma 65, Cushing's adenoma 58, Conn's adenoma 53, pheochromocytoma 24, metastases 9, myelolipoma 3, adrenogenital syndrome 1, carcinoma 1. LA by anterior transperitoneal approach is safe and effective in our experience, despite the inherent limitation that this was not a prospective randomized study. The main advantage of this route is early ligature of the adrenal vein on both sides, enabling the performance of associated surgical procedures and bilateral adrenalectomy.

Immunohistochemical properties of silent corticotroph adenoma and Cushing’s disease

Proopiomelanocortin processing in corticotroph cells is known to be operated by prohormone convertase (PC) 1/3 which is activating several pro-proteins and prohormones by intracellular limited proteolysis processing. In this study, we hypothesized that PC1/3 expression differs between Cushing's disease (CD) and silent corticotroph adenoma (SCA), and investigated whether PC1/3 expression is involved in the adrenocorticotropin (ACTH) silence of SCA. We performed immunohistochemical analysis of pituitary adenoma specimens for six adenohypophysial hormones, PC1/3 and chromogranin A (CgA). Subjects for this study consisted of 12 anterior pituitary adenomas of CD (1 male, 11 female; 14-70 years old) and 31 non-functioning adenomas (23 male, 8 female; 32-71 years old).ACTH immunoreactivity was observed in all of CD and three of 31 non-functioning adenomas. The three cases diagnosed as SCA were also positive for growth hormone and follicle-stimulating hormone. Cushing's adenomas and SCAs were all positive for PC1/3. PC1/3-positive cells did not always colocalize with ACTH but some of them colocalized with CgA in SCAs. Even if PC1/3 is not present in corticotroph cells, PC1/3 immunoreactivity in SCA may originate from CgA-positive cells. We conclude that immunohistochemistry for PC1/3 is not helpful for differential diagnosis between CD and SCA in clinical practice, though the regulation of PC1/3 expression is likely to be an important etiological factor in ACTH silence of SCA. The diversity of immunohistochemical properties of SCA leads us to speculate that it is not a single entity and may be a general diagnostic term for adenomas of varying etiology.

Adrenal involvement in multiple endocrine neoplasia type 1: results of 7 years prospective screening

Adrenal tumors are a common manifestation of the multiple endocrine neoplasia type 1 (MEN-1) syndrome. Prevalence in recent studies varies between 9 and 45%. A genotype-phenotype correlation has been described as well as the development of adrenocortical carcinomas. Long-term prospective data are still lacking. Thirty-eight MEN-1 patients with proven germline mutations have been prospectively observed in a regular screening program in our hospital. Adrenal glands have been screened by biochemical analysis and either by endoscopic ultrasound (EUS) or computed tomography (CT) or both. Median follow-up was 48 months (12-108 months). Age at diagnosis of MEN-1, type of adrenal tumor, genotype, therapy, and clinical characteristics have been analyzed. In 21 (55%) patients, adrenal involvement of the disease was detected. Adrenal lesions were detected in average 6.9 years after the initial diagnosis of MEN-1. Median tumor size was 12 mm (5-40 mm). Tumor size smaller than 10 mm was observed in 11 patients. Twelve patients had unilateral while nine had bilateral adrenal lesions. EUS detected all adrenal tumors, whereas CT failed in seven cases. In three patients, functioning tumors (one pheochromocytoma, one bilateral Cushing adenoma, and one adrenocortical carcinoma) and one nonfunctioning adenoma were diagnosed by histology and biochemical assessment. Two laparoscopic adrenalectomies and one laparoscopic subtotal resection were performed. Nonfunctioning adrenal lesions, not characterized by histology yet, were found in 18 patients. There was no statistical difference with regard to adrenal involvement between patients with germline mutations in exons 2 and 10 (12/21) and those with mutations in exons 3-9 (6/11). MEN-1-associated adrenal tumors are mostly small, benign, and nonfunctioning and much more common than previously reported. EUS was the most sensitive imaging procedure. The genotype-pheotype correlation previously suggested by our group could not be confirmed.

