Periodic Granulocyte Count Measuring Is Useful for Detecting Asymptomatic Agranulocytosis in Antithyroid Drug-Treated Patients with Graves' Disease

Abstract

Objective: Finding agranulocytosis (AG) at an early stage is important to improve outcome, but periodic granulocyte count monitoring is not generally recommended for patients with Graves' disease, because AG develops suddenly. Method: At the Kuma Hospital, Graves' patients under antithyroid drug (ATD) treatment in an outpatient clinic have a granulocyte count examination during each visit, and if it is <1,000/μl, a warning is immediately sent to the patient's physician. We evaluated the usefulness of this system. Results: We investigated 25 AG and 33 granulocytopenia (GP) cases over a recent 5-year period, excluding patients who developed AG or GP at another hospital and were referred to us for treatment. Among the 25 AG patients, 16 patients (64%; 9 asymptomatic and 7 very mild symptomatic cases) were discovered by the periodic granulocyte count examination at an outpatient clinic. The remaining 9 patients visited the Kuma Hospital or other hospitals because of infection symptoms. Most of the AG patients were given granulocyte colony-stimulating factor injections immediately and were admitted if a prompt increase in granulocytes could not be obtained. The final treatments for Graves' disease were ¹³¹I-radioisotope therapy (19 patients), thyroidectomy (2 patients), inorganic iodine (1 patient), or another ATD (1 patient). Among the 33 GP patients, 31 (94%), including 20 asymptomatic cases, were discovered during periodic granulocyte count monitoring. Most of them stopped ATD, and other treatments for Graves' disease were selected. Conclusion: Periodic monitoring of granulocyte counts is useful for identifying AG and GP patients with no or minimum infection symptoms.

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

“…The medical literature recommends monitoring the neutrophil count when certain drugs, such as clozapine, ticlopidine and ATDs, are prescribed [14,25]. The results of the present study seem to support this recommendation.…”

“…In this setting, ATD-induced neutropenia may often be asymptomatic [2,13]. This Grade 1 neutropenia discovery is linked to the routine follow-up of a patient under antithyroid treatment as recommended by several authors and endocrinology societies [2,14]. In this setting, life-threatening manifestations have been reported in more than 2/3 of the cases [11,12,15].…”

“…For example, there were no deaths in 109 cases of agranulocytosis related to ATDs managed at a Japanese endocrinology reference center where this pathology is known (numerous publications from this center), diagnosed early and treated in a codified manner, with the systematic use of HGFs (mainly G-CSFs) in particular [18]. One other explanation of the low reported mortality may be an early diagnosis of neutropenia as part of blood count monitoring as recommended by international thyroid societies [2,14]. The mortality of 6.6% represents one of the lowest rates reported in the literature even though our patients were relatively old and frail and with several comorbidities in 76.7% of cases.…”

“…The results of the present study seem to support this recommendation. The blood neutrophil count at every medical visit when prescribing ATDs has recently demonstrated to correctly diagnose 64% and 94% of patients with agranulocytosis without or with minimum infection symptoms when prescribing ATDs [14,26]. However, the lack of impact on mortality and morbidity leads to a debate regarding blood count monitoring [7,8].…”

Antithyroid Drug-Induced Agranulocytosis: State of the Art on Diagnosis and Management

“…However, as Tajiri et al [ 12 ] reported, this is the best method to diagnose asymptomatic patients. A standardized approach with granulocyte count examination at each visit was shown to correctly diagnose 64 and 94% of patients with agranulocytosis or granulocytopenia, respectively, with no or minimum infection symptoms [ 33 ]. On balance, one should try to avoid the most severe and yet unpredictable outcome and thus continue with routine measurements.…”