Thyroxine replacement therapy

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. 

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). 

Monitoring of thyroxine replacement therapy is done by clinical signs and symptoms and by measuring the TSH (elevated for underreplacement) and free T4 (below normal for underreplacement). 

Franklyn, J.A., Daykin, J., Betteridge, J., Hughes, E.A., Holder, R., Jones, S.R. and Sheppard, M.C. (1993) Thyroxine replacement therapy and circulating lipid concentrations. Clinical Endocrinology, 38, 453-4-59. 

Disorders of the thyroid gland are relatively common and can be due to either hyper-or hyposecretion of thyroid hormone. Hypersecretion is treated by surgery or with car-bamazepine or radioactive iodine. Hyposecretion is managed with thyroxine replacement therapy. 

We found that, in patients who had been receiving the same dose of thyroxine for at least 6 months, abnormalities in plasma B ALT, and GGT were more commonly found in patients who had an undetectable TSH than in patients with a normal or raised plasma TSH (G8). If the dose of T4 was reduced in the patients with undetectable TSH to a dose that normalized plasma TSH, the plasma levels of ALT and B, fell to within the reference range in practically all patients (G9). These data led us to suggest that the aim of thyroxine replacement therapy should be to normalize plasma TSH as it appeared that the thyrotrophic response to exogenous T4 was representative of the thyroid status of other tissues in the body. 

G9. Gow, S. M., Caldwell, G., Toft, A. D., Sweeting, V. M., and Beckett, G. J., Restoration of normal thyrotrophin secretion reduces the abnormally high glutathione S-transferase levels found in patients receiving thyroxine replacement therapy. Clin. Endocrinol. (Oxford) 29, 249-256 (1988). 

Hashimoto s and other thyroiditis causing hypothyroidism rarely cause goiter, as they are usually associated with atrophy of the thyroid gland. Nonetheless, goiters in these situations should be treated with thyroxine- replacement therapy. The replacement dose of thyroxine is lower in the elderly than in younger patients, and titration should also be slow in the elderly to avoid cardiac toxicity. Patients also require thyroxine therapy following surgical thyroidectomy or radioiodine ablation, to suppress serum TSH to below normal or undetectable levels to reduce the... 

Goiters associated with hypothyroidism can be regressed with thyroxine replacement therapy. Low doses of thyroxine should be used first and titrated in the elderly to avoid cardiac toxicity. 

As stated above, MRS provides a noninvasive diagnostic tool for the biochemical characterization of pathophysiological processes in the brain. Therefore, in a recent study by Akinci et al. (2006), MRS was used to detect the changes in brain metabolites of neonates with hypothyroidism, born to mothers living in iodine-deficient areas before and after thyroxine replacement therapy. 

Iodine is readily absorbed when PVP-I is applied to the skin of a newborn infant, because of high cutaneous permeability, and neonates are very sensitive to iodine overload, as described previously. Topical PVP-I therapy is associated with a significant risk of hypothyroidism in neonates, especially very-low-weight babies (Smerdely et ai, 1989). Many cases of hypothyroidism induced by topical use of PVP-I have been reported in newborn infants, mainly from iodine-deficient regions (Markou et ai, 2001). However, a case of severe hypothyroidism in a neonate was also reported from North America, an iodine-sufficient region (Khashu et al. 2005). A premature infant developed severe hypothyroidism that required L-thyroxine replacement therapy after application of PVP-I for 20 days. 

The only effective treatment is replacement therapy with thyroid hormones. Levothyroxine, a synthetic levoisomer of thyroxine (T4), is the drug of choice since it is stable, relatively inexpensive, free of antigenicity, and of uniform potency. It results in a pool of thyroid hormone that is rapidly converted into the more potent T3. Levothyroxine can be administered orally or... 

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). 

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. 

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. 

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 liothyronine is three to four times more potent than levothyroxine, it is not recommended for routine replacement therapy because of its shorter half-life (24 hours), which requires multiple daily doses its higher cost and the greater difficulty of monitoring its adequacy of replacement by conventional laboratory tests. Furthermore, because of its greater hormone activity and consequent greater risk of cardiotoxicity, T3 should be avoided in patients with cardiac disease. It is best used for short-term suppression of TSH. Because oral administration of T3 is unnecessary, use of the more expensive mixture of thyroxine and liothyronine (liotrix) instead of levothyroxine is never required. 

Bilberry extract 200 mg/(kg day) administered intraperitoneally to euthyroid rats increased radiolabeled triiodothyronine (T3) transport into the brain, compared to vehicle only (21). Postulated mechanisms include central or peripheral inhibition of L-thyroxine s (T4) deiodination to T3 inhibition of T3 protein binding or enhanced T3 binding to carrier proteins in the brain capillary wall (21). Whether bilberry could interact with thyroid replacement therapy remains to be seen. 

This patient has a high serum T j because the oestrogen component of hormone replacement therapy stimulates the synthesis of thyroxine-binding globulin. Thus, to maintain a normal level of the physiologically active Free T the total serum T, needs to be increased. 

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