Posterior Retroperitoneoscopic Adrenalectomy: A Comparison between the Initial Experience in the Invention Phase and Introductory Phase of the New Surgical Technique

Today, the posterior retroperitoneoscopic technique has become a standard procedure in adrenal surgery. The procedure allows direct access to the adrenal glands, but it seems to be difficult because of the uncommon anatomic view. This study compares the learning period of the new procedure of "posterior retroperitoneoscopic adrenalectomy" in the primary invention phase and the secondary introductory phase in a different hospital 10 years later. The analysis included 100 posterior retroperitoneoscopic adrenalectomies (PRA) and involved 50 procedures in each center. Group A consisted of 44 patients (14 males, 30 females; age: 48.7 +/- 14.5 years) undergoing surgery between 07/1994 and 8/1996 (24 right, 26 left; 8 Cushing adenomas, 14 Conn adenomas, 11 pheochromocytomas, 7 nonfunctioning adrenocortical adenomas, 10 ACTH-dependent adrenal hyperplasias). Group B consisted of 50 patients (12 males, 38 females; mean age 59.3 +/- 10.7 years) operated between 01/2004 and 01/2006 (28 right, 22 left tumors; 5 Cushing adenomas, 12 Conn adenomas, 4 pheochromocytomas, 29 nonfunctioning adrenocortical adenomas). All PRAs were performed with the patient in the prone position with 3-4 trocars placed caudally in the region of the 11th and 12th ribs. In group A, the surgical team developed the technique of PRA themselves. Before their first PRA, the surgical team of group B was introduced to the technique by the group A surgeons and afterwards were supervised continuously. No serious intraoperative or postoperative complication occurred in either group. Group A experienced 7 conversions to open surgery, whereas group B had one conversion and one early reoperation due to bleeding (P = 0.03; chi(2)-test). The mean operative time was 117 +/- 41 minutes versus 83 +/- 35 minutes (group A and B respectively; P < 0.001; t-test). Estimated blood loss was similar in the two groups (47.2 +/- 46.2 ml versus 54 +/- 16.3 ml, group A versus B, respectively; P = 0.36; t-test). The study demonstrates the feasibility, safety, and reproducibility of the new surgical method of PRA both when it is employed in the early phase of invention, as well as when performed by surgeon-learners. After comprehensive training, the operative time and conversion rate are dramatically reduced, allowing for a short learning period.

Posterior retroperitoneoscopic adrenalectomy—results of 560 procedures in 520 patients

The posterior retroperitoneoscopic adrenalectomy is less popular than the laparoscopic transabdominal method. Due to the direct approach to the adrenal glands, however, the posterior retroperitoneal access is easy to use and may offer advantages not available with other endoscopic procedures for adrenalectomy. Between July 1994 and March 2006, we performed 560 adrenalectomies (right side: n = 258; left side: n = 302) by the posterior retroperitoneoscopic approach in 520 patients (200 male, 320 female; age, 10 to 83 years). Of the 520 patients, 21 suffered from Cushing's disease, 499 patients had adrenal tumors (157 Conn's adenomas, 120 pheochromocytomas [13 bilateral], 110 Cushing's adenomas [6 bilateral], and 112 other tumors). Tumor size ranged from 0.5 to 10 cm (mean, 2.9 +/- 1.7 cm). The procedures were performed with the patients in the prone position usually with 3 trocars. Mortality was zero. Conversions to open or laparoscopic lateral surgery were necessary in 9 patients (1.7%). Major complications occurred in 1.3% of patients, minor complications in 14.4%. Mean operating time was 67 +/- 40 min and declined significantly (P < .001) from the early procedures (106 +/- 46 min) to the later operations (40 +/- 15 min). The posterior retroperitoneoscopic adrenalectomy is a safe and fast procedure. In experienced hands, this method represents the ideal approach in adrenal surgery.

Clinical outcomes and learning curve of a laparoscopic adrenalectomy in 103 consecutive cases at a single institute

