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Biomedical subjects

C S Pittman

Publications and source records attributed to C S Pittman.

At least 37 records · Page 2Linked to original sources
PubMed1977

Carbohydrate metabolism in hypothyroid myopathy.

The carbohydrate metabolism in hypothyroid patients was investigated. After an overnight fast, the blood glucose level was 24% lower and the blood lactate level was 35% lower in the untreated hypothyroid patients than that observed in the treated hypothyroid patients or in the normal subjects. There was no difference in the blood alanine or plasma free fatty acid values between the subject groups. Skeletal muscle biopsied from two hypothyroid patients with marked myopathy showed normal glycogen content, 0.83%-0.86% (normal 1.06%), but reduced activity of acid maltase, 32-50 nmoles/min/g (normal 97). Forearm ischemic stimulation applied to hypothyroid patients failed to elevate the level of lactate. The results are compatible with impaired glycogenolysis from the skeletal muscle, which may be a contributory factor in the myopathy in hypothyroidism.

Adolescent↗
PubMed1975

Reduced peripheral conversion of thyroxine to triiodothyronine in patients with hepatic cirrhosis.

The role of liver in the peripheral conversion of thyroxine (T4) to triiodothyronine (T3) was studied in normal subjects and patients with alcoholic liver disease by measurement of thyrotrophin (TSH) and total and free T4 and T3 in randomand serial serum samples. Also, T4 to T3 conversion rates and T3 disposal rates were compared by noncompartmental analysis. While the mean total serum T4 values were similar for the two groups, 8.6 and 8.1 mug/kl, the mean free T4 value was significantly higher in the cirrhotic patients (3.3 ng/dl) than in the normal subjects (2.1 ng/dl, P less than 0.001). The mean serum T3 value, 85 ng/dl, was significantly reduced in the hepatic patients as compared to a mean serum T3 value of 126 ng/dl in the normal subjects (P less than 0.001), while the free T3 value was 0.28 ng/dl in both groups. The reduction of the serum total and free T3 values were closely correlated with the degree of liver damage, as indicated by elevation of serum bilirubin (r equal -0.547) and reduction of serum albumin (r equal 0.471). The mean serum TSH level was 3.1 muU/ml in the normals and 7.1 muU/ml in the cirrhotic aptients ( less than 0.001). 15% of the hepatic patients had serum TSH values above 10 muU/ml, which, however, did not correlate with any of the four liver function tests studied. Serial blood sampling from two convalescing patients with alcoholic hepatitis showed a gradual normalization of serum TSH and T3 levels as the liver function improved. After oral T4 administration, 0.25 mg/day for 10 days, three of four cirrhotic patients studied failed to raise their serum T3 values. The mean T4 to T3 conversion rate of seven normal subjects was 35.7%. The mean T4 to T3 conversion rate of four cirrhotic patients studied was significantly reduced to 15.6% (P less than 0.001). The mean disposal rates of T4 and T3 of the normal subjects were 114 and 34 mug/day, respectively. The ratio of T4 disposal to T3 disposal was 3.5. In contrast, the mean T4 disposal rate, 82 mug/day, and the mean T3 disposal rate, 10 mug/day, were both reduced in the cirrhotic patients. Their ratio of T4 disposal to T3 disposal was 7.9. These findings suggest that impairment of T4 conversion in patients with advanced hepatic cirrhosis may lead to reduced T3 production and lowered serum T3 level. Therefore, the liver is one of the major sites of T4 conversion to T3.

Adult↗
PubMed1972

Urinary metabolites of 14 C-labeled thyroxine in man.

