Antithyroid Drug-Induced Agranulocytosis: How Has Granulocyte Colony-Stimulating Factor Changed Therapy?

Abstract

This study examined whether granulocyte colony-stimulating factor (G-CSF) is beneficial for the treatment of antithyroid drug-induced agranulocytosis. From January 1975 to December 2001, 30,798 patients with Graves' disease were treated with antithyroid drugs at Noguchi Thyroid Clinic & Hospital Foundation. During this period, 109 patients (0.35%) were found to have agranulocytosis caused by antithyroid drugs. In the symptomatic group, the recovery time from agranulocytosis was significantly shorter after the introduction of G-CSF (5.5 +/- 3.5 days, n = 19) compared to the symptomatic group before its introduction (9.2 +/- 4.4 days, n = 37, p < 0.01). In the asymptomatic group, the recovery time from agranulocytosis was significantly shorter after the introduction of G-CSF (2.3 +/- 1.9 days, n = 15) compared to the asymptomatic group before the introduction of GCSF (5.4 +/- 4.3 days, n = 34, p < 0.05). However, G-CSF therapy was ineffective in severe cases with granulocyte count below 0.1 x 10(9)/L and symptoms. We recommend that G-CSF therapy should be applied only in asymptomatic patients and symptomatic patients with granulocyte count above 0.1 x 10(9)/L, and not for symptomatic patients with granulocyte count below 0.1 x 10(9)/L. In conclusion, G-CSF therapy shortens the period of recovery from antithyroid drug-induced agranulocytosis and benefits patients, except those with symptoms and a granulocyte count below 0.1 x 10(9)/L.

The Effects of GCSF on the Recovery Time and Duration of Hospitalization in Patients with Anti-thyroid Drug-Induced Agranulocytosis in a Tertiary Hospital

“…The predominantly female composition of both groups was consistent with studies on ATD-induced agranulocytosis done in Japan, France and the Philippines. 1,[14][15][16][17] This may be attributed to the 1:5 male-to-female ratio of hyperthyroidism worldwide. 22 Most of the hyperthyroid patients who developed antithyroid drug-induced agranulocytosis were on imidazoles, as only a small proportion were on PTU.…”

“…22 Most of the hyperthyroid patients who developed antithyroid drug-induced agranulocytosis were on imidazoles, as only a small proportion were on PTU. 1,[14][15][16] Imidazoles are preferred over PTU due to their ability to rapidly achieve euthyroidism, once daily dosing assuring better compliance and less reported toxicity. 23 The most common initial adverse reactions to ATDs are pruritus and rashes.…”

“…17 The benefits of GCSF on ATD-induced agranulocytosis do not seem to be consistent across studies. [14][15][16][17][18][19][20] In studies done by Watanabe, Andres and Tamai, GCSF shortened the recovery period from agranulocytosis. 1,16,18,19 GCSF was ineffective against ATD-induced agranulocytosis in a prospective controlled study.…”

Radioiodine therapy of thyrotoxicosis in children and adolescents. Indications, efficacy and safety. Literature review

“…По этой причине с 2010 г. FDA (США) не рекомендует использование пропилтиоурацила у детей. Риск развития агранулоцитоза составляет 0,3%, который чаще всего проявляется в те-чение 100 дней от начала лечения [14].…”

The relationship between bone marrow characteristics and the clinical prognosis of antithyroid drug-induced agranulocytosis

“…G-CSF was found to be useful in shortening the duration of granulocyte recovery in ATD-induced agranulocytosis [21]. Although there were some studies showed disparate opinions on its effect [8,[22][23], most authorities recommended using G-CSF for agranulocytosis due to ATD [1,4,21]. The action of G-CSF included stimulation and differentiation of myeloid granulocyte progenitors, squeezing mature granulocytes from bone marrow and shifting neutrophils from the perivascular space to the vascular space [24].…”