Circadian rhythm of serum erythropoietin in myelodysplastic syndromes.

Myelodysplastic syndromes (MSD) are a group of clonal disorders of the hemopoietic stem cell, often evolving in acute leukemia. They are characterized by anemia, and it has been attributed either to a deficiency in erythropoietin (EPO) secretion or to a resistance to EPO itself. Since in healthy subjects the serum circulating EPO levels fluctuate during the day, the aim of the study was to investigate the diurnal rhythm of EPO in MDS. Two groups of subjects were admitted to the study: (A) 20 adult clinically healthy subjects, and (B) 20 patients with MDS without renal failure. After standard life conditions in hospital lasting one week, venous blood samples were drawn during the span of a whole day and every four hours, starting from midnight, for the measurement of serum EPO levels by RIA. Statistical analysis was carried out by means of the "cosinor" method. The results show that the controls present a significant (p < 0.05) circadian rhythms in serum EPO levels with acrophase in the late afternoon; on the contrary, no significant (p > 0.05) rhythm was detected in patients with MDS. Patients with MDS presented significantly higher (p < 0.05) MESOR and lower (p < 0.001) amplitude of EPO circadian rhythm in respect to the controls; moreover, a significant (p < 0.005) difference was found between the two groups in overall EPO rhythm. These data confirm the existence of a physiological circadian rhythm in serum EPO concentrations with maximum in the afternoon. Because EPO levels are increased in the patient group, EPO deficiency does not seem to be the cause of anemia in MDS. Reduced EPO amplitude may be a compensatory mechanism for enhancing its activity in MDS. Finally, the stimulatory therapy in MDS with recombinant human EPO should be administered in the late afternoon hours, in order to respecting and simulating the physiological circadian rhythm of endogenous EPO.