We examined the clinical outcomes and the learning curve for a laparoscopic adrenalectomy (LA) in 103 consecutive cases performed by three surgeons at our institute, according to the type of adrenal disorder. One hundred and three patients with adrenal tumors, including 38 cases of primary aldosteronism, 33 cases of Cushing syndrome (including preclinical Cushing syndrome), 15 cases of pheochromocytoma, and nine cases of non-functioning adenoma were evaluated, while focusing on the approaches, intraoperative and postoperative data, and the learning curve of LA, according the type of adrenal disorder. There was no significant difference in the operation time, estimated blood loss, incidence of conversion to open surgery and blood transfusion, or postoperative recovery among the patients treated by LA for aldosteronoma, Cushing adenoma, pheochromocytoma, and non-functioning adenoma. In the cases of aldosteronoma and Cushing adenoma, the learning curve for the operation time and blood loss in each operator tended to decrease as the number of operations increased. On the other hand, in the cases treated by LA for pheochromocytoma, no trends in either the operation time or blood loss were observed. However, there has been neither any conversion to open surgery nor blood transfusion in cases treated by LA since 1998 (our 42nd case), even after the changes in the operators. Our results clearly indicate that LA is becoming safer than before, probably due to improvements in the technique, education, and training of surgeons, in addition to the increased number of cases now treated by LA.

Improved DOP-PCR???Based Representational Whole-Genome Amplification Using Quantitative Real-Time PCR

In many cases, only a minute amount of partially degraded genomic DNA can be extracted from archived clinical samples. Diverse whole-genome amplification methods are applied to provide sufficient amount of DNA for comparative genome hybridization, single-nucleotide polymorphism, and microsatellite analyses. In these applications, the reliability of the amplification techniques is particularly important. In PCR-based approaches, the plateau effect can seriously alter the original relative copy number of certain chromosomal regions. To eliminate this distorting effect, we improved the standard degenerate oligonucleotide-primed PCR (DOP-PCR) technique by following the amplification status with quantitative real-time PCR (QRT-PCR). With real-time detection of the products, we could eliminate DNA overamplification. Probes were prepared from 10 different tumor samples: primary and metastatic melanoma tissues, epidermoid and bronchioloalveolar lung carcinomas, 2 renal cell carcinomas, 2 colorectal carcinomas, and a Conn and Cushing adenoma. Probes were generated by using nonamplified and amplified genomic DNA with DOP-PCR and DOP-PCR combined with QRT-PCR. To demonstrate the reliability of the QRT-PCR based amplification protocol, altogether 152 relative copy number changes of 44 regions were determined. There was 85.6% concordance in copy number alterations between the QRT-PCR protocol and the nonamplified samples, whereas this value was only 63.8% for the traditional DOP-PCR. Our results demonstrate that our protocol preserves the original copy number of different chromosomal regions in amplified genomic DNA than standard DOP-PCR techniques more accurately.

Laparoscopic adrenalectomy: Gaining experience by graded approach

Laparoscopic adrenalectomy (LA) has become a gold standard in management of most of the adrenal disorders. Though report on the first laparoscopic adrenalectomy dates back to 1992, there is no series of LA reported from India. Starting Feb 2001, a graded approach to LA was undertaken in our center. Till March 2006, a total of 34 laparoscopic adrenalectomies were performed with success. The endocrinology department primarily evaluated all patients. Patients were divided into Group A - unilateral LA and Group B - bilateral LA (BLA). The indications in Group A were pheochromocytoma (n=7), Conn's syndrome (n=3), Cushing's adenoma (n=2), incidentaloma (n=2); and in Group B, Cushing's disease (CD) following failed trans-sphenoid pituitary surgery (n = 8); ectopic ACTH- producing Cushing's syndrome (n=1) and congenital adrenal hyperplasia (CAH) (n=1). The lateral transabdominal route was used. The age group varied from 12-54 years, with mean age of 28.21 years. Average duration of surgery in Group A was 166.43 min (40-270 min) and 190 min (150-310 min) in Group B. Average blood loss was 136.93 cc (20-400 cc) in Group A and 92.5 cc (40-260 cc) in Group B. There was one conversion in each group. Mean duration of surgical stay was 1.8 days (1-3 days) in Group A and 2.6 days (2-4 days) in Group B. All the patients in both groups were cured of their illness. Three patients in Group B developed Nelson's syndrome. The mean follow up was of 24.16 months (4-61 months). LA though technically demanding, is feasible and safe. Graded approach to LA is the key to success.

