Comparative genomic hybridization reveals frequent losses of chromosomes 1p and 3q in pheochromocytomas and abdominal paragangliomas, suggesting a common genetic etiology.
(41/1819)
Pheochromocytomas and abdominal paragangliomas are rare, catecholamine-producing tumors that arise from the chromaffin cells derived from the neural crest. We used comparative genomic hybridization (CGH) to screen for copy number changes in 23 pheochromocytomas and 11 abdominal paragangliomas. The pattern of copy number changes was similar between pheochromocytomas and paragangliomas, with the most consistent finding being loss of 1cen-p31, which was detected in 28/34 tumors (82%). Losses were also found on 3q22-25 (41%), 11p (26%), 3p13-14 (24%), 4q (21%), 2q (15%), and 11q22-23 (15%), and gains were detected on 19p (26%), 19q (24%), 17q24-qter (21%), 11cen-q13 (15%), and 16p (15%). Losses of 1p and 3q were detected in the majority of tumors, whereas gains of 19p and q, 17q, and 16p were seen only in tumors with six or more CGH alterations. This progression of genetic events did not correspond with the conversion to a malignant phenotype. CGH alterations involving chromosome 11 were more frequent in the malignant tumors, compared with the benign tumors (9/12 versus 3/16). In summary, we propose that pheochromocytomas and abdominal paragangliomas, which share many clinical features, also have a common genetic origin and that the loss of 1cen-p31 represents an early and important event in tumor development. (+info)
Results of surgery for a compound adrenal tumor consisting of pheochromocytoma and ganglioneuroblastoma in an adult: 5-year follow-up.
(42/1819)
A rare, compound adrenal tumor consisting of ganglioneuroblastoma and pheochromocytoma was completely resected in an adult woman. Most of the tumor was occupied by the ganglioneuroblastoma component. This ganglioneuroblastoma was an intermixed tumor, which is known to have a favorable prognosis in children. Based on the lack of spread, the resectability of the tumor, and the histology of the ganglioneuroblastoma, no adjuvant therapy was employed. There was no evidence of recurrence at the 5-year follow-up. This suggests that adjuvant therapy may not be necessary in these compound tumors. (+info)
C-cell hyperplasia, pheochromocytoma and sympathoadrenal malformation in a mouse model of multiple endocrine neoplasia type 2B.
(43/1819)
Dominantly inherited multiple endocrine neoplasia type 2B (MEN2B) is characterized by tumors of the thyroid C-cells and adrenal chromaffin cells, together with ganglioneuromas of the gastrointestinal tract and other developmental abnormalities. Most cases are caused by substitution of threonine for Met918 in the RET receptor tyrosine kinase, which is believed to convert the RET gene to an oncogene by altering the enzyme's substrate specificity. We report the production of a mouse model of MEN2B by introduction of the corresponding mutation into the ret gene. Mutant mice displayed C-cell hyperplasia and chromaffin cell hyperplasia progressing to pheochromocytoma. Homozygotes did not develop gastrointestinal ganglioneuromas, but displayed ganglioneuromas of the adrenal medulla, enlargement of the associated sympathetic ganglia and a male reproductive defect. Surprisingly, homozygotes did not display any developmental defects attributable to a loss-of-function mutation. Thus, while our results support the conclusion that the Met918Thr substitution is responsible for MEN2B, they suggest that the substrate specificity of the RET kinase does not interfere with its normal role in the development of the kidneys and enteric nervous system. (+info)
Unusual MR findings of the brain stem in arterial hypertension.
(44/1819)
MR imaging findings have been reported in only a few cases of severe arterial hypertension. We report two cases of severe paroxysmal arterial hypertension associated with unusual brain stem hyperintensity. The lesions improved dramatically after stabilization of blood pressure, suggesting that edema could be the main cause of the MR imaging-observed hyperintensity. (+info)
Steroidogenic acute regulatory protein mRNA expression in adrenal tumours.