Studies were carried out to determine the chemical structures of thyroxine metabolites after total deiodination. Normal subjects were given thyroxine labeled with (14)C on the nonphenolic ring and the alanine side chain, 8-11 mug/day for 10 days. By paper chromatography of fresh urine, six or more (14)C-labeled compounds were separated. The (14)C-labeled metabolites were concentrated by passing the urine through a nonionic polymeric adsorbent. Two major thyroxine metabolites were identified. The identification was made by three different methods: (a) chromatography, (b) synthesis of derivatives, and (c) recrystallization to constant specific activity. One (14)C-labeled metabolite was identified as thyroacetic acid or 4-phenoxy-(4'-hydroxy) phenyl-acetic acid. Another one was identified as thyronine. Of the total urinary (14)C radioactivity, 43.7% was recovered as thyroacetic acid and 19.8% was recovered as thyronine. Approximately one-fifth of each of these metabolites was present in the urine in bound form which released the free metabolites during acid hydrolysis. The average daily excretion of thyroacetic acid was 13.7% of the renal disposal rate of thyroxine, or approximately 7.5 mug/day. The average daily excretion of thyronine was 6.5% of the renal disposal rate of thyroxine or approximately 3.9 mug/day while the urinary iodide made up 64.7% of the renal disposal rate of thyroxine. Our findings provide the needed proof that the major metabolic pathways of thyroxine remove the iodine atoms by substituting hydrogen for iodine and leave the diphenyl ether nucleus intact.

Carbon Isotopes↗
PubMed1971

The extrathyroidal conversion rate of thyroxine to triiodothyronine in normal man.

Eight normal subjects were administered tracer amounts of a (14)C-labeled thyroxine, L-[tyrosyl-(14)C] T(4), by multiple injections. Then serial blood samples were collected for isolation of the thyroxine, triiodothyronine, and tetraiodothyroacetic acid fractions by a combination of column and paper chromatographies. The chromatographic artifacts were corrected by adding to the sera a purified (3)H-labeled thyroxine, D,L-[alpha,beta-(3)H] T(4) immediately after the separation of sera from blood. 1-2% of the serum (14)C radioactivity was observed in the triiodothyronine fraction and 2-4% of the serum (14)C radioactivity was observed in the tetraiodothyroacetic acid fraction. Complete kinetic studies of thyroxine and triiodothyronine were compared in the same individual in four of the subjects. The extrathyroidal conversion rates of thyroxine to triiodothyronine were calculated from data obtained during both the injection and the postinjection periods as functions of the (14)C-labeled thyroxine and triiodothyronine remaining in the body at time t and their fractional turnover rates. The average daily rate of the extrathyroidal conversion of thyroxine to triiodothyronine was 4% of the extrathyroidal thyroxine pool or 33% of the total thyroxine production. The amount of triiodothyronine generated by this pathway (22 mug/day) was found to contribute 31% of the extrathyroidal triiodothyronine pool or 41% of the daily triiodothyronine production. This pathway is a major source of triiodothyronine production. The extrathyroidal conversions of thyroxine to triiodothyronine and tetraiodothyroacetic acid are major metabolic pathways of thyroxine in normal man.

Adult↗
PubMed1970

The integrity of the ether linkage during thyroxine metabolism in man.

The structures of thyroxine metabolites after total deiodination bear on the mode of thyroxine (T(4)) action in vivo. The present study was undertaken to determine the integrity of the ether linkage during thyroxine metabolism in man. Normal volunteers were given simultaneous intravenous injections of two thyroxines labeled with either (14)C or (3)H on the opposite sides of the ether linkage, D,L-[alpha,beta-(3)H]T(4) and D,L-[phenolic ring-(14)C]T(4). The ratio of alanine side chain to phenolic ring which was measured as (3)H:(14)C ratio was found to remain constant in the serum, urine, and feces during the subsequent 3 wk. The disappearance rates of the (3)H and (14)C radioactivity from blood were similar. The values of half-life were in the ranges of 4.2-6.7 days. 51-63% of the (3)H and 50-57% of the (14)C doses were recovered from urine and 13-20% of the (3)H and 15-20% of the (14)C doses were recovered from feces. Chromatography of the urinary metabolites confirmed that the phenolic ring and the nonphenolic ring including at least part of the side chain remained linked together.

Adult↗