催乳素瘤

催乳素瘤系指分泌催乳素的垂体肿瘤。大多数催乳素瘤的主要临床表现是继发于血清催乳素活性升高,包括月经紊乱和乳溢。约1/5患闭经的妇女具有高催乳素血症,催乳素瘤男性罕见,他们主要表现为高催乳素血症造成的性欲低下和阳萎。催乳素瘤在妇女中并非罕见,肿瘤几乎均为直径<1cm的微腺瘤。高分辨力CT扫描显示垂体异常的病人,若血清催乳素活性持续升高,则有力地提示催乳素瘤的存在。催乳素释放的动力学试验并不比随机的     

垂体催乳素瘤合并妊娠患者的管理

垂体催乳素瘤是最常见的功能性垂体腺瘤, 可导致育龄期女性出现月经紊乱及不孕症。经过多巴胺受体激动剂或手术等治疗可以恢复患者的排卵和生育能力。对于催乳素瘤合并妊娠患者的管理国内尚无统一规范。本文就有生育意愿的女性催乳素瘤患者的妊娠时机、妊娠期及产后管理进行相关讨论。     

双垂体催乳素瘤

1例42岁的女性有催乳素瘤病史2年.催乳素瘤诊断的确定是根据患者有高催乳素血症和溢乳症状.其它垂体激素TSH、FSH、LH、GH和ACTH的基线水平都在正常范围内.全面体格检查、神经系统检查及视野均为正常.MRI图像分析显示,垂体内有两个低信号病灶,与信号增强的正常垂体组织界限分明,未见视交叉受累,符合垂体微腺瘤(图1).患者用多巴胺激动剂治疗,催乳素水平降低至正常.鉴于内分泌评估正常,不需要经蝶骨垂体微腺瘤摘除手术,患者被纳入随访观察.     

20例男性垂体催乳素瘤MRI特征分析并文献复习

目的 探讨男性垂体催乳素瘤的临床及MRI特征,提高其正确诊断率.方法 回顾性分析20例经手术病理或内分泌治疗有效证实的男性催乳素腺瘤.结果 在MRI诊断的20例男性催乳素瘤患者中,微腺瘤9例,大腺瘤11例.平扫T1WI呈稍低或等信号,T2WI均为稍高～高信号,常规增强均可见明显强化.侵袭性者均为大腺瘤,多伴有视交叉受侵或蝶窦、海绵窦侵犯,部分伴骨质破坏.结论 男性垂体催乳索瘤的临床与MRI表现均与女性不同,MRI对催乳素瘤诊断有重要价值,但应注意临床与影像两者结合,以达到早期、准确诊断.     

催乳素分泌瘤的分子生物学研究进展

催乳素(prolactin,PRL)瘤是最常见的垂体前叶功能性腺瘤,通常认为其发病机制涉及调节因素的异常或垂体PRL分泌细胞本身的缺陷。     

高催乳素血症伴垂体腺瘤325例临床病理特点及疗效分析

<正>催乳素(prolactin,PRL),由198个氨基酸组成,由垂体前叶催乳素分泌细胞分泌与合成。1970年人催乳素的成功分离使高催乳素血症成为一个新的临床病理状态,同时也使催乳素分泌瘤与无功能腺瘤区分开来~([1])。高催乳素血症,即各种原因引起外周血PRL水平持续增高的状态~([2])。非产后高催乳素血症,可由催乳素腺瘤引起,约占所有垂体肿瘤的40%~([1])。此外,也可能来自下丘脑-垂体多巴胺通     

13例青少年起病的男性垂体催乳素瘤临床分析

目的探讨男性青少年催乳素瘤的临床特点、治疗与预后。方法回顾性分析13例青少年男性催乳素瘤患者临床表现及疗效。结果（1）男性青少年催乳素瘤以大腺瘤为主。头痛和第二性征发育障碍常见,但较少引起生长停滞。（2）溴隐亭治疗安全有效,与手术相比,可以保护垂体前叶功能,改善第二性征发育。结论男性青少年催乳素瘤采用溴隐亭治疗较手术更为可取,必要时,联合治疗有助于缓解病情。     

