PubMed Health⌕ Search

Biomedical subjects

W Miura

Publications and source records attributed to W Miura.

11 recordsLinked to original sources

Changes in clinical features and long-term prognosis in patients with pheochromocytoma.

To investigate changes in preoperative clinical features and the long-term outcome of tumor recurrence, mortality, and morbidity in patients with pheochromocytoma, we retrospectively examined changes in the clinical features by comparing 49 patients from 1957 to 1985 (group I) with 46 patients from 1986 to December 1995 (group II). In addition in these 95 patients (excluding 2 who had died before operation), we evaluated long-term postoperative outcome from the initial operation to August 1996 (909 patient-years). The mean age in group II was older than that of group I. The percentage of patients having proteinuria or hypertensive retinopathy in group II was less than that in group I. Of 20 patients with incidentally discovered pheochromocytoma, 7 (35%) were > or =60 years old, 7 asymptomatic, and 11 (55%) normotensive. Plasma and urinary catecholamines in these patients were significantly (P < .01) lower than in patients with pheochromocytoma having typical clinical features. Long-term cohort study showed 14 deaths. Relative survival rates were 91% at 5 years and 83% at 10 years and unchanged thereafter. The Kaplan-Meier estimate of pheochromocytoma-free survival was shorter in patients with a larger-than-median (60 g) tumor weight. Six patients had malignant recurrence 3 to 101 months (median, 45 months) after the initial operation. Of 65 patients confirmed alive at follow-up, 11 were hypertensive. In the Cox model, hypertension-free survival was not associated with age, a family history of hypertension, duration of hypertension, or creatinine clearance. Pheochromocytoma should be diagnosed from a wide spectrum of clinical features including those that are not generally suspected of resulting from excess catecholamines or hypertension, and after surgery, patients with this disease should be followed-up carefully for a long period (at least 10 years) because of the risk of tumor recurrence and the high prevalence of disease.

Adolescent↗

Expression of stanniocalcin in zona glomerulosa and medulla of normal human adrenal glands, and some adrenal tumors and cell lines.

Stanniocalcin (STC) is a calcium (Ca)-regulating hormone that was originally discovered in the fish Stannius body, which is a unique endocrine organ. Hypercalcemia increases STC secretion, which inhibits Ca uptake by the gills and normalizes serum Ca level. In this study we investigated the STC expression in human normal and abnormal adrenal cells. Immunohistochemistry using monoclonal antibody against STC revealed specific staining in zona glomerulosa and medulla of normal human adrenal glands. STC was also detected in human adrenal tumors, such as pheochromocytoma, differentiated neuroblastoma, and aldosterone-producing adenoma, and cultured adrenal tumor cells (rat pheochromocytoma PC-12 cells and human neuroblastoma NB-1 cells). However, undifferentiated human adrenal neuroblastoma was negative for STC staining. Reverse transcription polymerase chain reaction demonstrated STC mRNA expression in cultured PC-12 cells and NB-1 cells. Following several studies indicating that zona glomerulosa cells of adrenal glands express neuroendocrine properties, STC expression in normal and abnormal adrenal cells provides additional evidence to support the neuroendocrine differentiation of these cells. In conclusion, STC may be useful as a new cell marker of adrenal glands under physiological and pathological conditions.

Adrenal Medulla↗

Multiple endocrine neoplasia type 2A with the identical somatic mutation in medullary thyroid carcinoma and pheochromocytoma without germline mutation at the corresponding site in the RET proto-oncogene.

A germline mutation either in exon 10 or 11 of the RET proto-oncogene is found in the majority of patients with multiple endocrine neoplasia type 2A (MEN 2A). A 41-year-old female patient was referred for further evaluation of incidentally discovered right adrenal tumor. She had bilateral adrenal pheochromocytomas and medullary thyroid carcinomas detected by endocrinological and radiological examination, and diagnosed as MEN 2A. Molecular genetic testing of the RET exons 10 and 11 exhibited the identical somatic missense mutation at codon 634 in both tumors but did not confirm germline mutations in the corresponding sites. Possible mechanisms for tumorigenesis in this patient are discussed.

Adrenal Gland Neoplasms↗

Preferential changes in hepatosplanchnic hemodynamics in patients with borderline hypertension.

