Is pregnancy the best treatment for hyperprolactinaemia?

This paper reports the changes in prolactin levels after 12 spontaneous and 52 induced pregnancies in 54 women with unambiguous hyperprolactinaemia (median plasma prolactin levels 67.5 ng/ml, range 40-400). Twenty-three of the patients showed radiological evidence of prolactinoma. The pregnancies were induced in 37 patients by bromocriptine, in nine by metergoline, in two by lisuride and in four by other treatments. Of the 64 pregnancies, 16 ended in spontaneous abortion, while 48 went to term. Follow-up was continued for at least 6 months after delivery or until the end of lactation. In a control group of 32 hyperprolactinaemic women (median prolactin 70 ng/ml, range 40-400) not wishing to become pregnant, prolactin changes were similarly registered over a mean period of 15 months without any treatment (range 6-38 months). After pregnancy, a significant downward trend of plasma prolactin was observed in the puerperal women with a 'normalization' rate of 17%. No changes were observed in the 32 controls who did not become pregnant.     

Hypogonadism of male prolactinomas: Relation to pulsatile secretion of LH: Hypogonadisms des Mannes mit Prolaktinomen: Beziehungen zur pulsatilen LH-Sekretion

In order to investigate whether a hypothalamic disorder cause hypogonadism in male prolactinomas, LH pulsatile secretion was studied in 13 male patients. Serum PRL levels ranged from 186 to 45,000 ng ml-1 before treatment, and all the tumors were macroadenomas. Reduced LH secretion was revealed in 5 of 13 patients, and FSH was reduced in 1 of 13. Serum testosterone (T) levels were lower than the normal limit in all the patients. HCG tests in 3 patients showed good responses, but the peak values of T were lower than those of normal men. LH pulsatilities were examined in 5 hyperprolactinemic patients before treatment, in 4 hyperprolactinemic patients after operation, and in 8 normoprolactinemic patients after operation and/or bromocriptine treatment. There was no significant difference of the mean LH values, the frequencies of LH pulses, and amplitudes among the hyperprolactinemic patients before operation (n = 5), the normoprolactinemic patients after operation (n = 8), and normal men (n = 7). From these results, it was evident that the hypothalamus and pituitary function of male prolactinomas were well preserved, in spite of higher serum PRL levels and larger tumor size than those reported in females. It is suggested that the main cause of hypogonadism in these patients is due to testicular dysfunction resulting from excessive serum PRL.     

Long-term application of diethylstilbestrol upregulates expressions of μ- and m-calpains in pituitary intermediate lobe of female Wistar rats

