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67 巻, 7 号
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頻度と機序に関する検討家城 恭彦, 宮腰 久嗣, 永井 幸広, 番度 行弘, 臼田 里香, 宮本 市郎, 大沢 謙三, 小林 健一1991 年 67 巻 7 号 p. 755-763
発行日: 1991/07/20
公開日: 2012/09/24
ジャーナル フリーIt is generally accepted that acromegaly is often associated with hypercalciuria, but there are few reports on the frequency and the mechanisms of urolithiasis. Recently we consecutively experienced 2 cases of acromegaly with urolithiasis, and these experiences made us investigate the association between urolithiasis and acromegaly.
Among 18 acromegalies from 1977 to March 1990 (10 males, 8 females, 24-64 years old), 13 cases (72%) fulfilled the criteria of hypercalciuria (urinary calcium (u-Ca) ?200mg/day or u-Ca/urinary creatinine (u-Ca/u-Cr)?0.15), and 7 cases (39%) suffered from urolithiasis that was diagnosed by KUB (4 cases) or X- ray computed tomography (CT)(3 cases). Especially in the last 2 years, 5 out of 7 cases (71%) were complicated with urolithiasis and all 7 cases were associated with hypercalciuria. These results suggest that hypercalciuria and urolithiasis are both much more frequent than previously reported.
In 6 cases who were treated by pituitary adenomectomy from 1988-1989 (4 males, 2 females, 24-59 years old), we examined Ca metabolism before and after operation. Before operation, the levels of serum growth hormone (GH), u-Ca (mg/day), u-Ca/u-Cr (in all cases) and plasma somatomedin -C (Sm-C) (in 4 cases) were increased above the normal range. To determine the etiology of hypercalciuria, we performed the oral Ca load test under restriction of Ca (400mg/day) and P (650mg/day) intake. The results suggested that the hypercalciuria might be mainly due to the increased absorption of Ca from the intestine (so-called ”Absorptive hypercalciuria”). However, the levels of serum vitamin D (Vit. D) metabolites were all within the normal range before operation. After operation, GH and u-Ca/u-Cr (in 5 cases) and u-Ca (mg/day) (in all cases) decreased significantly compared with before operation, and the levels of Sm- C (in all cases), serum 25-(OH) D3, 1α,25-(OH)2D3 (in 4 cases) and 24,25-(OH)2D3 (in 3 cases) were also reduced after operation. Surprisingly, u-Ca and u-Ca/u-Cr normalized only in 4 cases who showed a reduction in 1α,25- (OH)2D3 levels after operation, although there were no correlations between u-Ca (mg/day) or u-Ca/u-Cr and 1α, 25-(OH)2D3. Significant correlations were found between u-Ca (mg/day) or u-Ca/u-Cr and Sm-C. The parathyroid function evaluated by the rapid Ca infusion test or nephrogenous cyclic adenosine monophosphate (NcAMP) was normal before and after operation.
In conclusion, the high frequency of urolithiasis in acromegaly observed in this study may be strongly ascribed to hypercalciuria, and the facts that (1) in the general population, the frequency of urolithiasis has increased and (2) our methods of confirming urolithiasis were more sensitive than those described in previous reports. The cause of hypercalciuria might be partly due to increased Ca absorption from the intestine mediated by 1α,25-(OH)2D3. Now we emphasize that urolithiasis in acromegaly is more common than previously considered, so it is important to prevent severe complications of urolithiasis by early diagnosis and treatment.抄録全体を表示PDF形式でダウンロード (926K) -
吉本 勝彦, 斎藤 史郎1991 年 67 巻 7 号 p. 764-774
発行日: 1991/07/20
公開日: 2012/09/24
ジャーナル フリーA review of 106 patients with multiple endocrine neoplasia (MEN) type 1 reported between 1966-1989 in Japan was conducted in order to clarify the natural history of this disease. Sporadic MEN 1 was found in 61 patients, and familial MEN 1 was found in 45 patients from 15 families. The mean ages at diagnosis of the two groups were 46.2 and 41.3 years, respectively, and the male to female ratio was 3: 4.
With regards to the involvement of the pituitary, parathyroid and endocrine pancreas, the combination of three endocrine glands was 31%, and that of two was 48%, in which the pituitary, parathyroid and endocrine pancreas had tumorous lesions in 60%, 88% and 63%, respectively.
The first clinical manifestations of MEN 1 were the symptoms of hyperparathyroidism (32%), pituitary tumors (26%), peptic ulcer (28%) and hypoglycemia (13%). These symptoms appeared between 6 and 57 years of age (mean 34 years). The main clinical symptoms of the pituitary tumors were acromegaly and gigantism (37%), galactorrhea-amenorrhea syndrome (20%), Cushing's disease (10%) and visual disturbance due to compression of the tumor (20%). The clinical manifestations of hyperparathyroidism were mainly asymptomatic hypercalcemia (41%), nephrolithiasis (42%) and osteitis fibrosa (5%). In the patients with pancreatic tumor, Zollinger-Ellison syndrome (52%) and hypoglycemic symptoms (42%) were found. Tumors in the adrenal cortex, thyroid, carcinoid and lipoma were detected in association with MEN 1 in the frequencies of 28%, 21%, 9% and 5%, respectively.
Death was reported in 37 patients between 9 and 86 years of age (mean 50.0 years). The cause of death was gastrointestinal bleeding and perforation (45%), surgery (24%) and disseminated carcinomatosis (18%).
