垂体泌乳素瘤下丘脑多巴胺调节功能的评价

本文以卡比多巴 左旋多巴(CD LD)和灭吐灵(MCP)试验,观察了11例垂体泌乳素(PRL)瘤和7例健康女性血TSH和LH水平的变化,同时与血PRL的变化作比较。结果表明PRL瘤患者血PRL不被CD LD抑制,但其TSH和LH可被显著抑制,并与正常组相似。患者血PRL对MCP的反应低减,而TSH和LH的反应却显著高于正常组,其升高幅度与血PRL基础值呈正相关。提示,PRL瘤患者下丘脑多巴胺调节功能正常,并存在多巴胺与PRL间反馈机制,以致下丘脑多巴胺含量相对过多。     

甲氰咪胍对PRL、LH及FSH分泌的调节作用

作者研究了10例健康男子单独肌注LHRH 100μg及加注甲氰咪胍(静脉和肌注各200mg)后LH,FSH及PRL的反应,发现加注甲氰咪胍后血清LH和FSH值均显著下降(P<0.05～0.001),反应曲线下绝对面积分别由4300±1050降为1805.90±394及527.71±131.10降为209.96±70.56mm~2以及LH和FSH的峰值/基础值的比值明显下降,均有显著差异,提示H_2-受体拮抗剂甲氰咪胍可抑制促性腺激素的释放。单独肌注LHRH后120分钟时相的血清PRL值较基础值增加1.66±0.20倍,P<0.05。加用甲氰咪胍,30分钟时相的血清PRL值明显升高,峰值提前出现,提示组胺通过H_1-受体兴奋PRL分泌或甲氰咪胍间接地降低多巴胺能活性而导致PRL释放。     

垂体PRL对TRH刺激试验的反应在女性垂体瘤中的诊断价值

本文报告了24例正常妇女、10例正常产妇、32例女性垂体PRL瘤、8例女性垂体GH瘤及5例女性其他垂体肿瘤患者血PRL对TRH刺激的反应。本文结果指出单凭峰/基比值来确定有无垂体PRL瘤或鉴别垂体PRL微腺瘤性及功能性高PRL血症是不够的。应全面分析PRL基础值、峰值、高峰时间及峰/基比值方能有助于诊断。     

男性老年肺心病患者垂体促性腺激素的储备和排泌功能研究

我们对老年男性肺心病急性发作期(n=12)和缓解期(n=6)均进行血基础激素水平测定和黄体生成素释放激素(LHRH)兴奋试验。结果表明,急性发作期和缓解期睾酮(T)、黄体生成素(LH)均低于健康对照组(P<0.01);经LHRH兴奋后LH反应峰值、绝对升高值(△LH)、峰值上升速率(△LH/△t)、峰值增高倍数均非常显著或显著低于对照组。     

LHRH兴奋试验早期鉴别诊断青少年的体质性青春发育延迟和男性低促性腺激素性功能低减的价值

目的　以LHRH兴奋试验鉴别诊断体质性青春发育延迟 (constitu tionaldelayedpuberty ,CDP)和男性低促性腺激素性性功能低减 (hypogonadotropichypogonadism ,HH)。 方法　所有患者试验时均处于生殖发育第Ⅰ期 ,试验时给患者静脉注射LHRH 10 0 μg ,分别于 -15、0、15、3 0、45、60、90及 12 0min取血 3毫升 ,用放免法测定血清黄体生成素 (LH)和促卵泡激素 (FSH )水平。此后患者在门诊每 3～ 2 4个月随诊一次 ,一直追查到 18岁以后即至确诊有无正常青春发育后为止。根据其青春发育情况将患者分为青春发育正常组 (n =3 4) ,CDP组 (n =16)及HH组 (n =3 1)。 3组患者接受LHRH兴奋试验的年龄分别为 ( 10 .2± 0 .9)岁 ( 9～ 14岁 ) ,( 16.0± 1.0 )岁 ( 14～ 18岁 )和 ( 17.1± 1.4)岁 ( 16～ 2 2岁 )。结果　正常组 ,CDP组和HH组血清LH基础值和达峰时间均无差异 ,而血清LH峰值 ,血清LH峰值与基础值间的差值即血清LH增加值 ,血清LH增加倍数及血清LH曲线下面积 (AUCLH) ,正常组均明显高于CDP组和HH组 (P均 <0 .0 0 1) ,CDP组也明显高于HH组 (P均 <0 .0 0 1)。在 3组受试者中 ,分别绘制血清LH峰值、LH增加值对LHRH兴奋试验的工作特性曲线 (ROC) ,根据ROC可以确定以下两指标的切点 :血清LH峰值 8IU/L ,血清LH增     

