Hypothyroidism replacement therapy

The primary method of treating hypothyroidism is to administer thyroid hormones as replacement therapy. Long-term administration of thyroid hormones is usually a safe, effective means of maintaining optimal patient health in hypothyroidism. Replacement therapy using thyroid hormone preparations is described below. 

Thyroid-stimulating hormone can be used clinically to test thyroid function but has not found practical apphcation in the treatment of human thyroid insufficiency. Direct replacement therapy with thyroid hormone is easy and effective, owing to a simple molecular stmcture. TSH has been used in the veterinary treatment of hypothyroidism, and preparations of TSH ate produced by Cooper Animal Health, Inc. and Armour Pharmaceuticals. 

Thyroid hormones are used as replacement therapy when the patient is hypothyroid. By supplementing the decreased endogenous thyroid production and secretion with exogenous thyroid hormones, an attempt is made to create a euthyroid (normal thyroid) state Levotliyroxine (Synthroid) is the drug of choice for hypothyroidism because it is relatively inexpensive, requires once-a-day dosages, and lias a more uniform potency than do other thyroid hormone replacement drugs. 

Replacement therapy is for life, witii the exception of transient hypothyroidism seen in those with tiiy-roiditis. 

Use serum TSH to identify patients with hypothyroidism and to monitor LT4 replacement therapy. 

The target TSH for patients on LT4 replacement therapy for hypothyroidism is 0.5 to 2.5 milliunits/L. Most patients feel best at a TSH level in the low- to middle-normal range (i.e., 0.5-1.5 milliunits/L). ... 

Interferon-a causes hypothyroidism in up to 39% of patients being treated for hepatitis C infection. Patients may develop a transient thyroiditis with hyperthyroidism prior to becoming hypothyroid. The hypothyroidism may be transient as well. Asians and patients with preexisting anti-TPOAbs are more likely to develop interferon-induced hypothyroidism. The mechanism of interferon-induced hypothyroidism is not known. If LT4 replacement is initiated, it should be stopped after 6 months to re-evaluate the need for replacement therapy. 

Children treated with GH replacement therapy rarely experience significant adverse effects, whereas adults are more susceptible to dose-related adverse effects. Treatment with GH may mask underlying hypothyroidism. GH-induced symptoms, such as edema, arthralgia, myalgia, and carpal tunnel syndrome, are common and necessitate dose reductions in up to 40% of adults. Benign increases in intracranial pressure may occur with GH therapy and generally are reversible with discontinuation of treatment. Often, GH therapy can be restarted with smaller doses without symptom recurrence. 

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. 

This disease is characterized by a decrease or lack of endogenic thyroid hormone secretion. When originating in childhood, it can be clinically described as cretinism (infantile hypothyroidism), and in adults as myxedema (adult hypothyroidism), which is expressed in a loss of mental or physical ability to work, suppression of metabolic processes in the body, and edema. Since thyroid function cannot be restored, the clinical effect is only visible when using thyroid hormones. Using thyroid hormones in hypothyroidism is a replacement therapy that does not correct the disease itself. 

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... 

Juvenile or adult patients with primary hypothyroidism (as indicated by low serum free T4 and high serum TSH concentrations) are usually treated with thyroxine with the aim of relieving symptoms and reducing the serum TSH concentration into the normal reference range. If the primary hypothyroidism is the result of iodine deficiency, then gradually increasing dietary iodine supplementation may also be instituted in addition to the thyroxine replacement therapy. Iodine supplementation alone may lead to the development of acute hyperthyroidism. 

Levothyroxine sodium (Levothwid, Synthroid, Levoxine) is the sodium salt of the naturally occurring levorota-tory isomer of T4. It is the preparation of choice for maintenance of plasma T4 and T3 concentrations for thyroid hormone replacement therapy in hypothyroid patients. It is absorbed intact from the gastrointestinal tract, and its long half-life allows for convenient once-daily administration. Since much of the T4 is deiodi-nated to T3, it is usually unnecessary to use more expensive preparations containing bothX4 and Tj.The aim is to establish euthyroidism with measured serum concentrations of T4, T3, and TSH within the normal range. 

Liotrix (Euthroid, Thywlar) is a 4 1 mixture of levothyroxine sodium and liothyronine sodium. Like levothyroxine, liotrix is used for thyroid hormone replacement therapy in hypothyroid patients. Although the idea of combining T4 and T3 in replacement therapy so as to mimic the normal ratio secreted by the thyroid gland is not new, it does not appear that liotrix offers any therapeutic advantage over levothyroxine alone. 

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. 

