Circadian Aspects of Growth Hormone–Insulin-Like Growth Factor Axis Function in Patients With Lung Cancer

Background and PurposeInsulin-like growth factor 1 (IGF1) promotes cell cycle progression and inhibition of apoptosis and may have a role in carcinogenesis and cancer promotion. Growth hormone (GH) stimulates IGF1 production in liver and other tissues. The aim of our study was to evaluate differences between healthy subjects and patients with lung cancer in the GH-IGF1 axis function.Patients and MethodsIn 11 healthy male patients (mean age ± standard error [SE], 43.6 ± 1.7), and 9 male patients with non–small-cell lung cancer (mean age ± SE, 51.0 ± 2.4), GH, total IGF1, melatonin, and interleukin (IL)-2 serum levels were measured in blood samples collected every 4 hours for 24 hours.ResultsA clear circadian rhythm was present for melatonin and GH serum levels in the group of healthy subjects and for melatonin in the group of patients with cancer. The midline estimating statistic of rhythm (MESOR) of GH was higher in patients with lung cancer (P < .001), the MESOR of IGF1 was higher in healthy subjects (P < .001), the MESOR of melatonin was not different between subjects (P = .383), and the MESOR of IL-2 was higher in patients with cancer (P = .02). The GH/IGF1 ratio was higher in patients with lung cancer (P = .006). Linear regressions across the stages of cancer showed a significant increasing slope for IL-2 (P < .001), GH (P < .001), and the GH/IGF1 ratio (P < .001), a decreasing slope for IGF1 (P < .001), but no significant trend for melatonin (P = .430).ConclusionThere is evidence that in patients with lung cancer there is a severe alteration of GH-IGF1 axis function, with loss of circadian rhythmicity of hormone secretion, which may play a role in the progression of neoplastic disease and must be considered in defining the therapeutic approach.