BACKGROUND: During formation of prolactin neoplasia, how cells and its structure in adenohypophysis affect prolactin cells should be further studied. Intermediate lobe can be regarded as a driving region to release prolactin (PRL) and may promote formation of prolactin neoplasia in pituitary anterior lobe. OBJECTIVE: To observe the effect of diethylstilbestrol (DES) on the expressions of μ and m-calpains in pituitary intermediate lobe of female Wistar rats. DESIGN: Observational contrast animal study. SETTING: Beijing Neurosurgical Institute. MATERIALS: A total of 21 female Wistar rats, 3 weeks old weighing 70–80 g were housed with free access to tap water and standard pellet food. They were kept in a CL-grade condition, at (24±1)℃ and a humidity of (55±5)%, and with a 12 hours day-night cycle. Caprine anti-μ- and m-calpains antibodies were provided by Santa Cruz Biotechnology, CA, USA; rabbit-anti-PRL antibodies by Dako, Denmark; rabbit-anti-ACTH antibody by Boster Company, Wuhan. METHODS: The experiment was carried out in Pathophysiological Department and Animal Laboratory, Beijing Neurosurgical Institute from August 2006 to January 2007. ① Rats were randomly divided into groups with 7 in each group, including vehicle control group, in which rats were injected intraperitoneally with sun-flower seed oil (1 mL/kg, twice a week) for 16 weeks; DES group, where animals were administered with DES (5 mg/kg, twice a week) for 16 weeks; DES + vehicle control group, in which DES was administered for 12 weeks at the same dose with those in DES group, and then was discontinued and replaced by sun-flower seed oil (1 mL/kg, twice a week) for the following 4 weeks. ② At 16 weeks later, pituitary tissue was dealt with HE staining and PRL immunohistochemical examination to observe evoke of tumor; meanwhile, immunohistochemical examination was used to observe expression of PRL of pituitary anterior lobe, expressions of μ- and m-calpains of pituitary intermediate lobe and distribution of adrenocorticotropin. MAIN OUTCOME MEASURES: ① Expression of PRL of pituitary anterior lobe, expressions of μ- and m-calpains of pituitary intermediate lobe and distribution of adrenocorticotropin. ② Morphological observation of pituitary tissue. RESULTS: All 21 rats were involved in the final analysis. ① Results of immunohistochemical examination: Morphological changes of neoplasia in DES group were strongly positive to PRL, and this suggested that formation of prolactin adenoma was observed in pituitary tissue. As compared with vehicle control group, expression of adrenoeorticotropic hormone (ACTH) was increased in both DES group and DES + vehicle control group. In addition, expressions of μ- and m-calpains in pituitary intermediate lobe were higher in DES group than that in vehicle control group. Otherwise, expressions of m-calpains in pituitary intermediate lobe was decreased in DES + vehicle control group, but expression of μ-calpains was still increased. ② Morphological observation of pituitary tissue: Gland tubes were orderly arranged in rats in vehicle control group. Anterior pituitary gland in rats of DES group demonstrated an apparent disappearance of gland tubes and a relatively large-scaled vasculature formation, namely the vascular lake lined by tightly arranged endothelial cells. Local integrated tumor cell arrangements were also detected. In addition, the border between the IL and the anterior lobe was locally blurred. The definite tumor-like changes in pituitary tissues were confirmed in 6 of 7 female Wistar rats in DES group, and one spontaneous occurrence of tumor formation was found in vehicle control group. In DES + vehicle control group, DES withdrawal led to the subtile emergence of gland tube cavity, although tumor-like cells still existed in 4 of 7 rats, suggesting occurrence of the tumor regression due to the withdrawal of DES. CONCLUSION: A long-term application of DES can enhance the expressions of ubiquitours neutral cysteine protease in pituitary intermediate lobe and this suggests that both of them play a key role in release of hormone and formation of prolactin neoplasia through directly promoting PRL expression and release of neighboring pituitary intermediate lobe.     

抗肌萎缩蛋白基因51号外显子的精确定位

抗肌萎缩蛋白基因是迄今发现的人类最大基因,长约2300 kb,含有75个外显子。对该巨大基因的研究是近年来医学分子生物学研究的一个热点。虽然抗肌萎缩蛋白基因HindⅢ片段排序后就知道第51号外显子位于3.lkb的第40号HlndⅢ片段中,由于抗肌萎缩蛋白基因组DNA至今未被克隆,233bP的第51号外显子在3.lkp HindⅢ片段中的部位并不知道,也不知道它两侧的DNA结构。51号外显子     

侵袭性巨大催乳素瘤的诊治

目的：探讨侵袭性巨大催乳素瘤的诊治方法及效果。方法：回顾分析我院收治的侵袭性巨大催乳素瘤18例，均经头颅MRI和内分泌检查确诊。纳入标准：（1）肿瘤直径〉4cm；（2）血浆PRL〉200ng／mL；（3）高催乳素分泌或占位效应引起的临床症状。手术治疗15例，术后给以药物（溴隐亭）治疗，结合放疗。非手术治疗3例，先药物（溴隐亭）治疗，结合放疗。结果：手术组随访12例，平均随访29．5mo，肿瘤体积缩小75％；非手术组随访3例，在平均随访的24mo内肿瘤体积缩小80％；肿瘤消失各1例。PRL控制在200ng／mL以下手术组6例，非手术组2例；视力视野改善手术组6例，非手术组2例。结论：对侵袭性巨大催乳素瘤可首选药物治疗，能有效地缩小肿瘤体积和控制PRL水平，部分可达治愈的目的，从而避免手术风险。早期手术仅适用于视力视野明显急剧下降者，肿瘤卒中引起显著临床症状者，服药不能耐受或耐药者，服药出现脑脊液漏需修补者。     

Aggressive prolactinomas responsive to temozolomide treatment: Report of two cases

Refractory aggressive prolactinomas are detected after the unresponsiveness to conventional therapies. We report two cases that underwent temozolomide treatment and have been in near‐complete remission ever since. We suggest the pathology techniques for earlier detection and, subsequently, treatment with temozolomide to reduce morbidities and better respond to therapy.     