A normal response is an increase in plasma TSH of 5 to 15 pU/mL above baseline. A response of less than 5 pU/mL above baseline is generally considered to be blunted (some laboratories consider a response below 7 pU/mL to be blunted) and may be consistent with a major depression. An abnormal test is found in approximately 25% of patients with depression. A blunted TSH response (especially in conjunction with an abnormal DST) may help in confirming the differential diagnosis of a major depressive episode and support continued antidepressant treatment. An increased baseline TSH or an augmented TSH response (higher than 30 pU/mL), in conjunction with other thyroid indices, might identify patients with hypothyroidism, mimicking a depressive disorder. These patients may benefit most from thyroid replacement therapy. 

In untreated women, the main risk factors for endometrial carcinoma are age, obesity, nulliparity, late menopause (and possibly early menarche), the Stein-Leventhal syndrome, exposure to exogenous estrogens, radiation, and certain systemic diseases, including diabetes mellitus, hypertension, hypothyroidism, and arthritis (SED-14, 1451) (88). Certain of these risk factors indicate that an altered endocrine state with increased estrogen stimulation is a predisposing cause, and one might thus in theory expect estrogen treatment (and notably hormonal replacement therapy) to increase the risk (SEDA-22, 466). 

Levothyroxine is used as replacement therapy in hypothyroidism and to suppress the production of thyro-trophin (thyroid-stimulating hormone) in patients with thyroid carcinoma. 

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). 

When replacement therapy is with levothyroxine only, the T4/T3 ratio is increased compared with healthy subjects, suggesting that thyroid secretion of T3 is physiologically important. Animal studies have shown that euthyroidism is not restored in all tissues by levothyroxine alone (13). Mood and neuropsychological function improved in hypothyroid patients when 50 micrograms of thyroxine was replaced by 12.5 micrograms of liothyr-onine (14). 

A 71-year-old woman who had undergone total thyroidectomy with subsequent irradiation because of follicular carcinoma 3 years before (22). Since then, she had taken oral levothyroxine 0.15 mg and 0.2 mg on alternate days. When latent hypothyroidism became evident despite replacement therapy, the dose of levothyroxine was increased to 0.3 mg/day. Three weeks later, she had formed an acute posterior myocardial infarction, although she had no previous history of coronary artery disease. Subsequent coronary arteriograms revealed no evidence of disease of the major vessels. Myocardial scintigraphy 3 weeks after infarction still showed a persistent perfusion defect. 

In subjects with treated hypothyroidism it has been reported that exogenous estrogen, given as hormone replacement therapy, can lead to increased thyroxine dosage requirements (78). 

Escobar-Morreale HF, Obregon MJ, Escobar del Rey F, Morreale de Escobar G. Replacement therapy for hypothyroidism with thyroxine alone does not ensure euthyroidism in all tissues, as studied in thyroidectomized rats. J Clin Invest 1995 96(6) 2828-38. 

El Kaissi S, Kotowicz MA, Berk M, Wall JR. Acute delirium in the setting of primary hypothyroidism the role of thyroid hormone replacement therapy. Thyroid 2005 15(9) 1099-101. 

The clinical manifestations of hyperthyroidism and hypothyroidism are listed in Table 31-2. From a pharmacotherapeutic standpoint, hyperthyroidism is treated with drugs that attenuate the synthesis and effects of thyroid hormones. Hypothyroidism is usually treated by thyroid hormone administration (replacement therapy). The general aspects and more common forms of hyperthyroidism and hypothyroidism are discussed here, along with the drugs used to resolve these primary forms of thyroid dysfunction. 

Escobar-Morreale HF, Botella-Carretero JI, Gomez-Bueno M, et al. Thyroid hormone replacement therapy in primary hypothyroidism a randomized trial comparing L-thyroxine plus liothyronine with L-thyroxine alone. Ann Intern Med. 2005 142 412-424. 

Although replacement therapy is basically limited to endocrine disorders, it still plays an important therapeutic role in clinical pharmacology. The number of people requiring replacement therapy for diabetes and hypothyroidism alone makes insulin and thyroid hormone among the most commonly prescribed drugs in the United States. For example, the drug Synthroid is taken daily by 8 million people to correct hypothyroidism, and its share of the market is worth 600 million per year. As more information is discovered about the role of other endogenous substances in the body, new examples of replacement therapy will occur. 

In the first year after treatment 20% of patients will become hypothyroid. After this 5% of patients become hypothyroid annually, perhaps because the capacity of thyroid cells to divide is permanently abolished so that cell renewal ceases. Patients must therefore be foUowed up indefinitely after radioiodine treatment, for most are likely to need treatment for hypothyroidism eventually. Because such followup over years may fail and because the onset of hypothyroidism may be insidious and not easily recongnised, some physicians prefer deliberately to render patients hypothyroid with the first dose and to educate them on the use of replacement therapy which is safe and effective. 

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. 

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