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PubMed2006

Clusterin is a secreted marker for a hypoxia-inducible factor-independent function of the von Hippel-Lindau tumor suppressor protein.

Germline mutations in the von Hippel-Lindau (VHL) tumor suppressor gene predispose people to renal cancer, hemangioblastomas, and pheochromocytomas in an allele-specific manner. The best documented function of the VHL gene product (pVHL) relates to its ability to polyubiquitinate, and hence target for destruction, the alpha subunits of the heterodimeric transcription factor hypoxia-inducible factor (HIF). pVHL mutants linked to familial pheochromocyctoma (type 2C VHL disease), in contrast to classical VHL disease, appear to be normal with respect to HIF regulation. Using a simple method for identifying proteins that are differentially secreted by isogenic cell line pairs, we confirmed that the HIF targets IGBP3 and PAI-1 are overproduced by pVHL-defective renal carcinoma cells. In addition, cells lacking wild-type pVHL, including cells producing type 2C pVHL mutants, were defective with respect to expression and secretion of clusterin, which does not behave like a HIF target. Decreased clusterin secretion by pVHL-defective tumors was confirmed in vivo by immunohistochemistry. Therefore, clusterin is a secreted marker for a HIF-independent pVHL function that might be especially important in pheochromocytoma development.

Adrenal Gland Neoplasms↗
PubMed2006

Stage 4S neuroblastoma, a disseminated tumor with excellent outcome.

OBJECTIVE: To review the clinical features and outcome of all cases of stage 4S neuroblastoma treated at our center. METHODS: We retrospectively reviewed the files of all patients (n=75) with neuroblastoma treated at King Abdul-Aziz Medical City, Jeddah, Kingdom of Saudi Arabia between 1986 and 2005. We studied the clinical features and outcome of patients with stage 4S neuroblastoma. RESULTS: Six patients (8%) were confirmed to have stage 4S neuroblastoma. Three were boys with a median age at diagnosis of 4.5 months (range 28 days-11 months). Four patients required no intervention. The remaining 2 patients were treated with chemotherapy due to progressive hepatomegaly and respiratory distress. No patient required radiotherapy or surgical intervention. With a median follow up of 4 years (range 9 months-15.5 years), all patients are alive and well. Two patients continue to have a residual abdominal mass, while complete resolution occurred in the others. CONCLUSION: Stage 4S neuroblastoma is a special tumor that carries excellent prognosis. Spontaneous regression may occur and intervention is only required in symptomatic patients.

Adrenal Gland Neoplasms↗
PubMed1985

Immunofluorescence microscopic evaluation of the intermediate filament expression of the adrenal cortex and medulla and their tumors.

Normal adrenal glands (10 specimens) and adrenal gland tumors (58 cases) were immunohistochemically evaluated for different types of intermediate filament (IF) proteins. Some of the normal cortical cells showed cytokeratin positivity, and no positivity was seen for epidermal keratin or other types of IF. In the adrenal medulla, neurofilament positivity was seen in nerve axons, some ganglion cells, and chromaffin cells; and cytokeratin-positive cells could not be detected. Only the vascular and connective tissue elements showed vimentin positivity in both cortical and medullary areas. In half of the cortical carcinomas (13/25), cytokeratin-positive tumor cells were found. Furthermore, vimentin-positive tumor cells were present in 10 of 25 cases, in some of them together with cytokeratin-positive cells. Thus, the results show heterogeneity among the adrenal cortical carcinomas. Interestingly, many benign adrenal cortical tissues and some carcinomas lacked immunoreactivity for all types of IF, suggesting a poorly developed IF system in these tissues. In contrast to adrenal cortical tumors, pheochromocytomas contained neurofilamentlike immunoreactivity. These results reflect the different cellular nature of adrenal cortical and medullary tumors, which apparently can be distinguished from each other with antibodies to intermediate filament proteins.

