Serum Beta-Glucuronidase in Thyroid Disease 1

The induction by thyroxine of metamorphosis in amphibia is associated with increased activity of several lysosomal enzymes in the resorbing tail, presumably in endocytic cells (1). One of these enzymes, beta-glucuronidase, has been shown to increase approximately 20-fold during metamorphosis (1, 2). Were thyroid hormone to have similar effects on mammalian tissues, changes in the amount or distribution of enzyme might be paralleled by changes in the activity of beta-glucuronidase in the sera of patients with diseases of the thyroid. Patients with hyperthyroidism might be expected to show increases in serum activity of the enzymes, myxedematous patients to show decreased activity; in either group, appropriate therapy should return these values to control levels. We should like to submit data indicating that the activity of beta-glucuronidase in the serum of humans does, in fact, appear to vary with the state of activity of the thyroid gland.

Materials and Methods. The beta-glucuronidase activity of fresh serum was determined by the method of Fishman et al. (3). Samples, 0.2 ml, were incubated with 2.0 ml of acetate buffer, pH 4.5, and 0.1 ml of a 0.01 M solution of phenolphthalein glucuronidate. The chromogen was developed after 18 hr incubation at 37°.

Diagnosis was on clinical grounds, and was verified in each case by determination of protein-bound iodine, uptake of ¹³¹I, or determination of protein-bound ¹³¹I at 72 hr. Patients with equivocal thyroid status were not included in the study, nor were patients with frank liver disease, jaundice, or renal failure. Thyroiditis was diagnosed clinically by signs and symptoms of inflammatory disease of the gland accompanied by an elevated erythrocyte sedimentation rate; each case responded to anti-inflammatory steroid therapy.

Results. The data in Fig. 1 show that patients with hyperthyroidism had greater levels of beta-glucuronidase activity in their serum than did euthyroid controls. When hyperthyroidism was brought under clinical control by treatment with ¹³¹I (three cases) or propylthiouracil (two cases), these elevated levels reverted to normal. Patients with myxedema had lower serum beta-glucuronidase activity than did euthyroid individuals; upon treatment with thyroid extract these levels rose as their clinical status became more nearly normal. The two highest values were obtained with sera from patients treated with triiodothyronine. Patients with thyroiditis did not show significant elevations of serum beta-glucuronidase. None was hyperthyroid at the time of testing.