中枢神经系统多巴胺对垂体泌乳素瘤分泌泌乳素的调节

为探讨垂体PRL瘤的发病机制,对7名正常成年女性及9例垂体PRL瘤女性患者进行静脉滴注多巴胺(DA)、口服左旋多巴(LD)及联合服用LD及卞比多巴(CD,不进入中枢神经系统的多巴脱羧酶抑制剂)试验。静滴DA及口服LD后.两组受试者血浆DA水平升高,血清PRL水平下降。联合服用LD及CD后,血浆DA停留于基础水平,血清PRL水平在对照组与单服CD者有相等的下降,但垂体PRL瘤组下降程度明显减少。结果提示垂体PRL瘤患者可能有中枢性DA抑制作用的减弱。     

用联合下丘脑释放激素兴奋试验评价特发性生长激素缺乏性侏儒其他垂体前叶激素的储备功能

联合使用GHRH、TRH、LHRH和CRH四种下丘脑释放激素检查6例正常青少年和50例未治疗IGHD患者血PRL、TSH、LH及F的反应,并从基础值、峰值、峰值增加值、峰值/基础值比值、激素反应曲线下面积和阳性反应率等六个方面比较两组结果。IGHD患者血PRL、TSH及F六项指标的反应与对照组比较差异无显著性,表明IGHD患者垂体PRL、TSH及ACTH细胞的储备功能正常。约2/3IGHD患者LH细胞的储备功能低下。在青春发育年龄的IGHD患者LH对LHRH的反应除峰值/基础值比值以外,另五项指标均非常明显低于对照组(P<0.001),这可能是成年IGHD患者性发育延迟及差的原因。     

灭吐灵作泌乳素兴奋试验对垂体泌乳素微腺瘤诊断的意义

本文对17例泌乳无排卵妇女采用肌肉注射灭吐灵(MCP)作泌乳素(PRL)兴奋试验。并以5例正常月经卵泡早期(EF)及4例产褥早期(PP)妇女作对照。探讨MCP兴奋试验在早期诊断垂体PRL微腺瘤方面的意义。结果显示:EF组给MCP后血PRL水平升高7倍以上。泌乳无排卵组血PRL升高倍数平均为1.51倍,其中4例无反应,显著低于EF组。肿瘤组与非肿瘤组间无显著差异,因此不支持MCP兴奋试验有助于鉴别垂体PRL微腺瘤及功能性高PKL血症的论点。本文还对上述两种疾病的关系及处理进行了讨论。     

急性脑血管病患者下丘脑-垂体-性腺轴及泌乳变化的探讨

目的观察急性脑血管病患者下丘脑一垂体一性腺轴的变化.方法用放免法测定急性脑血管病患者血中PRL、LH、FSH、E2、T.结果PRL、LH、FSH、E2明显增高,P、T下降.结论急性脑血管病影响下丘脑-垂体-性腺轴的功能变化.     

急性脑血管病患者下丘脑-垂体-性腺轴及泌乳素变化的探讨

目的　观察急性脑血管病患者下丘脑—垂体—性腺轴的变化。方法　用放免法测定急性脑血管病患者血中 PRL、LH、FSH、E2、T。结果　PRL、LH、FSH、E2明显增高 ,P、T下降。结论　急性脑血管病影响下丘脑—垂体—性腺轴的功能变化。     

神经性厌食患者内分泌功能的改变

目的　了解神经性厌食患者内分泌功能的改变及其临床特点。方法　分析 3 0例神经性厌食患者内分泌激素水平的变化及临床资料。结果　 (1)本组神经性厌食者均为女性 ,平均年龄 (18.4± 2 .1)岁 ,病程 1～ 6年。临床表现为厌食、严重营养不良和继发性闭经 ;(2 )大多数患者LH、FSH和E2 明显降低 ;8例患者行GnRH刺激时 ,LH、FSH呈延迟反应 ;(3 ) 15例患者甲状腺激素和TSH均正常 ,9例患者表现为单纯性T3 和FT3 减低 ,6例患者甲状腺激素均降低 ;(4 )血、尿皮质醇水平均正常 2 4例 ,增高 6例 ,出现节律紊乱 6例 ;(5 )GH升高 15例 (15 / 16) ,PRL均正常 2 0例(2 0 / 2 0 )。结论　严重营养不良和继发性闭经为神经性厌食患者的主要临床表现 ,伴有多种内分泌功能紊乱 ,继发性闭经是显著体重下降和下丘脑 垂体 性腺轴功能紊乱共同作用的结果。     

