On the Rate of Formation of Steroidal Glucuronosides in Patients with Familial and Acquired Jaundice*

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Abstract
After rapid intravenous administration of tetrahydrocortisone (THE), the rate of reduced steroid conjugation with glucuronic acid was assessed by measuring the rate of its plasma disappearance, and by analyzing urine collected at frequent intervals after infusion. These procedures yielded useful information concerning steroid metabolism provided renal function was normal. In 3 adult patients with familial jaundice previously shown to have hepatic deficiency of the enzyme uridine diphosphate (UDP)-transglucuronylase, but not in other patients with familial jaundice of differing etiology, THE glucuronoside formation was delayed without appreciable impairment in total synthesis. Quantitatively, the lesion was not so severe for steroid as it was for bilirubin and menthol. The metabolism of cortisol was normal. A delay in THE glucuronoside formation was also found in one subject with conjugated hyperbilirubinemia and a past history of viral hepatitis. In 1 patient with UDP-transglucuronlyase deficiency the defect in THE conjugation could not be detected after 1 g of menthol was administered 2 hours before a test dose of THE. In the patient with a past history of hepatitis the same dose of menthol also enhanced the rate of THE glucuronoside formation. This and other data suggest that the transferase for THE glucuronoside formation may be distinct from that of menthol. Two patients with severe hepatic insufficiency secondary to alcoholism but differ ing in their clinical and pathological findings were studied. One showed a severe disorder of both THE and cortisol metabolism, and the other did not. Thus patients with even marked impairment of liver function do not comprise a homogeneous group with respect to the disposition of steroid hormones. In 2 patients with untreated Addison''s disease, the metabolism of THE was essentially normal. Prolonged absence of normal amounts of substrate therefore does not affect the ability to metabolize it.