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长期使用卡麦角林治疗停药后高催乳素血症复发。

Recurrence of hyperprolactinemia after withdrawal of long-term cabergoline therapy.

作者信息

Kharlip J, Salvatori R, Yenokyan G, Wand G S

机构信息

Division of Endocrinology and Metabolism, Johns Hopkins University School of Medicine, Baltimore, Maryland 21201, USA.

出版信息

J Clin Endocrinol Metab. 2009 Jul;94(7):2428-36. doi: 10.1210/jc.2008-2103. Epub 2009 Mar 31.

Abstract

CONTEXT

Recurrence of hyperprolactinemia after cabergoline withdrawal ranges widely from 36 to 80%. The Pituitary Society recommends withdrawal of cabergoline in selected patients.

OBJECTIVE

Our aim was to evaluate recurrence of hyperprolactinemia in patients meeting The Pituitary Society guidelines.

DESIGN

Patients were followed from the date of discontinuation to either relapse of hyperprolactinemia or the day of last prolactin test.

SETTING

We conducted the study at an academic medical center.

PATIENTS

Forty-six patients meeting Pituitary Society criteria (normoprolactinemic and with tumor volume reduction after 2 or more years of treatment) participated in the study.

INTERVENTIONS

After withdrawal, if prolactin returned above reference range, another measurement was obtained within 1 month, symptoms were assessed by questionnaire, and magnetic resonance imaging was performed.

MAIN OUTCOME MEASURES

We measured risk of and time to recurrence estimates as well as clinical predictors of recurrence.

RESULTS

Mean age of patients was 50 +/- 13 yr, and 70% were women. Thirty-one patients had microprolactinomas, 11 had macroprolactinomas, and four had nontumoral hyperprolactinemia. The overall recurrence was 54%, and the estimated risk of recurrence by 18 months was 63%. The median time to recurrence was 3 months (range, 1-18 months), with 91% of recurrences occurring within 1 yr after discontinuation. Size of tumor remnant prior to withdrawal predicted recurrence [18% increase in risk for each millimeter (95% confidence interval, 3-35; P = 0.017)]. None of the tumors enlarged in the patients experiencing recurrence, and 28% had symptoms of hypogonadism.

CONCLUSIONS

Cabergoline withdrawal is practical and safe in a subset of patients as defined by The Pituitary Society guidelines; however, the average risk of long-term recurrence in our study was over 60%. Close follow-up remains important, especially within the first year.

摘要

背景

卡麦角林撤药后高泌乳素血症复发率差异很大,在36%至80%之间。垂体协会建议在部分患者中停用卡麦角林。

目的

我们的目的是评估符合垂体协会指南的患者中高泌乳素血症的复发情况。

设计

从停药之日起对患者进行随访,直至高泌乳素血症复发或最后一次泌乳素检测之日。

地点

我们在一家学术医疗中心开展了这项研究。

患者

46名符合垂体协会标准的患者(泌乳素正常且经过2年或更长时间治疗后肿瘤体积缩小)参与了研究。

干预措施

撤药后,如果泌乳素水平回升至参考范围以上,则在1个月内再次进行检测,通过问卷调查评估症状,并进行磁共振成像检查。

主要观察指标

我们测量了复发风险、复发时间估计值以及复发的临床预测因素。

结果

患者的平均年龄为50±13岁,70%为女性。31例为微泌乳素瘤,11例为大泌乳素瘤,4例为非肿瘤性高泌乳素血症。总体复发率为54%,18个月时的复发估计风险为63%。复发的中位时间为3个月(范围为1至18个月),91%的复发发生在停药后1年内。撤药前肿瘤残余大小可预测复发情况[每增加1毫米复发风险增加18%(95%置信区间为3%至35%;P = 0.017)]。复发患者中无一例肿瘤增大,28%有性腺功能减退症状。

结论

按照垂体协会指南定义,在部分患者中停用卡麦角林是可行且安全的;然而,在我们的研究中,长期复发的平均风险超过60%。密切随访仍然很重要,尤其是在第一年。

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