Secretion and metabolic clearance rates of thyroxine and triiodothyronine in streptozotocin-diabetic rats

This study was undertaken to evaluate the effects of streptozotocin-induced diabetes on T4 and T3 production rate (PR) and metabolism in rats. [125I]T4 and [125I]T3 were injected iv and sequential blood samples were obtained. Plasma ethanol extracts were analyzed for [125I]T4 and [125I]T3 by thin layer chromatography. T4 and T3 production rates and kinetic parameters of T4 and T3 metabolism in control, diabetic and insulin-treated diabetic rats were assessed by applying kinetic analyses to measurements of disappearance of injected T4 and T3 radiotracer from plasma. The metabolic clearance rate (MCR) and the fractional disappearance rate (K) of T4 in diabetic rats (0.72 +/- SD, 0.02 ml/h X 100 g, and 0.034 +/- 0.006 h-1, respectively) were significantly lower (P less than 0.001) than in the control group (1.01 +/- 0.04 ml/h X 100 g and 0.056 +/- 0.004 h-1). Similarly, the MCR and K values of T3 were also significantly reduced (P less than 0.001) in the diabetic animals: 16.2 +/- 0.7 ml/h X 100 g and 0.088 +/- 0.007 h-1 in controls vs 13.0 +/- 1.2 ml/h X 100 g and 0.058 +/- 0.009 h-1 in diabetics, respectively. Insulin therapy significantly reversed these alterations. There was also a significant reduction (P less than 0.001) in plasma T4 (18 +/- 6 ng/ml) and T3 (0.20 +/- 0.05 ng/ml) concentrations in the diabetic rats compared to control values, whose T4 and T3 levels averaged 65 +/- 10 and 0.68 +/- 0.09 ng/ml, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)     

The activity of thyroxine conversion to triiodothyronine in the liver and kidneys of rats]

Rat liver and kidney microsomal fractions contain 5'-deiodinase, converting thyroxin into 3,5,3'-triiodothyronine. In control animals a marked decrease in thyroxin concentration takes place when the blood passes through the liver and kidney (triiodothyronine level being preserved). Fasting causes a prominent decrease in blood thyroxin, a small decrease in triiodothyronine as well as a drop of glucose and insulin levels. At the same time a decrease in thyroxin deiodinase activity takes place in the liver; as for the kidney a decrease is less marked. Fasting rats have no gradients in the blood passing through the liver and kidney; triiodothyronine balance remains unchanged. The results show that the rat liver and kidney deiodinase activity regulation (during changes in the body physiological status) helps to maintain triiodothyronine optimum concentration in general circulation.     

Secretion rates of thyroxine, triiodothyronine, and reverse triiodothyronine in man during surgery

The secretion rates of T4, T3, and rT3 were studied in experiments of short duration by a new method based on determinations of the hormone difference across the thyroid combined with simultaneous electromagnetic thyroid blood flowmetry during surgery in 70 euthyroid patients. The secretion rate of T3 was similar in normal thyroid tissue and nodular goitre, but those of T4 and rT3 were lower in nodular goitre and solitary adenoma (P less than 0.05). In 61 patients with normal thyroid tissue or nodular goitre the secretion rates during surgery (mean +/- SEM) were for T4 222 +/- 28 nmol/day, for T3 27.4 +/- 3.1 nmol/day, and for rT3 3.5 +/- 0.5 nmol/day. In relation to the individual T4 secretion rate, the secretion rate of T3 was 12.5 +/- 3.0% and that of rT3 1.2 +/- 0.9%. In these short-term experiments we found a secretion rate for T4 during operation about 50% greater than in earlier long-term kinetic studies, but which tallied with a recent report using a 4-compartment model. For T3 and rT3 it was 2-3 times greater than earlier estimates. The secretion was estimated to be 50% of the total production rate for T3 and 6% for rT3. If proportional adjustment were performed to yield a T4 secretion of about 130 nmol/day. T3 and rT3 secretion rates would still be greater than earlier reported.     

Possible role of adrenergic mechanism in starvation-induced reduction in circulating thyroxine and triiodothyronine in rats.

