Thyroxine excess

Estrogen may increase hepatic production of thyroxine-binding globulin (TBG) and decrease TBG clearance, thus increasing serum total thyroxine (tT4) and, to a lesser extent, total triiodothyronine (tT3). As a result, increased tT4 and tT3 are seen in states of excessive estrogen and/or progestin, such as... 

Demonstration that the effects of thyrotoxicosis or goiter are due to an excess or deficiency in (thyroxine + T3) secretion does not explain how the diseases originate nor why development and metabolic rate are affected. It is thought that some cases of thyrotoxicosis (Graves disease) may be caused by abnormal immune responses mimicking the effects of thyroid-stimulating hormone on the thyroid gland. 

Thyroxine is used in hypothyroidism, a condition that may well present in elderly patients. Side-effects of thyroxine usually occur at excessive doses and include gastrointestinal disturbances (nausea, vomiting) as well as cardiac symptoms such as angina pain, arrhythmias, palpitation and tachycardia. Thyroxine should be used with caution in elderly patients as they are more prone to side-effects. A lower initial dose (25-50 pg daily) is recommended for patients who are over 50 years. Dose adjustments should take place at intervals of at least 4 weeks. A pretreatment electrocardiogram is recommended because changes induced by hypothyroidism (that would be present at baseline) may be confused with ischaemia. 

The thyroid hormone thyroxine is necessary for the development and function of cells throughout the body. It increases protein synthesis and oxygen consumption in almost all types of body tissue. Excess thyroxine causes hyperthyroidism, with increased heart rate, blood pressure, overactivity, muscular weakness, and loss of weight. 

In older patients with goiter due to iodine deficiency there is a risk of provoking hyperthyroidism by increasing iodine intake (p. 247) During chronic maximal stimulation, thyroid follicles can become independent of TSH stimulation ( autonomic tissue"). If the iodine supply is increased, thyroid hormone production increases while TSH secretion decreases due to feedback inhibition. The activity of autonomic tissue, however, persists at a high level thyroxine is released in excess, resulting in iodine-induced hyperthyroidism. 

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. 

The toxicity of thyroxine is directly related to the hormone level. In children, restlessness, insomnia, and accelerated bone maturation and growth may be signs of thyroxine toxicity. In adults, increased nervousness, heat intolerance, episodes of palpitation and tachycardia, or unexplained weight loss may be the presenting symptoms. If these symptoms are present, it is important to monitor serum TSH (Table 38-2), which will determine whether the symptoms are due to excess thyroxine blood levels. Chronic overtreatment with T4, particularly in elderly patients, can increase the risk of atrial fibrillation and accelerated osteoporosis. 

Albumin is a major transport facilitator of hydrophobic compounds which would otherwise disrupt cellular membranes. These compounds include free fatty acids and bilirubin as well as hormones such as cortisol, aldosterone, and thyroxine when these materials have exceeded the capacity of proteins normally associated with them. Albumin also binds ions, including toxic heavy metals and metals such as copper and zinc which are essential for normal physiological functioning but may be toxic in quantities in excess of their binding capacity for their carrier proteins. Binding of protons is the basis for the buffering capacity of albumin. 

Thyroid hormones are intimately involved in regulating the basal metabolic rate. Liver tissue of animals given excess thyroxine shows an increased rate of 02 consumption and increased heat output (thermogenesis), but the ATP concentration in the tissue is normal. Different explanations have been offered for the thermogenic effect of thyroxine. One is that excess thryroxine causes uncoupling of oxidative phosphorylation in mitochondria. How could such an effect account for the observations Another explanation suggests that the thermogenesis is due to an increased rate of ATP utilization by the thyroxine-stimulated tissue. Is this a reasonable explanation Why ... 

A small group of cyclic thioureas have been used in the treatment of excessive thyroid function. They include 6-n-propylthiouracil (176 R1 = H, R2 = Prn), 5-iodo-2-thiouracil (176 R1 = I, R2 = H), l-methyl-2-mercaptoimidazole (methimazole) and its ethoxycarbonyl derivative carbimazole (177), which lacks the bitter taste of the unacylated compound. These compounds block the synthesis of thyroxin by inhibiting the oxidation of iodide to iodine and the oxidative coupling of iodotyrosine residues. 

As with all forms of long-term therapy, adherence to the prescribed dosage of levothyroxine is not always optimal, and an unwarranted fear of thyroid-induced osteoporosis can add to this lack of adherence. Inadequacy of thyroxine replacement therapy is not always easily recognized. Several patients were reported with clearly inadequate or excessive consumption of levothyroxine despite a correct prescription. All patients had depression, which could be an additional susceptibility factor by promoting lack of adherence, and the resulting hypothyroidism or hyperthyroidism could further aggravate the depression (12). 

Exley A, O Malley BP. Depression in primary hypothyroidism masquerading as inadequate or excessive L-thyroxine consumption. Q J Med 1989 72(269) 867-70. 

The thyroid gland facilitates normal growth and maturation by maintaining the level of metabolism in the tissues that is optimal for their normal function. The two major thyroid hormones are T3 (triiodothyronine, the most active form), and T4 (thyroxine). Although the thyroid gland is not essential for life, inadequate secretion of thyroid hormone (hypothyroidism) results in bradycardia, poor resistance to cold, and mental and physical slowing (in children this can cause mental retardation and dwarfism). If, however, an excess of thyroid hormones is... 

EXCESS occurs in Graves Disease, in which there may be a goiter, exophthalmos (protrusion of one or both eyes), and hyperactivity, with increased body metabolic rate. Hyperthyroidism most commonly is due to overproduction of thyroxine by the thyroid gland. 

Hyperthyroidism (excessive production of thyroid hormones) asually requires surgery, but before. surgery the patient mu.st be prepared by preliminary abolition of the hyper-thyroidi.sm through the use of antithyroid drugs. Thiourea and related eompounds. show an antithyroid activity, but they arc too toxic for clinical use. The more useful drugs are 2-thiouracil derivatives and a closely related 2-thioimidazolc derivative. All of these appear to have a similar mechanism of action (i.c.. prevention of the iodination of the precursors of thyroxine and triiodothyronine). The main difference in the compounds lies in their relative toxieities. 

Phenylketonuria (PKU) is an inborn error of metabolism by which the body is unable to convert surplus phenylalanine (PA) to tyrosine for use in the biosynthesis of, for example, thyroxine, adrenaline and noradrenaline. This results from a deficiency in the liver enzyme phenylalanine 4-mono-oxygenase (phenylalanine hydroxylase). A secondary metabolic pathway comes into play in which there is a transamination reaction between PA and a-keto-glutaric acid to produce phenylpyruvic acid (PPVA), a ketone and glutamic acid. Overall, PKU may be defined as a genetic defect in PA metabolism such that there are elevated levels of both PA and PPVA in blood and excessive excretion of PPVA (Fig. 25.7). 

An excess production of thyroxine and triiodothyronine is called hyperthyroidism. 

As is true for all kinases, Mg is an obligate activating ion that forms complexes with ATP and ADP. The optimal concentration range for Mg is quite narrow, and excess Mg is inhibitory. Many metal ions, such as Mn, Ca , and Cu , inhibit enzyme activity, as do iodoacetate and other suhhydryl-binding reagents. Activity is inhibited by excess ADP and by citrate, fluoride, nitrate, acetate, iodide, bromide, malonate, and L-thyroxine. Urate and cystine are... 

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