皮质醇增多症的诊断和治疗现状

皮质醇增多症是因肾上腺过度分泌糖皮质激素引起的临床综合征 ,1912年由HarveyCushing首先报道 ,故又称库欣综合征 (Cushingsyndrome)。皮质醇增多症可在任何年龄发病 ,但多发于 2 0～ 4 5岁 ,女性多于男性 ,男女比例为 1:3～ 8。1　皮质醇增多症的诊断1.1　皮质醇增多症的分类　皮质醇增多症可分为促肾上腺皮质激素 (ACTH)依赖性和非依赖性两大类。ACTH依赖性皮质醇增多症是因下丘脑 -垂体或垂体外的肿瘤组织分泌过量ACTH或促肾上腺皮质激素释放激素 (CRH) ,引起双侧肾上腺皮质增生并分泌过量的皮质醇 ,最常见的为垂体分泌过量ACT…     

补锌对新兵血浆ACTH水平及耐寒力的影响

目的 :研究锌对寒区新兵促肾上腺皮质激素 (ACTH)分泌及耐寒的作用。方法 :选西北某部集训期新兵 5 4人 ,分为普食对照组 (2 5人 )和普食加锌组 (2 9人 ,每人补锌 30mg·d- 1) ,2 5d补锌前后 ,分别测定冷暴露 4h后血浆促上腺皮质激素 (ACTH)水平、血浆锌浓度以及冷暴露4h前后直肠温度、胸部皮温等。结果 :膳食调查结果显示 ,两组战士热能及各种营养素的摄取量基本满足要求 ,锌摄入量为 12 .5mg ,补锌后战士冷暴露后ACTH水平为 (5 36± 5 0 )ng·L- 1低于补锌前的 (710± 33)ng·L- 1和对照组相应时间的 (6 90± 4 5 )ng·L- 1,(P <0 .0 5 )。血清锌水平没有明显差异。补锌后、冷暴露后 ,直肠温度和胸部皮温下降的幅度分别为 (0 .6 2± 0 .0 4 )℃和 (0 .5 4±0 .0 1)℃ ,低于实验前的 (0 .80± 0 .0 8)℃和 (1.0 5± 0 .0 9)℃ ,(P <0 .0 5 )。结论 :适量补锌可提高人体的耐寒能力     

促肾上腺皮质激素治疗婴儿痉挛31例短期疗效观察

观察促肾上腺皮质激素(ACTH)对31例婴儿痉挛短期的疗效.方法:首先促肾上腺皮质激素(ACTH)静滴,20U/d观察2w,若无效则加量至40U/d,总疗程为4w.结果:完全缓解8例(26%),有效16例(52%),无效7例(22%).控制痉挛率为78%.结论:促肾上腺皮质激素(ACTH)短期内控制痉挛发作效果满意.     

培本方调节哮喘大鼠HPA轴紊乱的实验研究

[目的]研究培本方对哮喘大鼠下丘脑-垂体-肾上腺(HPA)轴紊乱的调节作用。[方法]采用卵蛋白(OVA)致敏、激发复制大鼠慢性哮喘模型,以阿斯美胶囊为对照药,通过检测血清皮质酮(CORT)、血浆促肾上腺皮质激素(ACTH)及下丘脑促肾上腺皮质激素释放激素(CRH)含量的变化,探讨培本方对大鼠哮喘模型的影响。[结果]模型组较正常组CORT及CRH含量均显著降低,ACTH含量无明显改变;经培本方治疗后,CORT及CRH含量均可明显升高,且培本方高剂量组可使ACTH水平有所增高。[结论]培本方抗哮喘作用的机制之一为纠正哮喘HPA轴紊乱。     

