A case of aldosterone-producing adenoma with severe postoperative hyperkalemia.
(9/1819)
It is known that some patients with primary aldosteronism show postoperative hyperkalemia, which is due to inability of the adrenal gland to secrete sufficient amounts of aldosterone. However, hyperkalemia is generally neither severe nor prolonged, in which replacement therapy with mineralocorticoid is seldom necessary. We report a case of a 46-year-old woman with an aldosterone-producing adenoma associated with severe postoperative hyperkalemia. After unilateral adrenalectomy, the patient showed episodes of severe hyperkalemia for four months, which required not only cation-exchange resin, but also mineralocorticoid replacement. Plasma aldosterone concentration (PAC) was low, although PAC was increased after rapid ACTH test. Histological examination indicated the presence of adrenocortical tumor and paradoxical hyperplasia of zona glomerulosa in the adjacent adrenal. Immunohistochemistry demonstrated that the enzymes involved in aldosterone synthesis, such as cholesterol side chain cleavage (P-450scc), 3beta-hydroxysteroid dehydrogenase (3beta-HSD), and 21-hydroxylase (P-450c21), or the enzyme involved in glucocorticoid synthesis, 11beta-hydroxylase (P-450c11beta), were expressed in the tumor, but they were completely absent in zona glomerulosa of the adjacent adrenal. These findings were consistent with the patterns of primary aldosteronism. Serum potassium level was gradually decreased with concomitant increase in PAC. These results suggest that severe postoperative hyperkalemia of the present case was attributable to severe suppression of aldosterone synthesis in the adjacent and contralateral adrenal, which resulted in slow recovery of aldosterone secretion. It is plausible that aldosterone synthesis of adjacent and contralateral adrenal glands is severely impaired in some cases with primary aldosteronism, as glucocorticoid synthesis in Cushing syndrome. (+info)
Influences of long-term administration of 24R, 25-dihydroxyvitamin D3, a vitamin D3 derivative, in rats.
(10/1819)
In order to examine the influences by long-term feeding of 24R, 25 dihydroxyvitamin D3[24R, 25(OH)2D3], an active form of vitamin D, Wistar rats (14-week-old, male, 20 rats/group) were fed a powder diet containing 0 or 5 ppm 24R, 25(OH)2D3 for 57 weeks. Final body weights and total food consumption were comparable between the groups. Urinary calcium levels were significantly (p < 0.05 or 0.01) increased by the administration of 24R, 25(OH)2D3 at weeks 3, 22 and 56, although the levels of serum calcium did not differ between the groups at the termination of week 57. In the 24R, 25(OH)2D3 group, weights of the adrenals and femurs were significantly (p < 0.01) increased. Histopathologically, this was found due to thickening of cortical bone in the femurs, and medullary hyperplasia and pheochromocytoma of the adrenals. Immunohistochemically, proliferating cell nuclear antigen (PCNA)-labeling indices for intact adrenal medulla, medullary hyperplasia and pheochromocytoma in the 24R, 25(OH)2D3 group were respectively 1.82 +/- 1.21, 5.88 +/- 4.13 and 16, all higher than that for the adrenal medulla in the control group (0.87 +/- 0.67). These results indicate that 24R, 25(OH)2D3 at a dose with which serum calcium is not chronically increased causes thickening of the cortex of the femur, and development of adrenal proliferative lesions, suggesting that rats may be too sensitive for results to be relevant to human risk assessment. (+info)
Malignant pheochromocytoma with multiple hepatic metastases treated by chemotherapy and transcatheter arterial embolization.
(11/1819)
A 62-year-old Japanese male developed multiple hepatic metastases two years after resection of pheochromocytoma of the right adrenal gland. Transcatheter arterial embolization (TAE) was performed for the purpose of the treatment of hepatic metastases resistant to 27 cycles of combined chemotherapy consisting of cyclophosphamide, vincristine, and dacarbazine. After TAE, the hepatic metastatic lesions decreased in size and hypertension passed its crisis. The present case suggests the utility of TAE for multiple hepatic metastases under careful blood pressure monitoring. (+info)
Clinical experience over 48 years with pheochromocytoma.