Adenoma↗
PubMed2000

Vascular endothelial growth factor and basic fibroblast growth factor evaluation in blood serum of patients with hormonally active and inactive adrenal gland tumours.

The vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) levels of 36 patients with adrenal gland tumours were analysed. The mean age of patients was 43 years (29-67 years), and there were 25 women (69.4%) and 11 men (31.6%). In 34 patients adrenalectomy was performed and in two cases lesions were considered inoperable. In all cases VEGF and bFGF were measured preoperatively and in all operated patients the level of VEGF was measured at 1 month postoperatively. A statistically significant increase in VEGF levels before surgery in comparison with the controls was recorded in all patients with adrenal tumours. No correlation between the size of a tumour and VEGF levels was observed. The serum level of VEGF decreased in patients after surgical removal of the tumour, no matter which type of tumour, with the exception of a patient showing a recurrence of cortex cancer. A statistically significant decrease was found only in patients operated on for cortex cancers and hormonally active and inactive cortex and medulla inactive benign tumours. The postoperative recurrence of the malignant tumour may be preceded by an increase in plasma VEGF levels. Such correlations were not found with bFGF.

Adrenal Cortex Neoplasms↗
PubMed1995

Echoplanar MR imaging for characterization of adrenal masses in patients with malignant neoplasms: preliminary evaluation of calculated T2 relaxation values.

OBJECTIVE: We undertook this study to assess the utility of echoplanar MR imaging for distinguishing benign from malignant adrenal masses in patients with known malignant neoplasms. MATERIALS AND METHODS: Thirty consecutive patients with 31 adrenal masses and a known malignant neoplasm underwent breath-hold echoplanar MR imaging with a repetition time of 6000 msec and four echo times (40, 80, 120, 160 msec) on a 1.5-T unit before biopsy. Subsequently, 10 masses were shown to be malignant at histologic examination, 12 masses were benign at histologic examination, and nine were thought to be benign because they had not changed in size at follow-up imaging. Mean lesion size was 2.4 +/- 2.1 cm. T2 calculations using regions of interest in the liver and adrenal mass were performed in each patient. RESULTS: The mean calculated T2 value of benign adrenal masses was 70.3 msec (SD, 11.6 msec) versus 104.6 msec (SD, 35.2 msec) for malignant adrenal masses (p = .013). Using a cutoff T2 value of 84 msec, 19 (90%) of 21 benign masses and nine (90%) of 10 malignant masses were correctly classified. The mean adrenal/liver T2 ratio was 1.4 (SD, 0.25) for benign lesions, and 2.1 (SD, 0.78) for malignant lesions (p = .017). Using a cutoff ratio of 1.60, 19 (90%) of 21 benign lesions and eight (80%) of 10 malignant lesions would have been correctly classified. CONCLUSION: This preliminary work suggests that obtaining T2 calculations from echoplanar MR images of adrenal masses is a useful technique for distinguishing benign from malignant adrenal masses in patients at risk for adrenal metastasis.

Adenoma↗
PubMedDate not supplied

[Adrenal incidentaloma: a dopamine-secreting pheochromocytoma with an atypical clinical picture. A case report and review of the literature].

