Dworakowska Dorota, Grossman Ashley B
Barts and the London School of Medicine, Centre for Endocrinology, London EC1M 6BQ, UK.
Endocr Relat Cancer. 2009 Mar;16(1):45-58. doi: 10.1677/ERC-08-0142. Epub 2008 Oct 31.
Tuberous sclerosis complex (TSC) is an autosomal dominant multisystem disorder characterised by the development of multiple hamartomas in numerous organs. It is caused by mutations of two tumour suppressor genes, TSC1 on chromosome 9q34 and TSC2 on chromosome 16p13.3, which encode for hamartin and tuberin respectively. The interaction between these two proteins, the tuberin-hamartin complex, has been shown to be critical to multiple intracellular signalling pathways, especially those controlling cell growth and proliferation. TSC may affect skin, central nervous system, kidneys, heart, eyes, blood vessels, lung, bone and gastrointestinal tract. Small series and case reports have documented that in tuberous sclerosis patients many endocrine system alterations might occur, affecting the function of the pituitary, parathyroid and other neuroendocrine tissue. There have been scattered reports of the involvement of such tissue in the pathological process of TSC, but no systematic review as to whether this is a true association. We have therefore systematically assessed all available published literature in this area. We conclude that there may be an association with pituitary and parathyroid tumours, and two recent descriptions of Cushing's disease are especially intriguing. However, the evidence seems more firm in the case of islet cell tumours, particularly insulinomas. As these latter may cause changes in mental state that may be confused with the cerebral manifestations of TSC per se, it is particularly important for physicians working with these patients to be aware of the putative and indeed likely association.
结节性硬化症（TSC）是一种常染色体显性多系统疾病，其特征是在多个器官中形成多个错构瘤。它由两个肿瘤抑制基因的突变引起，位于9号染色体q34的TSC1和位于16号染色体p13.3的TSC2，它们分别编码错构瘤蛋白和结节蛋白。这两种蛋白质（结节蛋白 - 错构瘤蛋白复合物）之间的相互作用已被证明对多个细胞内信号通路至关重要，尤其是那些控制细胞生长和增殖的信号通路。TSC可能会影响皮肤、中枢神经系统、肾脏、心脏、眼睛、血管、肺、骨骼和胃肠道。小型系列研究和病例报告记录了结节性硬化症患者可能会出现许多内分泌系统改变，影响垂体、甲状旁腺和其他神经内分泌组织的功能。关于此类组织参与TSC病理过程已有零星报道，但对于这是否是一种真正的关联尚无系统综述。因此，我们系统地评估了该领域所有已发表的文献。我们得出结论，可能与垂体和甲状旁腺肿瘤有关，最近对库欣病的两项描述尤其引人关注。然而，在胰岛细胞瘤，尤其是胰岛素瘤方面，证据似乎更确凿。由于后者可能导致精神状态改变，这可能与TSC本身的脑部表现相混淆，因此，治疗这些患者的医生意识到这种假定且确实可能存在的关联尤为重要。
