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Circadian melatonin and cortisol levels in rheumatoid arthritis patients in winter time: a north and south Europe comparison
  1. M Cutolo1,
  2. G J M Maestroni2,
  3. K Otsa3,
  4. O Aakre3,
  5. B Villaggio1,
  6. S Capellino1,
  7. P Montagna1,
  8. L Fazzuoli4,
  9. T Veldi3,
  10. T Peets3,
  11. E Hertens2,
  12. A Sulli1
  1. 1Division of Rheumatology, Department of Internal Medicine, University of Genova, Genova, Italy
  2. 2Cantonal Institute of Pathology, Locarno, Switzerland
  3. 3Division of Rheumatology, Tallinn Central Hospital, Tallinn, Estonia
  4. 4Division of Endocrinology, Department of Endocrinology, University of Genova
  1. Correspondence to:
    Professor M Cutolo
    Division of Rheumatology, Department of Internal Medicine, University of Genova, Viale Benedetto XV,6, 16136 Genova, Italy;


Background: Altered functioning of the hypothalamic-pituitary-adrenal axis and altered melatonin production might modulate the circadian symptoms in patients with rheumatoid arthritis.

Objective: To investigate the influence of different winter photoperiods on the circadian rhythms of serum melatonin, cortisol, tumour necrosis factor α (TNFα), and interleukin 6 (IL6) in patients with rheumatoid arthritis from a north Europe country (Estonia) and a south Europe country (Italy).

Methods: The patients from Estonia (n = 19) and Italy (n = 7) had similar disease severity and duration and were compared with healthy age and sex matched controls in the two countries. Blood samples were collected during the period January to February at 8 pm, 10 pm, midnight, 2 am, 4 am, 6 am, 8 am, and 3 pm. Melatonin was measured by radioimmunoassay using 125I-melatonin. Serum cortisol, TNFα, and IL6 cytokines were assayed by standard methods.

Results: Higher circadian melatonin concentrations from 10 pm and an earlier peak were observed in Estonian patients than in their age and sex matched controls (p<0.01). Starting from midnight, melatonin concentrations were significantly higher in the Estonian patients than in the Italian patients. No significant differences were observed for serum cortisol. Serum TNFα was higher (p<0.05) in Estonian patients than in their controls and was correlated with the melatonin levels.

Conclusions: In a north European country (Estonia), the circadian rhythm of serum concentrations of melatonin and TNFα in patients with rheumatoid arthritis were significantly higher than in matched controls or in rheumatoid patients from a south Europe country (Italy).

  • DAS, disease activity score
  • IL6, interleukin 6
  • TNFα, tumour necrosis factor α
  • UVR, ultraviolet radiation
  • TNFα
  • circadian rhythm
  • rheumatoid arthritis
  • melatonin

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