Laparoscopic Adrenalectomy By The Transperitoneal Approach And Typical Complications: Own Experience And Review Of Current Literature

Minimally invasive techniques play an increasingly important role in adrenal surgery. We report typical complications we have encountered. Between 1997 and 2003, 52 patients were referred to our centre for the surgical management of adrenal diseases. A laparoscopic approach was chosen for 25 patients. Indications for surgery were Conn's adenoma, phaeochromocytoma, Cushing's-adenoma, virilizing tumour, incidentaloma and lung cancer metastasis. Conversion to laparotomy in 4 patients was due to morbid obesity, inhalatory problems with anaesthesia, anatomical difficulties in surveying the surgical field, and intraoperative bleeding. Eight patients underwent partial adrenalectomy. LA is the treatment of choice for small benign tumours with a low rate of mortality and acceptable risk of morbidity. Because of the rare incidence of adrenal tumours, it will never be a common procedure and will become established primarily in centres with appropriate expertise in laparoscopic and endocrine surgery.

Laparoscopic adrenalectomy for functioning and non‐functioning adrenal tumors: Analysis of surgical aspects based on histological types

The aim of this study was to evaluate whether hormonal functions of the tumor influence the operative results of laparoscopic adrenalectomy, and to analyse the clinical outcomes in patients with various hormonally active adrenal tumors. Clinical and pathological records of 68 patients were reviewed. The average age of patients was 40 years (range 20-75); 39 were women and 29 men. For the comparison, patients were divided into the non-functioning tumor group (n = 22) and the functioning tumor group (n = 46). All laparoscopic adrenalectomies were finished successfully, and no open surgery was necessary. The median operative time and blood loss in the two groups were similar; however, in subgroup analysis, operative time for pheochromocytoma was significantly longer than that for non-functioning tumor (P = 0.044). No difference was noted in intra- and postoperative data between the groups. Of the 22 patients with aldosteronoma, 18 (81.8%) became normotensive and no longer required postoperative blood pressure medications. Adrenalectomy led to an overall reduction in the median number of antihypertensive medications (P < 0.001). All patients with Cushing adenoma had resolution or improvement of the signs and symptoms during follow-up periods. There was no evidence of biochemical or clinical recurrence in any patient with pheochromocytoma. The results of this retrospective review document that laparoscopic adrenalectomy is a safe and effective treatment for functioning as well as non-functioning adrenal tumors, although endocrinologic features may play a significant role.

Sub-mesocolic access in laparoscopic left adrenalectomy

This article reports an alternative laparoscopic access to left adrenal gland. From January 1994 to August 2004, 209 laparoscopic adrenalectomies were performed in our Department. Indications were Conn adenoma (55 cases), incidentaloma (64), Cushing adenoma (45), pheochromocytoma (32), adreno-genital syndrome (two), mielolipoma (two), and metastatic mass(nine). Of 209, in 12 cases the left adrenalectomy was performed through a submesocolic access (seven pheochromocytoma, two incidentaloma, two Cushing adenoma, one Conn adenoma,). The identification and closure of the adrenal vein with minimal gland manipulation resulted the main benefit of this approach. Moreover, the adrenalectomy was performed with minimal anatomical dissection. No mortality or major complications occurred. During the operation, the blood pressure and cardiac rhythm were significantly more stable, in the group of patients who underwent a left adrenalectomy by the submesocolic approach compared to the anterior or flank lateral transperitoneal group. Left adrenal lesions, as selected cases of pheochromocytoma, can be safely treated by laparoscopic submesocolic access.

Transcriptional regulation of the human somatostatin receptor subtypes (sst 1–5) in adrenal cortex and medulla cells

Background: Somatostatin (SRIF) is a widely distributed peptide with inhibitory effects on cell proliferation in normal and tumor tissues. In RNA obtained from normal adrenal gland, we demonstrated significant expression of all five ssts using RT/PCR. Pheochromocytomas, Conn adenomas, Cushing's adenomas and nonfunctional adenomas showed specific sst expression profiles for each tumor typ. To understand the regulation of sst expression in the adrenal gland, we investigated the transcriptional activity of the sst 1–5 promoters.

Work-up of the functional adrenal mass

Evaluation of a functional adrenal mass may be initiated based on symptomatic presentation or the detection of an incidental adrenal mass. Recent literature suggests that 10% to 20% of adrenal incidentalomas demonstrate subclinical hormonal dysfunction, which may place patients at a higher risk for metabolic or cardiovascular disorders. Many diagnostic algorithms have been proposed for the evaluation of pheochromocytoma, Cushing's adenoma, aldosteronoma, and hormonally active adrenal cortical carcinoma. In this article, the available literature on functional adrenal masses is reviewed and up-to-date methods of efficient diagnosis are proposed.

