Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy.
Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
Eur J Endocrinol. 2021 Jan;184(1):R29-R40. doi: 10.1530/EJE-20-0683.
Tyrosine kinase inhibitors (TKIs) are emerging as potentially effective options in the treatment of cancer, acting on the pathways involved in growth, avoidance of apoptosis, invasiveness, angiogenesis, and local and distant spread. TKIs induce significant adverse effects, that can negatively affect patients' quality of life. The most common adverse events (AEs) include fatigue, hand-foot skin reaction, decreased appetite, nausea, diarrhea, hypertension, vomiting, weight loss, endocrinopaties and metabolic disorders. Patients in therapy with TKIs can develop endocrine-metabolic disorders, including dyslipidemia (50%), diabetes (15-40%), and dysthyroidism (~20%). In some cases, patients show an improved glycemia or hypoglycemia. The effects of TKIs on adrenal or gonadal function are still not completely known. It was shown a higher prevalence of subclinical hypocortisolism in patients treated with imatinib, while an increase of cortisol was reported in patients receiving vandetanib. Long-term treatment with imatinib could impact significantly the ovarian reserve and embryo developmental capacity. It is important to evaluate patients, measure glucose levels, and manage hyperglycemia. Mild treatment-related hyperglycemia can be controlled modifying the diet and with exercise, while grade 3 and 4 hyperglycemia can lead to dose reductions and/or oral antihyperglycemic therapy. Regarding thyroid dysfunctions, it is recommendable to measure the thyroid-stimulating hormone (TSH)/free thyroxine (FT4) levels before starting the therapy, and every 3-4 weeks during the first 6 months as changes in FT4 levels precede the changes in TSH by 3-6 weeks. Additional studies are necessary to definitely clarify the mechanism of TKIs-induced endocrine-metabolic effects.
酪氨酸激酶抑制剂 (TKIs) 作为癌症治疗中潜在有效的选择，作用于生长、避免细胞凋亡、侵袭、血管生成以及局部和远处转移所涉及的途径。TKIs 会引起显著的不良反应，从而对患者的生活质量产生负面影响。最常见的不良反应 (AE) 包括疲劳、手足皮肤反应、食欲下降、恶心、腹泻、高血压、呕吐、体重减轻、内分泌和代谢紊乱。接受 TKI 治疗的患者可能会发生内分泌代谢紊乱，包括血脂异常（约 50%）、糖尿病（约 15-40%）和甲状腺功能障碍（约 20%）。在某些情况下，患者的血糖会改善或降低。TKI 对肾上腺或性腺功能的影响仍不完全清楚。有研究表明，接受伊马替尼治疗的患者亚临床皮质醇功能减退症的患病率较高，而接受凡德他尼治疗的患者皮质醇水平升高。长期接受伊马替尼治疗可能会对卵巢储备和胚胎发育能力产生重大影响。评估患者、测量血糖水平以及管理高血糖症非常重要。轻度的治疗相关高血糖可以通过调整饮食和锻炼来控制，而 3 级和 4 级高血糖可能导致剂量减少和/或口服抗高血糖治疗。关于甲状腺功能障碍，建议在开始治疗前测量促甲状腺激素 (TSH)/游离甲状腺素 (FT4) 水平，并在前 6 个月内每 3-4 周测量一次，因为 FT4 水平的变化比 TSH 变化早 3-6 周。需要进一步的研究来明确 TKI 诱导的内分泌代谢作用的机制。