Recently, the gene predisposing to this syndrome has been assigned to chromosome 11 (11q13) in non-Japanese cases but not yet in Japanese MEN 1 patients.抄録全体を表示PDF形式でダウンロード (1108K) -
市川 尊文, 阿部 好文, 金森 晃, 矢島 義忠1991 年 67 巻 7 号 p. 775-784
発行日: 1991/07/20
公開日: 2012/09/24
ジャーナル フリーA seventeen-year-old youth was presented with muscle cramps and convulsions. A brain CT scan showed calcification in the region of the ganglia, and a diagnosis of brain tumor was thus made and an anticonvulsant given for two years. At age nineteen, the patient developed pseudohypoparathyroidism owing to low serum calcium and high serum PTH levels. However, serum alkaline phosphatase and serum osteocalcin levels were high, and bone radiography indicated demineralization in the skull, and a multibubblated cystic lesion was detected in the femur neck. These data indicated that the bone remodeling response to PTH had remained intact in this patient. Serum osteocalcin is known to increase in primary hyperparathyroidism. However, unlike patients with hyperparathyroidism, those with pseudohypoparathyroidism show no increase in serum 1, 25 (OH)2D. The present case was thus useful for examining the direct effect of PTH on serum osteocalcin. The patient was administered 1α(OH)D, and his condition monitored for two years. During this period, osteocalcin and PTH levels decreased while that of 1,25 (OH)2D increased. Osteocalcin and PTH levels were found to be closely correlated (r=0.68, p<0.01). The present results indicate the possibility that PTH may increase serum osteocalcin independent of Vitamin D.抄録全体を表示PDF形式でダウンロード (2236K) -
in vivo及びin vitroにおける検討宮下 洋1991 年 67 巻 7 号 p. 785-795
発行日: 1991/07/20
公開日: 2012/09/24
ジャーナル フリーGrowth hormone (GH), which has been extracted from the pituitary gland since early times, has become easily available by the advance of genetic engineering in recent year. Its clinical application to treatment in various fields, involving obesity, wounds, fractures, gastric ulcers and so on, is being increasingly discussed.
The presence or absence of the effect of GH on leukopoiesis was studied in vivo and in vitro experiments. In the in vivo experiment, GH was administered to rats whose bone marrow production had been suppressed by the injection of mitomycin C, and time- course changes in the peripheral blood leukocyte count in these rats were compared with those in rats given physiological saline solution alone (control group). The in vitro experiment was performed by colony assay of mouse marrow cells. Insulin growth factor-1 (IGF-1) was also studied in the in vitro experiment.
The in vivo experiment revealed that GH promoted recovery of leukocytes from the nadir, and in the in vitro experiments GH and IGF -1 were demonstrated to increase the number of colonies in the presence of granulocyte macrophage colony stimulating factor (GM-CSF). GH was considered to exert effects on myeloid progenitor cells and the hemopoietic microenvironment simultaneously, resulting in an increase in leukocytes.抄録全体を表示PDF形式でダウンロード (996K) -
森 一弥1991 年 67 巻 7 号 p. 796-810
発行日: 1991/07/20
公開日: 2012/09/24
ジャーナル フリーThe study was undertaken to clarify the role of atrial natriuretic polypeptide (ANP) in essential hypertension (EH). Plasma levels of α-human ANP (αhANP) were measured in 13 normal subjects, 25 patients with EH, 5 patients with primary aldosteronism (PA), 3 patients with renovascular hypertension (RVH) and 3 patients with pheochromocytoma (PC). Plasma level of αhANP (normal: 38.1±20.5pg/ml) was high in all hypertensive subjects. Synthetic αhANP was intravenously administrated to these subjects as follows: first a dose of 0.01μg/kg/min for 30 minutes, second a dose of 0.03μg/kg/ min for 30 minutes, and then in normal subjects and EH 0.03μg/kg/min with a dose of 6.5μg/kg/min of metoclopramide (MC) for 30 minutes. After the infusion of 0.01μg/kg/ min α hANP, arterial blood pressure was significantly depressed in EH, RVH and PA, but not in PC. Marked diuretic and natriuretic responses were observed with increase in creatinine clearance and fractional sodium excretion in EH, RVH and PA, but not in PC. Sodium clearance/lithium clearance was slightly increased after infusion of 0.03μg/kg/ min of α hANP in hypertensive subjects. Plasma renin activity did not change in low and normal renin EH and PA after infusion of either dose of α hANP, but was suppressed after 0.03μg/kg/min of αhANP in normal subjects and high renin EH, RVH and PC. Plasma aldosterone concentration was suppressed after either dose of αhANP in normal subjects and in EH, RVH and PC, but not in PA. Plasma cGMP concentration and urinary cGMP excretion were decreased after either dose of αhANP in both normal and hypertensive subjects. Furthermore, the decrease of PAC by αhANP was normalized by MC in normal subjects and EH. The rise in plasma cGMP by αhANP was suppressed by MC in both normal subjects and EH, but no changes were observed in arterial blood pressure and natriuretic response.
These results suggest that αhANP secretion increases with elevation of blood pressure in EH, improving increase of circulatory blood volume, and αhANP may play a role in elevating blood pressure in EH. Moreover, it is considered that ANP increases sodium and water excretion through its effect on both renal glomeruli and distal tubules in EH. Hypotensive and natriuretic effects of ANP in EH may be concerned with dopaminergic activity which are probably related to the production of cGMP in the vascular wall and inhibition of the excretion of aldosterone in the adrenal cortex.抄録全体を表示PDF形式でダウンロード (1366K)
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