PIT-1及PROP-1与联合垂体激素缺乏症

垂体前叶特异性转录因子(PIT)-1及其祖先蛋白(PROP)-1异常可致联合垂体激素缺乏症(CPHD)。其中PIT-1与胚胎期垂体前叶的发育和促甲状腺激素(TSH)、催乳素(PRL)及生长激素(GH)基因的表达有关，其基因突变者典型表现为血TSH、PRL、GH完全缺乏，MRI示垂体萎缩。而PROP-1也是一种垂体特异转录因子，启动胚胎期PIT-1基因的起始表达及维持个体出生后的持续表达，并可直接促使PIT-1细胞系的前体分化为促性腺细胞系，其基因突变患者除GH、PRL、TSH缺乏外，尚有促黄体激素、促卵泡激素或促肾上腺皮质激素缺乏。     

贵州省地方性克汀病垂体—性腺系统功能对LHRH兴奋试验的反应

在已经加碘得到控制的碘缺乏性疾病病区,观察了地方性克汀病垂体--性腺系统对促黄体激素释放因子(LHRH)试验的反应。结果:男性克汀病病人组血清黄体生成激素(LH)和卵泡刺激素(FSH)基础值显著高于对照组,但其血清睾酮(T)值则显著低于对照组。静脉注射 LHRH100μg15分钟后,克汀病病人组血清 FSH 反应高于正常人组,LH 反应与正常对照组相似。两组血清 T 值于试验后无显著变化。静脉注射接着静脉滴注 LHRH,克汀病病人组 FSH 反应高于正常人,其 LH 最大增值和反应倍数均低于对照组,正常人组 LH、FSH 呈双相反应,克汀病病人组则无此反应。血清 T,正常人组试验后2-3小时显著升高,克汀病病人组无则显著变化。结果表明克汀病病人不仅有原发性 Leydig 和 Sertoli 细胞功能低下,而且还有垂体促性腺激素储备和再合成功能的减低。     

男性系统性红斑狼疮患者性激素变化的分析研究

目的:探讨男性系统性红斑狼疮(SLE)患者性激素指标睾酮(T)、泌乳素(PRL)、雌二醇(E2)、黄体生成素(LH)、卵泡刺激素(FSH)、孕酮(Pro)及其相关比值与病情的关系。方法:采用美国ARCHITECT i2000SR化学发光分析仪测定69例男性SLE患者(检测组)和41例健康者(对照组)的性激素6项指标。结果:与对照组比较,SLE组T水平显著降低(P0.05),PRL、E2、LH水平显著升高(P0.05),FSH、Pro差异无统计学意义(P0.05);T正常、PRL、E2、LH升高及PRL、E2、LH正常、T降低2组结果相关比值T/PRL、T/E2、T/LH均显著降低(P0.05)。SLE活动期PRL水平明显高于稳定期,差异有统计学意义(P0.05);活动期T、E2、LH、FSH、Pro水平与稳定期差异无统计学意义(P0.05)。结论:T、PRL、E2、LH水平及其相关比值与男性SLE病情密切相关,对评估SLE活动性评价有一定意义。     

垂体前叶病变性闭经

垂体前叶即腺垂体,以垂体门脉系统与下丘脑构成下丘脑-腺垂体系统,直接接受下丘脑神经内分泌激素的调控,可以分泌FSH、LH、PRL、TSH、ACTH和GH六种激素,即性腺六项。垂体前叶病变是引起闭经的重要组成部分。由于腺垂体器质性病变或功能失调引起其分泌激素异常,尤其是促性腺激素分泌异常,进而影响下游卵巢功能,引起闭经。     

