Thyroxine protein bound

Oral contraceptives have their most significant effect on endocrine parameters. Blood cortisol, thyroxine, protein-bound iodine, T3 uptake, and urinary free cortisol are elevated. Urinary 17,21-dihydroxy steroids, 17-ketosteroids, and estrogens are decreased. There is no effect on urinary catecholamines or VMA (Table 10) (LIO). The effect of thyroid functions tests is due to the administered hormone stimulating an increase in the production of thyroid-binding globulin which in turn binds 1-thyroxine. The lowering of free thyroxine stimulates the anterior pituitary to produce thyrotropin, which in turn stimulates the thyroid to produce more thyroxine. Since the additional thyroxine is bound to the extra protein, there is an equilibrium and the patient remains clinically euthyroid, but the protein-bound iodine and the thyroxine are elevated. 

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 thyroid hormones are lipophilic and relatively insoluble in the plasma. Therefore, they are transported throughout the circulation bound to plasma proteins such as thyroxine-binding globulin (75%) and albumins (25%). Approximately 99.96% of circulating thyroxine is protein bound. Bound hormone is not available to cause any physiological effects however, it is in equilibrium with the remaining 0.04% that is unbound. This free form of the hormone is able to bind to receptors on target tissues and cause its effects. Thyroid hormone has many metabolic effects in the body ... 

Oral contraceptives have also been reported to produce increases in sulfobromophthalein retention and other liver function tests, as well as in prothrombin time, clotting factors VII, VIII, IX, serum thyroxine, and protein-bound iodine (B8). In a group of 48 women the mean cholesterol value was 206 41 mg/100 ml while they were receiving a variety of oral contraceptives and 179 28 mg/100 ml when they were not receiving the drugs (W19). 

Endocrine effects Salicylates decrease the plasma protein bound iodine due to displacement of thyroxine from prealbumin and stimulation of central sympathetic centre causes release of adrenaline from the adrenal medulla. 

Oral contraceptives can cause an increase in total thyroxine (163) and a fall in the percentage of free thyroxine (164). The uptake of radioactive iodine in the thyroid is usually normal total uptake of radioactive iodine may be reduced (164). The effect of progestogens on thyroxinebinding globulin may possibly counteract the estrogenic action. The net result will be a rise in protein-bound iodine and a fall in resin triiodothyronine uptake (165). It has been suggested that oral contraceptives may actually have some protective effect against thyroid disease. 

Systemic iodine absorption can occur after intravaginal administration of povidone-iodine (11). There were increases in serum iodine, protein-bound iodine, and inorganic iodine, but not serum thyroxine, after a 2-minute vaginal administration of povidone-iodine in non-preg-nant women (12). 

Ultrafiltration has been used to determine the protein bound fraction of many drags, such as methadone (Wilkins et al. 1997), phenylacetate and phenylbu-tyrate (Boudoulas et al. 1996), etoposide (Robieux et al. 1997), doxorubicin and vincristine (Mayer and St-Onge 1995), disopyramide (Echize et al. 1995), and ketamine and its active metabolites (Hijazi and Boulieu 2002). Schumacher et al. (2000) have shown the applicability for the determination of erythro-cyte/plasma distribution. The method of UF has been applied in the measurement of free unaltered thyroxin or after displacement by salicylate as well after displacement by heparin in healthy people and in patients with non-thyroidal somatic illness (Faber et al. 1993). The protein binding of tritium labeled, antidiabetic repaglinide and its displacement by warfarin, furosemide, tolbutamide, diazepam, glibenclamide and nicardipine were determined by ultrafiltration (Plumetal. 2000). 

Total serum thyroxine levels as measured by the total protein bound levels after injury have been reported as raised (F4), unchanged, or lowered (SI) but it is now agreed that there is no significant increase in total hormone levels in blood in the postoperative period. 

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. 

The decreased secretion of TSH from the pituitary is a pan of a generalized hypopituitarism (hat leads to hypothy-loitlism. This type of hypothyroidism can be distinguished from primary hypothyroidism by the administration of TSH In doses. sufficient to increase (he uptake of radioiodinc or to elevate the blood or plasma protein-bound iodine (PBI) as a consequence of enhanced secretion of hormonal iodine (thyroxine). Interestingly. ma.ssive doses of vitamin A inhibit the secretion of TSH. Thyrotropin is used as a diagnostic agent to differentiate between primary and secondary hypothyroidism. Its use in hypothyroidism caused by pituitary deficiency has limited application other forms of treatment are preferable. 

Inherited decreases in TBG have been reported (R5, Tl). The serum of these patients was characterized by a low protein-bound iodine in the absence of demonstrable hypothyroidism. Tracer studies revealed decreased extrathyroidal thyroxine pools and normal absolute thyroxine turnover (C3, T2). The condition is probably transmitted as a dominant X chromosome-linked trait (N3, R5). No abnormalities in TBPA have been reported in these conditions. 

W4. Wolff, J., Staudgert, M. E., and Rail, J. E., Thyroxine displacement from serum proteins and depression of serum protein bound iodine by certain drugs. J. Clin. Invest. 40. 1373-1379 (1961). 

Proloits>ed stasis duriu > venepuncture. Plasma water diffuses into the interstitial space and the serum or plasma sample obtained will be concent rated. Proteins and protein-bound components of plasma such as calcium or thyroxine will be falsely elevated. 

Thyroglobulin contains thyroxine in its protein-bound form. This compound would never be used in thyrotoxicosis. The answer is (E). 

C13. Christensen, L. K., A method for determination of free, non-protein bound thyroxine in serum. Scand. J. Clin. Lab. Invest. 11, 326-331 (1959). 

Most clinical immunoassays require neither prior extraction nor purification of the sample containing the analyte before they are added to the reaction containing the appropriate amoimts of high-affinity specific antibody and label. This is not the case, however, for analytes such as thyroxin or cortisol, which are tightly boimd to highly avid binding proteins that compete with the antibody for both the analyte and the label. Some of the more important protein-bound analytes are shown in Table 3. 

The thyroxine in blood is not lost by dialysis and is recovered in the acid precipitate. These findings indicate that the circulating thyroxine is bound to macromolecules. The administration of radiothyroxine followed by paper or starch-gel electrophoresis of the blood proteins has established that circulating thyroxine is bound to albumin, a prealbumin (TBPA), and an a-globulin (TBG). 

The changes in iodine metabolism are quite typical. Iodine uptake by the thyroid is low, and the levels of protein-bound iodine are markedly reduced in the blood. Except in special cases (see below), the binding properties of TBG and TBPA in blood are not changed. Determination of free thyroxine concentrations in blood of hypothyroids has yielded values lower than 20% of normal (1.5 pg of free thyroxine iodine per 100 ml). If these symptoms are readily explainable on the basis of modem knowledge of thyroid physiology and biochemistry, the causes of the... 

Although most circulating thyroxine is protein bound, it is the free fraction which is physiologically active. The free thyroxine index corrects the total serum thyroxine for any abnormalities there may be in protein binding (e.g. the low TBG levels found in hypoproteinaemic states or the high TBG levels found in... 

Thyroxine can be measured as protein-bound iodine (FBI). This measures both thyroxine and the smaller proportions of T3. The method involves four basic steps ... 

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