T-2毒素对原代培养的小鼠睾丸间质细胞睾酮合成的影响

目的 探讨T-2毒素对原代培养的小鼠睾丸间质细胞(Leydig cells)睾酮合成的影响.方法 建立健康清洁级成年雄性昆明小鼠睾丸间质细胞原代培养模型,使细胞悬液密度为5×10~3个/ml,采用改进3β-羟基类固醇脱氢酶(HSD)染色法进行纯度鉴定.将其分为空白对照[0 ng/ml人绒毛膜促性腺激素(human chorionic gonadotrophin,hCG)+0 mol/L T-2毒素]组、诱导对照(10 ng/ml hCG+0 mol/L T-2毒素)组、10 ng/ml hCG+10~(-9)mol/L T-2毒素组、10 ng/ml hCG+10~(-8)mol/T~(-2)毒素组、10 ng/ml hCG+10~(-7) mol/L T-2毒素组,培养24 h后检测睾酮含量.结果 新鲜分离的小鼠睾丸间质细胞在有血清培养液中培养24h后,细胞贴壁良好,其纯度在90%以上.在10ng/ml hCG诱导下,原代培养的小鼠睾丸Leydig细胞培养液中睾酮合成量明显增加,差异有统计学意义(P＜0.05).与诱导对照组相比,10 ng/ml hCG+10~(-7)、10~(-8)、10~(-9)mol/的T-2毒素染毒组培养液中睾酮合成量均降低,差异有统计学意义(P<0.05或P<0.01);且睾酮合成量随着T-2毒素染毒浓度的升高而降低.结论 T-2毒素可以直接降低原代培养的小鼠Leydig细胞睾酮合成功能.

Abstract：

Objective To investigate the effects of T-2 toxin on testosterone biosynthesis in primary cultured Leydig cell derived from the mouse testis.Methods Leydig cells isolated from Kunming male mice were adjusted to 5×10~5/ml and the purity was identified by the modified 3β-hydroxysteroid dehydrogenase(HSD) staining method.Blank control group(treated with 0 n/ml hCG and 0 mol/L T-2 toxin),inductive control group(treated with 10 ng/ml hCG and 0 mol/L T-2 toxin),low dose T-2 toxin exposure group(treated with 10 ng/ml hCG and 10~(-9) mol/L T-2 toxin),middle dose T-2 toxin exposure group(treated with 10 ng/ml hCG and 10~(-8) mol/L T-2 toxin) and high dose T-2 toxin exposure group(treated with 10 ng/ml hCG and 10~(-7) mol/L T-2 toxin)were designed,respectively.The testosterone level was measured after 24 h of incubation.Results After 24 hours culture in liquid medium contained serum,the fresh isolated Leydig cells grew well and the purity exceeded 90%.Through 10 ng/ml hCG induce,the testosterone level of Legdig cells increased significantly and the difference compared to blank control was of statistical sense (P<0.05).Compared to inductive control group,the testosterone level in Legdig cells decreased significantly in all T-2 toxin exposure groups with a dose dependant manner (P<0.05 or P<0.01).Conclusion T-2 toxin can directly decrease the testosterone biosynthesis of the primary Leydig cells derived from the mouse testis.     