Menin蛋白与胰岛细胞增殖

Menin是多发性内分泌腺瘤病1型(MENl)基因编码的蛋白.MENl基因的突变引起Menin表达缺失,最终引起患者内分泌腺多发性肿瘤,主要临床表现为甲状旁腺腺瘤、胃肠胰肿瘤(以胃泌素瘤和胰岛素瘤常见)和垂体前叶瘤(以催乳素瘤常见).     

女性垂体催乳素疱术后长期观察

对垂体催乳素瘤的治疗争论较多,有主张药物治疗,使血清催乳素浓度迅速降至正常水平并进行避孕,有主张经蝶骨行显微外科手术治疗,尤以微腺瘤手术成功率高,可超过80%,但有关术后高催乳素血症或肿瘤复发的报告较少。     

溴隐亭治疗垂体肿瘤发生脑脊液鼻溢

溴隐亭广泛用于治疗高催乳素血症,最近发现它用于治疗垂体肿瘤,可使肿瘤缩小,尤其对催乳素瘤有效,长期治疗肿瘤可消退,但治疗期间可发生脑脊液鼻溢,本文报道二例:     

Long term follow-up of women with surgically treated prolactin-secreting pituitary tumors

To examine the long term effectiveness of transsphenoidal microsurgery for patients with PRL-secreting pituitary tumors, we studied 54 women at yearly intervals after transsphenoidal surgery. Five years after surgery, 19 women (35%) had normal serum PRL concentrations, and 23 (43%) had persistent hyperprolactinemia. Hyperprolactinemia recurred in 12 of 31 patients (39%) who had normal PRL concentration 6 weeks after surgery. None of the patients with recurrent hyperprolactinemia had radiographic evidence of tumor regrowth, and only 3 of 12 had amenorrhea. A serum PRL level below 6 ng/ml 6 weeks after surgery occurred more frequently in cured patients than in those who had a recurrence. PRL responses to TRH were normal in cured patients 1 and 5 yr after surgery and abnormal in those who had recurrent hyperprolactinemia. The PRL responses to chlorpromazine- and insulin-induced hypoglycemia were blunted in patients with normal as well as elevated PRL levels. Patients with recurrent, as well as those with persistent, hyperprolactinemia had no nocturnal rise in serum PRL 5 yr after surgery. The 39% recurrence rate of hyperprolactinemia and persistent abnormalities in pituitary-hypothalamic regulation of PRL secretion after transsphenoidal surgery raise important questions about the choice of primary therapy for patients with PRL-secreting tumors.     

Prolactinomas

Prolactin-secreting pituitary tumors are not rare. The diagnosis of a patient with hyperprolactinemia and possible tumor should be carried out in an orderly fashion by first excluding secondary causes. If the patient has pathologic hyperprolactinemia, assessment of pituitary anatomy with a high resolution CT scan (or MRI) should be done. In patients who have a macroadenoma, quantitative visual field examination should be a part of the ophthalmologic examination. The choice of therapy is dependent on the clinical findings, the risks of therapy, and patient preference. Currently, the most effective therapy for a patient with a macroadenoma is medical therapy with a dopamine agonist, but this must be given chronically. Regardless of the therapy selected, these patients must be followed regularly. Once fertility is established, there is usually no contraindication to pregnancy in women who wish to become pregnant.     

