De Bellis A, Colao A, Savoia A, Coronella C, Pasquali D, Conte M, Pivonello R, Bellastella A, Sinisi A A, Bizzarro A, Lombardi G, Bellastella G
Department of Clinical and Experimental Medicine and Surgery F. Magrassi, A. Lanzara, Second University of Naples, Italy.
Clin Endocrinol (Oxf). 2008 Aug;69(2):285-91. doi: 10.1111/j.1365-2265.2008.03200.x. Epub 2008 Jan 25.
The occurrence of antipituitary antibodies (APA) in patients with idiopathic hyperprolactinaemia (IH) and the effects of dopamine agonists on these antibodies and long-term pituitary function outcome have been so far not evaluated. This longitudinal study was aimed at investigating, in patients with IH the occurrence of APA and the effect of cabergoline on the pituitary function and behaviour of APA.
Sixty-six patients with IH were studied. APA (by indirect immunofluorescence) and pituitary function were investigated every year for 3 years.
Seventeen patients resulted APA positive (Group 1) and 49 APA negative (Group 2). Eight patients of Group 1 (Group 1a) and 24 of Group 2 (Group 2a) were asymptomatic and then not treated; instead, nine patients in Group 1 (Group 1b) and 25 in Group 2 (Group 2b), showing symptoms of hyperprolactinaemia, were treated with cabergoline for 2 years. Among the untreated patients, during the follow-up, those with APA positive (Group 1a) showed an increase of APA titres and PRL levels with partial pituitary impairment in some of them; instead those with APA negative (Group 2a) persisted negative with normal pituitary function despite persistent hyperprolactinaemia. Among the treated patients, those with APA positive (Group 1b) showed normalization of PRL levels, APA disappearance and recovery of pituitary function (when initially impaired) during cabergoline treatment, persisting also at last observation (off-therapy). Instead all patients of Group 2b persisted with APA negative during the follow-up with normalization of PRL levels and stable normal pituitary function during cabergoline therapy but showing a further increase of PRL at the last observation.
The presence of APA in some patients with IH suggests a possible occurrence of autoimmune hypophysitis at potential/subclinical stage; an early and prolonged cabergoline therapy could interrupt the progression to an overt clinical stage of the disease. However, the small amount of patients investigated suggests caution against generalization of our assumption and prompts to further controlled studies on a more numerous population to verify these conclusions.
迄今为止,尚未评估特发性高泌乳素血症(IH)患者中抗垂体抗体(APA)的发生情况以及多巴胺激动剂对这些抗体和垂体长期功能转归的影响。这项纵向研究旨在调查IH患者中APA的发生情况以及卡麦角林对垂体功能和APA行为的影响。
对66例IH患者进行研究。连续3年每年检测APA(采用间接免疫荧光法)和垂体功能。
17例患者APA呈阳性(第1组),49例APA呈阴性(第2组)。第1组中的8例患者(第1a组)和第2组中的24例患者(第2a组)无症状,因此未接受治疗;相反,第1组中的9例患者(第1b组)和第2组中的25例患者(第2b组)表现出高泌乳素血症症状,接受了2年的卡麦角林治疗。在未治疗的患者中,随访期间,APA呈阳性的患者(第1a组)APA滴度和PRL水平升高,部分患者出现垂体部分功能损害;而APA呈阴性的患者(第2a组)尽管高泌乳素血症持续存在,但仍保持阴性且垂体功能正常。在接受治疗的患者中,APA呈阳性的患者(第1b组)在卡麦角林治疗期间PRL水平恢复正常,APA消失且垂体功能恢复(最初有损害时),在最后一次观察(停药后)时仍保持这种状态。相反,第2b组的所有患者在随访期间APA持续呈阴性,PRL水平恢复正常,卡麦角林治疗期间垂体功能稳定正常,但在最后一次观察时PRL进一步升高。
部分IH患者中存在APA提示可能在潜在/亚临床阶段发生自身免疫性垂体炎;早期且长期的卡麦角林治疗可能会中断疾病向明显临床阶段的进展。然而,所研究的患者数量较少,提示我们在推广这些假设时需谨慎,促使我们对更多人群进行进一步的对照研究以验证这些结论。