促肾上腺皮质激素对N-甲基-D-天冬氨酸诱发幼鼠痉挛模型应激蛋白表达的影响

目的 分析促肾上腺皮质激素(ACTH)对婴儿痉挛模型应激蛋白表达的影响,为婴儿痉挛症的治疗提供理论依据。方法 将60只新生幼鼠随机分为对照组、N-甲基-D-天冬氨酸(NMDA)组和ACTH组,每组20只。幼鼠出生第11天,ACTH组腹腔注射10 mg/(kg·d) ACTH,其他两组注射等量的生理盐水。幼鼠出生的第15天,NMDA组和ACTH组腹腔注射15 mg/(kg·d) NMDA,对照组注射等量生理盐水。对三组幼鼠痉挛症状进行评分,采用q-PCR法测海马白介素1β(IL-1β)、白介素6(IL-6)和ACTH的mRNA转录水平,Western Blot法测海马促肾上腺皮质激素释放激素(CRH)和促肾上腺皮质激素释放激素1型受体(CRHR1)蛋白表达。结果 NMDA组中幼鼠的痉挛症状评分高于对照组(t=11.236,P<0.001); ACTH组幼鼠的痉挛症状评分低于NMDA组(t=-6.347,P<0.001)。与对照组相比,NMDA组海马IL-1β和IL-6的mRNA转录水平升高(IL-1β: t=6.237,P<0.001;IL-6: t=6.553,P<0.001),ACTH组海马中IL-1β和IL-6的mRNA转录水平低于NMDA组(IL-1β:t=-7.669,P<0.001;IL-6:t=-8.125,P<0.001)。ACTH组海马中ACTH mRNA转录水平高于NMDA组(t=7.758,P<0.001)。与对照组相比,NMDA组海马体CRH和CRHR1蛋白表达上调(CRH: t=7.517,P<0.001;CRHR1: t=7.745,P<0.001),ACTH组海马CRH和CRHR1蛋白表达低于NMDA组(CRH: t=-6.120,P=0.003;CRHR1: t=-6.050,P=0.005)。结论 ACTH可缓解幼鼠的痉挛症状,推测与降低海马体中IL-1β和IL-6的mRNA转录水平,上调ACTH的mRNA转录水平,抑制CRH和CRHR1蛋白表达有关。     

库欣综合征的围手术期处理

库欣综合征为各种病因造成肾上腺分泌过多糖皮质激素(主要是皮质醇)所致病症的总称,可分为依赖垂体促肾上腺皮质激素(ACTH)的库欣综合征和不依赖垂体促肾上腺皮质激素(ACTH)的库欣综合征,其中最多见者为前者.对库欣综合征患者的围手术期正确、恰当处理,能极大降低手术风险,改善预后.以下为笔者对库欣综合征患者的围手术期处理的一点体会.     

锌对免疫细胞功能影响的体外实验研究

用不同浓度含锌培养液在体外培养小鼠脾脏淋巴细胞。当锌浓度在0.12～0.5×10~(-4)mol/L时,~3H-TdR掺入淋巴细胞量明显增加;与分裂原共同培养时,锌明显促进淋巴细胞对ConA和LPS的增殖反应,其促增殖的最佳浓度为0.12×10~(-4)mol/L。锌浓度在1.0×10~(-4)mol/L以上时呈现对细胞的毒性作用。锌还促进混合淋巴细胞反应;增强胸腺细胞对IL-1的增殖反应。     

彗星试验检测叔丁基对苯二酚对苯骨髓毒性的保护作用

目的　用彗星试验检测叔丁基对苯二酚(tert- butylhydroquinone,t BHQ)对苯诱导的骨髓细胞毒性的保护作用。方法　体外培养的大鼠骨髓细胞行t BHQ(10 0 μm ol/ L)预处理12 h后以不同浓度(0、5、10、15、2 0 mm ol/ L)苯分别染毒2、4、6 h。用彗星试验检测骨髓细胞的DNA损伤,计算DNA迁移率和迁移度。结果　随苯染毒浓度的增加,染毒时间的延长,骨髓细胞DNA迁移率和迁移度增加。t BHQ预处理后5、10、15、2 0 mm ol/ L 苯染毒骨髓细胞的DNA迁移率和迁移度均减低(P<0 .0 5 )。结论　苯可诱导骨髓细胞DNA损伤,并呈现一定的时间、剂量依赖性;叔丁基对苯二酚对苯诱导的骨髓细胞毒性有保护作用。     

