Abstract
BackgroundAcromegaly 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.MethodsA 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.ResultsIn 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.ConclusionMetformin could act directly on tumor cell metabolism and may have an adjuvant role in benign lesion progression.
Highlights
The over-secretion of growth hormone (GH) characterizes acromegaly, a rare chronic disease with a worldwide prevalence of 40–130 per million, most commonly due to a pituitary tumor, and associated with multiple comorbidities, such as diabetes mellitus (DM), sleep apnea, arthropathy, cardiovascular system disorders, and cancer [1]
Data about malignancy familiarity were available for 142/197 patients, 99 of which without any familiarity and 43 with familiarity for cancer of unspecified nature; the prevalence of neoplasia was significantly correlated to a positive family history of malignancy ( 2 = 4.43 df = 1; p value (pV) = 0.035)
Treatment with metformin can be considered to be a protective factor in the onset of benign neoplasms
Summary
The over-secretion of growth hormone (GH) characterizes acromegaly, a rare chronic disease with a worldwide prevalence of 40–130 per million, most commonly due to a pituitary tumor, and associated with multiple comorbidities, such as diabetes mellitus (DM), sleep apnea, arthropathy, cardiovascular system disorders, and cancer [1]. The excess of insulin-like growth factor-1 (IGF-1) in acromegalic patients, ascribed to GH overexpression, seems to be involved in the onset of hyperglycemia (with a prevalence of DM ranging from 12 to 37%); it promotes insulin resistance by lipolysis, stimulating gluconeogenesis, and blocking the signaling of insulin mediators, such as p85 alpha and insulin receptor substrate (IRS-1) [3]. 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. Conclusion Metformin could act directly on tumor cell metabolism and may have an adjuvant role in benign lesion progression
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