雌激素受体在人类垂体腺瘤中的表达

目的检测雌激素受体(estrogen receptor,ER)在人类不同类型激素垂体腺瘤中的表达,探讨垂体腺瘤中分泌不同类型激素的腺瘤细胞与ER免疫组化阳性细胞之间的关系.方法采用免疫组化S-P法对53例垂体腺瘤标本进行激素分型,检测垂体腺瘤中ER蛋白的表达.采用免疫组化双标法检测多激素分泌型垂体腺瘤中垂体激素合并ER表达的情况.结果53例垂体腺瘤标本中,部分PRL(5/7)、FSH(2/3)、LH(1/1)单激素腺瘤及部分多激素腺瘤有ER蛋白表达,而全部GH、ACTH、TSH单激素腺瘤均无ER蛋白表达,4例无功能腺瘤无ER蛋白表达.在33例多激素型垂体腺瘤标本中,22例有ER蛋白表达,其中PRL ER双标染色阳性标本10例、LH ER双标染色阳性标本9例、FSH ER双标染色阳性标本7例、GH ER双标染色阳性标本2例,33例标本的ACTH ER和TSH ER的双标染色均为阴性.结论垂体腺瘤患者的性别不影响肿瘤组织中ER蛋白的表达.垂体腺瘤中,分泌PRL、LH或FSH的垂体腺瘤细胞可表达ER;分泌ACTH或TSH的垂体腺瘤细胞不表达ER;分泌GH的垂体腺瘤细胞是否表达ER可能与该垂体腺瘤是否同时分泌PRL有关.ER在PRL、LH及FSH垂体腺瘤细胞的发生、发展中发挥作用.     

GONADOTROPHIN, THYROTROPHIN AND PROLACTIN RESERVE IN β THALASSAEMIA

Gonadotrophin (Gn), thyrotrophin (TSH) and prolactin (PRL) reserve was evaluated in patients (aged 12-26 years old) with beta thalassaemia. Abnormalities were detected in Gn reserve only. When compared with young adult controls, three of the four female patients and one of the two adult males had markedly impaired Gn responses to LH-releasing hormone (LHRH). Of the five prepubertal males, one had no Gn rise following LHRH, while responses in the other four patients were comparable to those in boys with delayed puberty. Only one adult male had an exaggerated LH response to LHRH. TSH and PRL dynamics were normal. No correlation could be found between the severity of the disturbance in the gonadal axis and the total number of blood transfusions. Our findings correlate best with the severity of the disease process itself.     

THE INTERACTION OF GROWTH HORMONE RELEASING HORMONE WITH OTHER HYPOTHALAMIC HORMONES ON THE RELEASE OF ANTERIOR PITUITARY HORMONES

To determine whether the 29 amino-acid fragment of growth hormone releasing hormone (GHRH) can be combined with other hypothalamic releasing hormones in a single test of anterior pituitary reserve, the responses of anterior pituitary hormones to combinations of an i.v. bolus of GHRH(1-29)NH2 or saline with an i.v. bolus of either LH releasing hormone (LHRH) plus TRH, ovine CRH(oCRH) or saline were studied. Each infusion of GHRH(1-29)NH2 resulted in a rapid increment of the plasma GH value. Infusion of GHRH(1-29)NH2 also caused a small and transient rise in plasma PRL, but no change in the integrated PRL response. The combination of GHRH(1-29)NH2 with LHRH plus TRH caused a larger increment of peak and integrated plasma TSH levels than LHRH plus TRH alone. GHRH(1-29)NH2 did not affect the release of other anterior pituitary hormones after infusion with oCRH or LHRH plus TRH. Because of the finding of potentiation of the TSH-releasing activity of LHRH plus TRH by GHRH(1-29)NH2, the study was extended to the investigation of TSH release after infusion of TRH in combination with either GHRH(1-29)NH2 or GHRH(1-40). In this study the combination of TRH with both GHRH preparations also caused a larger increment of the peak and integrated plasma TSH levels than TRH alone. It is concluded that GHRH(1-29)NH2 possesses moderate PRL-releasing activity apart from GH-releasing activity. In addition, GHRH potentiates the TSH-releasing activity of TRH.(ABSTRACT TRUNCATED AT 250 WORDS)     

