Hyperthyroidism levothyroxine

Synthetic levothyroxine sodium is used most commonly and is the drug of choice. Oral doses are incompletely absorbed. In plasma levothyroxine is for more than 99% bound to proteins, mainly to TBG. Maximal effects are reached in 3 weeks and the activity persists for 1-3 weeks after withdrawal of chronic therapy. It has a half-life of 7 days which permits once-daily administration. Its adverse effects mainly consist of signs and symptoms of hyperthyroidism. 

Some evidence indicates that levothyroxine overtreatment (leading to a hyperthyroid state) could lead to long-term bone mass loss (especially in elderly women) or atrial fibrillation (especially in elderly people). Levothyroxine has a narrow therapeutic range, and small changes in absorption or... 

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). 

Insomnia, psychic stimulation, general nervousness, and tremor are among the hyperthyroid symptoms that result from relative overdosage. Pseudotumor cerebri has incidentally been observed shortly after levothyroxine was... 

In 50 women taking levothyroxine either for primary thyroid failure or for hypothyroidism secondary to radioiodine treatment for hyperthyroidism, there was no difference between the two groups in terms of bone density at the hip or spine and no difference from the reference population (31). In addition, there was no correlation between bone density and circulating thyroid hormone concentrations or duration of levothyroxine replacement. These findings are reassuring, although large studies of fracture risk are required, in view of previous evidence of an adverse effect of levothyroxine on bone mineral density, especially in post-menopausal women (32). 

Clinical and biochemical hyperthyroidism occurred in a 36-year-old woman, after previously stable levothyroxine replacement therapy, when antiretroviral drugs for HIV infection were introduced (85). She was reported to be taking a very large dose of... 

Failure of the thyroid to produce sufficient thyroid hormone is the most common cause of hypothyroidism and is known as primary hypothyroidism. Secondary hypothyroidism occurs much less often and results from diminished release of TSH from the pituitary. Treatment of hypothyroidism is achieved by the replacement of thyroid hormone, primarily T4. A synthetic preparation of T4 is available, levothyroxine (Synthroid ), which has been a popular choice for hypothyroidism because of its consistent potency and prolonged duration of action. No toxicity occurs when given in physiological replacement doses. Desiccated animal thyroid is also available at a lesser cost. Overdoses cause symptoms of hyperthyroidism and can be used as a guide in clinical management. Hypothyroidism is not cured by the daily intake of thyroid hormone it is a life-long regimen. 

Adverse effects of thyroid hormone parallel the increase in metabolic rate. The symptoms and signs are those of hyperthyroidism. Symptoms of myocardial ischaemia, atrial fibrillation or heart failure are liable to be provoked by too vigorous therapy or in patients having serious ischaemic heart disease who may even be unable to tolerate optimal therapy. Should they occur levothyroxine must be discontinued for at least a week and begim again at lower dosage. Only slight overdose is needed to precipitate atrial fibrillation in patients over 60 years. 

In another study, three patients with type 1 disease, two of whom had not responded to methimazole plus perchlorate, were successfully treated with a short course of iopanoic acid 1 g/day, resulting in a marked reduction in the peripheral conversion of T4 to T3 (153). Euthyroidism was restored in 7-12 days, allowing uneventful thyroidectomy. The patients were then treated with levothyroxine for hypothyroidism and amiodarone was safely restarted. The authors suggested that iopanoic acid is the drug of choice for rapid restoration of normal thyroid function before thyroidectomy in patients with drug-resistant type 1 amiodarone-induced hyperthyroidism. 

Inhibition of glucuronyl transferase activity by indinavir has been blamed for an interaction of indinavir with levothyroxine, causing hyperthyroidism (43). 

D Levothyroxine is the drug of choice for hypothyroidism since it provides the necessary hormone without causing the inaease peak effect of Tj administration, levothyroxine is converted to Tj in the periphery. Liotrix contains T4 and T3 in a 4 1 ratio. This combination is not necessary since the T4 is converted to T3 and the short rz> of liotrix requires multiple daily doses. Desiccated thyroid is unreliable in potency since it is standardized to iodine content and not to T4 or T3 content. Triiodothyronine is also not preferred since rapid gastric absorption can lead to hyperthyroid symptoms and can lead to cardiac effects. 

