Elevated serum granulocyte colony-stimulating factor levels in patients with Graves' disease

Agranulocytosis is a serious side effect of anti-thyroid drugs (ATD). Granulocyte colony-stimulating factor (G-CSF) is one of the cytokines that increase granulocyte number. The aim of this study was to examine the sequential variation of serum G-CSF levels in patients with Graves' disease before and after ATD therapy.

Sixty-three patients with Graves' disease were studied before, during and after treatment with methimazole (MMI). Serum samples from 71 healthy subjects were used as controls.

Serum levels of G-CSF were measured by a novel chemiluminescent enzyme immunoassay, which was sensitive enough to determine G-CSF levels in healthy subjects. Blood granulocyte counts, serum, thyroid hormone and TSH levels, and titres of thyroid autoantibodies were also measured.

Serum G-CSF levels in Graves' patients before and 2 weeks after MMI were significantly higher than in healthy subjects. There was a significant correlation between serum G-CSF levels and granulocyte counts in untreated patients with Graves' disease. Untreated patients with granulocyte counts less than 2 x 10(9)/I had significantly lower serum G-CSF levels as compared with other untreated patients. Serum G-CSF levels gradually decreased thereafter. No correlation was observed between serum G-CSF levels and serum thyroid hormone levels or titres of thyroid autoantibodies. After ATD treatment, no correlation was found between serum G-CSF levels and granulocytes counts. There was no significant correlation between the change of serum G-CSF levels and that of granulocyte counts before and after MMI treatment. Graves' patients with mild agranulocytosis had normal or elevated serum G-CSF levels.

Significantly elevated serum G-CSF levels were observed in patients with Graves' hyperthyroidism. During ATD therapy, deficiency of G-CSF was not identified as a cause of agranulocytosis in this study.