Cushing's Adenoma Research Articles

Investigation of ace genome insertion/deletion correlation with immunohistochemical profile in pituitary adenomas

The deletion polymorphism of the angiotensin-converting enzyme (ACE) genome causes neoplastic development in several organs by increasing the angiotensin 2 (A2) formation. In this study, we aimed to identify the ACE genome insertion/deletion polymorphism in pituitary adenomas and to compare it with the control group. Patients operated for pituitary adenomas were included in the study. Genomic DNA was extracted from tumoral tissues and peripheral blood samples of the patients by using the Miller method. Primary sequence was selected via targeting the polymorphic region of intron 16 of ACE genome 17q23. DNA samples were multiplied by PCR using HACE3s and HACE3as primers. Twenty-one operated cases were studied. In the study group; 44 % of the patients were identified as D/D, 33% of them as I/D and 23% of them as I/I. In 60%, D allele was identified. According to immunohistochemical investigation, we found that 100% of the patients with Cushing adenoma were D/D alleles. Presence of high rate of ACE genome deletion in patients with pituitary adenoma and grade 3-4 patients suggest that ACE genome polymorphism can be a risk factor for the development of pituitary adenomas.

Adrenal Surgery in Spain: Final Results of a National Survey

IntroductionThe indications for adrenalectomy could be changing by the availability of laparoscopy and the growing detection of incidentalomas. The Endocrine Surgery Section of the Spanish Association of Surgeons conducted a survey to analyse the current indications for adrenalectomy and their results in Spanish surgical departments. Material and methodsData were gathered as regards the type of hospital and department, volume of procedures, localisation studies and pre-surgical preparations, indications, surgical approach, and results in terms of morbidity and hospital stay. The results of the centres were compared as regards their volume of activity using the Mann–Whitney Test for the quantitative variables and chi squared for the qualitative ones. ResultsThirty-six centres completed the questionnaire and 301 adrenalectomies were reported to be performed in 2008. Most frequent indications were pheochromocytoma (25.2%), non-functioning adenoma (16.2%), aldosteronoma (15.9%), Cushing adenoma (11.2%), metastasis (10.3%), myelolipoma (5.6%), and carcinoma (4.9%).Laparoscopic adrenalectomy was performed in 83.7% of cases (6.7% required conversion to laparotomy). The mean hospital stay was 3.9 days for laparoscopic adrenalectomy and 7.4 days for laparotomy. High-volume units (more than 10 per year) used more frequently the laparoscopic approach (P=.019), and had a shorter overall hospital stay (P<.0001. Laparoscopic adrenalectomy was also associated with a shorter hospital stay (P<.0001). ConclusionsLaparoscopy for adrenalectomy has become the standard practice in Spain, with good results in terms of morbidity and hospital stay. High volume centres have better results as regards the use of minimally invasive surgery and hospital stay.

Cirugía suprarrenal en España: resultados finales de una encuesta nacional

Introduction The indications for adrenalectomy could be changing by the availability of laparoscopy and the growing detection of incidentalomas. The Endocrine Surgery Section of the Spanish Association of Surgeons conducted a survey to analyse the current indications for adrenalectomy and their results in Spanish surgical departments. Material and methods Data was gathered as regards the type of hospital and department, volume of procedures, localisation studies and pre-surgical preparations, indications, surgical approach, and results in terms of morbidity and hospital stay. The results of the centres were compared as regards their volume of activity using the Mann-Whitney Test for the quantitative variables and chi squared for the qualitative ones. Results Thirty-six centres completed the questionnaire and 301 adrenalectomies were reported to be performed in 2008. Most frequent indications were pheochromocytoma (25.2%), non-functioning adenoma (16.2%), aldosteronoma (15.9%), Cushing adenoma (11.2%), metastasis (10.3%), myelolipoma (5.6%), and carcinoma (4.9%). Laparoscopic adrenalectomy was performed in 83.7% of cases (6.7% required conversion to laparotomy). The mean hospital stay was 3.9 days for laparoscopic adrenalectomy and 7.4 days for laparotomy. High-volumen units (more than 10 per year) used more frequently the laparoscopic approach ( P = .019), and had a shorter overall hospital stay ( P < .0001). Laparoscopic adrenalectomy was also associated with a shorter hospital stay ( P < .0001). Conclusions Laparoscopy for adrenalectomy has become the standard practice in Spain, with good results in terms of morbidity and hospital stay. High volume centres have better results as regards the use of minimally invasive surgery and hospital stay.