下丘脑—垂体疾病患者血清促甲状腺激素对促甲状腺激素释放激素试验的反应

对51例下丘脑—垂体疾病患者进行促甲状腺激素释放激素(TRH)试验,以观察不同病变时血清促甲状腺激素(TSH)对TRH试验的反应。结果显示51例病人中TRH试验反应异常的有27例,占52.9%,与正常对照组有非常显著性差异(P<0.005)。其中下丘脑病变者反应较为一致,多呈延迟反应;垂体病变者反应变化较大。在判定结果时应考虑病变的性质,部位,激素与激素或神经递质间的相互关系以及病程和患者的营养状况等因素的影响。     

男性肝硬化失代偿期患者垂体及性腺激素水平变化

报告35例男性肝硬化失代偿期患者血清FSH、LH、PRL、E_2、T测定结果,并与50例正常健康人对照。结果显示血清PRL显著升高(P<0.001),E_2升高(P<0.05),T显著降低(P<0.001),FSH、LH近于正常水平(P>0.05)。提示肝硬化失代偿期患者存在下丘脑—垂体—性腺轴功能障碍。     

垂体促甲状腺素瘤的临床特点与诊治分析

目的 分析TSH瘤的临床特点和诊治经验.方法 对2006年1月至2011年9月在本院确诊治疗的16例垂体TSH分泌瘤患者的临床表现、实验室检查以及辅助检查和手术治疗效果进行分析.结果 (1)男性9例,女性7例,年龄(51.63±13.23)岁.就诊原因为甲状腺毒症症状占87.5％(14/16),仅2例分别因视物障碍和体检发现甲状腺功能异常.16例患者均无突眼、杵状指、胫前黏液性水肿.(2)血清FT4和FT3水平均高于正常,血清TSH(4.37±2.77)μIU/ml,25％(4/16)的患者同时合并血清甲状腺球蛋白抗体和(或)甲状腺过氧化物酶抗体阳性,促甲状腺素受体抗体全部阴性.9例行TRH兴奋试验:3例有反应(TSH高峰较基线上升5.45～9.20μIU/ml),6例无反应(TSH高峰较基线上升-0.01～3.15μIU/ml).11例患者行生长抑素试验:TSH平均被抑制到基线的27.15％(5.19％～99.15％).有2例患者分别合并血清催乳素和胰岛素样生长因子Ⅰ升高.垂体MRI显示垂体占位15例,其中微腺瘤10例,垂体大腺瘤5例;1例患者垂体未见异常,但见鼻腔内占位.(3)11例患者行手术治疗:9例行经蝶垂体瘤手术,1例行经额垂体瘤手术,1例行内镜下鼻中隔肿瘤手术.术后病理均为垂体腺瘤(11/11).结论 TSH不被抑制的甲状腺毒症需警惕TSH瘤,联合多种动态功能试验更有助于本病的早期诊断;另外在定性诊断符合TSH瘤,垂体影像未见异常的病例还需警惕异位TSH瘤.     

男性慢性肝炎和肝硬化患者内分泌激素的变化

用放射免疫法测定107例男性慢性肝炎和肝硬化患者血清三碘甲状腺原氨酸(T_3)、甲状腺素(T_4)、垂体促甲状腺素(TSH)、垂体促卵泡素(FSH)、黄体生成素(LH)、雌二醇(E2)、睾酮(T)和生长激素(GH)的浓度。结果示慢迁肝和慢活肝两组除血清TSH值显著升高外,其余各内分泌指标均无明显改变。肝硬化组T_2、T_4、T值显著下降,GH值显著升高。提示肝硬化患者有下丘脑—垂体—甲状腺轴、下丘脑—垂体—性腺轴功能障碍。     

Evaluation of dopaminergic tone in hyperprolactinemia. III. Thyroid-stimulating hormone response to metoclopramide in differential diagnosis and postoperative follow-up of prolactinoma patients

