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67 巻, 3 号
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Cushing病-病態と治療-三浦 清, 鳥飼 龍生, 吉永 馨, 佐藤 辰男1991 年 67 巻 3 号 p. 175-202
発行日: 1991/03/20
公開日: 2012/09/24
ジャーナル フリーWe followed up 21 Cushing's disease patients (16 females and 5 males) aged 15 to 46 years, treated with reserpine (R) plus pituitary irradiation (PI). Mean duration of R administration and mean dose of PI were 24.5±10.8 (mean±SD) months and 54.0±9.8 Gy, respectively. Of them, four patients did not respond, one who received 66 Gy had brain necrosis and panhypopituitarism, and the other 16 patients (78%, 16/21) achieved initial remission. Of these 16 patients, there were 10 (aged 15 to 46 years) who were irradiated with 50 Gy or less (mean, 45.5±6.9 Gy), and 7 of them had initial response. As previously demonstrated effectiveness of the present regimen (R plus PI) could be evaluated by subjecting the patients to R-test, higher rate of remission was obtained among R-test responders (J. Clin. Endocrinol. Metab. 41: 511, 1975). Eleven of our R-test responders in he present study showed an early onset of remission (6.9±5.7 months) as compared with 5 R-test non-responders (17.0±9.1, p<0.05). In addition, the response time positively correlated with the ratio of the difference between basal plasma cortisol (11-OHCS) levels before and after midnight administration of 8mg dexamethasone (ΔD8) divided by the difference between 24-h urinary excretion of 17-OHCS for 3 successive days before, during metyrapone (3.0g/day, 6 divided dose, 2 days) administration and one day after (ΔM). The sixteen patients were followed up until 1990 for a mean of 12.4 years (2.2 to 25.2 years). Among them, one died of unrelated illness with this regimen 4 years after achieving remission, 4 relapsed between 5 to 7 years follow-up, and the remaining 11 (52%, 11/21) had long-term remission for a mean of 15.7±9.0 years (2.2 to 25.2 years). Of them, there were 5 patients who were treated with PI with 50 Gy or less, and had long-term remission (5.8 to 24.4 with a mean of 17.6±7.6 years).
During the long-term follow-up period of these 11 patients, endocrine assessment was carried out while off therapy. Basal urinary excretion of cortisol or 17-OHCS were normal in all of the 11 patients, and 8 of 9 showed normal diurnal rhythm of plasma cortisol. Nine of 10 patients tested showed normal suppressibility by overnight 1mg dexamethasone test and 6 of 9 showed normal response to CRH. Other pituitary functions were also assessed; normal GH response to GRH was obtained in 4 of 8 patients tested, TSH and PRL to TRH in 7 of 8 and in 5 of 8, respectively, and gonadotropins to GnRH in 6 of 8. Basal plasma thyroid hormones were normal in all of the 9, and gonadal hormones were normal in all of the 8 patients with respect to their age and sex. Of the 8 premenopausal women, 4 had 9 pregnancies and the 7 babies showed normal intellectual and physical development.
With the above favorable findings, we highly recommend R and PI therapy for Cushing's disease because of its non-invasiveness and worldwide availability. The other endocrine results which suggest a possible correlation between the effectiveness of the therapeutic regimen and the pathophysiology of the disease evaluated by ΔD8/ΔM ratio or by R-test in Cushing's disease is described and discussed.抄録全体を表示PDF形式でダウンロード (2715K) -
Abbas E. Kitabchi, Cynthia K. Buffington, James Givens, Hiroshi Inouye1991 年 67 巻 3 号 p. 203-213
発行日: 1991/03/20
公開日: 2012/09/24
ジャーナル フリーIn a previous report we found extreme hyperinsulinemia associated with high testosterone levels in patients with polycystic ovarian syndrome (PCO) and normal insulin levels in a small group of patients with elevated dehydroepiandrosterone (DHEA). From these observations, we hypothesized that DHEA and testosterone may have opposing actions on insulin sensitivity. To test this hypothesis, we studied insulin sensitivity in vivo and in vitro in a) obese PCO women with elevated testosterone, b) obese patients with adult-onset adrenal hyperplasia (AH) and high levels of DHEA, c) weight-matched obese controls, and d) lean controls. Insulin sensitivity was determined by insulin responses to a standard OGTT, hypoglycemic responses to an IV insulin tolerance test (ITT), red blood cell (RBC) insulin binding and receptor kinase activity, and phytohemagglutinin (PHA)-activated T-lymphocyte (T-cell) insulin binding and PDH insulin sensitivity. In PCO patients, we found that basal and glucose-challenged insulin levels were significantly greater than, and hypoglycemic responses to IV insulin, significantly lower than, weight-matched control values. However, AH patients had insulin values significantly below, and hypoglycemic responses significantly above, those of the weight-matched controls. Their values were, in fact, comparable to those observed for the lean control subjects. Similar findings were observed with insulin binding and PDH insulin sensitivity. Insulin sensitivity in all study subjects was found to be negatively correlated to testosterone and positively correlated to DHEA and, more significantly, to the ratio of DHEA/testosterone. These data would suggest that, in females, DHEA and T may have opposing actions on insulin sensitivity. We conclude that in females insulin sensitivity in vivo and in vitro is modulated, at least in part, by the ratios of DHEA to testosterone.抄録全体を表示PDF形式でダウンロード (1022K) -