Control of hyperthyroidism usually is associated with a decrease in goiter size, but if the thyroid enlarges, hypothyroidism probably has been induced. When this occurs, the dose of the antithyroid drug should be significantly decreased and/or levothyroxine can be added once hypothyroidism is confirmed by laboratory testing. 

Levothyroxine (T4) (e.g., Synthroid) Replaces normal serum levels of T4 and T3 (T4 is converted into T3 by deiodination in the periphery). Drug of choice for hypothyroidism. No toxicity at replacement concentration. Overdose causes hyperthyroid effects (top of page). 

The side-effects of levothyroxine increase with the dose and resemble those of hyperthyroidism (tachycardia, cardiac arrhythmias, trembling, nervousness, restlessness, sleeping disorders, diarrhea, heat intolerance, hair and weight loss). Allergies may rarely occur and are due to other substances in the formulation rather than the natural hormone. 

Therapy with levothyroxine is very safe, provided that thyroid hormone levels are monitored and maintained within the normal range. Excess doses of T4 are associated with a loss of bone mass. A meta-analysis of 41 controlled studies on the impact of thyroid hormone therapy on bone mineral density (Uzzan et al., 1996) has shown that doses of T4 that suppress thyrotropin (TSH) secretion are associated with a significant loss of bone in the lumbar spine and hip in postmenopausal women. Another review of the evidence of the thyroid hormone effect of on skeletal integrity concluded that hyperthyroidism and the use of thyroid hormone to suppress TSH seem to have an adverse effect on bone, especially in postmenopausal women (Greenspan and Greenspan, 1999) however, thyroid hormone replacement seems to have a minimal effect on bone. 

Oversuppression of TSH with levothyroxine may also cause remarkable adverse cardiac effects. In a Framingham study, a cohort of 2007 persons 60 years of age or older who did not have atrial fibrillation at baseline were evaluated in order to determine the frequency of this arrhythmia during a 10-year follow-up period. This study showed that subjects with TSH levels <0.1mU/l presented a three-fold risk of developing atrial fibrillation in relation to subjects with normal TSH values (Sawin et al., 1994). A recent prospective study performed in individuals aged 65 years or older demonstrated that subjects with subclinical hyperthyroidism exhibited a greater incidence of atrial fibrillation compared with those with normal thyroid function (Cappola (S /., 2006). 

The serum theophylline level of an asthmatic patient was found to have doubled, from 15.2 to 30.9 mg/L, accompanied by toxicity, 3 months after treatment for hyperthyroidism with radioactive iodine ( I). At this point the patient was hypothyroid, and after treatment with levothyroxine was started, his serum theophylline returned to approximately the same level as before radioactive iodine treatment (13.9 mg/L). Another patient with Graves disease treated with a combination of thiamazole (methimazole)... 

It is established that changes in thyroid status may affect how the body handles theophylline. Monitor the effects and anticipate the possible need to begin to reduce the theophylline dosage if treatment for hyperthyroidism is started (e.g. with radioactive iodine, carbimazole, thiamazole, propylthiouracil, etc.). Similarly, anticipate the possible need to increase the theophylline dosage if treatment is started for hypothyroidism (e.g. with levothyroxine). Stabilisation of the thyroid status may take weeks or even months to achieve so that if monitoring of the theophylline dosage is considered necessary, it will need to extend over the whole of this period. 

Within the thyroid system, disease states can lead to hypothyroidism and hyperthyroidism. Hypothyroidism results from abnormally low production of thyroid hormone in thyroid glands. The prevalence of this condition is reported as being between 2% and 5% of the world population, although a substantial number are in the sub-clinical category. Hypothyroidism is much more common in females than in males, and the frequency of the disease increases with age. The problem may arise due to an insufficient intake of iodine in the diet. It may be due to an inherited disorder (Hashimoto s thyroiditis) or it may be due to inflammation of the thyroid gland (lymphocytic thyroiditis). The conventional treatment for this condition is use of thyroid hormones levothyroxine sodium or liothyronine sodium (Fig. 20.11). 

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