EFFECTS OF THERAPEUTIC AND TOXIC DOSES OF PROPYLTHIOURACIL IN RATS

¹ Department of Pathology, Baylor University College of Medicine, Houston, Texas

In an attempt to reduce the toxicity of propylthiouracil (PTU) by establishing different degrees of hypothyroidism, Wistar rats were pair-fed a semisynthetic balanced diet and administered 4 to 6 mg/kg/day (therapeutic dose) or 120 to 180 mg/kg/day (toxic dose) of PTU for 6 weeks. A significant difference between the two groups could not be established by 24-hr I¹⁸¹ uptake of thyroid, 24-hr serum protein-bound iodine (PBI¹⁸¹) conversion ratio, serum thyroxine level or serum total cholesterol or by comparing thyroid weights. Despite the isocaloric dietary intake, body weight gain in the toxic-dose group was less than in the controls, whereas weight gain in the therapeutic-dose group exceeded that of the controls. Hemoglobin, hematocrit and platelet counts of both groups were normal and similar, but the toxic-dose group had leukopenia with a reduction in all types of leukocytes. Histologic features of the thyroids of both groups were similar, showing extreme follicular hyperplasia with depletion of colloid and increased vascularity. The results indicate that the administration of a therapeutic dose of PTU produces a satisfactory degree of hypothyroidism without sacrificing excessively the general physical condition of animals.