ESPE Abstracts

Introduction: Neutropenia is known as a rare adverse event of anti-thyroid drug treatment (ATD) but has also been reported as pre-treatment neutropenia in Graves’ disease (GD). Studies on paediatric patients are rare. To the best of our knowledge, there are no data comparing the effects of methimazole (MMI) and carbimazole (CBZ) treatment in children on the absolute neutrophil count (ANC).

Methods: We analyzed retrospectively the clinical and biochemical data of 161 children (age 11.8 years ± 3.57) diagnosed with GD. 83% were Caucasian, 17% belonged to other ethnic groups such as Turkish or Syrian. Inclusion criteria were elevated free thyroxine (fT4) [normal range (NR): 10 – 25pmol/L], completely suppressed thyroid stimulation hormone (TSH) (NR: 0.5-4.5mIU/L) and elevated thyroid receptor antibodies (TSHRAb > 2.5 IU/l). Neutropenia was defined as ANC <1800/µL, and agranulocytosis as ANC < 500/µL. All patients received ATD with MMI or CBZ.

Results (mean ± SD): Nine patients had neutropenia at diagnosis (ANC: 1348/µL ± 250.12), with spontaneous normalization under ATD. One patient developed agranulocytosis (40/µl) three weeks after start of ATD due to either very high maximal dose of CBZ (1.8mg/kg/d) or thyreotoxicosis (fT3 > 30pg/ml (46pmol/l); fT4 > 8ng/dl (12.9pmol/l), both higher than measurable upper limit, TSHRAb 101.20 IU/l). Further 37 patients became neutropenic (ANC: 1479/µL ± 261.84) while receiving ATD. Neutropenia occurred on average after 551.8 days (range, 10-1376) after diagnosis. All patients achieved ANC normalization without a change in the treatment regime. Low ANC occurred significantly more often in patients receiving CBZ (50%; n=20/40) than in those receiving MMI (16.5%; n=18/109; P=0.0008). The groups do not differ in sex, age, antibody or hormone level. The maximal dose before neutropenia was not significantly different between the CBZ and the MMI group and between the neutropen and the non-neutropen group. The cumulative ATD dosages, analysed at four times when 25%, 50%, and 75% of the children developed neutropenia, were not significantly different between the treatment groups.

Discussion/Conclusion: Agranulocytosis is a rare ATD side effect in children suffering from GD. Neutropenia at diagnosis is not a contraindication for ATD use and mild to medium neutropenia under ATD is no indication for changing the treatment regime, because in both groups normalization of ANC can arise spontaneously. As neutropenia occurred significantly more often under CBZ than MMI in our cohort we suggest that children with GD should be treated with MMI. Further investigation is necessary to detect risk factors for neutropenia in children with GD.