Recently, it has been shown that patients with a PRL-secreting pituitary adenoma have a greater thyroid stimulating hormone (TSH) release after dopamine (DA)-receptor blockade than normal subjects. We have compared the TSH and PRL responses to metoclopramide (MCP) in normal and postpartum lactating women with those in 28 patients with hyperprolactinemia of different origin. Patients with a PRL-secreting pituitary adenoma were also tested after transsphenoidal removal of the tumor in order to establish the prognostic value of this test in such patients. Following MCP administration, percent increases in plasma PRL levels were greater in normal female subjects than postpartum lactating women. Plasma TSH levels did not increase in postpartum women and had a modest increment in normal subjects. In patients with hypothalamic tumors and empty sella syndrome plasma PRL and TSH levels showed modest or no increases after MCP administration. In ten patients harboring a microprolactinoma, plasma TSH levels showed an exaggerated increment after DA-receptor blockade. Postoperatively, despite normal or borderline PRL levels in the immediate postoperative period, a TSH response to MCP was present (in five patients one to two weeks after the operation, and in five patients one to three years after the operation), suggesting an increased DA activity even in the absence of hyperprolactinemia. In conclusion, the TSH test can easily detect increased DA-activity in patients with a microprolactinoma both preoperatively and postoperatively. It is possible that some patients with increased DA-activity in presence of normal PRL levels and normal PRL responsiveness to stimulation will experience a recurrence of hyperprolactinemia.(ABSTRACT TRUNCATED AT 250 WORDS)     

Exaggerated circadian variation in basal thyrotropin (TSH) and in the dopaminergic inhibition of TSH release in pathological hyperprolactinemia: evidence against a hypothalamic dopaminergic defect

In order to delineate more accurately the dopaminergic control of anterior pituitary function in normal subjects and in patients with pathological hyperprolactinemia, we investigated the nature of the circadian variation in the dopaminergic inhibition of TSH release in such subjects. Ten euthyroid women with hyperprolactinemia due to presumed PRL-secreting microadenomas (aged 18-60 yr) were compared with 11 normal, euthyroid women (aged 18-32 yr). Each received the dopamine receptor blocking drug domperidone (10 mg, iv) at 1100 and 2300 h (tests randomized and separated by at least 1 week). Blood was sampled 10, 20, 30, 45, and 60 min after drug administration. Normal women had a greater TSH response to domperidone and, hence, greater dopaminergic inhibition of TSH release at 2300 than at 1100 h (sum of TSH increments; mU/liter mean +/- SE, 8.5 +/- 1.3 vs. 4.8 +/- 0.5, P less than 0.01), whereas there was no difference in the dopaminergic inhibition of PRL release at each time of day. Hyperprolactinemic women also had a significantly greater TSH response to domperidone at 2300 than at 1100 h (42.0 +/- 10.2 vs. 19.1 +/- 2.8, P less than 0.001). The hyperprolactinemic women had a greater TSH response to domperidone than normal women at each time of day studied (1100 h, 19.1 +/- 2.8 vs. 4.8 +/- 0.5, P less than 0.001; 2300 h, 42.0 +/- 10.2 vs. 8.5 +/- 1.3, P less than 0.001). The incremental PRL responses to domperidone were significantly less in hyperprolactinemic than in normal women and did not differ at each time of day. In conclusion, the circadian change in the dopaminergic inhibition of TSH secretion is specific for TSH and not PRL. This indicates that the dopaminergic control of TSH and PRL secretion can be dissociated in normal subjects. Second, hyperprolactinemic women with presumed PRL-secreting microadenomas had qualitatively normal but quantitatively exaggerated circadian pattern of dopaminergic inhibition of TSH release. These data argue against a hypothalamic dopaminergic defect in hyperprolactinemia and support the view that the established dopaminergic defect in the inhibition of PRL release is related specifically to PRL control and may well be at the anterior pituitary level.     

Effects of dopamine and metoclopramide in polycystic ovary syndrome

A relative deficiency in dopamine has been suggested to explain the inappropriate gonadotropin secretion and postulated increased GnRH secretion characteristic of polycystic ovary syndrome (PCO). Previous studies demonstrated an exaggerated decrement in serum LH after large iv doses of dopamine (DA, 4-5 micrograms/kg X min). Normoprolactinemic patients with PCO and weight- and estrogen-matched normal women received iv infusions of DA in two doses (0.5 and 4 micrograms/kg X min). After DA, each subject also received iv metoclopramide (MCP; 10 mg). Serum LH decreased (P less than 0.05) during DA infusion to a similar degree in PCO [23 +/- 3% (+/- SE)] and normal women (20 +/- 2%). In PCO patients, the decrease in LH was similar with both DA doses. Serum PRL and TSH responses to DA were also similar in PCO and normal women. After MCP treatment, serum LH did not change, but serum PRL increased more in PCO (801 +/- 100%) than in normal women (467 +/- 73%; P less than 0.05), as did serum TSH. These data suggest that the sensitivity of LH to DA in patients with PCO is not increased. Further, increased responses of PRL and TSH to MCP may reflect increased dopaminergic activity or, in the case of PRL, the influence of chronic hyperestrogenism.     