To investigate changes in systemic and regional hemodynamics during the development of human hypertension, we simultaneously measured cardiac index (CI) by the indocyanine green (ICG) dye dilution method, hepatosplanchnic blood flow (HBF) by the ICG clearance method using a two-compartment model, and renal blood flow (RBF) by the p-aminohippurate clearance method in patients with borderline and essential hypertension. In patients with borderline hypertension (BH, n = 27), HBF (435 +/- 15 ml/min/m2) and HBF/CI (16 +/- 1%) were significantly (p < 0.05) lower than in age-matched normotensive controls (528 +/- 21 and 19 +/- 1, respectively, n = 21), while CI, RBF and RBF/CI were similar. In patients with essential hypertension (EH, n = 32), HBF, RBF, and RBF/CI were all significantly (p < 0.01) lower than in the control subjects. Hepatosplanchnic vascular resistance (HVR) in patients with BH was preferentially increased, while total peripheral resistance (TPR) and renal vascular resistance (RVR) remained in the normal range. In patients with EH, TPR, HVR, and RVR were all increased. These results indicate that hemodynamic changes in patients with BH do not occur uniformly among the various regional circulations and suggest that hemodynamic changes in the hepatosplanchnic region precede those in other organ circulations during the development of human hypertension.

Adolescent↗

Plasma chromogranin A in pheochromocytoma, primary hyperparathyroidism and pituitary adenoma in comparison with catecholamine, parathyroid hormone and pituitary hormones.

Plasma levels of chromogranin A (CgA) were measured by ELISA in 22 patients with pheochromocytoma (18 non-metastatic, 3 metastatic, and 1 mixed neuroendocrine-neural tumor), 9 patients with primary hyperparathyroidism, and 9 patients with pituitary adenoma. The plasma levels of CgA were compared with norepinephrine, epinephrine, parathyroid hormone and pituitary hormones, i.e., growth hormone and prolactin. In pheochromocytoma, CgA in preoperative plasma of the patients without metastasis was 228 +/- 38 U/L (mean +/- SEM) and significantly higher than healthy controls (30 +/- 11 U/L, n = 40). Plasma CgA was decreased after removal of the tumors (28 +/- 6.0 U/L), except in three patients with metastatic pheochromocytoma and a mixed neuroendocrine neural tumor. The concentration of CgA in the patients with non-metastatic pheochromocytoma was significantly correlated with that of plasma norepinephrine (P < 0.005, r = 0.68) and urinary norepinephrine (P < 0.05, r = 0.65), but not with that of epinephrine. There was an exceptional case in which CgA was extremely high, but the CA level was normal. This tumor was a highly malignant pheochromocytoma with extensive metastases composed of small tumor cells which were occasionally positive for tyrosine hydroxylase immunohistochemically. These cells were considered to be poorly differentiated tumor cells and synthesized a very small amount of norepinephrine. Plasma levels of the patients with primary hyperparathyroidism and the patients with pituitary adenoma were 44 +/- 4 U/L and 48 +/- 8 U/L, respectively. Only one patient with a growth hormone-producing pituitary adenoma had a high level of CgA. Plasma CgA is a useful tumor marker for pheochromocytoma, even for malignant pheochromocytoma without elevated CA level, but not for hyperparathyroidism, or pituitary adenoma.

Adenoma, Acidophil↗

Two cases of malignant pheochromocytoma treated with cyclophosphamide, vincristine and dacarbazine in a combined chemotherapy.

Two patients with malignant pheochromocytoma were treated with a combination chemotherapy regimen consisting of cyclophosphamide vincristine, and dacarbazine (CVD). With the first few cycles of the treatment, one patient, a 29-year-old man had a marked improvement of clinical symptoms and decreases in tumor size and catecholamine levels in plasma and urine. He had been in a clinically stable condition for 18 months but died 34 months after starting of this treatment because the CVD regimen became ineffective and rapid growth of the metastatic tumors occurred. The other patient, a 35-year-old man showed no significant change in tumor size but decreases in hormonal levels in response to CVD regimen. The patient has been in clinically stable condition in a follow-up of 24 months. The combined chemotherapy with CVD appears to be effective for advanced malignant pheochromocytoma.

Adrenal Gland Neoplasms↗

Renal dopamine spillover rate using 3H-dopamine radiotracer technique as an index of renal dopaminergic nerve activity.

