Clinical evaluation of serum thyroglobulin measurement using a commercial kit in the diagnosis of recurrent thyroid cancer.

The value of serum thyroglobulin assay employing a kit manufactured by Diagnostic Products Corporation in the detection of recurrence of thyroid carcinoma in patients treated by thyroidectomy and ablative therapy was assessed by clinical follow-up and radioiodine scanning of 122 patients over a 2-year period. A total of 204 specimens were analysed. The assay was found to be sensitive and highly specific for the detection of recurrent thyroid carcinoma provided that lipemic sera are clarified by ultracentrifugation prior to measurement and that results from those patients who demonstrate positive serum antithyroglobulin antibodies are excluded. The predictive value of a serum thyroglobulin level above 20 pmol/L was 96% for recurrence of thyroid carcinoma. The predictive value for non-recurrence was 98% for serum thyroglobulin levels below 10 pmol/L. The specificity and sensitivity of the assay were poor for serum thyroglobulin levels between 10 and 20 pmol/L. In recurrence-free patients, the serum thyroglobulin levels were not changed by withdrawal of thyroid replacement therapy 4-7 weeks prior to sampling.

Actions of dietary orotic acid on liver synthesis of phosphatidylcholine and phosphatidylethanolamine in rats.

The in vivo rates of the reactions of the cytidine pathways of liver phosphatidylcholine and phosphatidylethanolamine synthesis were measured in rats after 1 day of feeding on a semisynthetic diet containing 1% orotic acid. The calculations were made from the specific and total radioactivity versus time curves of the precursors and products following intraportal injection of [1,2-14C]choline, [2-14C]ethanolamine, and [2-3H]glycerol. The liver CTP level was increased twofold and the rates of CDP-choline and phosphatidylcholine synthesis were stimulated 4.5-fold in the rats fed orotic acid. The rate of CDP-ethanolamine synthesis was increased but could not be accurately quantified because of its extreme rapidity. No change occurred in the rate of the ethanolaminephosphotransferase reaction and the overall rate of phosphatidylethanolamine synthesis was unchanged by orotic acid feeding. The catalytic activities of the enzymes of the cytidine pathways of phosphatidylcholine and phosphatidylethanolamine synthesis were not affected by feeding orotic acid for 1 day. Similar findings were obtained 3 h following intragastric administration of 100 mg of orotic acid. The results suggest the possibility that changes in the levels of liver CTP may play a role in regulation of the cytidine pathway of liver phosphatidylcholine synthesis but not of phosphatidylethanolamine synthesis, because the latter pathway appears to be tightly controlled at the ethanolaminephosphotransferase step.

Early effects of dietary orotic acid upon liver lipid synthesis and bile cholesterol secretion in rats.

Dietary orotic acid is known to cause impaired fatty acid synthesis and increased cholesterol synthesis in rats. We found that the impaired fatty acid synthesis occurs during the first day of orotic acid feeding and, in studies with albumin-bound [1-14C]palmitic acid, an associated decrease in the rate of esterification of this fatty acid into triacylglycerol, phospholipid, and cholesteryl ester was observed. These changes may result from the known decreases in liver levels of adenine nucleotides or, as reported here, from decreased liver CoASH levels in orotic acid-fed rats. The increase in hepatic cholesterol synthesis occurred during the second day of orotic acid feeding. It was detected by increased incorporation of [1,2-14C]acetate into cholesterol by liver slices and by a 7-fold increase in HMG-CoA reductase activity. At the same time the biliary output of cholesterol was increased 2-fold and studies using 3H2O revealed that the output of newly synthesized cholesterol in bile was increased 5-fold. The content of cholesteryl ester in hepatic microsomes decreased during orotic acid feeding but free cholesterol was unchanged. The findings are interpreted to suggest that the increased bile cholesterol secretion caused by orotic acid is a result of impaired hepatic cholesterol esterification and that the increase in HMG-CoA reductase activity is a result of diminished negative feedback due to the depleted content of cholesteryl ester in the hepatic microsomes.

Increased catabolism of phosphatidylcholine to betaine regulates the liver phosphatidylcholine content in rats fed orotic acid.

Feeding a semi-synthetic diet containing 1% orotic acid to rats for one day stimulates the CDPcholine pathway of liver phosphatidylcholine synthesis 4.5-fold without significantly increasing the liver phosphatidylcholine level. The liver betaine level increases 1.6-fold. The present experiments were performed to investigate the source of the increased liver betaine. Orotic acid feeding did not alter the rate of oxidation of 1,2[14C] choline to betaine. After liver phosphatidylcholine was labelled in vivo with 2[14-C]-ethanolamine, over 90% of the choline-derived radioactivity was recovered in liver betaine and this was consistently increased in rats fed orotic acid. It is concluded that the increased synthesis of liver phosphatidylcholine caused by dietary orotic acid is accompanied by an increased rate of liver phosphatidylcholine catabolism, with betaine as the major end-product of the choline moiety.

Dietary orotic acid accentuates the hepatic response to phenobarbital in rats.

In rats treated with phenobarbital for 3 days and simultaneously fed a semisynthetic diet containing 1.0% orotic acid, the extent of the increases in liver microsomal phosphatidylcholine, phosphatidylethanolamine, total RNA, total protein, and cytochrome P-450 were significantly greater than they were in rats treated identically with phenobarbital but without dietary orotic acid. This is attributed primarily to the stimulation of hepatic phosphatidylcholine synthesis by dietary orotic acid. In the absence of phenobarbital, orotic acid was shown to cause some increase in liver smooth endoplasmic reticulum components, but not cytochrome P-450. Orotic acid also decreased the activity of microsomal phosphatidylethanolamine N-methyltransferase, which may have contributed to the increase in the microsomal content of phosphatidylethanolamine. The hypothesis is advanced that phospholipid availability is a limiting factor in the hepatic response to phenobarbital. When more phospholipid is available to provide the structural framework for biogenesis of endoplasmic reticulum, all of the hepatic actions of phenobarbital, including induction of cytochrome P-450, are amplified.