Thyroxine peripheral

Endocrine uses Hyperthyroidism P-blockade reduces unpleasant symptoms of sympathetic overactivity there may also be an effect on metabolism of thyroxine (peripheral deiodination from T to Tj. A nonselective agent (propranolol) is preferred to counteract both the cardiac (Pj and p ) effects, and tremor (p ). 

Propylthiouracil (PTU), but not methyl-mercaptoi-midazole (MMI), has an additional peripheral effect. It inhibits the monodeiodination of thyroxine to triiodothyronine by blocking the enzyme 5 mono-deiodinase [1]. In humans the potency of MMI is at least 10 times higher than that of PTU, whereas in rats PTU is more potent than MMI. The higher potency of MMI in humans is probably due to differences in uptake into the thyroid gland and subsequent metabolism, because in vitro inhibition of thyroid peroxidase by MMI is not significantly more potent than by PTU [1, 6]. Whether antithyroid drags have additional immunosuppressive actions is a matter of discussion [1, 2]. 

Thyroxine (3, 5, 3,5-L-teraiodothyronine, T4) is a thyroid hormone, which is transformed in peripheral tissues by the enzyme 5 -monodeiodinase to triiodothyronine. T4 is 3-8 times less active than triiodothyronine. T4 circulates in plasma bound to plasma proteins (T4-binding globulin, T4-binding prealbumin and albumin). It is effective in its free non-protein-bound form, which accounts for less than 1%. Its half-life is about 190 h. 

Triiodothyronine (3, 5,3-L-triiodothyronine, T3) is a thyroid hormone. It is producedby outer ring deiodination of thyroxine (T4) in peripheral tissues. The biologic activity of T3 is 3-8 times higher than that of T4. T3 is 99.7% protein-bound and is effective in its free non-protein-bound form. The half-life of triiodothyronine is about 19 h. The daily tur nover of T3 is 75%. Triiodothyronine acts via nuclear receptor binding with subsequent induction of protein synthesis. Effects of thyroid hormones are apparent in almost all organ systems. They include effects on the basal metabolic rate and the metabolisms of proteins, lipids and carbohydrates. 

The formation of triiodothyronine (T3) and tetra-iodothyronine (thyroxine T4) (see Figure 42—2) illustrates many of the principles of diversity discussed in this chapter. These hormones require a rare element (iodine) for bioactivity they are synthesized as part of a very large precursor molecule (thyroglobuhn) they are stored in an intracellular reservoir (colloid) and there is peripheral conversion of T4 to T3, which is a much more active hormone. 

Despite the availability of a wide array of thyroid hormone products, it is clear that synthetic levothyroxine (LT4) is the treatment of choice for almost all patients with hypothyroidism. LT4 mimics the normal physiology of the thyroid gland, which secretes mostly T4 as a prohormone. As needed, based on metabolic demands, peripheral tissues convert thyroxine (T4)... 

Mercuric chloride, given for short time, has been reported to inhibit Na + /K + -ATPase in hog thyroid membranous preparation [149]. The blood T4 (thyroxine) levels were reduced and iodotyrosine deiodinase was inhibited, and it was suggested that mercurials might cause a coupling defect in the synthesis of iodothyronines. In mouse thyroid serum T4 level was affected by mercuric chloride, while serum T3 was not [ 150 ]. It was suggested that thyroidal secretion of T4 was inhibited by mercuric chloride, but the peripheral conversion of T4 to T3 might not be affected in the maintenance of an active hormone level. 

The gland is situated in the neck across the front of the trachea. It secretes thyroxine (T4), which is converted to the active form of the hormone, triiodothyronine (T3), in peripheral tissues. It stimulates metabolic activity in tissues so that it increases heat production (for example, by stimulating protein turnover and substrate cycles). 

Figure 16.13 Deiodination of thyroxine in peripheral tissues formation of T3 and reverse-Ts. Thyroxine is 3,5,3, 5 tetraiodo-thyroxine (T4) which is converted to 3,5,3 triiodothyronine (T3) in normal condition but is converted to 3,3, 5 triiodothyronine (reverse T3) during starvation. The prime ( ) indicates the carbon number to which the iodine is attached in the second ring.

Thyroid abnormalities Am o6arone inhibits peripheral conversion of thyroxine (T4) to triiodothyronine (T3), prompting increased T4levels, increased levels of inactive reverse T3 and decreased levels of T3. It is also a potential source of large amounts... 

PTU possesses special benefit it inhibits peripheral deiodination, thereby blocking the conversion of thyroxine to the active hormone tri-iodothyronine. PTU is rapidly absorbed from the gut, reaching peak blood levels within one hour, and is excreted in urine as the inactive glucuronide within 24 hours. In contrast methimazole which is absorbed at variable rates, is excreted slower (only 65-70% within 48 hours in urine). The short plasma half-life of... 

Amiodarone inhibits the peripheral and possibly in-trapituitary conversion of thyroxine (T4) to triiodothyronine (Tj) by inhibiting 5 -deiodination. The serum concentration of T4 is increased by a decrease in its clearance, and thyroid synthesis is increased by a reduced suppression of the pituitary thyrotropin T3. The concentration of T3 in the serum decreases, and reverse T3 appears in increased amounts. Despite these changes, most patients appear to be maintained in an euthyroid state. Manifestations of both hypothyroidism and hyperthyroidism have been reported. 

