煅狗骨对实验性骨折愈合作用的垂体TSH,GH细胞免疫细胞化学研究

为检测煅狗骨促进骨折愈合过程中垂体前叶促甲状腺激素(TSH)细胞和生长激素(GH)细胞结构和功能变化,本实验选用家兔54只,制成双侧桡骨标准骨折模型,分成煅狗骨用药组和对照组,术后每周定期取材。脑垂体常规石蜡包埋切片,行免疫细胞化学染色。结果显示对照组骨折后垂体TSH细胞及GH细胞数量均减少,而煅狗骨用药组则并未出现对照组的抑制性变化,TSH细胞数量一直维持较高水平,尤其GH细胞数量随术后时间延长而大幅度上升,因而说明煅狗骨能促进垂体TSH、GH细胞的功能,有利于骨折的愈合。     

Multiple Pituitary Hormone Gradients from Cavernous Sinus Sampling in Patients with Cushing's Disease

Summary  Objective. Cavernous sinus sampling in patients with adrenocorticotropic-hormone (ACTH) secreting pituitary adenomas has been used to identify directly ACTH hypersecretion from the pituitary and to predict the lateralization of a microadenoma. In our previous series, cavernous sinus sampling provided a sufficient central/peripheral (c/p) ratio of ACTH and the correct laterality of the pituitary lesion in all microadenomas situated in the lateral wing. To clarify the diagnostic value of other anterior pituitary hormones in relation to ACTH gradients, we evaluated multiple pituitary hormone gradients between a cavernous sinus and a peripheral vein and between both cavernous sinuses in patients with Cushing's disease.  Methods. Cavernous sinus sampling was done in 11 patients with clinical and biochemical features of ACTH-dependent Cushing's syndrome. In 9, pituitary adenoma was detected during transsphenoidal surgery and histologically confirmed, while 2 others were suspected of having ectopic lesions. Serum ACTH, prolactin (PRL), thyroid stimulating hormone (TSH), growth hormone (GH), luteinizing hormone (LH), and follicle-stimulating hormone (FSH) from catheters in both cavernous sinuses and from a peripheral vein were measured. The c/p ratios of each hormone and the intercavernous gradients were evaluated.  Results. The c/p ratio of ACTH indicated the presense of pituitary lesions in all 9 patients with ACTH-secreting microadenomas. In addition, the intercavernous gradients of ACTH indicated the correct localization of microadenomas in all 6 patients with lateralized lesions. As for other hormones, the c/p ratios of GH, PRL, TSH and LH were significantly high in number 7, 6, 6 and 3 patients, respectively. In contrast, the significant step up of FSH was observed only in one patient. The intercavernous gradients of GH and PRL were significantly high in number 5 and 4 patients, respectively.  Conclusions. The intercavernous gradients of GH and PRL tend to indicate the lateralization of a microadenoma. The measurement of GH and PRL during cavernous sinus sampling may provide additional information, in the lateralization of ACTH-secreting microadenomas.     

Investigation of Peripheral Androgen Resistance in Genital Hypoplasia associated with Congenital Growth Hormone Deficiency

In a male infant with congenital growth hormone deficiency and genital hypoplasia (micropenis, cryptorchidism and small scrotum) androgen receptors, tissue specific 5 alpha reductase and steroid excretion pattern were determined in order to test the hypothesis of peripheral androgen resistance. A reduced number of cytosolic binding sites (Nmax) was found for the T and DHT receptor in patients foreskin compared to controls (n = 9) of similar age. The specific affinity (Kd) of the cytosolic receptor, however, was normal. Tissue specific 5 alpha reductase determination revealed a Vmax of 3.3 pmol/mg/h (controls 15.8 +/- 1.4). Analysis of urinary steroid excretion pattern revealed decreased levels of T metabolites, indicating impaired T metabolism. We postulate, that genital hypoplasia in patients with congenital GH deficiency is associated with impaired target organ responsiveness to androgen hormones caused by abnormalities within the pathway of intracellular reactions of T utilization.     