中野 修, 坂本 長逸, 西崎 朗, 誉田 芳孝, 松田 康平, 和田 謙, 長尾 宗彦, 的崎 尚, 春日 雅人1991 年 67 巻 3 号 p. 214-221
発行日: 1991/03/20
公開日: 2012/09/24
ジャーナル フリーIn order to further investigate the precise mechanisms of cholecystokinin (CCK)-induced pepsinogen secretion from gastric chief cells, we compared the signal transducing mechanisms activated by CCK with those activated by sodium fluoride (NaF) in isolated guinea pig gastric chief cells. NaF stimulated a monophasic increase in diacylglycerol accumulation with a peak value observed at 15 sec, while CCK strongly stimulated its biphasic accumulation. NaF evoked an increase in initial Ca2+ influx rate with a slow and smooth increase in intracellular free Ca2+ concentration ([Ca2+]i) monitored by fura-2, while CCK stimulated a rapid increase in [Ca2+]i followed by a late sustained phase of [Ca2+]i increase. Lanthanum chloride (La3+) effectively (unlike either nifedipine or verapamil) blocked NaF-stimulated increase in [Ca2+]i, but it blocked only CCK-stimulated late sustained phase of [Ca2+]i increase. La3+ reduced NaF-or CCK-stimulated maximal pepsinogen secretion to 57.0±2.5% and 73.1±3.1% of control, respectively. These results suggest that NaF activates a signal transducing mechanism which seems to be distinct from that activated by CCK, thereby inducing an increase in diacylglycerol accumulation, Ca2+ influx and pepsinogen secretion in guinea pig gastric chief cells.抄録全体を表示PDF形式でダウンロード (715K) -
石原隆 , 中津正二 , 日野恵 , 服部尚樹 , 森寺邦三郎 , 池窪勝治 , 倉八博之1991 年 67 巻 3 号 p. 222-229
発行日: 1991/03/20
公開日: 2012/09/24
ジャーナル フリーWe report a patient with pregnancy-induced lymphocytic adenohypophysitis complicated by postpartum painless thyroiditis.
A 27-year-old female noticed visual field defect in the 36th week of pregnancy. After delivery in the 39th week by cesarean section, she was admitted for close examination. Goiter was not palpable, and postpartum galactorrhea was not observed. Routine examination revealed no abnormal findings. On October 8, 1989, magnetic resonance imaging (MRI) revealed a tumor image (height 22.4mm) from the sella turcia to suprasellar cistern with a lower signal intensity than that of the white matter on Ti weighted images and a high signal intensity on T2 weighted images. Gd-DTPA contrast images showed a symmetrical and homogeneous tumor image at the same site. However, the posterior lobe of the pituitary gland appeared normal. These findings suggested lymphocytic adenohypophysitis. The LH was<0.3mIU/ml. The FSH (7.8mIU/ml), PRL (12ng/ml), GH (1.6ng/ml) and cortisol (10μg/dl) levels were normal. T4 was 5.3 μg/dl, T3 67ng/dl, fT4 0.53ng/dl, which indicated mild hypothyroidism, but the TSH was normal. TRH test showed a slight increase in TSH and no response of PRL. Insulin tolerance test showed delayed response of GH and normal response of cortisol. LHRH test revealed no response of LH and delayed response of FSH. Anti-GH3 cell antibody and anti-thyroglobulin antibody were positive, but the anti-AtT20 cell antibody was negative.
Since visual disturbance improved, and slight reduction in the mass (height 20.1mm) was confirmed by MRI after delivery on October 21, her course was observed without treatment. After 1 month, the LH became detectable, but the PRL and cortisol decreased to 2.5ng/ml and 6.0μg/dl, respectively. The height of the mass was 13.4mm by MRI on November 6. After 3 months, since anorexia and fever suddenly developed and persisted, she was admitted to hospital. Her face was pale and painful, indicating a preshock state. No pain was present in the thyroid gland which was normal in size. The cortisol level was 2.1μg/dl. T4 was 15.6μg/dl, T3 283ng/dl, fT4 4.7ng/dl and TSH<0.14μU/ml, which indicated thyrotoxicosis. The 99mTcO4-uptake was only 0.08%. TSH binding inhibitory immunoglobulin was negative. A functional decrease in ACTH-cortisol seemed to have been complicated by postpartum painless thyroiditis, resulting in adrenal crisis. Following hydrocortisone administration, her general condition improved, and MRI showed a rapid reduction of the pituitary gland to normal (height 4.9mm) on December 18. At present, she is well controlled by oral administration of hydrocortisone at a daily dose of 25mg. The cortisol, GH, and PRL levels have decreased, but the LH, FSH, and TSH levels are normal.
