Demetriou Elpida, Fokou Maria, Frangos Savvas, Papageorgis Panagiotis, Economides Panayiotis A, Economides Aliki
Department of Medicine, School of Medicine, European University Cyprus, 2404 Nicosia, Cyprus.
Nuclear Medicine Department and Thyroid Cancer Clinic, Bank of Cyprus Oncology Center, 2404 Nicosia, Cyprus.
Life (Basel). 2023 May 31;13(6):1292. doi: 10.3390/life13061292.
A widely discussed topic in the pathophysiology of thyroid nodules is the role of obesity, a state that leads to increased systemic inflammatory markers. Leptin plays a vital role in forming thyroid nodules and cancer through several mechanisms. Together with chronic inflammation, there is an augmentation in the secretion of tumor necrosis factor (TNF) and the cytokine interleukin 6 (IL-6), which contributed to cancer development, progression and metastasis. In addition, leptin exerts a modulatory action in the growth, proliferation and invasion of thyroid carcinoma cell lines via activating various signal pathways, such as Janus kinase/signal transducer and activator of transcription, mitogen-activated protein kinase (MAPK) and/or phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt). Through several proposed mechanisms, aberrant endogenous estrogen levels have been suggested to play a vital role in the development of both benign and malignant nodules. Metabolic syndrome triggers the development of thyroid nodules by stimulating thyroid proliferation and angiogenesis due to hyperinsulinemia, hyperglycemia and dyslipidemia. Insulin resistance influences the distribution and structure of the thyroid blood vessels. Insulin growth factor 1 (IGF-1) and insulin affect the regulation of the expression of thyroid genes and the proliferation and differentiation of thyroid cells. TSH can promote the differentiation of pre-adipocytes to mature adipocytes but also, in the presence of insulin, TSH possesses mitogenic properties. This review aims to summarize the underlying mechanisms explaining the role of obesity in the pathophysiology of thyroid nodules and discuss potential clinical implications.
甲状腺结节病理生理学中一个广泛讨论的话题是肥胖的作用，肥胖会导致全身炎症标志物增加。瘦素通过多种机制在甲状腺结节和癌症的形成中发挥重要作用。与慢性炎症一起，肿瘤坏死因子（TNF）和细胞因子白细胞介素6（IL-6）的分泌增加，这有助于癌症的发展、进展和转移。此外，瘦素通过激活各种信号通路，如Janus激酶/信号转导和转录激活因子、丝裂原活化蛋白激酶（MAPK）和/或磷脂酰肌醇3激酶（PI3K）/蛋白激酶B（Akt），对甲状腺癌细胞系的生长、增殖和侵袭发挥调节作用。通过几种提出的机制，异常的内源性雌激素水平被认为在良性和恶性结节的发展中起重要作用。代谢综合征通过高胰岛素血症、高血糖和血脂异常刺激甲状腺增殖和血管生成，从而引发甲状腺结节的发展。胰岛素抵抗影响甲状腺血管的分布和结构。胰岛素生长因子1（IGF-1）和胰岛素影响甲状腺基因表达的调节以及甲状腺细胞的增殖和分化。促甲状腺激素（TSH）可以促进前脂肪细胞向成熟脂肪细胞的分化，但在胰岛素存在的情况下，TSH也具有促有丝分裂特性。本综述旨在总结解释肥胖在甲状腺结节病理生理学中作用的潜在机制，并讨论潜在的临床意义。
