Thyroxin, elevated levels

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). 

Evidence for chemically mediated disruption of thyroid function in wild reptile populations includes the finding of elevated thyroxine levels in male alligators from Lake Apopka, although a causal relationship with specific chemicals has not been established. ... 

Hypothyroid women frequently have anovulatory cycles and are therefore relatively infertile until restoration of the euthyroid state. This has led to the widespread use of thyroid hormone for infertility, although there is no evidence for its usefulness in infertile euthyroid patients. In a pregnant hypothyroid patient receiving thyroxine, it is extremely important that the daily dose of thyroxine be adequate because early development of the fetal brain depends on maternal thyroxine. In many hypothyroid patients, an increase in the thyroxine dose (about 30-50%) is required to normalize the serum TSH level during pregnancy. Because of the elevated maternal TBG levels and, therefore, elevated total T4 levels, adequate maternal thyroxine dosages warrant maintenance of TSH between 0.5 and 3.0 mll/L and the total T4 at or above the upper range of normal. 

An advantage of T-3/L-triiodothyronine administration over T-4/L-thyroxine was the lack of dependence upon the liver enzyme responsible for T-4/T-3 conversion. During diet restricted periods the liver naturally decreases the liver enzyme levels as a control measure to prevent metabolic rate induced starvation. Just as the liver increases production of this enzyme in response to elevated calorie intake it also reduces levels in response to decreased calorie intake. Remember that T-4 /L-thyroxine is only 20% as active as T-3/L-triiodothyronine. 

In fact, despite losses of thyroxin-binding globulin in the urine, proportional to total proteinuria and accompanied by the loss of bound T3 and T4, plasma concentrations of T4, T3, and thyroid stimulating hormone (TSH) are usually normal in nephrotic subjects. Sometimes T3 levels may be lowered and T4 levels slightly elevated with increased reverse T3, with normal TSH levels excluding the diagnosis of hypothyroidism. Hypoalbuminemia is to be taken into consideration also in hypothyroid patients on thyroxine substitution therapy. 

In addition to the possibility of decreases in receptor number, a corresponding condition of upregulation can take place. In this case sensitization can occur by an increase in receptor number. For example, chronic exposure to high levels of thyroid hormone (i.e., thyroxin) can lead to an increase in myocardial P receptors with corresponding increased sensitivity to P agonists. A corresponding result could be elevated heart rate, which is often present in hyperthroidism. 

Metallic Mercury. A 13-year-old boy exposed to mercury vapors for 2 weeks developed a thyroid enlargement with elevated triiodothyronine, and thyroxine and low thyroid-stimulating hormone levels (Karpathios et al. 1991). Serum-free thyroxine (T4) and the ratio of free thyroxine to free 3,5,3 -triiodo-... 

Other Systemic Effects. Studies of workers exposed to mercury vapor found no effect on serum levels of thyroid-stimulating hormone (Erfurth et al. 1990 McGregor and Mason 1991). However, an enlarged thyroid, with elevated triiodothyronine and thyroxine, as well as reduced thyroid-stimulating hormone developed in a 13-year-old boy exposed to mercury vapor for 2 weeks (Karpathios et al. 1991). Animal... 

Thyroid function tests typically run a triphasic course. Initially, serum thyroxine levels are elevated owing to release of preformed thyroid hormone from disrupted follicles. The 24-hour RAIU during this time is less than 2% owing to thyroid inflammation and TSH suppression by the elevated thyroxine level. As the disease progresses, intrathyroidal hormone stores are depleted and the patient may become mildly hypothyroid with an appropriately elevated TSH level. During the recovery phase thyroid hormone stores are replenished and serum TSH elevation gradually returns to normal. Recovery is generally complete within 2 to 6 months. Most patients remain euthyroid and recurrences of painful thyroiditis are extremely rare. The patient with painful thyroiditis should be reassured that the disease is self-limited and is unlikely to recur. Thyrotoxic symptoms may be relieved with /3-blockers. Aspirin (650 mg orally every 6 hours)... 

B. This patient appears to have a hyperthyroid condition even though the thyroid does not appear to be enlarged. Thyroid function tests would be most helpful to determine if this is the case. The free thyroxine level is a direct measure of the amount of free T, the biologically active T, in the serum. Elevation of the free T indicates a hyperthyroid condition. 

Several subjects have also been studied whose serum had an elevated thyroxine-binding capacity (B5, F3, 15, J2). Although high PBI levels were present, patients were euthyroid. Free thyroxine concentration was normal in these patients (15), pool sizes were increased, and absolute thyroxine turnover was normal. 

It is usually performed either at birth, soon after the finding of elevated neonatal TSH levels, at 3 years of age after 1 month of L-thyroxine withdrawal, or on administration of RhTSH, which allows a precise diagnosis to be made and thus avoids the hypothyroid state. Finally the severe hypothyroidism resulting from TPO mutations should be promptly tteated with the thyroid hormone, in order to maintain TSH levels at the lower limit of the normal range. 

Serum total T4 (TT4), FT4 and TSH levels of the neonates and serum total T3 (TT3), TT4 and TSH levels of their mothers were measured. All the neonates with hypothyroidism had hormonal findings that were diagnostic of hypothyroidism. After 8 weeks of thyroxine therapy, euthyroidism was achieved in all the hypothyroid neonates (Table 65.2). The borderline elevation of TSH levels, accompanied by increased TT3 and near-normal TT4 levels, indicated the presence of subcfinical hypothyroidism in the mothers of neonates with hypothyroidism (Table 65.3)... 

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