促肾上腺皮质激素释放激素在足月产及早产中的作用

1981年,Vale从羊的下丘脑提纯出一种激素,因此激素控制着促肾上腺皮质激素(adrenocorticotropic hormone,ACTH)的释放,调节下丘脑-垂体-肾上腺(hypothalamic-pituitary-adrenal,HPA)轴对应激的反应,故命名为促肾上腺皮质激素释放激素(corticortropin-releasing hormone,CRH)。以后的研究表明CRH不仅在脑组织中广泛分布,也可来源于外周组织及人的胎儿胎盘单位。现已证明人类胎盘中有CRH、CRH受体(CRH-receptor,CRH-R)、CRH结合蛋白(CRH-binding protein,CRHBP)及CRH信使RNA(CRHmRNA)的表达。 CRH为41个氨基酸的肽类,分子量4 670,基因定位于第8号染色体的长臂上,由2个外显子和1     

Effect of S(−)- and R(+)-salsolinol on the POMC gene expression and ACTH release of an anterior pituitary cell line

Tetrahydroisoquinolines (TIQs) are thought to play an important role in the process of development of alcohol dependence. Being a condensation product between the alcohol metabolite acetaldehyde and dopamine they might be involved in the balance of the opioid system as well as the reward system. Therefore, the influence of the TIQ salsolinol (SAL) on the pro-opiomelanocortin (POMC) gene expression was investigated using the AtT-20 mouse anterior pituitary tumor cell line. Our results show a significant decrease in the POMC gene expression by the S(−)-enantiomer of SAL. The basal secretion of adrenocorticotropin (ACTH) as well as the corticotropin-releasing factor (CRF)-stimulated ACTH release remained unchanged after R(+)- and S(−)-SAL treatment. Interestingly, it was clearly shown that a reduction of intracellular cAMP level occurred after the treatment of the cells with S(−)-SAL whereas R(+)-SAL did not affect the cAMP production. The obtained results suggest that S(−)-SAL is possibly involved in the establishment of the opioid deficiency in alcoholics.     

Lack of Adrenal Androgen Stimulation by ACTH in Extreme Hyperprolactinemia

Acute and prolonged α 1 -24 corticotropin stimulation was performed on a treated chromophobe adenoma patient with partial ACTH deficiency and extreme hyperprolactinemia. Cortisol and aldosterone stimulated normally. However, the basal concentrations of androstenedione (A) and dehydroepiandrosterone (DHA) were low, and that of DHA-sulfate (DHAS) was undetectable. Furthermore, A and DHA did not stimulate normally, and DHAS did not stimulate at all. It has been claimed that adrenal androgen production is increased in hyperprolactinemia. However, the inability of prolactin (Prl) to maintain adrenal androgen (AA) secretion, with and without added ACTH, is demonstrated in this patient.     

Evaluation of the accuracy of inferior petrosal sinus sampling in the differential diagnosis of ACTH-dependent Cushing's syndrome

The differentiation of adrenocorticotropic hormone producing pituitary adenoma (Cushing's disease) from the ectopic ACTH syndrome is always a complex and difficult task, and in rare cases it is not possible to differentiate between the two disorders, even with the use of dynamic endocrine tests and the most advanced imaging techniques. Inferior petrosal sinus sampling (IPSS) with subsequent ACTH measurements became the gold-standard method of the differential diagnostic process. 34 patients with ACTH dependent Cushing's syndrome in whom the source of ACTH secretion couldn't be identified unambiguously with imaging techniques and/or dynamic endocrine tests underwent altogether 41 IPSS between 1999 and 2005. The sensitivity of the method was calculated on the basis of 31 samplings of 25 patients who had definite endocrinological diagnosis confirmed by the recovery from Cushing's syndrome after surgical intervention and/or by histological examinations (22 patients with ACTH-producing pituitary adenoma and 3 patients with ectopic ACTH syndrome). As a result of IPSS, pituitary-dependent Cushing's disease was diagnosed with a baseline central to peripheral ACTH ratio of >2.0 or with a ratio of >3.0 after corticotropin releasing hormone (CRH) administration. IPSS correctly identified ACTH-producing pituitary adenoma in 20 of 28 sampling procedures, with a sensitivity of 71.4%. Three patients had true negative and 8 had false negative results. There was no false positive result. Four of the 8 patients with false negative first sampling had a repeat sampling procedure leading to true positive result in each patient. In patients with Cushing's disease having true positive interventions, the basal and 5 minutes post-CRH ACTH concentrations were diagnostic in 14 and 19 cases, respectively. The sensitivity of IPSS within this series, reported for the first time from Hungary, was lower than it was found in much larger series published in international literature. In addition to technical difficulties, the lower sensitivity can be accounted also for the highly selected nature of the patient group.     