(45/1819)
The rate limiting step in steroidogenesis is cholesterol transport through the outer to the inner mitochondrial membrane and the cytochrome P450 side chain cleavage (P450scc) complex. The protein factor responsible for this transport, and as such necessary for regulating the acute production of steroids, has been identified and named the steroidogenic acute regulatory protein (StAR). We investigated the expression of StAR in functional and non-functional adrenal neoplasms and compared the expression with that of P450scc. Poly A RNA was extracted from normal adrenal glands (NAG, n=5), aldosterone producing adenomas (APA, n=4), cortisol producing adenomas (CPA, n=5), adrenocortical carcinomas (ACC, n=6) and non-functional adenomas (NFA, n=3), electrophoresed through a 1% agarose gel, blotted and hybridised with a PCR-generated cDNA labelled with [(32)P]CTP. The blots were stripped and re-hybridised with a P450scc cDNA and a mouse beta-actin probe. Compared with P450scc, StAR mRNA expression showed little variability in the magnitude of expression and did not correlate with the endocrine profiles (NAG: StAR 100+/-16%, P450scc 100+/-14%; APA: StAR 80+/-3%, P450scc 94+/-13%; CPA: StAR 71+/-10%, P450scc 109+/-15%; NFA: StAR 64+/-9.5%, P450scc 18+/-5%; means+/-s.e.m.). ACC expressed low levels of both genes probably as a result of dedifferentiation (StAR 29+/-9%, P450scc 46+/-18%). Incubation of the NCI-h295 tumour cell line with 10nmol ACTH and 10micromol forskolin induced an increase in the abundance of StAR and P450scc mRNA, demonstrating gene regulation by the cAMP protein kinase A pathway. Furthermore, we incubated the NCI-h295 tumour cell line with the adrenostatic compounds, aminoglutethimide and metyrapone. We could not detect an effect on the expression of StAR mRNA, whereas the expression of P450scc mRNA was significantly reduced. We conclude that, in contrast to P450scc, StAR seems to be evenly expressed in adrenocortical adenomas. Therefore, the endocrine activity of a given tumour cannot be explained by the abundance of StAR expression. In ACC, both StAR and P450scc expression is low, explaining the relatively inefficient steroid production of these tumours. (+info)
High levels of tyrosine phosphorylated proto-ret in sporadic phenochromocytomas.
(46/1819)
Pheochromocytomas are tumors originating from chromaffin cells, the large majority of which are sporadic neoplasms. The genetic and molecular events determining their tumorigenesis continue to remain unknown. On the other hand, RET germ-line mutations cause the inheritance of familial tumors in multiple endocrine neoplasia (MEN)-2 diseases, which account for a minority of pheochromocytomas. We investigated the expression of the RET gene in 14 sporadic tumors harboring no activating mutations. A subset of highly RET-expressing tumors (50%) could be distinguished. They showed RET transcript, protein amounts as well as Ret-associated phosphotyrosine levels similar to those measured in MEN-2A-associated pheochromocytomas. We also determined the GDNF and GDNF family receptor alpha (GFRalpha)-1 transcript levels in tumors and in normal tissues. Whereas the GFRalpha-1 transcripts were detected at similar levels in normal tissues and in tumors, GDNF was frequently found expressed in sporadic tumors at levels several times higher than in controls. These results led us to propose the existence of an autocrine or paracrine loop leading to chronic stimulation of the Ret signaling pathway, which could participate in the pathogenesis of a number of sporadic pheochromocytomas. (+info)
Dynamic left ventricular outflow tract obstruction in a patient with pheochromocytoma.
(47/1819)
Symmetric left ventricular hypertrophy or asymmetric septal hypertrophy associated with pheochromocytoma simulating hypertrophic obstructive cardiomyopathy have been rarely reported. In this report, we present a case with pheochromocytoma that had dynamic left ventricular outflow tract obstruction without asymmetric septal hypertrophy. A surface echo revealed resolution of the systolic anterior motion of the mitral valve and all Doppler evidence of left ventricular outflow tract obstruction following removal of the tumor. Dynamic left ventricular outflow tract obstruction seen in this patient was probably due to excessive secretion of cathecolamines by the tumor. (+info)
The surgical approach to the adrenal gland: a comparison of the retroperitoneal and the transabdominal routes in 326 operations on 284 patients.
(48/1819)
BACKGROUND: To compare the results of adrenalectomy using a retroperitoneal and a transabdominal approach, especially for adrenal carcinoma and pheochromocytoma. METHODS: A retrospective study was carried out at the Leiden University Medical Center. Charts of 284 patients who had undergone 326 adrenal operations between 1947 and 1995, including 44 patients with adrenal cancer and 60 patients with pheochromocytoma, were reviewed. The main outcome measures were operation time, blood loss, hospital stay and intra- and post-operative complications. RESULTS: In patients who underwent adrenalectomy (ADX) using a retroperitoneal (RP) approach, duration of operation, intra-operative blood loss, hospital stay and post-operative morbidity compared favourably with those undergoing a transabdominal approach (TA-ADX). However, most of these differences could be explained by the more frequently benign nature and smaller size of the lesions in patients undergoing RP-ADX. However, blood loss remained lower after correction for confounding in all patients undergoing RP-ADX. In patients with larger adrenal lesions, adrenal cancer and pheochromocytoma, that would nowadays be held unsuitable for laparoscopic adrenalectomy, RP-ADX was associated with shorter operation time, less blood loss and less intra-operative complications. CONCLUSION: Although laparoscopic adrenalectomy is the treatment of choice for small and benign adrenal lesions, larger lesions and/or adrenal malignancy require open adrenalectomy. In these cases the retroperitoneal approach is the preferred route. (+info)