A case of subclinical Cushing syndrome due to primary pigmented nodular adrenocortical disease associated with adrenocortical adenoma

To the Editor, Primary pigmented nodular adrenocortical disease (PPNAD) is a rare disorder associated with ACTH-independent Cushing syndrome (CS). Most patients with PPNAD present with clinically overt CS until young adulthood, and the condition is sometimes associated with Carney complex (CNC) [1, 2]. We report a case of a 58-year-old man who was initially diagnosed with subclinical CS because of a solitary adrenal tumor. Histological findings revealed the coexistence of a cortisol-producing adenoma and PPNAD nodules. He had no apparent Cushingoid features (height, 163 cm; weight, 73 kg). He had no family history and clinical manifestation of CNC. He received medication for hypertension, hyperlipidemia, hyperuricemia, diabetes, and liver dysfunction; his blood pressure, HbA1c level, LDL cholesterol level, and triglyceride level were 169/94 mmHg, 6.7%, 120 mg/dl, and 606 mg/dl, respectively. Computed tomography (CT) revealed a right adrenal mass (16 9 15 mm). Endocrinological tests showed subclinical hypercortisolism [3]; the morning plasma ACTH and cortisol levels were 11.0 pg/ml and 15.1 lg/dl, respectively. At 2300 h, the cortisol level was slightly high (5.5 lg/dl). Dexamethasone suppression tests (DSTs) (1 and 8 mg) showed that the morning cortisol levels were not fully suppressed (3.9 and 6.8 lg/dl, respectively). The right adrenal gland was extirpated laparoscopically; the resected adrenal showed multiple cortical nodules. The largest nodule was an adrenocortical adenoma, and the others histopathologically corresponded to PPNAD. This adenoma consisted of numerous clear and compact cells, whereas PPNAD-like nodules mainly consisted of eosinophilic compact cells. Steroidogenic enzymes such as 3b-hydroxysteroid dehydrogenase, 17a-hydroxylase, 21-hydroxylase, and cholesterol side-chain cleavage enzyme were abundantly expressed in both cortical adenoma and the PPNAD nodules [4]. Dehydroepiandrosterone-sulfotransferase (DHEA-ST) immunoreactivity was markedly detected in all PPNAD-like nodular cells, whereas it was detected only in small foci in the tumor cells of the adenoma. DHEAST expression is usually not observed in Cushing adenoma [5]. Therefore, this heterogeneous expression pattern suggests that this adenoma has some association with PPNAD. The DHEA-ST immunoreactivity in the non-neoplastic adrenals was much weaker than that in the PPNAD-like nodules, indicating continuous suppression of the hypothalamo–pituitary–adrenal axis in the present case, because DHEA-ST expression is strongly dependent on ACTH [5]. Notably, in the zona reticularis of the non-neoplastic region, a few small clusters of cortical cells consisting of M. Yoshida (&) K. Ogawa M. Miyata M. Murakami Department of Endocrinology and Diabetes, Nagoya Ekisaikai Hospital, 4-66, Shounen-cho, Nakagawa-ku, Nagoya 454-8502, Japan e-mail: myavp@zm.commufa.jp

Metabolic, Cardiovascular, and Cerebrovascular Outcomes in Growth Hormone-Deficient Subjects with Previous Cushing's Disease or Non-Functioning Pituitary Adenoma