Partial versus Total Adrenalectomy by the Posterior Retroperitoneoscopic Approach: Early and Long‐term Results of 325 Consecutive Procedures in Primary Adrenal Neoplasias

The retroperitoneoscopic approach is a standardized operative procedure for primary adrenal gland tumors. It allows direct access with a detailed view of the adrenal gland. Thereby, a clear differentiation between normal and neoplastic adrenal tissue is often possible, which permits a planned partial resection of the gland in selected cases. Between July 1994 and November 2003 325 posterior retroperitoneoscopic adrenalectomies were performed for primary benign adrenal gland tumors (106 Conn's adenomas, 83 pheochromocytomas, 76 Cushing's adenomas, 60 nonfunctioning tumors; size: 2.8 +/- 1.5 cm; site: 160 right, 165 left) in 318 patients (122 M, 196 F, age: 49.0 +/- 14.3 years). In 96 patients 100 tumors were removed by partial adrenalectomy (30 Conn's adenomas, 33 pheochromocytomas, 20 Cushing's adenomas, 17 nonfunctioning tumors; site: 61 right, 59 left) maintaining tumor-free parts of the adrenal gland. Of this group, 15 patients suffered from bilateral adrenal neoplastic diseases. During the same period, 225 total adrenalectomies (76 Conn's adenomas, 50 pheochromocytomas, 56 Cushing's adenomas, 34 nonfunctioning tumors; site: 109 right, 116 left) were performed in 224 patients. There was no mortality. Major complications were seen in 1.8%, minor complications in 14.5%. Three conversions were necessary to an open or a laparoscopic approach (2 patients and 1 patient, respectively). There are no differences between the two groups (total versus partial adrenalectomy) with regard to tumor size (2.8 +/- 1.6 cm versus 2.8 +/- 1.5 cm), operating time (80 +/- 44 minutes versus 79 +/- 42 minutes), and blood loss (33 +/- 71 ml versus 29 +/- 31 ml). In all patients with partial adrenalectomy, biochemical healing was proven. Fourteen of 15 patients with bilateral diseases had preservation of adrenocortical function. After a mean follow up of 51 months (range: 7-120 months) local recurrence or relapse of the initial diseases was noticed in 6 patients after total adrenalectomy: in 4 patients with Conn's syndrome and bilateral hyperplasia, and in 2 patients with malignant pheochromocytoma and adrenocortical carcinoma, respectively. Our data demonstrate that partial adrenalectomy is a safe procedure not only perioperatively but also in the long-term follow-up.

Nur-related factor 1 and nerve growth factor-induced clone B in human adrenal cortex and its disorders.

Nerve growth factor-induced clone B (NGFI-B; NR4A1) and Nur-related factor 1 (Nurr1; NR4A2) are members of NGFI-B family of orphan receptors. We recently demonstrated induction of CYP11B2 (aldosterone synthase) by Nurr1 and NGFI-B, suggesting possible important roles of these transcriptional factors in the regulation of adrenocortical steroidogenesis. Therefore, we immunolocalized Nurr1 and NGFI-B in various human adrenal specimens to study their biological significance. In nonpathological adrenal glands (n = 25), Nurr1 and NGFI-B immunoreactivities were detected at high levels in the fetal definitive zone or postnatal zona glomerulosa. NGFI-B immunoreactivity was increased according to development in the zona fasciculata, reaching a level similar to that in the zona glomerulosa in adult adrenal cortex. In adrenocortical neoplasms (n = 44), Nurr1 immunoreactivity was higher in aldosteronoma than in Cushing's adenoma or adrenocortical carcinoma. NGFI-B immunoreactivity was also higher in aldosteronoma than in adrenocortical carcinoma, but was not significantly different among the types of adenoma. Both Nurr1 and NGFI-B mRNA expressions were correlated with their immunoreactivities in adrenocortical neoplasms (n = 23), and mRNA expression of Nurr1 was significantly (P < 0.0001) associated with that of CYP11B2. These results suggest that the expression of Nurr1 and NGFI-B plays an important role in human adrenal cortex and its neoplasms, including possible regulation of steroidogenesis.