Renal and total dopamine (DA) spillover rates at rest were measured in 25 conscious rabbits with chronically implanted renal vein catheters. Renal DA spillover rate was calculated from veno-arterial difference in plasma free DA concentrations across the kidney corrected by the fractional extraction of infused 3H-DA. Plasma free DA concentrations were 11.0 +/- 2.7 pg/ml in the artery and 14.3 +/- 3.6 in the renal vein. Renal and total DA spillover rates were 0.51 +/- 0.08, 2.61 +/- 0.30 ng/min, respectively, both of which were significantly (p < 0.001) lower than the respective norepinephrine (NE) spillover rates (renal: 16.3 +/- 1.4, total: 39.6 +/- 1.7). The fractional extraction of 3H-DA across the kidney (55 +/- 3%) and the total DA clearance (285 +/- 31 ml/min) were both significantly (p < 0.05) higher than that of 3H-NE (45 +/- 3) and the total NE clearance (198 +/- 9), respectively. The ratio of renal to the total spillover rate of DA (0.23 +/- 0.05) was significantly (p < 0.05) lower than that of NE (0.41 +/- 0.04). These results demonstrate that DA is released into plasma within the kidney and suggest that the measurement of renal DA spillover rate using 3H-DA radiotracer technique is useful to detect resting renal dopaminergic nerve activity.

Animals↗

Effect of dexamethasone on plasma free dopamine: dopaminergic modulation in hypertensive patients.

To investigate the peripheral dopaminergic modulation in the pathogenesis of human hypertension, we examined the responses of plasma free dopamine (DA) to dexamethasone (Dx) administration, which is suggested to activate dopaminergic activity. We administered Dx 2 mg intravenously to patients with primary aldosteronism (PA), essential hypertension (EH), and normotensive controls (NT). Plasma free DA was increased significantly in all groups and the responses were more remarkable in PA than in EH and NT. Plasma epinephrine (E) showed a gradual increase while plasma norepinephrine (NE) tended to decrease in all groups. The responses of both plasma DA and E were completely blocked by 250 mg of alpha-methyl-p-tyrosine, a tyrosine hydroxylase (TH) inhibitor, suggesting that Dx may stimulate peripheral dopaminergic activity by increasing catecholamine synthesizing enzyme (probably TH) activities. These data suggest that DA itself plays an inherent role in the sympathoadrenal regulation rather than only as a precursor of NE and that dopaminergic hyperresponses may be involved in the pathophysiology of PA.

Adult↗

Plasma free dopamine: physiological variability and pathophysiological significance.

Dopamine (DA) is the most abundant catecholamines in human plasma and exists mostly in the sulfo-conjugated form (DA sulfate), a biologically inactive metabolite. The paucity of unconjugated DA (PDA) in plasma throws doubt on its physiological significance. However, PDA, when measured with a highly sensitive radioenzymatic method, showed quite different features from norepinephrine and epinephrine in some types of clinical hypertension, lower in essential hypertension and higher in primary aldosteronism and pheochromocytoma. There was a weak but significant correlation between the values of PDA and DA sulfate measured in the same specimens, but DA sulfate was more susceptible to impaired renal function. Upright posture, high salt diets and an intravenous injection of metoclopramide (MCP, 10 mg), a DA receptor antagonist, induced a slight but significant increase in PDA in normal and hypertensive subjects. An intravenous dexamethasone (2 mg) caused a gradual increase in PDA over 150 min after medication, which was completely blocked by concomitant administration of alpha-methyl-p-tyrosine, a tyrosine hydroxylase inhibitor. The responses of PDA to both high salt diets and MCP were blunted in salt-sensitive patients with uncomplicated essential hypertension. The results suggest that DA is not only a precursor of norepinephrine biosynthesis but also plays an inherent role as an active neurotransmitter in the peripheral sympathoadrenal system, and that PDA is a sensitive marker of peripheral dopaminergic activity, which may operate to modulate the cardiovascular and endocrine functions and participate in the pathogenesis of some types of hypertension.

Dexamethasone↗

Two cases of pheochromocytoma diagnosed histopathologically as mixed neuroendocrine-neural tumor.

We treated two rare cases of pheochromocytoma which were histopathologically diagnosed as mixed neuroendocrine-neural tumor (MNNT): a 35-year-old male patient associated with ganglioneuroblastoma and cutaneous neurofibromatosis and a 42-year-old male patient with ganglioneuroma. Both patients showed typical clinical manifestations of pheochromocytoma without any familial traits. Although each of the diseases has its own entity and clinical features, these tumors are all derived from the neural crest tissues. The tumorigenesis of MNNT is still unknown. Here, a brief review of the recent literature on this subject is discussed.

Adrenal Gland Neoplasms↗