(12/1819)
OBJECTIVE: To analyze the presentation, localization, surgical management, pathology, and long-term outcome of a large series of patients with pheochromocytomas. SUMMARY BACKGROUND DATA: There are several areas of controversy pertaining to pheochromocytomas. Although many studies report a higher rate of malignancy for extraadrenal pheochromocytomas than for adrenal pheochromocytomas, the number of patients with the former tumor are small and statistical analysis is lacking. There has also been recent debate as to whether microscopic features of the tumor may be predictive of future behavior. METHODS: From 1950 to 1998, the authors observed 108 pheochromocytomas in 104 patients. The outcome of these patients has been followed prospectively. The medical records of these patients were reviewed for data on the presentation, localization, surgical management, pathology, and outcome. Patient survival was analyzed using Kaplan-Meier survival distributions. RESULTS: This study included 66 female patients and 38 male patients. The average age at surgery was 42.3 years. Sporadic cases accounted for 84% of the patients; the other 16% had multiple endocrine neoplasia type 2, von Recklinghausen's disease, von Hippel-Lindau disease, or Carney's syndrome. Of 64 adrenal tumors, 55 were initially considered benign, 6 had microscopic malignant features, and 3 had malignant disease. Mean patient follow-up was 12.6 years. To date, in five additional patients (none with microscopic disease) malignant disease developed (13% overall rate of malignancy). Recurrence occurred as late as 15 years after resection. Of 26 extraadrenal pheochromocytomas, 14 were initially considered benign, 8 had microscopic malignant features, and 4 had malignant disease. Thus, 46% of patients had either malignant disease or tumors with malignant features. Mean patient follow-up was 11.5 years. In one patient with benign disease and in one patient with malignant features, malignant disease developed (23% overall rate of malignancy). The difference in the rate of malignancy was not statistically significant between adrenal and extraadrenal pheochromocytomas. Patients with adrenal and extraadrenal pheochromocytomas also had similar rates of survival (p = NS). CONCLUSIONS: The data suggest that patients with extraadrenal pheochromocytomas have the same risk of malignancy and the same overall survival as patients with adrenal pheochromocytomas. Lifelong follow-up of these patients is mandatory. (+info)
pG2 gene expression and its regulation in human adrenocortical and medullary tumors.
(13/1819)
The cDNA clone pG2 was originally isolated from a human pheochromocytoma. The respective gene was found to be strongly expressed in normal adrenal zona glomerulosa and medulla, as well as in Conn's adenomas and pheochromocytomas. To shed more light on the expression and regulation of the pG2 gene, we investigated its expression in a wide variety of different adrenal neoplasms and cultured adrenal cells. Northern blot analysis was used to determine the steady state level of pG2 mRNA. Besides normal adrenals, Conn's adenomas and pheochromocytomas, we found abundant expression of pG2 mRNA in Cushing's, virilizing and nonfunctional adrenocortical adenomas and carcinomas, as well as in hyperplastic adrenals. The relative levels of pG2 mRNA in various adrenocortical tumors were not significantly different from those in normal adrenals and pheochromocytomas. In primary cultures of normal adrenal cells, treatment with adrenocorticotropin induced a 3- to 15-fold increase in the expression of pG2 mRNA (P<0.01), and this effect was reproduced by incubation with (Bu)2cAMP. In cultured pheochromocytoma cells, treatment with (Bu)2cAMP and a protein kinase inhibitor, staurosporine, increased pG2 mRNA accumulation (2- to 4-fold over the control level, P<0.01, and 3- to 8-fold, P<0.01, respectively). These results indicate that pG2 is widely expressed in normal and pathological adrenal tissues from both cortical and medullary origin, which eliminates its usefulness as a specific marker for zona glomerulosa or medullary adrenal tumors. Accumulation of pG2 mRNA is regulated by multiple differentiating factors through different pathways in primary cultures of normal adrenal and pheochromocytoma cells. (+info)
Fifteen years' review of advanced childhood neuroblastoma from a single institution in Hong Kong.