Lipid synthesis and secretion in HepG2 cells is not affected by ACTH

Apolipoprotein B (apoB) containing lipoproteins, i.e. VLDL, LDL and Lp(a), are consequently lowered by ACTH treatment in humans. This is also seen as reduced plasma apoB by 20-30% and total cholesterol by 30-40%, mostly accounted for by a decrease in LDL-cholesterol. Studies in hepatic cell line (HepG2) cells showed that apoB mRNA expression is reduced in response to ACTH incubation and is followed by a reduced apoB secretion, which may hypothesize that ACTH lowering apoB containing lipoproteins in humans may be mediated by the inhibition of hepatic apoB synthesis. This was recently confirmed in vivo in a human postprandial study, where ACTH reduced transient apoB48 elevation from the small intestine, however, the exogenic lipid turnover seemed unimpaired. In the present study we investigated if lipid synthesis and/or secretion in HepG2 cells were also affected by pharmacological levels of ACTH to accompany the reduced apoB output. HepG2 cells were incubated with radiolabelled precursors ([¹⁴C]acetate and [³H]glycerol) either before or during ACTH stimuli. Cellular and secreted lipids were extracted with chloroform:methanol and separated by the thin layer chromatography (TLC), and [¹⁴C]labelled cholesterol and cholesteryl ester and [³H]labelled triglycerides and phospholipids were quantitated by the liquid scintillation counting. It demonstrated that ACTH administration did not result in any significant change in neither synthesis nor secretion of the studied lipids, this regardless of presence or absence of oleic acid, which is known to stabilize apoB and enhance apoB production. The present study suggests that ACTH lowers plasma lipids in humans mainly mediated by the inhibition of apoB synthesis and did not via the reduced lipid synthesis.     

Cadmium, zinc and copper in horse kidney metallothionein

Cadium, zinc, and copper were determined in kidney cortex samples and in protein fractions obtained from 20 normal Swedish horses. Cadmium concentrations in kidneys ranged from 0.01 to 1.46 mmole/kg. Zinc concentrations in kidneys increased with increasing cadmium concentrations. At low concentrations of cadmium the increase of zinc was almost equimolar with the increase in cadmium, but at higher concentrations of cadmium the increase of zinc was less pronounced. Copper concentrations ranged from 0.07 to 0.22 mmole Cu/kg and were not related to the cadmium concentration. The increase of zinc in kidney cortex took place in the metallothionein (MT) fractions, where also almost all cadmium was recovered. The molar ratio of zinc and cadmium in MT was close to one at low concentrations (below 0.1 mmole/kg) of cadmium but the ratio decreased with increasing cadmium concentrations in the kidney. This change in molar ratio of zinc and cadmium in MT explains the leveling off in zinc increase at cadmium concentrations in kidney exceeding 0.6 mmole/kg.     

Behavior of biochemical stress reactions in real professional performance of teachers in relation to age and occupational ability

In order to investigate the strain of teachers as persons with chiefly psychic load several hormonal parameters (ACTH, HGH, cortisol, catecholamines) and trace elements (zinc, copper) were measured at a teaching day as well as at a teaching-free day. The different influences of age and reduced professional performance on the concentrations of the biochemical parameters were shown. It seems that the variation of release of catecholamines is the most important parameter for the diagnostic of strain in such professional load.     

