垂体ACTH腺瘤的诊断和治疗(附29例报告)

目的 分析和探讨垂体ACTH腺瘤的诊断和治疗。方法 对我科收治的29例垂体ACTH腺瘤患者的临床特点和治疗效果进行了回顾性分析。结果 垂体ACTH微腺瘤的诊断较为困难，有库欣氏综合征表现的患者，辅以血清ACTH、地塞米松抑制试验等并结合影像学资料方可确诊，经蝶手术切除肿瘤复发率仅为6．9％。结论 垂体ACTH腺瘤的诊断须依靠临床表现、实验室检查和影像学检查等。经蝶手术切除肿瘤是治疗垂体ACTH腺瘤的首选方法。     

胸部类癌

本文报道了３１例胸部类癌，其中胸腺类癌１４例，支气管类癌１７例，伴有异位ＡＣＴＨ综合征者１７例。１２例患者发生转移（３９％），２４例行原发肿瘤全部或部分切除，术后放疗或化疗或两者均有者１７例，４例仅行探查并取活检，２８例经手术及病理证实。     

脑卒中患者下丘脑─垂体─肾上腺皮质轴功能改变及临床意义

观察了１７２例脑卒中患者血清促肾上腺皮质激素（ＡＣＴＨ）、皮质醇的变化，发现ＡＣＴＨ、皮质醇水平明显高于正常对照组，脑出血组高于脑梗塞组；病情轻重与ＡＣＴＨ、皮质醇的变化明显相关。治疗前后ＡＣＴＨ、皮质醇水平明显不同，治疗后明显降低（Ｐ＜０．０１）。说明治疗后可改善下丘脑－垂体－肾上腺皮质轴（Ｈ／Ｐ／Ａ）功能紊乱。     

Effects of chronic stress on plasma corticosterone, ACTH and prolactin

Rats were placed in a stressful environment for 24 hr per day and levels of plasma hormones were measured after varying numbers of days in the environment. Rats were habituated to operant chambers placed in sound-attenuated enclosures. Food pellets were available by lever press on a FR1 schedule. After 3 days of habituation, rats in the “stressed” group were trained to pull a ceiling chain to avoid or escape shock. Following training, stress trials, consisting of a consecutive sequence of 5 sec each of a warning light, warning tone and 0.16, 0.32, 0.65, 1.3 and 2.6 mA of footshock, occurred approximately once per 5 min around-the-clock. For the first day, the sequence was terminated when the ceiling chain was pulled. On subsequent days, 90% of all shock presentations could be avoided or escaped by chain pull; the remaining 10% of trials were inescapable and the entire sequence was presented. Control rats lived in identical chambers without presentation of shock. Rats were sacrificed after 1, 2, 3, 4, 7 or 14 days in this environment and levels of plasma corticosterone, ACTH and prolactin were determined. Levels of plasma corticosterone were elevated during the first 7 days in the stressful environment, but returned to control values by day 14. Levels of plasma ACTH and prolactin were similar in stressed and control rats at all time points measured. These data suggest that stress-induced changes in glucocorticoids but not in ACTH or prolactin might mediate some of the physiological changes that occur as the result of chronic stress.     

Reduced ACTH/cortisol responses to naloxone in men with Parkinson's disease

Summary In order to establish whether the inhibitory control exerted by endogenous opioid peptides on ACTH/cortisol secretion changes in patients affected by Parkinson's disease, ten parkinsonian male subjects and eight age matched normal controls were tested with naloxone (4 mg an i.v. bolus plus 10 mg infused in two hours). In a different occasion all subjects were tested with normal saline. Experiments started at 09.00 h. Plasma ACTH and cortisol concentrations showed a slight physiological decline during saline test in both groups. In the normal controls and in the parkinsonian patients both ACTH and cortisol levels were significantly higher after naloxone administration than during saline test. However, both naloxone induced ACTH and cortisol responses were significantly higher in normal than in parkinsonian subjects. In agreement with the well-known opioid deficiency characterizing the parkinsonian brain, these data show a reduced opioid inhibitory control of ACTH/cortisol secretion in patients with Parkinson's disease.     

中枢和外周脑钠素(BNP)调节醛固酮分泌的不同作用

将BNP和AT-Ⅱ、ACTH AVP单独或BNP与这3种肽分别合并在大鼠icv或iv注入后观察血Ald浓度的变化。实验结果表明:①iv给予AVP(5μg/3ml·h~(-1))、ACTH(5μg/3ml·h~(-1))和AT-Ⅱ(5 v.g/3 ml·h(-1)),1h后均能增加血Ald的浓度。iv给予BNP(5μg/3ml·h(-1))能明显抑制AVP和ACTH的刺激作用,而不影响AT-Ⅱ的刺激作用。②icv给予BNP(2 Vg/10 pl NS)能降低血Aid浓度。icv给予AVP(2μg/10μl NS)能增加血Aid浓度,但ACTH(2μg/10μl NS)和AT-Ⅱ(2μg/10μl NS)无此种作用。但如脑室同时给予BNP(2μg/10μlNS)却可明显刺激Aid分泌。③icv注入BNP对外周注入的3种多肽的刺激作用无任何影响。从上述的实验结果可看出:脑内BNP可“反常”地增加AT-Ⅱ、ACTH和AVP对Ald分泌的刺激作用,与外周抑制AVP,ACTH的刺激作用不同。而脑内BNP不影响这3种多肽的外周刺激作用。结论是脑内BNP以其独特的方式调节Ald的分泌,控制水盐代谢。     

