Propylthiouracil

About: Propylthiouracil is a(n) research topic. Over the lifetime, 2181 publication(s) have been published within this topic receiving 46996 citation(s). The topic is also known as: Thyreostat® & 2,3-dihydro-6-propyl-2-thioxo-4(1H)-pyrimidinone.

Adrenergic activation of triiodothyronine production in brown adipose tissue

Abstract: There are several mechanisms by which homeothermic animals increase heat production, including shivering, sympathetic nervous system activation and stimulation of thyroid hormone secretion. Studies in rats have shown that increased sympathetic activity causes increased heat production in brown adipose tissue (BAT) after cold exposure or food ingestion1–3. Acute cold exposure also increases circulating thyroid hormones4 which in turn stimulate cellular metabolism through induction5 of various enzymes. Most metabolic effects of thyroxine (T4) are thought to be due to the triiodothyronine (T3) which is produced from T4 by a process of 5′ monodeiodination. There are two enzymes responsible for this reaction6–8: type I, or propylthiouracil (PTU)-sensitive iodothyronine deiodinase (5′D-I), which is reduced in hypothyroidism, stimulated in hyperthyroidism and probably provides most of the circulating T3 in the adult rat9. Type II 5′-deiodinase (5′D-II) is characteristic of brain and pituitary, is increased by thyroidectomy, is not inhibited by PTU and provides 50–80% of the intraceUular T3 in these two tissues. Recently, 5′D-II activity was identified in interscapular BAT10. As the sympathetic nervous system influences the metabolic activation of BAT, we have studied the effects of noradrenaline and acute cold exposure on BAT 5′D-II. We report here that both noradrenaline and cold exposure increase BAT 5′D-II through α1-adrenergic receptors, whereas depletion of catecholamines with α-methyl-p-tyrosine (MPT) prevents the effect of cold but not that of noradrenaline. These results suggest that the sympathetic nervous system may increase T3 production in rats by stimulating BAT 5′D-II. By increasing metabolic rate, this rise in T3 would enhance the thermogenic response to sympathetic stimulation.

Vasculitis and antineutrophil cytoplasmic autoantibodies associated with propylthiouracil therapy

Abstract: Vasculitis is a rare complication of propylthiouracil therapy. Antineutrophil cytoplasmic antibodies (ANCA) have been described in association with several vasculitic disorders. We report detection of ANCA against human neutrophil elastase, proteinase 3, and myeloperoxidase in serum from six patients who developed evidence of vasculitis during propylthiouracil treatment of hyperthyroidism. On withdrawal of the drug ANCA concentrations fell and clinical symptoms resolved completely.

2018 European Thyroid Association Guideline for the Management of Graves' Hyperthyroidism

Abstract: Graves' disease (GD) is a systemic autoimmune disorder characterized by the infiltration of thyroid antigen-specific T cells into thyroid-stimulating hormone receptor (TSH-R)-expressing tissues. Stimulatory autoantibodies (Ab) in GD activate the TSH-R leading to thyroid hyperplasia and unregulated thyroid hormone production and secretion. Diagnosis of GD is straightforward in a patient with biochemically confirmed thyrotoxicosis, positive TSH-R-Ab, a hypervascular and hypoechoic thyroid gland (ultrasound), and associated orbitopathy. In GD, measurement of TSH-R-Ab is recommended for an accurate diagnosis/differential diagnosis, prior to stopping antithyroid drug (ATD) treatment and during pregnancy. Graves' hyperthyroidism is treated by decreasing thyroid hormone synthesis with the use of ATD, or by reducing the amount of thyroid tissue with radioactive iodine (RAI) treatment or total thyroidectomy. Patients with newly diagnosed Graves' hyperthyroidism are usually medically treated for 12-18 months with methimazole (MMI) as the preferred drug. In children with GD, a 24- to 36-month course of MMI is recommended. Patients with persistently high TSH-R-Ab at 12-18 months can continue MMI treatment, repeating the TSH-R-Ab measurement after an additional 12 months, or opt for therapy with RAI or thyroidectomy. Women treated with MMI should be switched to propylthiouracil when planning pregnancy and during the first trimester of pregnancy. If a patient relapses after completing a course of ATD, definitive treatment is recommended; however, continued long-term low-dose MMI can be considered. Thyroidectomy should be performed by an experienced high-volume thyroid surgeon. RAI is contraindicated in Graves' patients with active/severe orbitopathy, and steroid prophylaxis is warranted in Graves' patients with mild/active orbitopathy receiving RAI.

Kinetic evidence suggesting two mechanisms for iodothyronine 5'-deiodination in rat cerebral cortex

Abstract: Enzymatic 5'-deiodination of 3,3',5'-triiodothyronine (rT3) and 3,3',5,5'-tetraiodothyronine (thyroxine, T4) was studied in microsomal preparations of rat cerebral cortex. Evidence was obtained for the existence of two thiol-dependent 5'-deiodinase entities. One of these predominates in tissue from euthyroid and long-term hypothyroid rats, is specific for rT3, follows "ping-pong" kinetics with dithiothreitol as the cosubstrate, and is inhibited by propylthiouracil (PrSUra) and iodoacetate. Inhibition by PrSUra is uncompetitive with rT3 and competitive with dithiothreitol. These properties are shared with the 5'-deiodinase activity of liver and kidney. The activity of a second type of 5'-deiodinase is highest in cerebral cortex from short-term hypothyroid rats, prefers T4 to rT3 as the substrate, is insensitive to PrSUra and iodoacetate, and follows "sequential" reaction kinetics. A similar PrSUra-insensitive 5'-deiodinase activity is also found in pituitary but is not detectable in liver and kidney; it seems, therefore, characteristic of tissues in which local T4 to 3,3',5-triiodothyronine (T3) conversion supplies a major portion of the total intracellular T3.