Metabolic, Cardiovascular, and Cerebrovascular Outcomes in Growth Hormone-Deficient Subjects with Previous Cushing's Disease or Non-Functioning Pituitary Adenoma

Adrenal lesions in patients of multiple endocrine neoplasia type 1

To investigate the prevalence and characteristics of adrenal lesions in Chinese multiple endocrine neoplasia type 1 (MEN-1) patients. Adrenal CT scan and clinical manifestations were retrospectively reviewed in 32 consecutive MEN-1 patients who were evaluated at our hospital during January 1986 to December 2009. Adrenal lesions were identified in 16 of 32 (50%) MEN-1 patients. Five (31.3%) patents with adrenal involvement showed bilateral lesions, including bilateral adenoma (n=1), bilateral hyperplasia (n=2) and adenoma and hyperplasia on each side (n=2). Unilateral adrenal lesion was presented in 11 (68.7%) patients. Among which, 63.6% had adenomas with a mean diameter of 2.3 cm (0.8-4.0 cm) and the remainder was of hyperplasia or enlargement. In two patients, functioning adrenal abnormalities were detected including Cushing adenoma (n=1) and aldosterone-secreting adenoma (n=1). The prevalence of adrenal lesion in MEN-1 patient is similar between China and western countries. These tumors are mostly benign, small and nonfunctioning. Taking into account a high incidence of adrenal carcinoma in previous foreign studies, routine screening and close surveillance are still recommended for adrenal lesions in MEN-1 patients.

TMEFF2: a new endogenous modulator of the CRH signaling in corticotroph cells

We have previously demonstrated that retinoic acid (RA) inhibits CRH signaling in corticotroph cells. In order to elucidate the mechanisms controlling RA action, cDNA microarray analysis was perfomed. From 87 genes regulated by RA in the corticotroph cell line AtT-20, we selected TMEFF2 for further studies. TMEFF2 is a transmembrane protein containing an altered epidermal growth factor (EGF)-like motif, two follistatin-like domains and a cytosolic tail which a putative G protein-activating motif. TMEFF2 is predominantly expressed in brain and prostate and has been implicated in cell signaling, neuronal cell survival and tumor suppression. Although TMEFF2 function is unknown, its structural domains suggest that it may have a role in the regulation of growth factor signalling. Since there is no previous evidence for an involvement of TMEFF2 in Cushing's disease or CRH signalling, we have studied the effects of TMEFF2 on the signal transduction pathway of CRH. Our results show that CRH-signaling is under the inhibitory effects of endogenous TMEFF2. TMEFF2 expression in corticotroph cells inhibits the effects of CRH on the production of intracellular cAMP, CREB and POMC transcriptional activity. Regulation of CRH activity by TMEFF2 does not require the cytoplasmic tail, while deletion of the follistatin and EGF modules abolishes the inhibitory function of TMEFF2. Moreover, a soluble secreted protein containing these three extracellular domains is sufficient for CRH signaling inhibition. TMEFF2-induced inhibition depends on serum components. Furthermore, TMEFF2 seems to regulate non-cannonical Activin/BMP-4 signaling, leading to the inhibition of the PI3K pathway (Akt) and Erk1/2 activation. Whether TMEFF2 acts upstream to Akt to regulate cAMP production and PKA activity remains to be elucidated. We found that TMEFF2 expression in human Cushing's adenoma is reduced as compared to the normal human pituitary, which may indicate that TMEFF2 acts as a tumor suppressor in these adenomas. Consistent with this hypothesis, the overexpression of TMEFF2 decreased cell proliferation in corticotroph cells. Our results also indicate a potential therapeutic use of TMEFF2 or factors that stimulate TMEFF2 activity for the treatment of corticotroph tumors in order to reduce their ACTH secretion and proliferation.