Cervical sympathectomy affects adrenocorticotropic hormone and thyroid-stimulating hormone in rats

To examine the effects of bilateral cervical sympathectomy on the secretion of adrenocorticotropic hormone (ACTH), thyroid-stimulating hormone (TSH), growth hormone (GH), and prolactin (PRL), 18 male rats were divided into three groups: control (Cont), sham operation (Sham), and bilateral cervical sympathectomy (Symp). All rats were kept under a normal circadian rhythm for 2 weeks. Subsequently, blood was collected and plasma ACTH as well as serum TSH, GH, and PRL levels were measured. The difference in ACTH levels between the Cont and Sham groups was not significant, but ACTH levels in the Symp group were significantly higher than those in the other groups. The difference in TSH levels between the Cont and Sham groups was also not significant, but TSH levels in the Symp group were significantly lower than those in the Cont group. There were no statistically significant differences in GH and PRL levels among these groups. The present results suggest that cervical sympathectomy in the rat increases ACTH secretion and decreases TSH secretion in the pituitary. These effects seem to be due to a mildly increased secretion of melatonin in the pineal body that probably in turn increases corticotropin-releasing factor (CRF) secretion and decreases thyrotropin-releasing hormone (TRH) secretion in the hypothalamus. Extrapolation of these findings to humans suggests that longterm and repeated stellate ganglion block would affect the pituitary secretions of ACTH and TSH.     

43例垂体瘤术后成人生长激素水平调查

[摘要]目的了解垂体瘤患者在接受治疗后生长激素的储备功能及生长激素缺乏与多种垂体激素缺乏之间的关系。方法以2008年5月至2013年7月间,以在河北省沧州市中心医院接受治疗的43位垂体瘤患者作为调查对象,进行胰岛素低血糖兴奋试验（11Tr）,分析生长激素（GH）、促性腺激素（Gn）、促甲状腺激素（TSH）、精氨酸加压素（AVP）和促肾上腺皮质激素（ACTH）的分泌功能。结果共入组43例垂体瘤患者,男性29例,女性14例,中位年龄为48岁。其中仅5例Irrr实验兴奋后GH分泌正常,余38例均患严重的生长激素缺乏症,且表现出一种或一种以上的垂体激素缺乏症状。结论垂体瘤术后,生长激素缺乏症的发生率很高;患有一种或一种以上垂体激素缺乏的患者都会伴有生长激素缺乏症。     

Hormonal effects on the morphology of bone defect healing.

Standard defects were produced in the radii of hypophysectomized immature rats. All animals were injected with Methimazole, and grouped according to hormone supplementation, growth hormone (GH), thyroxine (T4), the combination, or no hormones. Lack of GH and T4 caused a retardation of defect healing and callus formation but not a total cessation. The presence of GH in the hypophysectomized animal caused a larger callus due to greatly increased chondrogenesis throughout the 6 week study. Thyroxine in the hypophysectomized animal increased bone metabolism and caused more cartilage and bone formation than seen in the hormone deficient group, but not as great as that seen in the GH injected animals or the T4 and GH injected animals. Growth hormone allowed greater chondrogenesis; T4 enhanced maturation to bone. The combination allowed the development of a callus similar in stage and proportion of tissue to that observed in the pituitary intact animals. The influences of GH and T4 on the healing of a bone defect in the immature rat correspond to influences of GH and T4 on growing epiphyseal plate.     