Prolactin-secreting pituitary adenomas: prolactin dynamics before and after transsphenoidal surgery.

Twenty women with hyperprolactinaemia secondary to a pituitary adenoma were studied before and after selective transsphenoidal removal of the tumour. Pre-operatively, thyrotrophin-releasing hormone (TRH) (200 micrograms iv) and metoclopramide (MCP) (10 mg po) did not produce a positive PRL response in the tumour patients. By contrast, 14 post-partum lactating women, who were used as controls, exhibited a positive response to MCP administration. Methergoline (4 mg po) was shown to decrease serum PRL levels in 8 normal subjects, in 6 puerperal women, and 9 of 10 tumour patients. Bromoergocriptine (CB-154, 2.5 mg po) decreased serum PRL levels in 10 tumour patients. Following transsphenoidal removal of the adenoma serum PRL levels were reduced in all patients, and returned to normal in 14 patients. Prognostics for completely normalizing PRL secretion after transsphenoidal surgery is bettery when initial serum PRL levels are below 200 ng/ml. After surgery all hyperprolactinaemic patients failed to show a positive PRL response to TRH and MCP. Nine normoprolactinaemic patients had a positive response to both stimuli while 3 patients failed to show a positive response immediately following surgery. Long-term studies, however, showed that a positive PRL response was obtained in all patients tested 8-14 months after treatment. A positive PRL response to methergoline and bromocriptine was observed post-operatively in the patients tested regardless of their basal PRL level. Data from this study indicate that surgically proven PRL-secreting adenomas are invariably associated with negative PRL responses to TRH and MCP. The normalization of the prolactin regulation after surgery points toward the intrapituitary localization of the lesion associated with PRL-secreting adenomas.     

Metoclopramide effect on serum prolactin LH and FSH in patients with polycystic ovary syndrome

In order to investigate the DA activity in polycystic ovary syndrome (PCOS) we studied the response of LH, FSH and PRL to a dopamine receptor antagonist metoclopramide (MCP-10 mg iv) in 12 PCO subjects (7 with normal and 5 with elevated levels of prolactin). The prolactin and LH responses to metoclopramide were compared to those obtained in 6 normal cycling women. Although a significant increase in PRL levels was documented after MCP administration in all PCO patients and normal cycling women (p less than 0.01), the highest increment in PRL levels was observed in normoprolactinemic PCO subjects. In contrast a blunted PRL response was observed in hyperprolactinemic PCO patients. There was a negative correlation between basal PRL levels and the maximum net increase in PRL after MCP. In both groups of PCO subjects MCP administration caused initial decrease in LH levels followed by an increase after 4 h. In hyperprolactinemic PCO patients this observed MCP effect on LH was more pronounced and significantly different in comparison with normoprolactinemic PCO patients (p less than 0.01). MCP administration did not cause significant acute alterations in LH levels in normal cycling women and no significant FSH changes in either PCO or control subjects. A relative dopamine deficiency might cause hypersecretion of PRL and LH in patients with PCOS and hyperprolactinemia.     

Effect of ritanserin, specific 5HT-2 antagonist, on PRL secretion in normal subjects and in different hyperprolactinaemic conditions

The availability of a new specific anti 5HT-2 compound, ritanserin (RTS), led us to further investigate the role of serotonin in controlling PRL secretion. The drug was administered to normoprolactinaemic subjects and to patients with differing hyperprolactinaemic conditions. While RTS failed to modify PRL levels in normoprolactinaemic subjects and in patients with PRL-secreting pituitary adenomas, a marked decrease in the hormone was obtained in patients with functional and puerperal hyperprolactinaemia. The lack of effect of RTS in PRL-secreting pituitary adenomas suggests that the reported suppression of PRL by other antiserotoninergic drugs, such as metergoline, is probably due to their concomitant dopaminergic activity.     

THE ACUTE EFFECTS OF A DOPAMINE ANTAGONIST (DOMPERIDONE) ON LUTEINISING HORMONE, FOLLICULE STIMULATING HORMONE, PROLACTIN AND THYROTROPHIN SECRETION IN POLYCYSTIC OVARIAN SYNDROME: DIFFERENTIAL EFFECT OF OVULATION

An alteration of the hypothalamic dopaminergic regulation of LH secretion has been implicated in the abnormal LH secretion of polycystic ovarian syndrome (PCOS). To investigate this, the acute effect of dopamine (DA) receptor blockade on LH, FSH, PRL and TSH secretion was determined. No effect was observed on either LH or FSH secretion in the PCOS patients or in normal women and LH pulsatility appeared to be maintained. When the PCOS patients were divided into those who ovulated in the preceding cycle and those who were anovulatory, it was observed that the ovulatory patients had a normal PRL and TSH response; whereas in the anovulatory patients, the PRL rise was blunted and the TSH response was absent. We conclude that this study gives no evidence to support the hypothesis of altered hypothalamic DA regulation of LH secretion in PCOS. The lack of LH response to DA blockade suggests that a physiological role of DA in the control of LH secretion seems unlikely as determined under these experimental conditions. The differences in PRL and TRH response may reflect anovulation rather than a fundamental abnormality in PCOS.     