Radiation therapy and stereotactic radiosurgery for the treatment of Cushing's disease: an evidence-based review

The indications, efficacy, and safety of radiation therapy and stereotactic radiosurgery for Cushing's disease are evaluated.We queried PubMed using the terms, 'Cushing's disease', 'radiotherapy', and 'radiosurgery', then evaluated each study for the number of patients, method of radiation delivery, type of radiation therapy or radiosurgical device used, treatment parameters (e.g. maximal dose, tumor margin dose), length of follow-up, tumor-control rate, complications, rate of hormone normalization, newly onset loss of pituitary function, and method used to assess endocrine remission. A total of 39 peer-reviewed studies with 731 patients were included. The reported rates of tumor-volume control following radiotherapy and radiosurgery vary considerably from 66-100%. Additionally, the reported rates of endocrine remission vary substantially from 17-100%. The incidence of serious complications following radiosurgery is quite low. Although post-treatment hypopituitarism and disease recurrence were uncommon, they did occur, and this underscores the necessity for long-term follow-up in these patients. Radiosurgery and, in the modern era, less commonly, radiation therapy, offer both well tolerated and reasonably effective treatment for recurrent or residual Cushing's adenomas.

Results of adrenal surgery. Data of a Spanish National Survey

Given the availability of laparoscopy and the rising detection of incidentalomas, indications for adrenalectomy may be changing. The Endocrine Surgery Section of the Spanish Association of Surgeons designed a survey to assess its indications, techniques, and results in Spanish Surgical Departments. Collected data included hospital and department type, yearly hospital volume of procedures; location studies and preoperative preparation performed, indications, surgical approach and instruments used, and results in terms of morbidity and overall hospital stay. The analysis included a comparison between results of high- or low-volume centers and surgeons, using the Student's t test for quantitative and chi-square test for qualitative variables. Level of significance was set at 0.05. Nineteen centers returned the questionnaire, including 155 adrenalectomies performed in 2008. Most frequent indications were pheochromocytoma (23.2%), aldosteronoma (16.7%), incidentaloma (12.2%), metastasis (10.3%), Cushing adenoma (9.6%), and carcinoma (3.8%). Laparoscopy was performed in 83.9% of cases (9.4% required conversion to laparotomy). Four patients required urgent reoperation. Average hospital stay: 4.6 days (3.3 days after laparoscopy, 7 days after laparotomy). High-volume centers had a greater proportion of laparoscopically treated cases (p = 0.008), more malignant lesions treated (p = 0.03), a shorter overall stay (p < 0.0001), and a shorter stay after laparotomic adrenalectomy (p = 0.01). High-volume surgeons had similar results, and less in-hospital morbidity (p = 0.02). In Spain, adrenalectomy is performed in hospitals of varying complexity. Laparoscopic approach is the rule, with good results in terms of morbidity and stay. High-volume centers and surgeons had best results in terms of use of minimally invasive surgery and hospital stay.

Usefulness of composite methionine–positron emission tomography/3.0-tesla magnetic resonance imaging to detect the localization and extent of early-stage Cushing adenoma

Fifty to eighty percent of Cushing disease is diagnosed by typical endocrine responses. Recently, the number of diagnoses of Cushing disease without typical Cushing syndrome has been increasing; therefore, improving ways to determine the localization of the adenoma and making an early diagnosis is important. This study was undertaken to determine the present diagnostic accuracy for Cushing microadenoma and to compare the differences in diagnostic accuracy between MR imaging and PET/MR imaging. During the past 3 years the authors analyzed the diagnostic accuracy in a series of 35 patients with Cushing adenoma that was verified by surgical pituitary exploration. All 35 cases of Cushing disease, including 20 cases of "overt" and 15 cases of "preclinical" Cushing disease, were studied. Superconductive MR images (1.5 or 3.0 T) and composite images from FDG-PET or methionine (MET)-PET and 3.0-T MR imaging were compared with the localization of adenomas verified by surgery. The diagnostic accuracy of superconductive MR imaging for detecting the localization of Cushing microadenoma was only 40%. The causes of unsatisfactory results for superconductive MR imaging were false-negative results (10 cases), false-positive results (6 cases), and instances of double pituitary adenomas (3 cases). In contrast, the accuracy of microadenoma localization using MET-PET/3.0-T MR imaging was 100% and that of FDG-PET/3.0-T MR imaging was 73%. Moreover, the adenoma location was better delineated on MET-PET/MR images than on FDG-PET/MR images. There was no significant difference in maximum standard uptake value of adenomas evaluated by MET-PET between preclinical Cushing disease and overt Cushing disease. Composite MET-PET/3.0-T MR imaging is useful for the improvement of the delineation of Cushing microadenoma and offers high-quality detectability for early-stage Cushing adenoma.