TRH: Pathophysiologic and clinical implications

Summary Thyrotropin releasing hormone is thought to be a tonic stimulator of the pituitary TSH secretion regulating the setpoint of the thyrotrophs to the suppressive effect of thyroid hormones. The peptide stimulates the release of normal and elevated prolactin. ACTH and GH may increase in response to exogenous TRH in pituitary ACTH and GH hypersecretion syndromes and in some extrapituitary diseases.The pathophysiological implications of extrahypothalamic TRH in humans are essentially unknown.The TSH response to TRH is nowadays widely used as a diganostic amplifier in thyroid diseases being suppressed in borderline and overt hyperthyroid states and increased in primary thyroid failure. In hypothyroid states of hypothalamic origin, TSH increases in response to exogenous TRH often with a delayed and/or exaggerated time course.But in patients with pituitary tumors and suprasellar extension TSH may also respond to TRH despite secondary hypothyroidism. This TSH increase may indicate a suprasellar cause for the secondary hypothyroidism, probably due to portal vessel occlusion. The TSH released in these cases is shown to be biologically inactive.     

Hyperthyroidism with an FSH-and TSH-secreting pituitary adenoma

A 34-year-old man was found to have elevated thyroxine (T4), triiodothyronine (T3), calculated free T4, thyroid-stimulating hormone (TSH), follicle-stimulating hormone (FSH), and alpha subunits of TSH and FSH. A computed tomography scan of the head showed a 16-mm macroadenoma of the pituitary gland. There was no evidence of loss or excess secretion of other pituitary hormones. The large chromophobe adenoma was removed via a transphenoidal approach. The patient has been taken off all medication. Thyroid function has returned to normal and there has been no loss of pituitary secretory capacity of other pituitary hormones. The occurrence of a combined TSH- and FSH-secreting pituitary adenoma is rare; to the authors' knowledge, only one case has been documented in the literature.     

Plurihormonal pituitary adenoma with concomitant adrenocorticotropic hormone (ACTH) and growth hormone (GH) secretion: a report of two cases and review of the literature

Plurihormonal pituitary adenomas are tumours that show immunoreactivity for more than one hormone that cannot be explained by normal adenohypophysial cytodifferentiation. The most common combinations in these adenomas include growth hormone (GH), prolactin (PRL) and one or more glycoprotein hormone sub-units (β-TSH, β-FSH, β-LH and αSU). The authors report two cases of a plurihormonal pituitary adenoma expressing the rare combination of ACTH and GH. They both underwent successful transphenoidal hypophysectomy (TSH). Long-term post-operative follow-up revealed no evidence of tumour recurrence. Due to the multiple secretions and plurihormonal characteristics clinical diagnosis of composite pituitary adenomas can be difficult. The authors discuss the diagnosis and management of composite pituitary adenomas and review the literature regarding this rare phenomenon.     

Anterior pituitary hormone in severe head injury--with special reference to the GH, TSH, LH and FSH response to TRH and LH-RH

Measurement of the serum level of anterior pituitary hormones (GH, TSH, LH and FSH) and the response of these hormones to their releasing hormones were made in 45 uncomplicated head injury patients within 24 hours after injury. We classified these 45 patients into three groups according to the Glasgow Outcome Scale of six months after head injury, such as good outcome group (GR or MD), poor outcome group (SD or PVS) and dead group. The serum level of the anterior pituitary hormones in dead group were higher than those in the good or poor outcome group, especially the level of GH. The serum level of GH was 14.7 +/- 3.0 ng/ml in the dead group, whereas 5.8 +/- 0.9 ng/ml in the good outcome group and 4.0 +/- 2.1 ng/ml in the poor outcome group. The response of TSH, LH or FSH to the administration of TRH or LH-RH were depressed in the dead group. On the other hand, there were normal response of TSH, LH or FSH following administration of TRH or LH-RH in the other two survival groups. These findings suggested that the measurement of the anterior pituitary hormones and the response of these hormones to their releasing hormones were useful to evaluate the severity of head injury.     

