Costa Denise, Ceccato Filippo, Lauretta Rosa, Mercuri Valeria, D'Amico Tania, De Vito Corrado, Scaroni Carla, Appetecchia Marialuisa, Gargiulo Patrizia
Department of Experimental Medicine, Endocrinology-Pituitary Disease, "Sapienza" University of Rome, Rome, Italy.
Endocrinology Unit, Department of Medicine DIMED, University-Hospital of Padua, Padua, Italy.
Int J Clin Oncol. 2021 Jun;26(6):1015-1021. doi: 10.1007/s10147-021-01895-y. Epub 2021 Mar 13.
Acromegaly is a rare disease due to chronic growth hormone (GH) excess and the consequent increase in insulin-like growth factor-1 (IGF-1) levels. Both GH and IGF-1 play a role in intermediate metabolism affecting glucose homeostasis. The association between hyperinsulinemia/impaired glucose tolerance and an increased risk of cancer has been clarified. Insulin has a mitogenic effect through its interaction with the IGF-1 receptor (IGF-1R) that also binds IGF-1. On the other hand, metformin, an anti-hyperglycemic drug that decreases serum levels of insulin and IGF-1, could have a protective role in the treatment of endocrine tumors.
A retrospective, observational, multicenter study in 197 acromegalic patients, receiving/not receiving metformin, was performed to assess whether the prevalence of neoplasms might be correlated with insulin resistance and could eventually be modified by metformin treatment.
In general, the occurrence of secondary neoplasia among our patients was significantly (pV = 0.035) associated with a positive family history of malignancy and with disease duration; a trend towards significance was observed in patients aged > 50 years. Acromegalic subjects who had undergone surgery showed a lower probability of developing a malignant tumor, whereas a higher prevalence of malignancies was observed in obese patients. No significant statistical difference was found when comparing metformin-treated or -untreated subjects for the presence of a second tumor. More interestingly, a trend towards statistical significance (pV = 0.065) was demonstrated in the metformin-treated group for the onset of a benign neoplasm.
Metformin could act directly on tumor cell metabolism and may have an adjuvant role in benign lesion progression.
肢端肥大症是一种罕见疾病，由慢性生长激素（GH）分泌过多以及随之而来的胰岛素样生长因子-1（IGF-1）水平升高所致。GH和IGF-1均在影响葡萄糖稳态的中间代谢中发挥作用。高胰岛素血症/糖耐量受损与癌症风险增加之间的关联已得到明确。胰岛素通过与也能结合IGF-1的IGF-1受体（IGF-1R）相互作用而具有促有丝分裂作用。另一方面，二甲双胍作为一种降低胰岛素和IGF-1血清水平的降糖药物，可能在内分泌肿瘤的治疗中具有保护作用。
对197例接受/未接受二甲双胍治疗的肢端肥大症患者进行了一项回顾性、观察性、多中心研究，以评估肿瘤的患病率是否与胰岛素抵抗相关，以及二甲双胍治疗最终是否可以改变这种情况。
总体而言，我们的患者中继发性肿瘤的发生与恶性肿瘤家族史阳性以及病程显著相关（pV = 0.035）；在年龄大于50岁的患者中观察到有显著趋势。接受手术的肢端肥大症患者发生恶性肿瘤的可能性较低，而肥胖患者中恶性肿瘤的患病率较高。在比较接受或未接受二甲双胍治疗的患者是否存在第二种肿瘤时，未发现显著的统计学差异。更有趣的是，在二甲双胍治疗组中，良性肿瘤的发生有统计学意义的趋势（pV = 0.065）。
二甲双胍可能直接作用于肿瘤细胞代谢，并且可能在良性病变进展中起辅助作用。