Single‐Access Retroperitoneoscopic Adrenalectomy (SARA) Versus Conventional Retroperitoneoscopic Adrenalectomy (CORA): A Case–Control Study

Stimulated by the concept of Natural Orifice Transluminal Endoscopic Surgery (NOTES), minimizing the access even further has become a new trend in minimally invasive surgery. We compare our recently described new method of endoscopic single-access adrenalectomy with the conventional retroperitoneoscopic approach in a matched-pairs study. Fifty single-access retroperitoneoscopic adrenalectomies (SARA) were performed in 47 selected patients suffering from Conn's adenomas (n = 20), pheochromocytomas (n = 15), Cushing's adenomas (n = 6), and other diseases (n = 6). For SARA, a single 2-cm skin incision beneath the 12th rib was used. Following creation of the retroperitoneal space with the rigid endoscope, dissection was carried out single-handed. Another 47 patients served as control group; they were treated by the traditional retroperitoneoscopic three-port approach (CORA). Patients were matched with respect to gender, body mass index, diagnoses, tumor size, and tumor site. Mortality was zero and no major complications occurred in both groups. SARA was completed in 41 cases (86%). The overall complication rate was 8.5% in SARA and 6.4% in CORA. Operative time was longer for SARA (56 +/- 28 min) than for CORA (40 +/- 12 min) (P < 0.05). Postoperatively, pain medication was administered in 47% of SARA patients and in 75% of CORA patients (P = 0.01). Mean hospital stay was 2.4 +/- 0.7 days (SARA) and 3.1 +/- 1.2 days (CORA) (P < 0.01). Because feasibility and safety of SARA could be demonstrated in a large group of selected patients, this surgical technique may represent a new milestone in minimally invasive endocrine surgery.

Desarrollo y evolución de la suprarrenalectomía laparoscópica en una unidad especializada: de los casos iniciales al hospital de día

BackgroundAfter the first reports in 1992, laparoscopic adrenalectomy (LA) has evolved technically until becoming the standard approach for the treatment of most of the adrenal gland diseases. Material y methodsRetrospective and descriptive study of 67 patients who underwent 68 LA between January-1998 and December-2008 in the Laparoscopic Surgery Unit of the General and Digestive Surgery Service in a third level hospital (only one case of bilateral LA). The group was divided in 2 periods, P-1 (1998-2003, 22 cases) and P-2 (2004-2008, 45 cases), which have been compared to evaluate the evolution of the LA technique. ResultsIndications for LA were: 19 incidentalomas, 19 primary hyperaldosteronism, 18 pheocromocitoms, 5 cases of symptomatic and non-functioning adrenal masses, 4 Cushing adenomas and 2 metastases. There was no mortality, only 4 patients had minor complications (6%) and conversion rate was only 3% (2 cases). Mean size of adrenal glands resected was 3,83 cm and the mean operative time was 86 minutes. Mean postoperative hospital stay was 3 days and in P-2 seventeen patients were discharged on an outpatient basis (hospital stay less than 23 hours). Conclusionsin our experience, LA for the treatment of adrenal diseases has shown to be safe, effective and reproducible with low complications and excellent tolerance by patients. When the learning curve is overcome, hospital stay and operative time clearly decrease. As a consequence, LA can be planned in selected cases as outpatient surgery with good results.