A chemical mutagenesis screen to identify modifier genes that interact with growth hormone and TGF-beta signaling pathways

We describe a phenotype-driven mutagenesis screen in which mice carrying a targeted mutation are bred with ENU-treated males in order to provide a sensitized system for detecting dominant modifier mutations. The presence of initial mutation renders the screening system more responsive to subtle changes in modifier genes that would not be penetrant in an otherwise wild type background. We utilized two mutant mouse models: 1) mice carrying a mutation in growth hormone releasing hormone receptor (Ghrhr) (denoted 'lit' allele, Ghrhr(lit)), which results in GH deficiency; and 2) mice lacking Smad2 gene, a signal transducer for TGF-beta, an important bone growth factor. The Smad2(-/-) mice are lethal and Ghrhr(lit/lit) mice are dwarf, but both Smad2(+/-) and Ghrhr(lit/)(+) mice exhibit normal growth. We injected 6-7 weeks old C57BL/6J male mice with ENU (100 mg/kg dose) and bred them with Ghrhr(lit/)(+) and Smad2(+/-) mice. The F1 mice with Ghrhr(lit/)(+) or Smad2(+/-) genotype were screened for growth and skeletal phenotypes. An outlier was identified as >3 SD units different from wild type control (n=20-30). We screened about 100 F1 mice with Ghrhr(lit/)(+) and Smad2(+/-) genotypes and identified nine outliers. A backcross established heritability of three mutant lines in multiple generations. Among the phenotypic deviants, we have identified a mutant mouse with 30-40% reduced bone size. The magnitude of the bone size phenotype was amplified by the presence of one copy of the disrupted Ghrhr gene as determined by the 2-way ANOVA (p<0.02 for interaction). Thus, a new mouse model has been established to identify a gene that interacts with GH signaling to regulate bone size. In addition, the sensitized screen also demonstrated higher recovery of skeletal phenotypes as compared to that obtained in the classical ENU screen in wild type mice. The discovery of mutants in a selected pathway will provide a valuable tool to not only to discover novel genes involved in a particular process but will also prove useful for the elucidation of the biology of that process.     

Studies on nonthyroidal illness after heart surgery

The concentrations of pituitary hormones (TSH and PRL), thyroid hormones (free-T4 and free-T3), thyroid hormone binding protein (TBG) and lipids (TG and FFA) in the blood were measured in order to examine the physiology of nonthyroidal illnesses that occurred as a result of heart surgery as well as their effects on the pituitary and thyroid glands. The subjects of the study consisted of 30 adults with congenital and acquired heart disease. Blood concentrations of TSH, PRL, free-T4, free-T3, and TBG decreased, and those of FFA increased, on the 2nd day following surgery. On the 2nd day following surgery, the decrease in the concentrations of free-T4 and free-T3 in the blood were considered due to a decrease in secretion of T4 from the thyroid gland, as well as due to a decrease in the activity of iodothyronine 5'-deiodinase in the peripheral organs. In the 3rd week following surgery, the concentrations of these items returned to their original values on the day prior to surgery.     

Immunohistochemical Observations on TSH Secreting Cells in Pituitary Glands of Goat Kids with Congenital Goitre

Pituitary glands of normal‐termed stillborn goat kids with congenital goitre and normal‐termed stillborn goat kids without congenital goitre were examined macroscopically, histopathologically and immunohistochemically. Thyroid glands of these animals were also examined grossly and microscopically. The pituitary glands of kids with goitre were larger than those of normal kids, and on histopathological examination there was hyperplasia of the acidophil cells in the ventral part of the glands. However, it was impossible to distinguish thyroid stimulating hormone (TSH)‐secreting cells from other acidophil cells in sections stained with haematoxylin and eosin (HE). Red granules were observed in the cytoplasm of these hyperplastic cells in periodic acid‐Schiff (PAS)‐stained sections. Sections were also immunostained with an antibody against TSH using the streptavidin–biotin peroxidase technique. Immunohistochemistry revealed TSH‐secreting cells to have increased in number in the pituitary glands of kids with congenital goitre because of the extensive proliferation when compared with those of normal kids. The present study indicated that the presence of multiple fetuses (twins or triplets) may be a predisposing factor for congenital goitre.     

