Thyroid hormone therapy dosing

Case Conclusion GM began thyroid hormone therapy with T4. Her dose was initiated at the lower-than-recom-mended dose because GM has a history of AF, which may increase her sensitivity to the cardiac effects of T4. GM will return to the clinic in 4 to 6 weeks to assess her thyroid function and symptoms. Symptoms should begin to resolve in 2 to 3 weeks and should disappear by 6 weeks. 

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. 

Patients with coronary artery disease who require bypass grafting, angioplasty, or stenting may be managed without full replacement doses of T4 if this treatment induces an increase in myocardial oxygen needs and symptoms of cardiac ischemia. In this setting, the coronary blood flow should be addressed first, and thyroid hormone therapy should be initiated afterwards (Stathatos and Wartofsky, 2003). 

There is definitely an overlap in responses obtained in normd subjects and those obtained in patients with partial thyroid deficiency, even if the number of injections of TSH is reduced. However, failure of the thyroid uptake and total T4 to increase after TSH is strong evidence of primary thyroid disease. In the patients receiving thyroid hormone therapy, a significant response to TSH fairly conclusively excludes underlying thyroid failure unless the patient has been taking this therapy in full doses for many years. The test is probably most useful in distinguishing idiopathic thyroid failure from secondary or pituitary hypothyroidism. 

Large doses of iodide inhibit the synthesis and release of thyroid hormones. Serum T4 levels may be reduced within 24 hours, and the effects may last for 2 to 3 weeks. Iodides are used most commonly in Graves disease patients prior to surgery and to quickly reduce hormone release in patients with thyroid storm. Potassium iodide is administered either as a saturated solution (SSKI) that contains 38 mg iodide per drop or as Lugol s solution, which contains 6.3 mg iodide per drop. The typical starting dose is 120 to 400 mg/day. Iodide therapy should start 7 to 14 days prior to surgery. Iodide should not be... 

Thyroid cancer Exogenous thyroid hormone may produce regression of metastases from follicular and papillary carcinoma of the thyroid and is used as ancillary therapy of these conditions with radioactive iodine. Larger doses than those used for replacement therapy are required. 

In patients with longstanding hypothyroidism and those with ischemic heart disease, rapid correction of hypothyroidism may precipitate angina, cardiac arrhythmias, or other adverse effects. For these patients, replacement therapy should be started at low initial doses, followed by slow titration to full replacement as tolerated over several months. If hypothyroidism and some degree of adrenal insufficiency coexist, an appropriate adjustment of the corticosteroid replacement must be initiated prior to thyroid hormone replacement therapy. This prevents acute adrenocortical insufficiency that could otherwise arise from a thyroid hormone-induced increase in the metabolic clearance rate of adrenocortical hormones. 

Treatment is thyroid hormone replacement. The goal of the therapy is to relieve the symptoms of hypothyroidism by normalizing the levels of circulating thyroid hormones. In addition to the amelioration of symptoms, the clinical effectiveness of the thyroid hormone replacement may be monitored by periodically measuring the serum TSH concentration. The lowest dose of thyroid hormone that is needed to normalize the serum TSH concentration is usually the appropriate dose. Most or all of the symptoms of hypothyroidism should improve with appropriate thyroid hormone replacement, but this may require weeks or months of therapy. 

Beta blockers without intrinsic sympathomimetic activity (eg, metoprolol, propranolol, atenolol) are effective therapeutic adjuncts in the management of thyrotoxicosis since many of these symptoms mimic those associated with sympathetic stimulation. Propranolol has been the 3 blocker most widely studied and used in the therapy of thyrotoxicosis. Beta blockers cause clinical improvement of hyperthyroid symptoms but do not typically alter thyroid hormone levels. Propranolol at doses greater than 160 mg/d may also reduce T3 levels approximately 20% by inhibiting the peripheral conversion of T4 to T3. 

Thyroid function tests are often altered by somatropin because of increased conversion of T4 to T3, but this is clinically insignificant at low doses (SEDA-21, 453). One child with Prader-Willi syndrome had a fall in serum thyroxine concentration during somatropin therapy and needed thyroxine replacement (33). Hypothyroidism developed in 11 of 46 growth hormone-deficient children treated with somatropin (34). Prior abnormalities in hypothalamic-pituitary function and alterations in thyroid hormone metabolism, probably both, contributed to the high incidence of hypothyroidism, which was similar to that in previous studies. 

Quick relief can be obtained with a p-adrenoceptor blocking drug (judge dose by heart rate) though these do not block all the metabolic effects of the hormone, e.g. on the myocardium, and the basal metabolic rate is unchanged. For this reason they should not be used as sole therapy except in mild thyrotoxicosis in preparation for radioiodine treatment, and should be continued in these patients until the radioiodine has taken effect. They do not alter the course of the disease, nor biochemical tests of thyroid function. Any effect on thyroid hormonal action on peripheral tissues is clinically unimportant. It is desirable to choose a drug that is nonselective for pj and p2 receptors and lacks partial agonist effect (e.g. propranolol 20-80 mg 6-8-hourly, or timolol 5 mg once daily). Usual contraindications to P-blockade (see p. 478) should be observed, especially asthma. 

The natural history of Graves disease is of alternating remission and relapse. Progression to hypothyroidism can occur, especially after 1 treatment. Such patients should have long-term follow-up, and are likely to require thyroid hormone replacement therapy Severe forms of thyroid eye disease should be treated with steroids and immunosuppresants or low-dose radiotherapy. Urgent surgical decompression can be required for eyophthalmos. 

In contrast to other protein-bound drugs for which a loading dose is given to achieve rapid steady-state concentrations, a slow and stepwise increase in thyroid hormone replacement therapy is advisable. This is preferred mainly to avoid sudden cardiac adverse effects, especially in older patients with long-standing myxedema. Moreover, since thyroid hormone substitution can change the metabolic clearance of this drug, steady-state concentrations are obtained only after several months (SEDA-6, 363). 

Ingestion of excessive amounts of thyroid hormones can cause sjmptoms and signs similar to those that result from endogenous overproduction. However, the sjmptoms and signs are generally relatively trivial in those who take standard doses of levothyroxine replacement therapy. 

The initial dose of levothyroxine is dependent on the patient s age, and the presence of associated disorders, as well as the severity and duration of hypothyroidism. In young patients with longstanding disease and patients over age 45 without known cardiac disease, therapy should be initiated with 50 meg daily of levothyroxine and increased to 100 meg daily after 1 month. The recommended initial daily dose for older patients or those with known cardiac disease is 25 meg per day titrated upward in increments of 25 meg at monthly intervals to prevent stress on the cardiovascular system. Some patients may experience an exacerbation of angina with higher doses of thyroid hormone. Although the TSH is very sensitive for under- or overreplacement, chnicians often fail to alter the dose of T4 based on TSH clearly outside of the normal range. ... 

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