Postoperative evaluation of dopaminergic tone in prolactinoma patients. II. Plasma thyrotropin response to metoclopramide

In 24 patients who had a PRL-secreting pituitary adenoma, diagnosed by pituitary dynamic function tests and CT scan, and confirmed at surgery, the TSH response to a dopamine (DA)-antagonist drug, metoclopramide (MCP), was studied pre- and postoperatively to elucidate whether altered DA tone was present and related to hyperprolactinemia. Preoperatively, a TSH response to MCP occurred in 18 patients. Plasma TSH levels did not increase after MCP in 5 patients who had a macroprolactinoma and in 1 patient with a microprolactinoma located just beneath the diaphragm of the sella turcica. Postoperatively, in all patients who had a prolonged clinical remission and normalization of PRL dynamic tests TSH did not respond to MCP (9 of 24 patients). In 4 patients who had normal or borderline PRL levels in the immediate postoperative period, the TSH response to MCP disappeared, but became evident later together with progressive elevation of PRL levels. TSH increases after MCP occurred in all patients who had abnormal PRL levels after surgery, except in 2 patients with a macroprolactinoma infiltrating the neighboring structures. In conclusion, these results confirm the existence of increased DA tone in patients with a prolactinoma. However, the presence of an increased TSH response to DA antagonist drugs could be masked in patients who had large tumors or tumors located just beneath the sellar diaphragm. The TSH test after MCP administration can readily detect increased DA tone in the postoperative period even when PRL levels remain slightly elevated or borderline.     

Serum prolactin response to thyrotropin-releasing hormone and metoclopramide in patients with prolactin-secreting tumors before and after transsphenoidal surgery.

Seven female patients with amenorrhea, galactorrhea, and hyperprolactinemia were examined before and after selective transsphenoidal removal of a PRL-secreting microadenoma. Before adenomectomy, metoclopramide (MCP; 10 mg orally) and TRH (200 micrograms iv) did not increase PRL blood levels in any of the seven patients. On the contrary, after oral administration of 10 mg MCP, a positive response was noted in a group of eight lactating women 3 days postpartum. After surgery, serum PRL level returned to normal in all patients. A positive PRL response to MCP and TRH was found in six of the seven patients 1 month after surgery. One patient, who had the lowest PRL level, failed to show a PRL increase after both stimuli. These findings indicate that hypothalamic pituitary function can be restored to normal after transsphenoidal removal of PRL-secreting pituitary tumors.     

Acceleration of luteinizing hormone pulse frequency in functional hypothalamic amenorrhea by dopaminergic blockade

A constellation of neuroendocrine secretory aberrations, including reduced LH pulse frequency and PRL concentrations, has been documented in women with functional hypothalamic amenorrhea (FHA). As pituitary function was preserved, these aberrations were attributed to an alteration in hypothalamic neuromodulation. To investigate the participation of the dopaminergic system in the genesis of the reduced LH pulse frequency and suppressed PRL levels in FHA, we studied six women with FHA and six cyclic women in the early follicular phase by obtaining blood samples at 15-min intervals for 48 h during sequential 24-h infusions of saline and a dopamine receptor blocker, metoclopramide (MCP). A hypothalamic vs. pituitary site of action was inferred from the pulsatility characteristics. MCP consistently elicited an increase in the LH pulse frequency in the women with FHA [7.3 +/- 1.2 (+/- SE) to 10.5 +/- 1.3 pulses/24 h; P less than 0.005]. In contrast, the eumenorrheic women did not show a significant change in LH pulse frequency in response to MCP (15.2 +/- 1.0 to 14.3 +/- 0.9 pulses/24 h). While the PRL concentrations were significantly lower in the FHA group during the infusion of saline (P less than 0.001) and MCP (P less than 0.005), the relative increases in PRL during MCP were similar in both groups. The acceleration of LH pulse frequency by blockade of dopamine receptors implies that there is increased hypothalamic dopaminergic inhibition of GnRH pulse frequency in women with FHA.