术前短期口服小剂量甲状腺素片对体外循环心脏直视术后患儿正常甲状腺病态综合征的预防效果

目的 评价术前短期口服小剂量甲状腺素片对体外循环心脏直视术后患儿正常甲状腺病态综合征(ESS)的预防效果.方法 择期体外循环下行先天性心脏病矫正术的患儿40例,年龄3～12岁,体重10～30 kg,ASA分级Ⅰ或Ⅱ级,心功能分级Ⅰ级,随机分为2组(n=20):安慰剂组(P组)和甲状腺素片组(T组).T组患儿术前4 d开始每天口服甲状腺素片0.4 mg/kg,连续4 d;P组给予安慰剂.常规建立体外循环,采用浅低温、中度血液稀释、高流量灌注.于入院时(基础状态)、术后第1、2、4天时采集桡静脉血样5 ml,采用酶联免疫法测定血清三碘甲状腺原氨酸(T3)、四碘甲状腺素(T4)、促甲状腺激素(TSH)浓度,于入院时、术毕即刻及术后第1、2天时记录患儿SP、DP和HR.记录患儿气管导管保留时间、ICU停留时间、正性肌力药物的使用情况及术后ESS的发生情况.结果 两组患儿血液动力学指标、ICU停留时间和气管导管保留时间比较差异无统计学意义(P＞0.05).与基础值比较,P组和T组术后第1、2、4天时血清T3浓度降低,术后第1天时血清TSH浓度降低,P组术后第1天时血清T4浓度降低(P＜0.05).与P组比较,T组血清T3和T4浓度升高,术后ESS严重程度和正性肌力药物使用率降低(P＜0.05).结论 体外循环心脏直视手术患儿术前口服小剂量甲状腺素片4 d(0.4 mg·kg-1·d-1)虽可减轻术后正常甲状腺病态综合征的严重程度,但不能预防术后正常甲状腺病态综合征的发生.     

Changes of hypothalamo-pituitary-thyroid function after open heart surgery--especially evaluated by TRH test

Changes of pituitary and thyroid functions after operation were studied in the cases with cardiopulmonary bypass (ECC group) and without bypass (Control group). To know mechanisms of these changes, reaction of hypothalamo-pituitary-thyroid axis by using thyrotropin-releasing hormone (TRH) test and influence of serum cortisol level were examined. Serum concentrations of free T3, free T4 and TSH decreased after open heart surgery. The levels of TSH and free T4 were recovered at the second or third post operative day in Control group, but remained low level at the third POD in ECC group. The level of free T3 continued low level at the 7th POD. The feedback mechanism of the hypothalamo-pituitary-thyroid system was not seen in this series. The response of TSH and free T3 due to TRH test decreased in ECC group, and it was suppressed more clearly in the cases of longer bypass than in those of shorter ones. Serum cortisol level was significantly increased at the 3-hours after the operation in ECC group, and was more increased in the cases of longer bypass than in those of shorter ones. The results indicate that the pituitary and thyroid function on the post bypass period remains euthyroid sick syndrome and hypothalamo-pituitary axis remains suppressed state. Those phenomenon suggest that TRH test may be useful in evaluation of the intensity of surgical stress, especially in those who undergo the cardiopulmonary bypass.     

Pituitary resistance to L-thyroxine after thyroidectomy. A case report

The clinical and laboratory findings in a 29-year-old Saudi Arabian woman were compatible with a state of resistance to thyroid hormones by the pituitary gland. Symptoms of hypothyroidism, amenorrhoea and secondary infertility developed 10 years after partial thyroidectomy for an euthyroid goitre. Before therapy, serum thyroxine (T4) and thyroid-stimulating hormone (TSH) values were elevated; serum tri-iodothyronine (T3) value was at the upper limit of normal while %T3 resin uptake and serum free T4 level were both normal. Treatment with L-thyroxine 150 micrograms/dl was not effective. After this was increased to 200 micrograms/d, serum T4 value rose, TSH was still elevated and there was improvement in symptomatology, and a return of both menses and fertility.     

