Thyroid hormone indications

Myxedema and goiter are the main conditions for which thyroid preparations are indicated. The treatment of cretinism is difficult because it is recognized only at or after birth. Even if this disease could be diagnosed m utero, thyroid hormones do not readily cross the placental barrier. In addition, the fetus, as does a premature infant, rapidly deactivates the thyroid hormones. The halogen-free analogue DlMlT [26384-44-7] (3), which is resistant to fetal deiodinases, may prove useful for fetal hypothyroidism (cretinism). 

Figure 42-11. Model of iodide metabolism in the thyroid follicle. A follicular cell is shown facing the follicular lumen (top) and the extracellular space (at bottom). Iodide enters the thyroid primarily through a transporter (bottom left). Thyroid hormone synthesis occurs in the follicular space through a series of reactions, many of which are peroxidase-mediated. Thyroid hormones, stored in the colloid in the follicular space, are released from thyroglobulin by hydrolysis inside the thyroid cell. (Tgb, thyroglobulin MIT, monoiodotyrosine DIT, diiodotyro-sine Tj, triiodothyronine T4, tetraiodothyronine.) Asterisks indicate steps or processes that are inherited enzyme deficiencies which cause congenital goiter and often result in hypothyroidism.

Lithium is concentrated in the thyroid gland and can impair thyroid hormone synthesis. Although goiter is uncommon, as many as 30% of patients develop at least transiently elevated thyroid-stimulating hormone values. Lithium-induced hypothyroidism is not usually an indication to discontinue the drug. Patients can be supplemented with levothyroxine if continuation of lithium is desired.30... 

Current information indicates that OATP-E [30] is ubiquitously expressed in tissues [30, 37]. Some substrates transported by OATP-E include estrone-sulfate [30], prostaglandin E2 [30] and taurocholate [37]. The capacity for T3 and T4 transport and the wide tissue distribution suggests that OATP-E is largely responsible for the peripheral uptake of thyroid hormone [37]. Further studies are required to assess whether OATP-E is an important determinant of drag distribution. 

Thyrotoxicosis factitia is hyperthyroidism produced by the ingestion of exogenous thyroid hormone. This may occur when thyroid hormone is used for inappropriate indications, when excessive doses are used for accepted medical indications, or when it is used surreptitiously by patients. 

An elevated 24-hour radioactive iodine uptake (RAIU) indicates true hyperthyroidism the patient s thyroid gland is overproducing T4, T3, or both (normal RAIU 10% to 30%). Conversely, a low RAIU indicates that the excess thyroid hormone is not a consequence of thyroid gland hyperfunction but is likely caused by thyroiditis or hormone ingestion. 

TSH-induced hyperthyroidism is diagnosed by evidence of peripheral hypermetabolism, diffuse thyroid gland enlargement, elevated free thyroid hormone levels, and elevated serum immunoreactive TSH concentrations. Because the pituitary gland is extremely sensitive to even minimal elevations of free T4, a normal or elevated TSH level in any thyrotoxic patient indicates inappropriate production of TSH. 

In thyrotoxic Graves disease, there is an increase in the overall hormone production rate with a disproportionate increase in T3 relative to T4 (Table 20-1). Saturation of thyroid-binding globulin is increased due to the elevated levels of serum T4 and T3, which is reflected in an elevated T3 resin uptake. As a result, the concentrations of free T4, free T3, and the free T4 and T3 indices are increased to an even greater extent than are the measured serum total T4 and T3 concentrations. The TSH level is undetectable due to negative feedback by elevated levels of thyroid hormone at the pituitary. In... 

General supportive measures, including acetaminophen as an antipyretic (aspirin or other nonsteroidal antiinflammatory drugs may displace bound thyroid hormone), fluid and electrolyte replacement, sedatives, digoxin, antiarrhythmics, insulin, and antibiotics should be given as indicated. Plasmapheresis and peritoneal dialysis have been used to remove excess hormone in patients not responding to more conservative measures. 

During treatment of hyperthyroidism, Lp(a), as well as LDL cholesterol and apolipoprotein B, increases, indicating an effect of thyroid hormone on receptor activity and on protein synthesis. The opposite effect is observed in treatment of hypothyroidism (B27, E9, K16). 