(14/1819)
OBJECTIVE: To assess the progress in the treatment of advanced childhood neuroblastoma. METHODS: From 1981 to 1996, there were 32 children with neuroblastoma (NB) diagnosed, staged and treated in our institution. There were 4 patients with stage II NB (12%), 5 stage III (16%), 21 stage IV (66%) and 2 stage IV s (6%). The NBs were excised if CT scan indicated that the tumors were operable. For advanced NB, stages III and IV, multiple drug chemotherapy was started first and operability was assessed with serial CT scan examinations. Once the X-ray imaging indicated the tumors were operable, surgical interventions were done. The medical records of the advanced NB were reviewed. RESULTS: In the initial period of the study, 9 patients were treated using the VAC protocol [vincristine (vcr), adriamycin (adria) and cyclophosphamide (cyc)]. No patient was convertible to operable and all died with a mean survival of 10 months. OPEC [vcr, cyc, VM26, cisplatin (cis)], Rapid COJEC (carboplatin, VP16, vcr, cis and cyc) and more recently N6 protocol (cyc, adria, vcr, VP16, cis) was used for 17 patients. 80% of them were converted to operable. In 4 patients, surgical specimens showed only necrotic tissue without viable tumor tissue and 6 (35%) tumors were converted to ganglioneuroma or ganglioneuroblastoma. Although 2 (12%) patients died of fungal septicemia and 1 (6%) developed Fanconi's syndrome after chemotherapy, the mean survival period increased to 27 months. In the 10 survivors (60%), 4 had megatherapy with melphalan followed by autologous peripheral blood stem cell (PBSC) transplantation and 2 were waiting for transplantation. CONCLUSIONS: There is a high percentage of advanced NB on presentation in Hong Kong. With more potent multiple drug chemotherapy for advanced stage NB there are (1) improvement in the survival of these patients, (2) opportunities for more operations for tumor excision and (3) opportunities for autologous PBSC transplantation for better tumor eradication. (+info)
Molecular level investigation of exocytosis in cultured human pheochromocytoma cells: insights from high resolution scanning electron microscopy combined with autoradiogram and cytochemistry.
(15/1819)
OBJECTIVE: To investigate molecular events of exocytosis in cultured human pheochromocytoma cells with stimulation. METHODS: The cultured pheochromocytoma cells prepared from human adrenal pheochromocytoma tumor were stimulated for the release of catecholamines by depolarization with the administration of 50 mmol/L KCl. Transmission electron microscopy (TEM) and high resolution scanning electron microscopy (HR-SEM) combined with autoradiography and cytochemistry were used to observe molecular mechanisms of exocytotic release of catecholamines from the stimulated cells labelled with 3H-noradrenaline and the filipin-treated cells. RESULTS: TEM and HR-SEM observations of the stimulated cells labelled with 3H-noradrenaline revealed that the initial exocytotic fusion pores even less than 10 nm in diameter in human pheochromocytoma cells can be clearly observed in a single lipid bilayer. Furthermore, HR-SEM examinations of the filipin-treated cells showed that the derangement of the particles of the filipin-sterol complexes (FSCs) in the fused membranes of granule and plasma membranes occurred as the exocytotic fusion pores opened. In addition, the aggreates of the FSCs particles were consistently demonstrated around the openings of the differently sized closing exocytotic pores. CONCLUSIONS: Based on our results, it is suggested that the rearrangement of the sterol molecules in the fused membranes of granule and plasma membranes plays an important role in the opening and closing mechanisms of exocytotic fusion pores. We hope that morphological data obtained in this study can provide some new insights into the understanding of molecular mechanisms of exocytosis, particularly the opening and closing of exocytotic fusion pores in relation to the distribution of the membrane sterols. (+info)
Palliative chemotherapy for malignant pheochromocytoma: symptomatic palliation of two cases.
(16/1819)
Malignant pheochromocytoma is a rare tumor with a poor prognosis because excess production of catecholamines leads to potentially lethal complications. Several chemotherapy regimens have been reported to be effective against this tumor, but a standard form of chemotherapy has not been established. We treated two patients with histologically confirmed pheochromocytoma after surgical removal of the primary lesion. Non-cardiogenic pulmonary edema was resolved and bone metastases were controlled by individualized chemotherapy that decreased the catecholamine levels, and the performance status was improved in both cases. Palliative chemotherapy should be designed to improve the quality of life of cancer patients. (+info)