Medical Unit, Charing Cross and Westminster Medical School, Westminster Hospital, Page Street, London SW1P 2AP, UK.
J Neuroendocrinol. 1989 Oct 1;1(5):321-6. doi: 10.1111/j.1365-2826.1989.tb00123.x.
Abstract We have described a patient with a thyrotrophin-secreting pituitary adenoma and correlated a detailed physiological and anatomical investigation of the surgically resected tumour with its in vivo regulation. Thyrotrophin secretion was inhibited by circulating thyroid hormones, dopaminergic agonists and the somatostatin analogue SMS 201-995 but could not be stimulated by thyrotrophin-releasing hormone or further inhibited by exogenous triiodothyronine. Prolonged treatment with SMS 201-995 caused tumour shrinkage as shown by successive computed tomography scans but was accompanied by tumour desensitization and the development of diabetes mellitus. This is the first thyrotroph adenoma in which somatostatin receptors have been directly demonstrated and shown to completely block thyrotrophin-releasing hormone-induced inositol phospholipid accumulation when occupied. In addition, preincubation with triiodothyronine significantly inhibited thyrotrophin-releasing hormone-induced inositol phospholipid turnover in dispersed pituitary cells indicating that in this tumour, circulating thyroid hormones were exerting feedback inhibition at the level of the pituitary either by reducing the number of thyrotrophin-releasing hormone receptors and/or their coupling to second messenger pathways. In keeping with this hypothesis, the acute reduction in intrapituitary triiodothyronine by sodium ipodate in vivo had no effect on peripheral thyrotrophin over 6 h suggesting that the onset of the effect of triiodothyronine withdrawal on thyrotrophin secretion was suitably delayed. The importance of the inositol phospholipid second messenger pathway in transducing the secretory response in this tumour was further corroborated by electrophysiological studies which demonstrated thyrotrophin-releasing hormone-induced changes in K(+) currents which are dependent on intracellular Ca(2+) ions, presumably mobilized via the inositol phospholipids. In addition to thyrotrophin and alpha subunit, growth hormone mRNA and growth hormone were found throughout the tumour as were two populations of cells distinguished electron microscopically by the size of their secretory granules. Although acromegalic features are not unusual in thyrotroph adenomas, our patient showed no evidence of inappropriate growth hormone secretion during surgery or in response to pre- or post-operative insulin stress tests.
摘要 我们描述了一例促甲状腺素分泌垂体腺瘤患者，并将手术切除肿瘤的详细生理学和解剖学研究与体内调节相关联。促甲状腺素的分泌受到循环甲状腺激素、多巴胺激动剂和生长抑素类似物 SMS 201-995 的抑制，但不能被促甲状腺素释放激素刺激或被外源性三碘甲状腺原氨酸进一步抑制。连续 CT 扫描显示，长期使用 SMS 201-995 导致肿瘤缩小，但同时伴随着肿瘤脱敏和糖尿病的发生。这是首例直接证明生长抑素受体存在并显示完全阻断促甲状腺素释放激素诱导的内源性磷脂酰肌醇积累的促甲状腺素腺瘤。此外，三碘甲状腺原氨酸的预孵育显著抑制了分散垂体细胞中促甲状腺素释放激素诱导的内源性磷脂酰肌醇周转，表明在这种肿瘤中，循环甲状腺激素通过减少促甲状腺素释放激素受体的数量和/或其与第二信使途径的偶联，在垂体水平发挥反馈抑制作用。与这一假说一致，体内用碘酸钠急性减少颅内三碘甲状腺原氨酸对 6 小时内外周促甲状腺素没有影响，这表明三碘甲状腺原氨酸撤退对促甲状腺素分泌的影响开始时间适当延迟。电生理学研究进一步证实了内源性磷脂酰肌醇第二信使途径在传递该肿瘤分泌反应中的重要性，该研究表明，促甲状腺素释放激素诱导的 K(+)电流变化依赖于细胞内 Ca(2+)离子，可能通过内源性磷脂酰肌醇动员。除了促甲状腺素和α亚单位外，生长激素 mRNA 和生长激素在整个肿瘤中都有发现，电子显微镜还显示出两种细胞群，其特征是分泌颗粒的大小不同。尽管促甲状腺素腺瘤中生长激素分泌过多并不罕见，但我们的患者在手术中或对术前和术后胰岛素应激试验没有表现出不适当的生长激素分泌的证据。