P18 Baseline characteristics and quality of life in patients with childhood-onset growth hormone deficiency due to Cushing's disease and non-functioning pituitary adenoma

P18 Baseline characteristics and quality of life in patients with childhood-onset growth hormone deficiency due to Cushing's disease and non-functioning pituitary adenoma

Immunohistochemical detection of somatostatin receptor subtype 5 (SSTR-5) in cushing adenoma

The actions of somatostatin hormone are mediated by specific transmembrane receptors (somatostatin receptors). These receptors are G-protein linked receptors encoded on five different chromosomes: SSTR1–SSTR5. At the protein level, SSTR-5 was found to have the highest level of expression in corticotroph adenomas [1, 2]. These data suggest that SSTR-5 may be a potential in situ target for medical therapies of adrenocorticotrophic hormone (ACTH) producing corticotroph adenomas [3]. As Cushing adenomas tend to be small and often are not identified by MR imaging [4–6], we hypothesized, based on the previous data, that SSTR-5 may be a potential target for localization of unidentified Cushing adenomas on MRI. Here, we present the results of a pilot study on immunohistochemical staining of 3 Cushing adenomas using the monoclonal SSTR-5 antibodies. Three paraffin blocks containing ACTH producing adenomatous and normal periadenomatous tissue of human pituitary were utilized. For immunohistochemistry, all mouse monoclonal anti-SSTR-5 antibodies were commercially obtained from Advanced Targeting Systems (San Diego, CA, USA). Paraffin sections were dewaxed in xylene and rehydrated through a graded series of ethanol, the antigen was retrieved in 0.01 M citrate buffer (with EDTA added) for 25 min, and the sections were incubated in 3% hydrogen peroxide for 5 min. Sections were then rinsed in TRIS buffer saline pH 7.8 twice for 3 min and blocked in mouse serum for 10 min. Sections were subsequently incubated for 30 min in mouse monoclonal SSTR-5 antibodies at 2ug/ml, rinsed in TRIS buffer saline twice for 3 min, incubated in anti-mouse IgG, biotinylated for 30 min, and rinsed again in TRIS buffer saline twice for 3 min. Sections were then incubated in strepavidin-HRP for 30 min, rinsed in TRIS buffer twice for 3 min and visualized with DAB (diaminobenzidine) for 5 min, counterstained with hematoxylin for 5 min, and cover slips were applied. The results were consistent in the 3 samples. Immunoreactivity was detected primarily in the cytoplasm and the cell membrane of the normal periadenomatous tissue. Immunopositivity was strongly correlated with ACTH-producing cells in the normal pituitary tissue as seen in slides immunostained for ACTH that had been obtained at diagnosis. Cushing adenoma was negative in all 3 samples (Fig. 1). In the literature, detection of somatostatin receptor subtypes was limited to qualitative or real-time PCR analysis of their mRNA [1, 2, 7–10]. Immunohistochemical detection and localization of somatostatin receptor subtypes has been reported in prostate tissue from patients with bladder outlet obstruction. To the best of our knowledge, there are no reports of immunohistochemical detection of SSTR-5 in ACTH-producing corticotroph adenomas. In conclusion, immunohistochemical staining was performed using monoclonal SSTR-5 antibodies on three specimens of ACTH-producing adenoma and their adjacent normal periadenomatous tissue. Our results demonstrated negative immunoreactivity for SSTR-5 in the adenomatous tissue. Studies on SSTR-5 epitopes are warranted before any trial of targeting the receptor for either localization or treatment of Cushing adenomas. W. Hassaneen (&) D. P. Cahill G. N. Fuller N. B. Levine The University of Texas, M. D. Anderson Cancer Center, Houston, TX, USA e-mail: whassaneen@mdanderson.org

Telomerase activity in benign and malignant adrenal tumors.