Relationship between zinc and cellulose intakes in growing rats

We have studied the effect of cellulose on the intestinal absorption of zinc and its metabolism with weanling male rats. Experimental diets were cellulose (5, 8 or 20%) and noncellulose containing normal zinc (AIN-76 mineral mix., 3.0 mg%) or high zinc (10 times of normal, 30 mg%). Weanling rats fed on these diets ad libitum for 16-42 days. There were no significant differences between noncellulose-feeding and cellulose-feeding groups in body weight gain or protein and DNA concentrations in the liver. The inhibitory effect of 20% cellulose on zinc absorption was observed in the long term experiment, as the concentrations of plasma zinc of the group receiving 20% cellulose were decreased significantly more than that of noncellulose-feeding group.     

Stimulation of bile-pancreatic zinc, protein and carboxypeptidase secretion in response to various proteins in the rat

The objective of this study was to determine the rate of bile-pancreatic secretion of zinc, protein and carboxypeptidase (CP) in response to three different dietary proteins, egg white (EW), soy protein isolate (SPI) and casein. The infusion of protein into the duodenum stimulated a significant increase in the secretion rate of zinc, protein and CP in bile-pancreatic juice. There was a high degree of correlation between the concentration of zinc and enzyme activity (CPA and CPB) in bile-pancreatic juice indicating that zinc in bile-pancreatic juice is associated with CP activity. The average secretion rate of zinc, protein and CP during the 1-h period after infusion of protein was significantly greater after SPI infusion than after casein. The bile-pancreatic secretion rate of protein, zinc and CPB in response to EW infusion was consistently intermediate between SPI and casein and did not differ statistically from either. Only CPA secretion rate was significantly greater after EW than after casein. Differences in protein digestibility appear to account for the greater pancreatic response to SPI, and this factor may be important in understanding the effect of protein source on zinc bioavailability.     

The effect of sodium intake on zinc excretion in patients with sickle cell anemia.

Urinary zinc excretion is known to be elevated in subjects with sickle cell anemia. Sodium intake has been suggested to influence zinc excretion in normal subjects. In order to assess the effect of sodium on zinc excretion in subjects with sickle cell anemia, urinary zinc excretion was measured in thirteen children and adolescents with sickle cell anemia on both a high (140 mEq/day) and low (20 mEq/day) sodium intake. Urinary zinc excretion was elevated on both diets. The mean urinary zinc excretion on the high sodium diet (775 +/? 238 micrograms/24 h) was significantly lower (P less than .005) than that on the low sodium diet (947 +/? 344 micrograms/24 h). The zinc excretion did not correlate with calcium or magnesium excretion or aldosterone secretion rates or plasma renin activity. Although elevated, the urinary zinc excretion in patients with sickle cell anemia is still significantly lowered by increasing sodium intake.     

Influence of dietary zinc and cadmium on iron bioavailability in mice and rats: oyster versus salt sources

Two feeding studies with young mice and one in situ intestinal perfusion study with adult rats were conducted to evaluate the influences of intrinsic (oyster) and extrinsic sources of cadmium and zinc on iron metabolism. When oyster was included in the diets, less cadmium accumulated in small intestines whether the cadmium was supplied as cadmium chloride or cadmium intrinsic to oyster. Increasing the zinc concentration of diets containing 2 ppm cadmium reduced cadmium retention in the small intestine regardless of whether the zinc supplied was intrinsic to oyster or as zinc carbonate. Dietary cadmium (20 ppm) reduced iron retention in the small intestine. Increasing dietary intrinsic zinc from 290 to 450 ppm reduced iron retention in small intestine whereas zinc carbonate did not. Inclusion of oyster in low cadmium diets reduced iron retention in the liver. Short-term in situ studies indicated salt sources of cadmium and zinc reduce uptake of iron from the intestine. Iron concentrations in the blood peaked between 20 and 55 min after exposure whether the iron was supplied alone or in combination with cadmium or zinc. The results suggest foods containing high concentrations of cadmium and zinc may reduce the availability of iron.