Hyperthyroidism Propranolol blocks the peripheral conversion of thyroxine to triiodothyronine. It controls palpitation, nervousness, tremor sweating etc. 

Excessive catecholamine action is an important aspect of the pathophysiology of hyperthyroidism, especially in relation to the heart (see Chapter 38). The 13 antagonists are beneficial in this condition. The effects presumably relate to blockade of adrenoceptors and perhaps in part to the inhibition of peripheral conversion of thyroxine to triiodothyronine. The latter action may vary from one 13 antagonist to another. Propranolol has been used extensively in patients with thyroid storm (severe hyperthyroidism) it is used cautiously in patients with this condition to control supraventricular tachycardias that often precipitate heart failure. 

Albumin is the most abundant protein in human and other animal plasma. It is estimated that up to 40% of the total albumin in humans is in circulation transporting essential nutrients, especially those that are sparingly soluble in aqueous-based plasma. For example, the fatty acids, which are important fuel molecules for the peripheral tissue, are distributed by albumin. In addition, albumin is the plasma transport protein for other substances including bilirubin, thyroxine, and steroid hormones. Also, many drugs including aspirin, sulfanilamides, clofibrate, and digitalis bind to albumin and are most likely carried to their sites of action by the protein. 

Burger A, Dinichert D, Nicod P, Jenny M, Lemarchand-Beraud T, Vallotton MB. Effect of amiodarone on serum triiodothyronine, reverse triiodothyronine, thyroxin, and thyrotropin. A drug influencing peripheral metabolism of thyroid hormones. J Clin Invest 1976 58(2) 255-9. 

Despite the fact that she was clinically euthyroid, the authors suggested that this patient had amiodarone-induced hyperthyroidism. However, amiodarone inhibits the peripheral conversion of thyroxine to triiodothyronine it can therefore increase the serum thyroxine and suppress the serum TSH, as in this case. On the other hand, the reduced uptake by the thyroid gland is consistent with type 2 amiodarone-induced hyperthyroidism. The authors did not report the serum concentrations of free thyroxine and triiodothyronine. 

Propranolol inhibits the conversion of thyroxine (T4) to tri-iodothyronine (T3) by peripheral tissues (180), resulting in increased formation of inactive reverse T3. There have been several reports of hyperthyroxinemia in clinically euthyroid patients taking propranolol for non-thyroid reasons in high dosages (320-480 mg/day) (181,182). The incidence was considered to be higher than could be accounted for by the development of spontaneous hyperthyroidism, but the mechanism is unknown. 

The many effects of lithium on thyroid physiology and on the hypothalamic-pituitary axis and their clinical impact (goiter, hypothyroidism, and hyperthyroidism) have been reviewed (620). Lithium has a variety of effects on the hypothalamic-pituitary-thyroid axis, but it predominantly inhibits the release of thyroid hormone. It can also block the action of thyroid stimulating hormone (TSH) and enhance the peripheral degradation of thyroxine (620). Most patients have enough thyroid reserve to remain euthyroid during treatment, although some initially have modest rises in serum TSH that normalize over time. 

Tiihonen M, Liewendahl K, Waltimo O, Ojala M, Valimaki M. Thyroid status of patients receiving longterm anticonvulsant therapy assessed by peripheral parameters a placebo-controlled thyroxine therapy trial. Epilepsia 1995 36(ll) 1118-25. 

Because thyroxine contains four iodine residues, this compound is also referred to by the abbreviation T4. Likewise, triiodothyronine contains three iodine residues, hence the abbreviation T3. There has been considerable discussion about which hormone exerts the primary physiologic effects. Plasma levels of T4 are much higher than T3 levels, but T3 may exert most of the physiologic effects on various tissues, which suggests that T4 is a precursor to T3 and that the conversion of T4 to T3 occurs in peripheral tissues.23 Regardless of which hormone ultimately affects cellular metabolism, both T4 and T3 are needed for normal thyroid function. 

Peripheral metabolism of thyroxine. (Modified from Greenspan FS The Thyroid Gland. In Greenspan FS, Gardner D [editors] Basic ClinicalEndocrinology, 6th ed. McGraw-Hill, 2001.)... 

It has been reported that high doses (138 and 430 mg/kg) of omeprazole to rats interfere with the peripheral conversion of thyroxine (T4) to tri-iodothyronine (T3) resulting in the decrease of serum T3, unchanged serum T4 and no change in the morphology of the thyroid gland [119]. 

The rate of disappearance of radiothyroxine from the plasma has been reported as raised after operation. Oppenheimer and Bernstein (01), on the other hand, found a decrease in the fractional removal of T4 from plasma in the absence of a diminished degradative clearance. It has been suggested that H T< may be redistributed either in the extravascular spaces or even in the gut. A significant increase in radioiodinated thyroxine in the urine has been found after injury and it is suggested that there is an increase in the peripheral degradation of thyroxine after injury (B5). 

It would appear that there is a sudden increase in thyroid activity in terms of available or free hormone and an alteration in thyroxine-binding protein which starts probably during surgery and anesthesia and is associated with an increased peripheral utilization of thyroid hormone. Although changes in protein-bound iodine (FBI) and TSH concentrations are not necessarily related to secretion rates, the exact extent of any increase in secretion of thyroid hormone secretion remains uncertain. 

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