Histological analysis of surgically removed adrenal masses often fails to differentiate between benign and malignant tumors. In normal cells, the telomeric ends of the chromosomes are shortened with each cell division, leading to chromosome destabilization and cellular senescence after a critical number of cell cycles. In tumor cells, telomere shortening is prevented by a specific DNA polymerase, called telomerase. In an effort to clarify the role of telomerase in the pathogenesis of adrenal tumors, and to test whether its activity could serve as marker of malignancy, we measured telomerase activity in 41 human adrenal tissue samples that were classified both by the clinical course and by histological examination. Telomerase activity was determined by TRAP ELISA and expressed as high (>50% of positive control telomerase activity), medium (31-50%), low (11-30%), very low (< or = 10%), or absent (0%). The 8 normal adrenal tissue samples showed very low levels of telomerase activity. Mean telomerase activity also very low in 3/3 incidentalomas, 6/6 Cushing adenomas, 6/6 Conn adenomas, 7/7 adrenocortical carcinomas, 8/8 benign pheochromocytomas, and 2/3 malignant pheochromocytomas. In contrast, one malignant pheochromocytoma showed high telomerase activity. These data indicate that telomerase activity may not be a suitable marker for malignancy in the adrenal gland. Our results also challenge the current dogma of close correlation between cell dedifferentiation and telomerase activity.

Transperitoneal laparoscopic adrenalectomy for adrenal neoplasm: a report of 371 cases

Open adrenalectomy has been almost replaced by mini-invasive laparoscopic surgery. There are two popular mini-invasive laparoscopic adrenalectomy approaches: retroperitoneal and transperitoneal approaches. This study was to summarize our experience in transperitoneal laparoscopic adrenalectomy. In total 371 cases undergoing transperitoneal adrenalectomy in the First Affiliated Hospital of Zhengzhou University from February 2003 to August 2008 were reviewed retrospectively. There were 127 cases of primary hyperaldosteronism adenoma, 117 cases of Cushing's adenoma, 58 cases of phaeochromo-cytoma, 37 cases of incidentoma and 32 cases of other types. The type of adrenal diseases, operating time, blood loss, complications and prognosis were summarized and the operating method was analyzed. Three hundred and sixty-five out of 371 patients (98.4%) were successfully operated, five cases (1.4%) were transferred to open surgery, and one patient gave up surgery due to extensive invasion. The operating time was 40-240 min (average, 70 min). The blood loss was 20-1000 ml (average, 80 ml). Two patients suffered from diaphragm injuries, one patient had right renal vein injury and one had colon injury. The mean time of hospital stay was five days. Transperitoneal laparoscopic adrenalectomy is one of the favorable approaches for the treatment of adrenal neoplasm.

Laparoscopic Adrenalectomy: Norwegian Single-Center Experience of 242 Procedures

The last 15 years have been characterized by a rapid expansion of minimally invasive surgery as treatment for adrenal diseases. During these years, both indications and surgical techniques have shown improvements. This study analyzed an 11-year single-center experience with laparoscopic adrenalectomy. Between January 1997 and April 2008, 242 laparoscopic adrenalectomies were performed in 220 patients at Rikshospitalet University Hospital. Of these, 192 patients were operated on for benign lesions, 23 for malignant lesions, and in 5 cases "en bloc" adrenalectomies were performed. Benign lesions included 136 hormonally active lesions (41 pheochromocytomas, 48 Conn adenomas, 25 Cushing adenomas, and 18 patients with Cushing's disease) and 56 with hormonally inactive lesions (among them, 47 nonfunctional adenomas). Malignant lesions included 16 adrenal metastases and 7 adrenocortical carcinomas. All adrenalectomies were completed laparoscopically. The median time of unilatateral adrenalectomy was 85 (range, 35-325) minutes. The median blood loss was 0 (range, 0-1100) mL. There were 6 intraoperative and 7 postoperative minor complications. The number of complications did not differ between the types of adrenal pathology. Only 19% of the patients required opioids postoperatively. Per- and postoperative parameters were homogeneous among patients with different adrenal lesions. The patients with adrenocortical carcinoma had a distinctive intraoperative course with an evidently longer operative time and higher blood loss. The median postoperative hospital stay was 2 (range, 1-15) days. Hospital stay was the only postoperative parameter where a difference was found between patients with different adrenal lesions. The patients with carcinoma, pheochromocytoma, and Cushing's disease had the longest median postoperative stay, respectively, 5 (range, 2-6), 3 (range, 1-15), and 3 (range, 2-6) days. Laparoscopic adrenalectomy is a safe, effective procedure providing improved fast and uncomplicated patient recovery independent of the type of adrenal lesion. Laparoscopic adrenalectomy can be easily introduced and may soon replace traditional open surgery in specialized centers.