PRIMARY HYPOTHYROIDISM OF CHILDHOOD: EVALUATION OF THE HYPOTHALAMIC-PITUITARY GONADAL AXIS BEFORE AND DURING L-THYROXINE REPLACEMENT

Hypothyroidism is frequently associated with abnormal sexual development. To determine the longitudinal influence of thyroxine replacement on the hypothalamic pituitary gonadal axis, we studied five prepubertal hypothyroid girls and two boys before, and all the girls six weeks and one year after, thyroxine replacement. All girls showed significantly elevated basal gonadotrophin concentrations before treatment. Following one year of therapy, despite all girls having begun puberty, basal gonadotrophin concentrations were significantly decreased in the four euthyroid girls as compared with our normal pubertal girls. The fifth girl studied at one year was hypothyroid at the time of testing and her gonadotrophin values were increased even above previous basal values. Pretreatment serum TSH values inversely correlated with maximum pretreatment incremental LH (r = -0.54) and FSH (r = -0.52) responses to LHRH. Serum TSH values directly correlated with PRL concentrations (r = +0.82). Of the two hypothyroid boys evaluated, Patient 1 was mildly hypothyroid and showed normal prepubertal basal LH, FSH, testosterone and low normal LHRH responsiveness. Patient 2, who was more severely hypothyroid, had elevated basal gonadotrophin secretion and responsiveness to LHRH but prepubertal testosterone concentrations. These data indirectly show that thyroxine may increase the biological/immunological potency of gonadotrophins. The elevated gonadotrophin values in the hypothyroid state suggest that the metabolic clearance rate of gonadotrophins is prolonged. The more severe the elevation in TSH secretion, the more marked was the alteration in the hypothalamic pituitary axis in respect to PRL secretion and delta max LH and FSH response to LHRH. Replacement with thyroxine was followed by normal pubertal development, and normal pubertal oestradiol and PRL concentrations, despite low immunoreactive gonadotrophin secretion.     

DECREASED LH RESPONSE TO THE SECOND OF CONSECUTIVE DAY LUTEINIZING HORMONE RELEASING HORMONE (LHRH) INFUSIONS AMONG PATIENTS WITH CONSTITUTIONAL DELAY OF PUBERTY: A PHENOMENON OF PUBERTAL MATURATION?

Consecutive day LHRH stimulation by continuous infusion has been used to evaluate pituitary reserve. Different responses on the 2 days were not present among non-pubertal hypopituitary patients, pubertal growth hormone deficient patients or adult males. However, patients with constitutionally delayed puberty demonstrated a greater serum LH response on day 1 than day 2. Urinary LH responses suggest a similar but not statistically significant pattern. This response may be a normal phenomenon of puberty or may represent part of the reason for constitutionally delayed puberty.     

THE INTERRELATIONSHIPS BETWEEN PROLACTIN AND THYROTROPHIN SECRETION FOLLOWING DOPAMINERGIC BLOCKAGE IN PATIENTS WITH MILD HYPERPROLACTINAEMIA WITHOUT ANY DEMONSTRABLE PITUITARY TUMOUR

