Reduction in extrathyroidal triiodothyronine production by propylthiouracil in man.

Abstract

A B S T R A C T To determine if propylthiouracil (PTU)inhibited extrathyroidal thyroxine (T4) to triiodothyronine (Ts) conversion in man, PTU was administered to T4-treated hypothyroid patients and serial measurements of T4, T3, and thyrotropin (TSH) carried out. All patients had proven thyroidal hypothyroidism and had been receiving 0.1 or 0.2 mg T4 daily for at least 2 mo before study. Hormone measurements were made for 5 consecutive days before and daily during a 7-day treatment period with PTU, 1,000 mg/day.In eight patients receiving 0.1 mg T4 daily, administration of PTU resulted in a prompt fall in mean serum T3 concentrations from 78±6 ng/100 ml (SEM) to 61±3 ng/100 ml after 1 day. The mean serum Ts concentrations ranged from 55 to 60 ng/100 ml during the remainder of the PTU treatment period (P < 0.01):The mean control serum TSH concentration was 29.6 AU/ml and it increased to a peak of 40 /U/ml on the 5th and 6th days. In five patients receiving 0.2 mg T4 daily, the mean control serum Ta concentration was 84±7 ng/ 100 ml. It fell to 70+5 ng/100 ml after 1 day and 63±7 ng/100 ml after 2 days of PTU administration and thereafter ranged from 61 to 69 ng/100 ml (P < 0.01

Hypothyroidism in rats decreases peripheral glucose utilisation, a defect partially corrected by central leptin infusion

“…Reverse T3 (rT3) was infused subcutaneously (25 nmol·100 g body weight p<0.05 at least vs the hypothyroid leptin-treated group feeding conditions. Such effects of PTU on thyroid hormones were similar to those reported in humans [39,40]. The state of hypothyroidism induced by PTU was also documented by the observation of a marked decrease in the mRNA expression of liver D1 (51.1±4.7 arbitrary units in hypothyroid pair-fed rats vs 100.0±14.2 arbitrary units in euthyroid pair-fed rats, p<0.001).…”

Type 1 iodothyronine deiodinase in human physiology and disease

“…Nevertheless, the long-life of D1 protein and T 3 upregulation of D1 activity, just the opposite of what would be expected in a typical feedback loop, raise some questions about this assumption. Moreover, clinical studies have showed a maximum decrease of 25% in serum T 3 in athyreotic, T 4 -replaced, euthyroid individuals treated with higher doses of PTU (Geffner et al 1975, Saberi et al 1975. Indeed, subsequent cumulative data on the biochemical and molecular properties of D2 indicate that this enzyme also contributes a significant portion of serum T 3 levels in humans (Bianco et al 2005, Maia et al 2005.…”

Physiological role and regulation of iodothyronine deiodinases: A 2011 update

“…The relative contribution of the two enzymes is still a matter of debate, as suggested by multicompartimental analysis (21). In patients with hypothyroidism receiving fixed replacement doses of L-thyroxine, PTU administration (which blocks D1) resulted in a 20-30% decrease in serum T3, suggesting D1-catalyzed T3 production is not the only contributor to extrathyroidal T3 production (22). Later studies have further suggested that D2 may contribute significantly to plasma T3 in humans (23).…”

“…In these patients, one day treatment with a combination of iodide and PTU resulted in 50% greater decrease in plasma T3 than treatment with iodide plus methimazole. In euthyroid subjects, high doses of PTU cause a decrease in serum T3 ranging from 0 to 25% (22,77). Thyroidal D2 is also increased in Graves' thyroid tissues or in other forms of hyperthyroidism, despite elevated circulating levels of thyroid hormones, leading to an increase of intrathyroidal T4-to-T3 conversion (19).…”