Evidence of a different sort also indicates wide variability with respect to thyroid function. In endemic areas not all of the individuals exhibit endemic goiters, only certain individuals. These, it would be assumed, are individuals who for some reason connected with the production of thyroid hormone need more iodine than their fellows. Similarly, it may be noted that in areas where sea food is abundantly used and iodine is therefore relatively plentiful, there are still some individuals who develop simple goiter. 

We have already cited evidence to indicate that iodine needs vary substantially from individual to individual. Not only does the thyroid hormone content of the blood show high inter-individual variation, but in endemic regions not all individuals exhibit simple goiter due to iodine deficiency. And, in nonendemic regions where the iodine content of the foods is sufficient for most individuals, there are still some who suffer deficiency. Furthermore, even the iodine in iodized salt is said to be sufficient to yield unfavorable results for some individuals. 

The Class III effects of amiodarone develop over several weeks. This time-course is similar to that seen in thyroid gland ablation [25]. It is well known that patients with hypothyroidism have long QT intervals which are indicative of prolonged action potentials. Amiodarone has been shown to inhibit the conversion of thyroxine (T4) to triiodothyronine (T3) both in human subjects [26] and in vitro [27]. It has been argued that the Class III effects of amiodarone are due to its effects on thyroid hormones [28]. Others, however, argue that there is no relationship between prolongation of ventricular refractory period by amiodarone and thyroid state [29]. 

When laboratory testing indicates that a patient with BPAD is clinically hypothyroid, even if lithium is the readily apparent cause, we recommend starting thyroid hormone replacement. Lithium should not be discontinued, particularly if it has otherwise managed the BPAD well. Thyroxine should be started at 50 ag/day. TSH levels can then be checked 6-8 weeks later. The daily dose of thyroxine can be increased in 25 g increments every 1-2 months until TSH levels have normalized. 

Camarasa and Serra-Baldrich [94] reported allergic contact dermatitis after repeated contact with TPP-treated plastics. Meeker and Stapleton [95] indicated endocrine disruptive properties for TPP and TDCiPP, through a negative correlation with semen quality and thyroid hormone levels, respectively. Kanazawa et al. [71] associated mucosal symptoms of the sick building syndrome with high indoor exposure to TBP. These symptoms include irritation to the eyes, nose, and throat symptoms such as flushing, and mucosal symptoms such as irritation to the eyes, nose, and throat the latter symptoms were strongly associated with TBP levels in air and dust. 

Treatment-related altered serum th5Toid hormone levels indicate that chlorine dioxide and chlorite may exert toxic effects that are mediated through the neuroendocrine axis. Changes in thyroid hormones have been reported in laboratory animals that were either directly exposed to chlorine dioxide (repeated doses as low as 9 mg/kg/day), or exposed to chlorine dioxide or chlorite via their mothers (maternal doses of chlorine dioxide and chlorite as low as 13 and 9 mg/kg/day, respectively) during pre- and postpartum development (Bercz et al. 1982 Carlton and Smith 1985 Carlton et al. 1987, 1991 Mobley et al. 1990 Orme et al. 1985). 

A body of literature indicates that thyroid hormones are effective as adjuncts to antidepressants and that they enhance antidepressant activity, accelerate rate of response, and decrease treatment resistance. The accumulated literature is convincing that 25-50 mg of T3 is very effective as an adjunct to TGA when added to TGA nonresponders [Aronson et al. 1996]. Of special interest is the short period, 1 week, that is necessary for the T3... 

Thyroid Hormone Data from a limited number of controlled studies indicate that, particularly in women, adding triiodothyronine may produce remission in a nonresponder (377). However, most of these studies have been done with TCAs rather than the newer antidepressants. 

Lithium blocks the release of thyroid hormones, which are known to potentiate b-noradrenergic receptor sensitivity. This has led to the speculation that excessive thyroid activity may contribute to an episode of mania in susceptible patients, and that the antimanic effect of lithium is, at least in part, due to its antithyroid action (26). In this context, CBZ can also decrease various thyroid indices. 

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