To elucidate the possible role of adrenergic mechanism in thyroid hormone metabolism during starvation, serum thyrotropin (TSH), thyroxine (T4), and 3,5,3'-triiodothyronine (T3) levels and conversion of T4 to T3 in perfused liver were investigated in fasting (60 h) and fed rats. Propranolol (0.5 mg/kg), yohimbine (0.3 mg/kg) or phentolamine (5.0 mg/kg) was subcutaneously injected to the rat every 12 h. Serum levels of TSH, T4, and T3 were significantly lower in fasting rats than in fed rats. Although propranolol, yohimbine, and phentolamine administration did not significantly alter circulating TSH, T4 and T3 levels in fed rats, phentolamine partly inhibited the starvation-induced reduction in circulating TSH, T4, and T3. Thyroxine uptake and T3 production in perfused liver were significantly lower in fasting rats than in fed rats. Phentolamine treatment did not alter the T4 uptake and T3 production in perfused liver of fasting rats. These results suggest that alpha-adrenergic mechanism may have some role in starvation-induced reduction in circulating T4 and T3, and that phentolamine partly inhibited this phenomenon probably through the inhibitory effect on reduction in circulating TSH during starvation.     

Plasma thyrotropin, thyroxine, triiodothyronine, free thyroxine, free triiodothyronine, and cortisol levels in blind prepubertal boys

Findings on thyroid function in blind subjects are lacking. The aim of this study was to investigate the thyroid hormonal pattern in prepubertal blind subjects. Six healthy and 8 blind males, aged 7-10 yr, in Tanner stage one puberty, living at Institute "Martuscelli" for blind young subjects, Napoli, Italy, were studied. Each had a TRH (200 micrograms) test at 08:00 h after nocturnal rest. Plasma TSH, T4, T3, free T4(FT4), free T3(FT3) and cortisol (F) were measured by RIA. Our blind subjects show levels of TSH (basal values and absolute peak after TRH), T4, T3 and F normal but FT4 levels significantly higher than controls (39 pg/ml +/- 4.7 vs 12 +/- 0.6, p less than 0.001; 14 pg/ml +/- 1.3 vs 4.7 +/- 0.2, p less than 0.001, respectively). Our results, similar to those found in some patients with euthyroid hyperthyroxinemia, suggest that the prolonged inability to receive light signal could influence the metabolism of thyroid hormones and/or cause a tissue resistance to their action, even if this hypothesis must be verified by future more extensive investigations.     

Serum free thyroxine and triiodothyronine concentrations in subacute thyroiditis

Serum absolute free T4 (AFT4) and T3 (AFT3) concentrations were studied in 10 patients with subacute thyroiditis whose total serum T4 levels were elevated, and values were compared with those obtained in 10 patients with untreated Graves' disease, whose total serum T4 concentrations were elevated to the same level as in the former group. The mean (+/- SD) basal metabolic rate in patients with subacute thyroiditis was 16 +/- 14.8%, significantly (P less than 0.001) lower than that in patients with Graves' disease (48.7 +/- 15.7%). Serum T4-binding globulin concentrations measured by RIA were normal and did not differ from those in Graves' disease patients. The percentage of free T4 and AFT4 were both elevated in subacute thyroiditis to a degree comparable to that seen in Graves' disease. The serum total T3, serum free T3 fraction and AFT3 were also elevated, but both total T3 and AFT3 were significantly (P less than 0.05 and P less than 0.05, respectively) lower than in Graves' disease patients. Therefore, the ratios of T3 to T4 and AFT3 to AFT4 were significantly (P less than 0.01 and P less than 0.01, respectively) lower than in Graves' disease patients. These results indicate that the significantly lower basal metabolic rate and milder manifestations of thyrotoxic symptoms in subacute thyroiditis than in Graves' disease might be explained by the low ratios of T3 to T4 and AFT3 to AFT4 as well as the short duration of chemical hyperthyroidism.     

5-fluorouracil-induced increase of total serum thyroxine and triiodothyronine

Total serum thyroxine and triiodothyronine levels in a group of 15 patients with advanced mammary carcinoma significantly increased during weekly treatment with 5-fluorouracil, whereas serum free thyroxine levels and serum thyroid stimulating hormone levels were unchanged. No clinical signs of hyperthyroidism in these treated patients have been observed.