No abstract

This retrospective study was aimed at revealing the incidence of normal white blood cell (WBC) count agranulocytosis in patients treated with antithyroid drugs (ATDs). From January 1975 to December 2001, 109 patients (0.35%) presented with ATD-induced agranulocytosis at our clinic. In 18 patients (16.5%), the WBC count exceeded 3.0 x 10(9)/L at the onset of agranulocytosis. Ten showed a downward trend in WBC count (3.0-3.9 x 10(9)/L) after the initiation of ATDs. Four had symptoms of infection. In the remaining 4 patients, routine WBC and granulocyte count monitoring detected an agranulocytosis. During the first 3 months of ATD treatment, 3347 patients (10.9%) had WBC count 3.0-3.9 x 10(9)/L even once with no symptom and normal granulocyte count and 26672 patients had WBC count >or= 4.0 x 10(9)/L with no symptom and normal granulocyte count. When agranulocytosis was found, twelve patients with normal WBC count agranulocytosis (0.36%) had WBC count 3.0-3.9 x 10(9)/L with no symptom, whereas only 2 patients with agranulocytosis (0.008%) had WBC count >or= 4.0 x 10(9)/L with no symptom. In conclusion, clinicians should take normal WBC count agranulocytosis into consideration at least during the first 3 months of antithyroid drug therapy, especially when WBC count is 3.0-3.9 x 10(9)/L.

Twenty-two patients with spontaneously occurring primary hypothyroidism were studied to evaluate the spontaneous reversibility of the hypothyroid state. Twelve (54.5%) became euthyroid after restriction of iodine intake for 3 weeks (reversible type). In the remaining 10 patients, thyroid function did not improve with restriction of iodine alone, and thus, replacement therapy was required, (irreversible type). In the reversible type, 1) radioactive iodine uptake after 1 week of restricted iodine intake was higher than in the irreversible type [50.0 +/- 12.2% (+/- SD) vs. 4.3 +/- 3.2%; P less than 0.01], 2) the perchlorate discharge test was positive in 2 of 10 patients, and 3) the iodine-perchlorate discharge test, carried out in 7 of 8 patients with negative perchlorate discharge test, was positive in 6. Seven patients with the reversible type were given 25 mg iodine daily for 2-4 weeks; all became hypothyroid again. Two patients had a history of habitual ingestion of seaweed (25.4 and 43.1 mg iodine, respectively), but the remaining 10 patients ingested ordinary amounts of iodine (1-5 mg) daily. The patients with reversible hypothyroidism had focal lymphocytic thyroiditis changes in the thyroid biopsy specimen, whereas those with irreversible hypothyroidism had more severe destruction of the thyroid gland. These results indicate the existence of a reversible type of hypothyroidism sensitive to iodine restriction and characterized by relatively minor changes in lymphocytic thyroiditis histologically. Attention should be directed to this type of hypothyroidism, because thyroid function may revert to normal with iodine restriction alone.

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.

T2 relaxation time measurements with MR allow noninvasive detection of acute muscle inflammation and predict which patients with GO will likely benefit from antiinflammatory therapy.