An autoimmune process is considered to be involved in the development of lymphocytic adenohypophysitis and chronic thyroiditis. In this patient, painless thyroiditis may have been caused by delivery and gradually progressed to secondary adrenal insufficiency. There are few reported patients in whom detailed pituitary dysfunction after delivery was followed up by MRI. Our case suggests the involvement of an autoimmune process in the development of pituitary dysfunction after delivery.抄録全体を表示PDF形式でダウンロード (1036K) -
梅原 次男, 熊本 悦明, 三熊 直人, 伊藤 直樹, 南部 明民, 新田 俊一1991 年 67 巻 3 号 p. 230-238
発行日: 1991/03/20
公開日: 2012/09/24
ジャーナル フリーSalivary testosterone (Salivary-T) was measured in 133 normal boys at puberty (8-14 years old) and 21 adult males (24-36 years old) by using radioimmunoassay. Also, a simultaneous measurement was performed on salivary-T and serum total testosterone (Total-T) and free testosterone (Free-T) in order to study the correlation between saliva and serum.
The results were summarized as follows:
(1) Good correlations were observed in the values between Salivary-T and Total-T or Free-T. The correlation coefficient value was 0.54 between Salivary-T and Total-T, 0.84 between Salivary-T and Free-T when measured by DPC kit. Correlation coefficient value was 0.59 between Salivary-T by Wien kit and Total-T by DPC kit, also 0.77 between Salivary-T by Wien kit and Free-T by DPC kit.
(2) Salivary-T, in the mean level, increased by age. The most rapid increase of Salivary-T was observed at 13 years of age.
(3) Diurnal change of Salivary-T was observed at 13 years of age through adult age. Salivary-T level was highest in the morning and declined toward evening.
(4) These results suggest that Salivary-T measurement was highly reliable and applicable for use in the monitoring of androgen status.抄録全体を表示PDF形式でダウンロード (644K) -
千葉 泰子, 谷 長行, 田村 紀子, 中村 宏志, 五十嵐 一雅, 百都 健, 津田 晶子, 伊藤 正毅, 柴田 昭, 田村 哲郎, 黒木 ...1991 年 67 巻 3 号 p. 239-248
発行日: 1991/03/20
公開日: 2012/09/24
ジャーナル フリーWe report a case of a 47-year-old woman with McCune-Albright syndrome associated with unusual growth-hormone and prolactin hypersecretion. Acromegaly was suspected on clinical examination, and she was referred to us. She had no history of precocious puberty or pathological fracture. She was 154cm tall, weighing 62kg with so-called acromegalic facies. There were two lumps, one of which was on her right lateral forehead. The other on the right lower extremity seemed to be due to a bone deformity. Some brown pigmented macules with irregular borders were present on her lips and oral mucosa. Endocrine examination revealed elevated basal levels of plasma GH (54ng/ml) and PRL (36.2ng/ml), which paradoxically increased after injection of TRH. Plasma levels of these hormones did not change after LHRH test, and plasma GH level increased after GHRH test. A skull X-ray film showed a double floor of the sella turcica and hyperostotic formation of the right sphenoid bone. MRI and CT showed a tumor shadow in the right sella turcica. Bone roentogenography of the right fibula and tibia showed a large centrally expanding lesion with a ground-glass or cystic appearance and a thin cortex. The left fibula showed a similar lesion. We recognized similar findings in other bones which also showed abnormal accumulation in a radionuclide bone scan with99mTc. On the basis of physical, endocrinological and roentogenographical examination, we diagnosed her as displaying McCune-Albright syndrome. We operated on her by transsphenoidal surgery and confirmed a functioning chromophobe adenoma which was removed during surgery. She has been free of GH and PRL hypersecretion since then. The pathology of the sphenoidal sinus affected with fibrous bone was in accordance with the findings of fibrous dysplasia.
McCune-Albright syndrome (MCAS) is known as a syndrome characterized by polyostotic fibrous dysplasia and cutaneous pigmentation and multiple endocrinopathy. Its etiology is unknown. This syndrome with acromegaly is rare, and although 26 cases have been described in literature, pathological examinations have been undertaken in only three cases. This case was very rare and valuable because, by operating on her by the transsphenoidal route in spite of the sphenoidal sinus being affected with fibrous bone, we were able to confirm a chromophobe adenoma secreting both GH and PRL. We recognized that acromegaly with MCAS was endocrinologically, morphologically and immunohistologically the same as acromegaly without MCAS. Therefore, we concluded that acromegaly with MCAS is much the same as acromegaly without MCAS.抄録全体を表示PDF形式でダウンロード (4006K)
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