Analysis on clinical characteristics of Graves′ disease patients with methimazole-induced agranulocytosis combined with septicemia

Abstract

Objective To explore the clinical characteristics of Graves′disease patients with methimazole-induced agranulocytosis combined with septicemia. Methods The study was based on a previous retrospective analysis of the clinical data in Graves′ disease patients admitted to the First Affiliated Hospital of Xi′an Jiaotong University from January 2000 to December 2015 due to antithyroid drug-induced agranulocytosis and focused on the 7 patients who developed agranulocytosis combined with septicemia (septicemia group) after taking methimazole. Relevant data was re-extracted from the medical records of the 7 patients. The clinical characteristics of patients with septicemia were explored through the analysis on their clinical manifestations, bacteriological characteristics, treatment and outcomes, and the comparison of above contents with those of the 55 patients with methimazole-induced agranulocytosis without septicemia (non-septicemia group). Results Seven patients in the septicemia group were female, aged 20 to 56 years. Of the 7 patients, 3 combined with hyperthyroid heart disease, 1 combined with life-threatening thyrotoxicosis; 6 patients with multiple organ infections (2 with suppurative tonsillitis and pulmonary infection; 2 with suppurative tonsillitis and gastrointestinal infection; 1 with suppurative tonsillitis, pulmonary infection, and submandibular abscess; 1 with suppurative tonsillitis, pulmonary infection, and periodontal abscess) and 1 patient with pulmonary infection alone. The main clinical symptoms of patients with septicemia included fever, sore throat, anorexia, and palpitations. The proportions of patients with suppurative tonsillitis, lung infections, and the lowest absolute neutrophil count (ANC) value of 0 in the septicemia group were higher than those in the non-septicemia group [6/7 vs. 43.6% (24/55), 5/7 vs. 21.8% (12/55), and 5/7 vs. 29.1% (16/55)]. The minimum white blood cell count in patients in the septicemia group was significantly lower than those in the non-septicemia group[0.23 (0.17, 0.60)×109/L vs. 0.92 (0.50, 1.47)×109/L]. The duration of fever, recovery time of agranulocytosis, and hospitalization days in patients in the septicemia group were significantly longer than those in the non-septicemia group [13 (7, 21) d vs. 6(3, 9) d and 29 (17, 37) d vs. 14 (9, 21) d]. The differences were all statistically significant (P<0.05 or P<0.01). After the diagnosis of agranulocytosis, methimazole was stopped in all patients. Their septicemia was effectively controlled and ANC returned to normal after the treatments with broad-spectrum antibiotics, recombinant human colony-stimulating factor (rhG-CSF), and glucocorticoids. Conclusions Graves′disease patients, who developed agranulocytosis combined with septicemia after taking methimazole, often had multiple organ infections. Their clinical symptoms were critical and difficult to treat. The early and rational application of broad-spectrum antibacterial drugs and simultaneous treatments with rhG-CSF and glucocorticoids were expected to improve patients′outcomes. Key words: Methimazole; Antithyroid drugs; Agranulocytosis; Sepsis; Septicemia