Effect of ACTH,adrenalectomy and the combination treatment on the density of 5-HT2 receptor binding sites in neocortex of rat forebrain and 5-HT2 receptor-mediated wet-dog shake behaviors

The effect of ACTH and/or adrenalectomy on serotonin (5-HT)₂ receptor binding sites was evaluated in the neocortex of rat forebrain. One day after the adrenalectomy or sham operation, ACTH (50 µg/day) was injected subcutaneously into adult male SD rats for 10 consecutive days. Saturation analysis showed that subchronic ACTH treatment significantly increased the B_max values for³H-ketanserin binding without any change in the K_d values. Moreover, this ACTH-induced increase in the B_max values was prevented by adrenalectomy. The concentrations of 5-HT and 5-hydroxyindole acetic acid (5-HIAA) measured by HPLC-ECD were not altered by these manipulations. Ten-day administration of corticosterone (20 and 50 mg/kg) also increased 5-HT₂ receptor density in the neocortex of rat forebrain. 5-HT₂ (and 5-HT_1C) receptor agonist, (±)DOI-induced wet-dog shakes in ACTH and/or adrenalectomy-treated rats were also examined. Ten-day administration of ACTH enhanced (±)DOI-induced wet-dog shakes and this increase was prevented by adrenalectomy. These results indicate that subchronic adrenocorticotropinadrenal axis activation of rats increases both the number of 5-HT₂ receptors in neocortex of forebrain and the wet-dog shake responses induced by (±)DOI.     

Adrenocorticotropic Hormone Immunoreactivity in the Hippocampal Formation of Temporal Lobe Epilepsy Patients

Summary: Purpose: We wished to identify immunocytochemically the distribution of proopiomelanocortin-related peptides in the hippocampal formation of patients with epilepsy.
Methods: Surgical hippocampal specimens from temporal lobe epilepsy (TLE) patients and autopsy control tissue were examined immunocytochemically for ACTH, α-melanocyte-stimulating hormone (α-MSH) and α-endorphin.
Results: There was a dense distribution of ACTH-immunoreactive neurons in the hippocampal formation of patients with mesial TLE syndrome (MTLE). These hippocampal specimens showed significant cell loss. ACTH-positive neurons were most prominent in the subiculum, with scattered ACTH-immunoreactive neuronal elements distributed in the cornu ammonis fields and hilus. Light ACTH immunoreactivity was detected in the tumor-related epileptic hippocampal specimens, which showed minimal cell loss. Although autopsy control tissue from the hypothalamus showed intense ACTH staining patterns in cells and fibers, there was little or no ACTH immunoreactivity in the autopsy hippocampal tissue. The expression of ACTH immunoreactive elements was correlated with patterns of cell loss. No α-MSH- or β-endorphin-immunoreactive neurons were detected in any of the hippocampal specimens.
Conclusions: ACTH has anticonvulsant properties, and its novel expression in the glutamatergic subicular neurons, which provide the main outflow of the hippocampal formation, may represent an attempt by the damaged hippocampal circuit to restore the balance of excitatory/inhibitory neurotransmission in TLE.     

Induction of muricidal behavior by ACTH or adrenalectomy in young male wistar rats

ACTH administered IP induces a muricidal behavior in 52% of male Wistar rats that do not express it before; such behavior is also observed spontaneously in 68% of adrenalectomized animals. This change in behavior is characterized by an exceptionally long duration (several months in some animals), and by its prevention by previous or substitutive treatments with dexamethasone. Data obtained using hypophysectomized or adrenalectomized animals with or without ACTH treatments suggest that the muricidal-inducing effect of ACTH might have, at least partially, a central origin.     

Antiserotonergic inhibition of calcitonin-induced increase of β-endorphin,ACTH, and cortisol secretion

Summary In a previous study we observed that calcitonin increases -endorphin, ACTH, and cortisol secretion. We assumed that calcitonin might have a modulatory role on the pituitary function. The present study was initiated to clarify whether this effect is due to a direct pituitary stimulation or to an indirect stimulation through CRF (corticotropin releasing factor).Fourteen healthy subjects, aged 30–60 years were investigated. All the subjects received 100IU Salmon calcitonin Sandoz i.v. at 8a.m. (time 0). Plasma -endorphin, ACTH and cortisol were estimated every 30min from – 30 to 120 min by specific radioimmunoassay. The same parameters were estimated a second time, at the same intervals, when cyproheptadine 8 mg (7 subjects) and 40 mg propranolol (7 subjects) were given per os at – 30 min and calcitonin i.v. at time 0. -endorphin, ACTH and cortisol levels (Mean ±SEM) rose significantly after calcitonin (peak value at 30–90 min) from 5.2 ±0.7 to 15.1±2.6 pmol/l; from 43.0±2.7 to 70.7±4.1 pg/ml and from 10.6±1.5 to 19.6 ±2.1 g/100 ml respectively (p< 0.0001 by analysis of variance and covariance and repeated measures). Propranolol 40 mg (per os) administered at time – 30 did not alter the response of -endorphin, ACTH and cortisol to calcitonin (infused at time 0).Cyproheptadine, the antiserotonergic substance that inhibits the synthesis and release of CRF completely inhibited the stimulatory effect of calcitonin.We conclude that probably calcitonin has a modulatory role on the hypothalamo-pituitary adrenal axis and that it acts at the hypothalamic level probably by stimulating CRF secretion.