Drugs and prolactin

Medications commonly cause hyperprolactinemia and their use must be differentiated from pathologic causes. The most common medications to cause hyperprolactinemia are the antipsychotic agents, although some of the newer atypical antipsychotics do not do so. Other medications causing hyperprolactinemia include antidepressants, antihypertensive agents, and drugs which increase bowel motility. Often, the medication-induced hyperprolactinemia is symptomatic, causing galactorrhea, menstrual disturbance, and erectile dysfunction. In the individual patient, it is important differentiate hyperprolactinemia due to a medication from a structural lesion in the hypothalamic–pituitary area. This can be done by stopping the medication temporarily to determine if the prolactin (PRL) levels return to normal, switching to another medication in the same class which does not cause hyperprolactinemia (in consultation with the patient’s physician and/or psychiatrist), or by performing an MRI or CT scan. If the hyperprolactinemia is symptomatic, management strategies include switching to an alternative medication which does not cause hyperprolactinemia, using estrogen/testosterone replacement, or cautiously adding a dopamine agonist.     

Effectiveness and long-term tolerability of the slow release oral form of bromocriptine on tumoral and non-tumoral hyperprolactinemia.

The effectiveness and long-term tolerability of a new formulation of bromocriptine with slow gastrointestinal release (Parlodel SRO) has been evaluated on ten patients with macroprolactinoma, seven patients with microprolactinoma and five patients with nontumoral hyperprolactinemia during a period of 1-30 months. Six out of ten macroprolactinoma-bearing patients obtained a rapid normalization of plasma PRL levels with reduction of the tumor size recorded by CT scan follow-up. Four of six microprolactinomas and all the five nontumoral hyperprolactinemic patients became normoprolactinemic with recovery of gonadal functions while in two other microprolactinomas Parlodel SRO significantly reduced plasma PRL levels with restoration of menses. Only in two patients the treatment was withdrawn for the appearance of side effects. In conclusion, Parlodel SRO is an effective drug in the management of tumoral and nontumoral hyperprolactinemia. The good long-term tolerability together with the hypoprolactinemic activity makes this drug a very good choice therapy in hyperprolactinemic syndromes even in case of poor tolerability to the standard formulation of the drug.     

Bromocriptine-induced regression of a suprasellar extending prolactinoma during pregnancy

A 21-year-old amenorrheic woman with hyperprolactinemia had rapid pituitary tumor enlargment during a bromocriptine-induced pregnancy. Before treatment the sella turcica was normal. In the 31st week of pregnancy she developed bitemporal hemianopsia and markedly decreased visual acuity. Computerized tomography showed a pituitary adenoma with suprasellar extension. Reinstitution of bromocriptine therapy resulted in rapid recovery of normal vision and radiologically verified tumor regression. Pregnancy continued to term and a healthy child was born. If pituitary tumor complications should occur during pregnancy, reinstitution of bromocriptine is the primary treatment of choice.     

Life events in the pathogenesis of hyperprolactinemia

OBJECTIVE: Little is known about the relationship between recent life events and onset of hyperprolactinemia, despite the well-known effect of acute psychological stress on prolactin levels in healthy subjects. Recent life events in patients with hyperprolactinemia compared with healthy controls were investigated. DESIGN: Case-control study. METHODS: Fifty-two consecutive patients with hyperprolactinemia (45 females/7 males; mean age 34.9+/-10.1 years, range 18-60 years) and 52 healthy subjects matched for socio-demographic variables were studied. Nineteen patients (18 females/1 male) had no pituitary tumor and were diagnosed as suffering from idiopathic hyperprolactinemia. Patients with additional pathology or with high prolactin due to medications were excluded. All patients were interviewed by Paykel Interview for Recent Life Events while on remission after surgery or pharmacological treatment. The time period considered was the year preceding the first signs of hyperprolactinemia, and the year before interview for controls. RESULTS: Patients with hyperprolactinemia reported significantly more life events than control subjects (P<0.001). The same significant difference compared with controls applied to patients with (n=16) and without (n=36) depression. All categories of events (except events that were likely to be under the subject's control) were significantly more frequent. There were no significant differences between patients with prolactinoma (n=33) and those with idiopathic hyperprolactinemia (n=19). CONCLUSIONS: Within the complexity of phenomena implicated in the pathogenesis of hyperprolactinemia, our findings emphasize a potential role of emotional stress in either prolactin-secreting pituitary tumors or idiopathic hyperprolactinemia. Appraisal of life stress may have implications in clinical assessment (e.g. functional hyperprolactinemia) and decisions (e.g. termination of long-term pharmacological treatment).     

