Tumor-Size Dependent Circadian Endocrine Disturbances in Untreated Patients With Primary Prostate Cancer

The aim of this study was to analyse the circadian profiles of central and peripheral circulating hormones in patients with unoperated primary localized prostate cancer (PC) as well as in age-matched controls with benign prostatic hyperplasia (BPH) in order see whether tumor-specific endocrine disturbances may occur. The hormones analysed in serum included melatonin, prolactin (PRL), growth hormone (GH), thyroid-stimulating hormone (TSH), total thyroxine (T4), luteinizing hormone (LH), testosterone (T), and cortisol (Cor). Blood was collected at four-hourly intervals over one complete 24-h cycle from 19 patients with PC (68 ± 3 years; T₁N₀M₀-T₄N_xM₀) and 20 patients with BPH (69 ± 3 years; BPH+-BPH+++). The most prominent result was that the circadian amplitude of melatonin was drastically depleted in PC (-71%) compared to BPH, and patients with T₂ as well as T_3/4 showed extremely low melatonin leading to a loss of circadian rhythmicity. A similar trend existed for PRL where no circadian rhythms were detectable in PC with larger tumors. Loss of circadian rhythmicity was also observed for GH in PC, and TSH-concentrations were clearly depleted by 43 – 53% in patients with T₂-and T_3/4-tumors compared to patients with medium- and large-sized BPH although T4 was within normal limits. LH as well as T and Cor did not show any changes in PC compared to BPH. This indicates that the growth of PC leads to specific endocrine changes affecting melatonin, PRL, GH and TSH without influencing peripheral hormones (T4, T, Cor) as well as LH. The possible significance of these findings for the prognosis of patients with PC is discussed, as well as the potential underlying mechanisms focussing on the question why circulating melatonin may be diminished in PC and whether this could be functionally involved in the observed endocrine disturbances.