PRL, TSH and gonadotrophin responses to the dopaminergic antagonist, metoclopramide, were studied in mildly hyperprolactinaemic patients with normal sella radiology and CT scan. Eleven female patients with basal PRL levels ranging from 23 to 124 ng/ml were challenged with intravenous metoclopramide (10 mg) and on subsequent occasions with TRH (200 micrograms) and LHRH (100 micrograms). On the basis of the PRL secretory pattern following metoclopramide and TRH stimulation, the patients were divided into two groups. Group I comprised six subjects who were PRL non-responsive to TRH and metoclopramide. Group II (five subjects) demonstrated PRL responses to TRH and metoclopramide indistinguishable from female controls. Mean +/- SD basal PRL levels were 68.5 +/- 29.9 ng/ml in Group I and not different in Group II (40.6 +/- 12.0 ng/ml). Basal LH levels were increased in Group II, whereas FSH was increased in Group I. Basal TSH levels were lower in Group I than the controls. Following metoclopramide, Group I patients had an increase in TSH from a basal of 2.4 +/- 0.7 microU/ml to a peak of 5.9 +/- 2.7 microU/ml (P less than 0.005) which occurred at 30 min. TSH values were increased above basal at all time intervals following metoclopramide. In contrast, TSH levels did not change in Group II patients or the controls after metoclopramide administration. Both patient groups had TSH responses to TRH similar to the controls. Following LHRH, the LH increase was greater in Group II and the FSH in Group I. In neither group nor the controls did gonadotrophin levels change after metoclopramide. In Group II females, PRL responsiveness to metoclopramide was associated with TSH non-responsiveness. In Group I females, PRL levels failed to rise, whereas TSH increased. The PRL and TSH profile in Group I females is typical of a prolactinoma. It is concluded that PRL as well as TSH determinations following metoclopramide are useful indices in the assessment of hyperprolactinaemia and may be of value in differentiating the functional state from that of a pituitary tumour.     

THE EFFECT OF LISURIDE HYDROGEN MALEATE, AN ERGOT DERIVATIVE ON ANTERIOR PITUITARY HORMONE SECRETION IN MAN

The effects of single oral doses of 0.2 mg of lisuride hydrogen maleate, a semisynthetic ergot derivative, on serum levels of prolactin (PRL), growth hormone (GH), thyroid stimulating hormone (TSH), luteinizing hormone (LH), follicle stimulating hormone (FSH), cortisol and blood glucose were studied in six normal males. Lisuride effectively inhibited basal PRL secretion as well as the PRL response to TRH given 3 h later. In addition, the drug raised basal GH levels and decreased basal and TRH stimulated TSH secretion. No significant differences between lisuride and control were observed in basal LH and FSH, LHRH stimulated gonadotrophins or in cortisol. Drowsiness was noted by all subjects, one became nauseated and another vomited, 60 and 90 min respectively after administration of lisuride. No changes were seen in pulse rate and blood pressure. The endocrine effects of lisuride were attenuated by the prior administration of the dopamine antagonist metoclopramide. These results suggest that lisuride acts as a long-acting dopamine agonist and that therefore this drug could be of therapeutic use in hyperprolactinaemic states and acromegaly.     

Premature thelarche and central precocious puberty: the relationship between clinical presentation and the gonadotropin response to luteinizing hormone-releasing hormone

Premature thelarche is a benign condition that affects young girls. In contrast, central precocious puberty is considered a more serious disorder that causes progressive secondary sexual development, accelerated growth and skeletal maturation, early epiphyseal fusion, and short adult stature. Differentiation between these 2 conditions is important, but may be difficult on clinical grounds, since patients with both disorders may present initially as isolated breast development. To examine the potential usefulness of gonadotropin measurements in distinguishing early central precocious puberty from premature thelarche, we measured basal and LHRH-stimulated plasma gonadotropin levels in 58 girls with idiopathic premature breast development. The girls were divided into six clinically distinct groups, based on the severity of clinical presentation, ranging from isolated breast development (group A) to complete secondary sexual development and accelerated growth and skeletal maturation (group F). The mean basal plasma LH levels and the peak LH response to LHRH stimulation were significantly less in girls with isolated thelarche (group A) than in girls with complete sexual development (group F). The mean basal plasma FSH levels did not differ between these groups, but the peak FSH response to LHRH was greater in girls with isolated thelarche than in girls with complete sexual development. Thus, girls with isolated premature thelarche had a FSH-predominant response to LHRH [mean ratio of peak LH to peak FSH, 0.29 +/- 0.10 (+/- SD)], while girls with complete sexual development had a LH-predominant response (peak LH/FSH, 4.16 +/- 1.80). All girls with isolated thelarche had peak LH/FSH ratios less than 1, and all girls with complete sexual development had a ratio greater than 1. Girls with early or intermediate manifestations of central precocious puberty, who had features of puberty in addition to breast development but lacked all of the features of group F, comprised groups B-E. These girls also had intermediate peak LH/FSH ratios, ranging from 0.29 +/- 0.10 (group B) to 3.35 +/- 2.66 (group E). We conclude that girls with early central precocious puberty frequently have LH and FSH responses to LHRH that are indistinguishable from the FSH-predominant responses of girls with isolated thelarche. These data are consistent with the hypothesis that premature thelarche and central precocious puberty may represent different positions along a continuum of hypothalamic LHRH neuron activation.     