INTRODUCTION: The increasing and consolidated uses of US and CT scan in the diagnosis of abdominal diseases has improved the detection of adrenal asymptomatic masses. Current literature points out that these nodules are identified by 1:100 abdominal CT every year. On the other hand, about 50% of the adrenal tumors are discovered by autopsy. The diagnostic difficulties may be due both to clinical silence and to atypical clinical expressions of the neoplasm--as in the case report--where a pheochromocytoma shows non-specific abdominal symptoms rather than the typical signs of catecholamine overproduction. CASE REPORT: Author,s report a suprarenal right pheochromocytoma, secreting dopamine prevalently. The tumor showed abdominal symptoms without history of hypertensive paroxysms, or better still in normotension regimen. DISCUSSION AND CONCLUSIONS: According to current literature, abdominal symptoms occur in about 7% of all suprarenal pheochromocytomas. Most of these tumors prevalently secrete dopamine, that seems to make the prognosis worse. US, CT scan and CT-guided fine needle biopsy weren't able to characterize the real nature of the adrenal incidentaloma. On the contrary, the hormonal screening--by monitoring the urinary VMA and fractioned catecholamines through 24 hours--was decisive for the diagnosis of pheochromocytoma. The adrenal incidentalomas diagnostic significance is tied to the concept that adrenalectomy can change their prognosis, especially in case of pheochromocytoma, where a recovery rate about 90% can be achieved. Authors agree that adrenalectomy my must be performed in all case of "functioning" adrenal tumors and "nonfunctioning" ones with > 6 cm size. Of last years the laparoscopic approach has extended the adrenalectomy's indications to mass with size ranging between 3 and 6 cm., while lesions < 3 cm. size require only a follow up by means of imaging techniques and hormonal monitoring.

Adrenal Gland Neoplasms↗
PubMed1984

Hyperadrenalism in childhood and adolescence.

Hyperadrenalism in childhood and adolescence has unique features that influence diagnosis and management. We reviewed our experience with 18 patients, ranging in age from 18 months to 18 years. Nine had bilateral adrenal hyperplasia, eight had adrenal neoplasms, and one had micronodular hyperplasia. Patients with congenital adrenal hyperplasia and hyperaldosteronism were excluded. Six patients with Cushing's disease diagnosed in earlier years were treated by total adrenalectomy and recently two patients underwent transsphenoidal removal of pituitary tumors. Bilateral adrenalectomy was carried out in one patient with micronodular hyperplasia and in a second because of elevated adrenocorticotrophic hormone (ACTH) levels from an undefined source. Eight patients had adrenal neoplasms, including five adenomas and three carcinomas. We found no reliable criteria to differentiate before surgery between adrenal adenomas and adrenal carcinomas. The most recognizable characteristic of malignancy was tumor size, specifically weight greater than 75 gms. Of the three patients with adrenal carcinoma, one expired 20 months after adrenalectomy and 8 months after receiving palliative partial hepatectomy for liver metastasis. Two patients are well with normal growth and development at 11 and 20 years following adrenalectomy. With the exception of one patient who died 6 years after surgery from a glioblastoma multiforme, all patients with adrenal adenomas are well. Eight patients underwent bilateral adrenalectomy for hypercortisolism. Five of the six who have reached their adult stature are significantly stunted. Four of six patients with Cushing's disease, treated by total adrenalectomy, have developed Nelson's syndrome at 2, 6, 10, and 12 years after surgery. Of the two patients undergoing transsphenoidal surgery, one had recurrent disease at 2 years and was treated by pituitary irradiation with recovery. The patients undergoing adrenalectomy for micronodular hyperplasia and ectopic ACTH are well at 2 and 4 years, respectively. Cushing's disease in children and adolescents is best treated by transsphenoidal removal of the pituitary adenoma. Adrenalectomy, once the most accepted approach, plays a secondary role and is indicated primarily in micronodular adrenal hyperplasia, in patients with ectopic ACTH production of an undefined source, and in recurrent Cushing's disease following prior pituitary irradiation. The high incidence of Nelson's syndrome in children treated by adrenalectomy mandates that patients at risk be monitored lifelong for the progression of a pituitary tumor.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenoma↗
PubMed2002

Results of laparoscopic adrenalectomy for suspected and unsuspected malignant adrenal neoplasms.

