Altered diurnal rhythm of prolactin in systemic sclerosis

OBJECTIVE: Mild hyperprolactinemia has been reported in systemic lupus erythematosus (SLE) and systemic sclerosis (SSc). We investigated whether the elevated serum level of prolactin (Prl) detected in SSc is due to a sustained increase over 24 h and/or a shift in the diurnal rhythm, and whether Prl autoantibodies--originally described in SLE--may interfere in the assay. METHODS: The serum level of Prl was measured by ELISA and compared between 73 patients with SSc and 73 age and sex matched controls (78% women, age 56 +/- 11 years). The diurnal rhythms of Prl and thyrotropin (thyroid stimulating hormone, TSH) were compared between 3 patients with SSc and 10 healthy controls. Blood was taken at 2-3, 6-7, 10-11 a.m., and 2-3, 6-7, 10-11 p.m. The serum level of Prl autoantibodies was measured by ELISA and compared between matched patients with SSc and SLE and controls (n = 42 each). Standard curves of the Prl ELISA were spiked with 10% sera containing high levels of Prl autoantibodies to test interference. RESULTS: Serum levels of Prl measured in the morning (8-10 a.m.) were significantly higher in patients with SSc (17.9 +/- 7.7 ng/ml), compared with controls (9.3 +/- 4.2 ng/ml; p < 0.05). In SSc, 40% of patients had Prl levels > 20 ng/ml, but no correlation was found with Scl-70 or Prl autoantibodies. Younger patients (< 50 years, n = 23/73) showed higher serum levels of Prl than older patients (21.3 +/- 10.3 vs 16.3 +/- 6.2 ng/ml; p < 0.05). The diurnal rhythm of Prl revealed that both a sustained increase over 24 h and some shift occurred in SSc. Peaks of secretion were detected between 6 and 11 a.m., instead of 2-6 a.m. The median levels of TSH over 24 h in patients with SSc ranged within the normal limits. Nevertheless, in SSc, a significant correlation (r = 0.59, p < 0.01) was found between diurnal rhythms of Prl and TSH. The prevalence of Prl autoantibodies in serum was 8% in SSc, 27% in SLE, and < 5% in controls. However, the presence of Prl autoantibodies did not interfere with our assay. CONCLUSION: Our data confirm that mild hyperprolactinemia occurs in a subgroup of patients with SSc, and showed that the elevated serum level of Prl is due to both a sustained increase over 24 h and a shift in the diurnal rhythm. The correlation between diurnal rhythms of Prl and TSH suggests common regulatory mechanisms.