Severe Neutropenia and Agranulocytosis Related to Antithyroid Drugs: A Study of 30 Cases Managed in A Single Reference Center

• Main Authors: Emmanuel Andrès, Noel Lorenzo-Villalba, Rachel Mourot-Cottet, Frédéric Maloisel, Martine Tebacher, Jacques-Eric Gottenberg, Bernard Goichot, Raoul Herbrecht, Abrar-Ahmad Zulfiqar
• Format: Article
• Language: English
• Published: MDPI AG 2020-03-01
• Series: Medicines
• Subjects: neutropenia; agranulocytosis; antithyroid drug; carbimazole; propylthiouracil; diagnosis; fever; infection; hematopoietic growth factor; granulocyte colony-stimulating factor
• Online Access: https://www.mdpi.com/2305-6320/7/3/15

<b>Background:</b> The most important series devoted to antithyroid drug-induced severe neutropenia and agranulocytosis are Japanese studies, almost specifically in relation to the intake of methimazole. The clinical data of 30 Caucasian patients followed up for antithyroid drug-induced neutropenia at a third-level hospital are reported. <b>Methods:</b> The data of 30 patients with idiosyncratic antithyroid drug-induced neutropenia and agranulocytosis from a cohort study on drug-induced neutropenia and agranulocytosis conducted at the University Hospital of Strasbourg (France) were retrospectively reviewed. <b>Results:</b> The mean patient age was 61.7 years old (range: 20&#8722;87), and the gender ratio (F/M) was 4. Several comorbidities were reported in 23 patients (76.7%), with the mean Charlson comorbidity index of 1. The causative drugs were carbimazole and benzylthiouracil, in 28 (93.3%) and 2 cases, respectively, prescribed primarily for multi-hetero-nodular goiter or thyroid nodule to 18 patients (60%). Sore throat and acute tonsillitis (40%), isolated fever (20%), septicemia (13.3%), documented pneumonia (6.7%), and septic shock (6.7%) were the main clinical features upon admission. The mean neutrophil count at nadir was 0.02 and 0 &#215; 10⁹/L (range: 0&#8722;0.3). Regarding the patients&#8217; hospital course: 13 cases (43.3%) worsened during hospitalization, severe sepsis was found in 26.7%, systemic inflammatory response syndrome&#8212;in 13.3%, and septic shock&#8212;in 3.3% of the cases, respectively. Broad-spectrum antibiotics were indicated for all the patients, and 21 (73.3%) of them received hematopoietic growth factors. Hematological recovery (neutrophil count &#8805; 1.5 &#215; 10⁹/L) was seen at 8.3 days (range: 2&#8722;24), but faster in those receiving hematopoietic growth factors (4.9 days, <i>p</i> = 0.046). Two patients died during hospitalization, and the rest had a favorable clinical outcome. <b>Conclusions:</b> Antithyroid drug-induced neutropenia represents a serious complication resulting from the rates of severe infections especially in those cases severe neutropenia. In this setting, an established procedure for the management of patients seems useful or even indispensable in view of potential mortality.