BACKGROUND: Laparoscopic resection for malignant adrenal tumors is controversial, because they are rare and limited data exist in the literature. HYPOTHESIS: Laparoscopic adrenalectomy for malignant adrenal tumors is safe and effective. PATIENTS AND METHODS: Twenty-three patients who had a laparoscopic approach for suspected and unsuspected malignant adrenal tumors were studied retrospectively. The adrenal mass was suspected to be metastatic if the patient had a history of previous extra-adrenal primary malignancy and/or positive fine-needle aspiration cytologic findings. A primary adrenal cancer was suspected if there were positive fine-needle aspiration cytologic findings and/or a malignant adrenal imaging phenotype. MAIN OUTCOME MEASURES: (1) Margins of tumor resection, (2) tumor recurrence (locoregional, port site, and distant), and (3) disease-free survival. RESULTS: Twenty-three patients (15 men and 8 women) had 24 laparoscopic procedures (20 adrenalectomies, 3 biopsies, and 1 diagnostic laparoscopy). Permanent histologic specimens in the 23 patients showed 5 adrenocortical cancers, 1 undifferentiated adrenal cancer, 13 adrenal metastases, 2 lymphomas, and 2 cases with no evidence of tumor. Clinically suspected adrenal metastases were true positive in 19 patients (83%). The sensitivity of fine-needle aspiration cytology was 57% (n = 7). Only 1 of 6 patients with primary adrenal cancer was suspected to have a malignant tumor preoperatively. The tumor resection margin was negative in all adrenalectomies. There were 3 locoregional recurrences (2 local and 1 lymph node metastasis) in the 6 patients with primary adrenal cancer, no port site recurrences, and 4 distant recurrences in 13 patients with metastatic adrenal tumors. The disease-free survival was 65% at a mean follow-up time of 3.3 years (range, 1-7 years). CONCLUSIONS: A laparoscopic approach in patients with suspected adrenal metastasis can be both diagnostic and therapeutic, and achieves complete tumor resection. In contrast, laparoscopic adrenalectomy for clinically unsuspected adrenocortical cancer is associated with a high recurrence rate. Furthermore, preoperative fine-needle aspiration cytology for the evaluation of suspected malignant adrenal tumors is unreliable.

Adrenal Gland Neoplasms↗
PubMed1992

[Adrenal myelolipoma. A case report and review of the literature].

Myelolipoma is a rare benign neoplasm of the adrenal gland, histologically characterized by the presence of mature fat cells and bone marrow elements. In the international literature were reported 126 cases of adrenal myelolipoma surgically treated. The indications to surgical removal of this tumor are the presence of large symptomatic tumours, high risk of spontaneous haemorrhage, and suspicion of malignant neoplasms. The authors present a case of adrenal myelolipoma, preoperatively identified with an abdominal MNR, and surgically removed.

Adrenal Gland Neoplasms↗
PubMed1993

Adrenal tumor complicating untreated 21-hydroxylase deficiency in a 5 1/2-year-old boy.

OBJECTIVE: A 5 1/2-year-old boy presenting with virilization was diagnosed as having classic 21-hydroxylase deficiency complicated by an adrenal tumor. We attempted to document a reduction in the size of the tumor with glucocorticoid therapy. DESIGN: Case study. SETTING: Referral center. INTERVENTION: Glucocorticoid therapy was instituted for congenital adrenal hyperplasia. Surgery for the adrenal mass was deferred, and the size of the mass was monitored by serial ultrasonography. RESULTS: Baseline values of serum 17 alpha-hydroxyprogesterone (186.6 nmol/L) and testosterone (24.7 nmol/L [7.1 ng/mL]) were elevated. After instituting steroid treatment, 17 alpha-hydroxyprogesterone was suppressed (13.0 nmol/L), and testosterone remained undetectable on follow-up. However, the size of the mass increased during 6 months. Unilateral adrenalectomy performed at that time revealed a well-encapsulated adenoma in a hyperplastic gland. CONCLUSIONS: Untreated classic congenital adrenal hyperplasia may be complicated by an adrenal tumor even at a young age. Suppression of adrenal androgens by glucocorticoid therapy was not accompanied by regression of the tumor in our patient.

Adenoma↗