Prolactin responsiveness to TRH and metoclopramide in thalassaemia

PRL and gonadotrophin secretion has been evaluated in six prepubertal male thalassaemic patients and nine females. Four of the latter were sexually immature (group 1) and the remainder had more advanced sexual development (group 2). Subjects were challenged with LHRH (100 μg), TRH (200 ug) as well as the dopaminergic antagonist, metoclopramide (10 mg) and their responses compared with normal adult controls. The male patients had low testosterone, oestradiol and basal and peak LH responses to LHRH. FSH values were intact. Basal PRL levels, as well as PRL responses to TRH and metodopramide were normal. There was a further increase in PRL response to TRH after the administration of a long acting testosterone preparation. In group 1 females, basal and peak gonadotrophins and oestradiol were decreased. Basal PRL was normal, but there was a markedly impaired PRL response to both TRH and metoclopramide. Oestradiol valerate administration restored the impaired PRL response to TRH, but not to metoclopramide in group 1 female subjects, although conjugated oestrogens had no effect. Group 2 females had normal gonadotrophin profiles, but low oestradiol levels. Their PRL response to TRH was normal, but they also demonstrated an impaired PRL response to metoclopramide. It is concluded that the impaired PRL reserve in female thalassaemic patients could be due to iron infiltration in the pituitary, or to oestradiol deficiency. It may also be related to the low LH levels or, alternatively, it may represent some alteration in dopamine tone.     

Central hypocortisolism as part of combined pituitary hormone deficiency due to mutations of PROP-1 gene

BACKGROUND: One of the causes of combined pituitary hormone deficiency (CPHD) is represented by Prophet of Pit-1 (PROP-1) gene inactivating mutations. This disorder is generally characterized by GH, TSH, prolactin (PRL), and gonadotropin deficiency, but recent papers have described a concomitant alteration of the corticotrope function. OBJECTIVE: To make a detailed investigation of the hypothalamic-pituitary-adrenal axis in two sisters with PROP-1 gene mutations. PATIENTS: Two female siblings (17 and 16 years old) with CPHD, belonging to a Brazilian family of consanguineous parents, presented with growth retardation and central hypothyroidism during childhood, and showed central hypogonadism at the age of puberty. No clear clinical symptoms and signs of hypocortisolism were present. METHODS: GH, TSH, free thyroxine, total tri-iodothyronine, PRL, LH, FSH, ACTH and cortisol were measured in basal condition and after appropriate testing. The molecular study was performed by PCR amplification and sequencing analysis of PROP-1 gene. RESULTS: Both patients showed GH, PRL, LH and FSH deficiencies, associated with absent responses to an insulin tolerance test (ITT), TRH and GnRH injection. Circulating concentrations of TSH were normal in basal conditions, but failed to respond to a TRH test. Plasma ACTH concentrations were normal, but serum cortisol concentrations were below the lower limit of the normal range, showing a trend to decrease during 6 years of follow-up. The serum ACTH response to ITT was impaired, whereas its response to CRH was normal and prolonged. The cortisol response to both tests, and to the ACTH test, was clearly impaired. In both sisters, the genetic analysis showed the presence of a homozygous 2-bp deletion (296delGA) of PROP-1 gene, which results in the synthesis of a protein with no residual functional activity. CONCLUSION: In addition to GH, TSH, PRL and gonadotropin deficiency, patients with PROP-1 gene mutations can present with late-onset central hypocortisolism, possibly beause of the lack of important paracrine factors normally produced by the cells surrounding the corticotropes and absent in the pituitary of these patients, or because of progressive corticotrope apoptosis. This finding indicates the need for life-long endocrine monitoring of PROP-1-deficient patients.