Medical Management of Prolactin-Secreting Pituitary Adenomas

Prolactinomas are a common cause of reproductive/sexual dysfunction. Once other causes of hyperprolactinemia have been excluded with a careful history and physical examination, routine chemistries, a pregnancy test and a TSH, imaging with MRI or CT will delineate the size and extent of the tumor. Medical therapy is the initial treatment of choice. When infertility is the primary indication for treatment, bromocriptine use has an extensive safety experience and is preferred. However, for other indications, cabergoline appears to be more efficacious and better tolerated. Transsphenoidal surgery remains an option, especially for patients with microadenomas, when medical therapy is ineffective.     

Pituitary production of prolactin and prolactin-suppressing drugs.

Prolactin secretion from the anterior pituitary is mediated via dopaminergic pathways. Any process that alters dopamine production or transport in the central nervous system may lead to hyperprolactinemia. Most cases of hyperprolactinemia are due to prolactin secreting pituitary tumors or to medications which alter dopamine production. Prolactinomas cause amenorrhea, galactorrhea and infertility in women and impotence and neurological deficits in men. Dopamine receptor agonists are the mainstay of therapy for hyperprolactinemia as they rapidly lower serum prolactin and cause tumor shrinkage. In this paper we review the regulation of prolactin secretion, the clinical features and causes of hyperprolactinemia, and the use of dopamine agonists.     

Disorders of prolactin secretion.

Prolactinomas are a common cause of reproductive/sexual dysfunction. Once other causes of hyperprolactinemia have been excluded with a careful history and physical examination, routine chemistries, and an assay for TSH, MR imaging, or CT will delineate the size and extent of the tumor. Medical therapy is the initial treatment of choice. When infertility is the primary indication for treatment, bromocriptine use has an extensive safety record and is preferred. For other indications, cabergoline seems to be more efficacious and better tolerated. Transsphenoidal surgery remains an option, especially for patients with microadenomas, when medical therapy is ineffective.     

Effects of nomifensine on growth hormone and prolactin secretion in normal subjects and in pathological hyperprolactinemia

We have studied the effect of the oral administration of 200 mg nomifensine (nom), a drug which activates the dopaminergic system, on GH and PRL secretion in 15 normal subjects, 18 patients with idiopathic hyperprolactinemia, and 17 patients with tumoral hyperprolactinemia. GH levels increased significantly after nom in normal subjects (basal, 0.96 +/- 0.76 ng/ml; peak 4.6 +/- 0.61 ng/ml; P less than 0.01) and patients with hyperprolactinemia, both idiopathic (basal, 1.0 +/- 0.38 ng/ml; peak, 4.2 +/- 1.0 ng/ml; P less than 0.05) and tumoral (basal 0.88 +/- 0.3 ng/ml, peak 6.68 +/- 1.2 ng/ml; P less than 0.01). Peak GH levels higher than 5 ng/ml were observed in 8 of 15 normal subjects, 6 of 18 patients with idiopathic hyperprolactinemia, and 8 of 17 patients with tumoral hyperprolactinemia. PRL levels decreased in response to nom in normal subjects, but not in patients with idiopathic or tumoral hyperprolactinemia. A reduction in plasma PRL levels of at least 30% below the baseline was observed only in two patients with idiopathic hyperprolactinemia and in none of the patients with tumoral hyperprolactinemia. These results demonstrate that nom does not discriminate between idiopathic and tumoral hyperprolactinemia. Since nom probably requires a hypothalamic pool of dopamine to bring about its GH stimulatory effect, the suggestion that the lack of a PRL-lowering effect of the drug is attributable to a dopamine deficiency is not supported by our data.