Thyroid hormone therapy

Thyroid hormones accelerate metabolism. Their release (A) is regulated by the hypophyseal glycoprotein TSH, whose release, in turn, is controlled by the hypothalamic tripeptide TRH. Secretion of TSH declines as the blood level of thyroid hormones rises by means of this negative feedback mechanism, hormone production is automatically adjusted to demand. 

The thyroid releases predominantly thyroxine (T4). However, the active form appears to be triiodothyronine (T3) T4 is converted in part to T3, receptor affinity in target organs being 10-fold higher for T3. The effect of T3 develops more rapidly and has a shorter duration than does that of T4. Plasma elimination tip for T4 is about 7 d that for T3, however, is only 1.5 d. Conversion of T4 to T3 releases iodide 150 pg T4 contains 100 pg of iodine. 

For therapeutic purposes, T4 is chosen, although T3 is the active form and better absorbed from the gut. However, with T4 administration, more constant blood levels can be achieved because degradation of T4 is so slow. Since absorption of T4 is maximal from an empty stomach, T4 is taken about V2 h before breakfast. 

Replacement therapy of hypothyroidism. Whether primary, i.e caused by thyroid disease, or secondary, i.e resulting from TSH deficiency, hypothyroidism is treated by oral administration of T4. Since too rapid activation of metabolism entails the hazard of cardiac overload (angina pectoris, myocardial infarction), therapy is usually started with low doses and gradually increased. The final maintenance dose required to restore a euthyroid state depends on individual needs (approx. 

Thyroid suppression therapy of euthyroid goiter (B). The cause of goiter (struma) is usually a dietary deficiency of iodine. Due to an increased TSH action, the thyroid is activated to raise utilization of the little iodine avail-Liillmann, Color Atlas of Pharmacology 2000 Thieme All rights reserved. Usage subject to terms and conditions of iicense. 

Because of the negative feedback regulation of thyroid function, thyroid activation can be inhibited by administration of T4 doses equivalent to the endogenous daily output ( 150 pg/day). Deprived of stimulation, the inactive thyroid regresses in size. 

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Infertility Thyroid hormone therapy is unjustified for the treatment of male or female infertility unless the condition is accompanied by hypothyroidism. 

Endocrine disorders Thyroid hormone therapy in patients with concomitant diabetes mellitus or insipidus or adrenal insufficiency (Addison disease) exacerbates the intensity of their symptoms. 

Autoimmune polyglandular syndrome-Chron c autoimmune thyroiditis may occur in association with other autoimmune disorders. Treat patients with concomitant adrenal insufficiency with replacement glucocorticoids prior to initiation of treatment. Failure to do so may precipitate an acute adrenal crisis when thyroid hormone therapy is initiated. Patients with diabetes mellitus may require upward adjustments of their antidiabetic therapeutic regimens. Nontoxic diffuse goiter or nodular thyroid disease Use caution when administering levothyroxine to patients with nontoxic diffuse goiter or nodular thyroid disease in order to prevent precipitation of thyrotoxicosis. If the serum TSH is already suppressed, do not administer levothyroxine. 

The hallmarks of infantile hypothyroidism (e.g., retardation of mental development and growth) become manifest only in later infancy and are largely irreversible. Consequently, early recognition and initiation of replacement therapy are crucial. In the absence of thyroid hormone therapy, the symptoms of infantile hypothyroidism include feeding problems, failure to thrive, constipation, a hoarse cry, and somnolence. In... 

Subclinical hypothyroidism, defined as an elevated TSH level and normal thyroid hormone levels, is found in 4-10% of the general population but increases to 20% in women older than age 50. The consensus of expert thyroid organizations concluded that thyroid hormone therapy should be considered for patients with TSH levels greater than 10 mlU/L while close TSH monitoring is appropriate for those with lower TSH elevations. 

A possible link between breast cancer in women and thyroid hormone therapy was suggested on the basis of a retrospective study of patients with breast cancer (SEDA-3, 340). A subsequent statistical re-analysis of the original data failed, as did later studies, to confirm such a relation (SEDA-3, 340 SEDA-4, 294 57). 

Ribot C, Tremollieres F, Pouilles JM, Louvet JP. Bone mineral density and thyroid hormone therapy. Clin Endocrinol (Oxf) 1990 33(2) 143-53. 

Cytomel is the synthetic form of T-3/L-triiodothyronine and was a commonly known trade or brand name among athletes. T-3/L-triiodothyronine is used as a form of thyroid hormone therapy mostly in Europe. Most bodybuilders favored this drug over synthetic forms of T-4/L-thyroxine due to its vastly superior activity level. 

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. 

Clinical use Thyroid hormone therapy can be accomplished with either thyroxine or triiodothyronine. Synthetic levothyroxine (T ) is the form of choice for most cases. Tj (liothy-ronine) is faster-acting but has a shorter half-life and is more expensive. 

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). 

List classes of drugs that interact (interfere) with thyroid hormones therapy. 

Respiratory depression is not a complication of thyroid hormone therapy. 

Grapefruit juice is contraindicated when taking some medications, but not thyroid hormone therapy. 

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. 

It has been generally accepted, mainly on the basis of animal experiments (159,160), that the production of bile acids is increased in hyperthyroid and decreased in hypothyroid patients. Treatment of the latter subjects with thyroid hormones was actually shown to increase the turnover of cholic acid (161). The determination of fecal bile acids indicated, however, that bile acid elimination was inconsistently decreased in hypothyroid patients and that thyroid hormone therapy increased the bile acid excretion insignificantly (89,162). 

The extent of the hazard of radioiodine absorbed by the thyroid became apparent only after a decade of study. The work also confirmed the high risk of mental retardation among children born with impaired thyroid function unless they received thyroid hormone therapy. Once again, research was demonstrating how vulnerable the human fetus and children are to radiation. 

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