Prospective evaluation of 100 robotic-assisted unilateral adrenalectomies

Our aim was to determine the learning curve for robotic adrenalectomy and factors that influence operative time and cost. We prospectively evaluated of 100 consecutive patients who underwent robotic, unilateral, transperitoneal adrenalectomy. The mean operative time for robotic-assisted adrenalectomy was 95 minutes and conversion rate was 5%. Pathology was aldosteronoma (n = 39), pheochromocytoma (n = 24), nonfunctional adenoma (n = 19), Cushing adenoma or hyperplasia (n = 16), and cyst (n = 2). Morbidity and mortality rates were 10% and 0%, respectively. The mean operative time decreased by 1 minute every 10 cases. Operative time improved more for junior surgeons than for senior surgeons (P = .006) after the first 50 cases. By multiple regression analysis, surgeon's experience (-18.9 +/- 5.5), first assistant level (-7.8 +/- 3.2), and tumor size (3 +/- 1.4) were independent predictors of operative time (P < .001 each). The robotic procedure was 2.3 times more costly than lateral transperitoneal laparoscopic adrenalectomy (euro4102 vs euro1799). Surgeon experience, resident training level, and tumor size are important variables for robotic-assisted, unilateral adrenalectomy and should be taken into account when this approach is evaluated. Controlled studies need to be performed to show potential relevant clinical benefits that could balance costs.

Unexpected histological findings of lesions diagnosed in the adrenal region in a series of 420 patients submitted to adrenal surgery. Review of our experience

The incidence of adrenal incidentalomas is reported to be up to 30% in the current literature; nevertheless, in some patients undergoing surgery, a final diagnosis of non-adrenal origin of the mass is performed. In this paper we present our experience of 13 patients with unexpected histological findings of lesions diagnosed in the adrenal region. From June 1986 to December 2004, 420 patients underwent adrenalectomy in our Department. Since the introduction of videolaparoscopic technique in 1993, 228 adrenalectomies have been performed videolaparoscopically. Pre-operative diagnosis was: incidentaloma (34.0% of patients), Conn's adenoma (29.0%), Cushing's adenoma (13.9%), pheochromocytoma (8.8%), suspicious metastasis (7.3%), Cushing's disease (6.0%), other (1.0%). Final histology revealed an unexpected diagnosis of non-adrenal origin of the mass in 13 patients (3.1%). Histology demonstrated a benign neurogenic tumor in 10 patients. In the other 3 patients diagnosis was respectively of lymphnode, hemangioma and a gastric metastasis of melanoma. Five patients out of 7 had a successful laparoscopic resection of the lesion. Mean operative time in this group was higher compared to laparoscopic resection for adrenal lesion (95.3 min vs 73.2 min). A small percentage of our patients (3.1%) demonstrated unexpected findings of the lesion pre-operatively misinterpreted as an adrenal mass. Despite a complete pre-operative assessment, adrenal lesions might reveal a different origin, increasing the surgical challenge as well as the morbidity for the patient.

P-28 Metabolic status at baseline and after 3 years of GH treatment in patients with Cushing's disease and non-functioning adenomas: a hypopituitary control and complications study analysis

P-28 Metabolic status at baseline and after 3 years of GH treatment in patients with Cushing's disease and non-functioning adenomas: a hypopituitary control and complications study analysis