溴隐亭对斑马鱼胚胎早期发育的影响

目的 探讨溴隐亭对斑马鱼胚胎生存率、孵化时间和形态发育异常的影响。方法 取斑马鱼胚胎随机分成溴隐亭溶液组（10μmol/L组、20μmol/L组、50μmol/L组、100μmol/L组）,control组（空白对照组）和0.5%二甲基亚砜（DMSO）对照组,比较各组胚胎生存率、孵化时间、幼鱼鱼鳔充气、幼鱼畸形及发育异常情况。结果 48受精后发育小时数（HPF）时,溴隐亭溶液组胚胎孵化率低于2个对照组（P<0.05）;120 HPF时,20μmol/L组、50μmol/L组、100μmol/L组斑马鱼幼鱼鱼鳔充气率、水肿率分别低于、高于其余组（P<0.05）,但各组畸形率比较,差异无统计学意义（P>0.05）;144 HPF时,50μmol/L组、100μmol/L组较其余4组斑马鱼幼鱼生存率降低（P<0.05）。结论 高浓度溴隐亭可引起斑马鱼胚胎孵化延迟、斑马鱼幼鱼生存率降低、水肿及鱼鳔充气障碍,但对斑马鱼胚胎发育畸形则无影响。     

泌乳素瘤多巴胺受体激动剂治疗相关冲动控制障碍的诊疗进展

泌乳素瘤是最常见的功能性垂体腺瘤,首选多巴胺受体激动剂作为一线治疗方案。在接受多巴胺受体激动剂治疗的泌乳素瘤患者中可能出现各种类型的冲动控制障碍(impulse control disorders,ICDs),如病理性赌博、强迫性购物、性欲亢进、强迫性进食等。这些不良反应会对患者的工作和生活造成严重的影响。然而目前国内缺少相关研究报道,内分泌学界对冲动控制障碍的临床表现、诊断及治疗缺乏全面的认识。本文就泌乳素瘤中ICDs的发生比例、发生机制、危险因素、诊断及治疗等方面展开综述,以深入了解泌乳素瘤多巴胺受体激动剂治疗相关ICDs,为今后在临床诊治中筛查识别及诊治提供帮助。     

Pituitary disease and anaesthesia

Patients with pituitary gland tumours comprise a significant proportion of the neurosurgical population, making transsphenoidal pituitary surgery a relatively common procedure. Such patients present anaesthetists with unique challenges resulting from hormone hypersecretion, pituitary hypofunction or tumour mass effect. To understand this pathophysiology requires a good working knowledge of normal pituitary anatomy and physiology. An appreciation of the respiratory and cardiovascular comorbidities associated with pituitary tumours is also essential to the anaesthetist. We aim to review the key principles involved in the preoperative assessment, intraoperative management and postoperative care of these patients.     

Diagnosis of prolactinoma in two male‐to‐female transsexual subjects following high‐dose cross‐sex hormone therapy

Male‐to‐female transsexual persons use oestrogens + antiandrogens to adapt their physical bodies to the female sex. Doses are usually somewhat higher than those used by hypogonadal women receiving oestrogen replacement. Particularly in cases of self‐adminstration of cross‐sex hormones, doses may be very high. Oestrogens are powerful stimulators of synthesis and release of prolactin and serum prolactin levels are usually somewhat increased following oestrogen treatment. Prolactinomas have been reported in male‐to‐female transsexual persons, both after use of high and conventional doses of oestrogens but remain rare events. We report two new cases of prolactinomas in male‐to‐female transsexual persons, one in a 41‐year‐old subject who had used nonsupervised high‐dose oestrogen treatment since the age of 23 years and another one in a 42 year old who had initiated oestrogen treatment at the age of 17 years. Their serum prolactin levels were strongly increased, and the diagnosis of a pituitary tumour was confirmed by imaging techniques. Both cases responded well to treatment with cabergoline treatment whereupon serum prolactin normalised. Our two cases are added to the three cases of prolactinomas in the literature in persons who had used supraphysiological doses of oestrogens.