Physiology of the pituitary, thyroid and adrenal glands

The pituitary gland is made of clusters of cells producing specific hormones that control growth (growth hormones, GH), thyroid function (TH), adrenal function (ACTH), gonadal function (FSH and LH). In addition, the neurons that join the posterior pituitary (neurohypophysis) secrete vasopressin - the antidiuretic hormone involved in maintaining water balance.The negative feedback loop is the basic mechanism to control the regulation of all endocrine glands. Hypothalamic peptides - releasing hormones (e.g. TRH, CRH) reach the hypophysis via the portal venous system and induce the secretion of specific stimulating hormones (e.g. TSH, ACTH) that drive the end-target endocrine cells to secrete hormones (e.g. thyroid hormones - T3 and T4 or adrenal hormones - cortisol, DHEAS). The plasma levels of these circulating hormones inhibit the pituitary (short feedback) or the hypothalamus (long feedback) and limit the further release of releasing- and stimulating- hormones.The effects of circulating hormones on different tissues are mediated via specific receptors on the cell membrane (e.g. vasopressin receptors), in the cytoplasm (steroid receptor for cortisol) or in the nucleus (e.g. thyroid hormone receptors). Understanding the physiological effects of peripheral hormones helps understanding the mechanisms by which clinical signs and symptoms developed in diseases characterised by excessive hormone secretion (e.g. thyrotoxicosis, Cushing syndrome, phaeochromocytomas) or lack of hormone secretion (e.g. diabetes insipidus).     

Hypothalamic-pituitary-adrenal activity among Armenian adolescents with PTSD symptoms

This study evaluated basal levels and responsiveness to exercise of plasma adrenocorticotropic hormone (ACTH), and serum thyroid stimulating hormone (TSH), growth hormone (GH) and cortisol among adolescents from two differentially exposed groups 61/2 years after the 1988 earthquake in Armenia. Severity of total PTSD and Category C and D symptoms were negatively correlated with baseline cortisol. Preexercise ACTH was significantly lower, and preexercise TSH higher, among adolescents with more exposure. Depressive symptoms were negatively correlated with baseline cortisol and positively with TSH. Mean GH, TSH, and cortisol levels in both groups fell within normal limits. The pre- to postexercise increase in GH, TSH, and cortisol suggests that exercise challenge may be useful in the field investigation of neurohormonal activity among traumatized individuals.     

Comparison of pituitary-thyroid function in patients with endstage renal disease and in age- and sex-matched controls

The response to i.v. bolus thyrotropin-releasing hormone (TRH) of 14 dialysis patients with end-stage renal disease (ESRD) was compared to the response of 14 age- and sex-matched renal clinic patients (controls) with normal renal function (serum creatinine concentrations less than 1.2 mg/dl). The mean basal serum levels of thyrotropin (TSH) were similar in the two groups. There was no difference between the two groups in the mean maximal increase in TSH after TRH (6.3 microU/ml and 7.2 microU/ml in ESRD and control groups, respectively); The rate of fall in TSH from 60 to 90 min after TRH was slower in the ESRD group than in the controls. The mean increase in serum triiodothyronine (T3) concentration after TRH was similar in both groups (25.4 ng/dl, ESRD; 18.4 ng/dl, controls). As previously reported, basal serum T3 content was subnormal in the ESRD patients. Serum thyroxine (T4) concentrations were comparable in control and ESRD groups and did not change significantly during the 90-min TRH test in either group. We conclude that ESRD patients, clinically stable on dialysis, have normal pituitary TRH responsiveness and normal thyroidal response to endogenous TSH secretion, as compared with an age- and sex-matched group of patients with normal renal function. The results of this study support the contention that ESRD patients are eumetabolic.