Hypothyroidism Resources

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Thyroid Research Studies

The results speak for themselves.

Desiccated Thyroid Extract Compared With Levothyroxine in the Treatment of Hypothyroidism: A Randomized, Double-Blind, Crossover Study

In a double blind study published in The Journal of Clinical Endocrinology & Metabolism, almost half (48.6%) the participants preferred desiccated thyroid extract (DTE), or natural thyroid hormones, over levothyroxine (L-T4), which is a synthetic hormone. Those that preferred the natural treatment felt a significant improvement in their hypothyroid symptoms and lost an average of four pounds.1

Conclusion

DTE therapy did not result in a significant improvement in quality of life; however, DTE caused modest weight loss and nearly half (48.6%) of the study patients expressed preference for DTE over l-T4. DTE therapy may be relevant for some hypothyroid patients.

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Levothyroxine Monotherapy Cannot Guarantee Euthyroidism in All Athyreotic Patients

FT4 levels were significantly higher and FT3 levels were significantly lower (p<0.001 in both cases) in levothyroxine-treated athyreotic patients than in matched euthyroid controls. Among the levothyroxine-treated patients 15.2% had lower serum FT3 and 7.2% had higher serum FT4 compared to euthyroid controls. A wide range of FT3/FT4 ratios indicated a major heterogeneity in the peripheral T3 production capacity in different individuals. The correlation between thyroid hormones and serum TSH levels indicated an abnormal feedback mechanism in levothyroxine-treated patients.2

Conclusion

Athyreotic patients have a highly heterogeneous T3 production capacity from orally administered levothyroxine. More than 20% of these patients, despite normal TSH levels, do not maintain FT3 or FT4 values in the reference range, reflecting the inadequacy of peripheral deiodination to compensate for the absent T3 secretion. The long-term effects of chronic tissue exposure to abnormal T3/T4 ratio are unknown but a sensitive marker of target organ response to thyroid hormones (serum TSH) suggests that this condition causes an abnormal pituitary response. A more physiological treatment than levothyroxine monotherapy may be required in some hypothyroid patients.

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Differences in hypothalamic type 2 deiodinase ubiquitination explain localized sensitivity to thyroxine

Normalization of serum TSH with L-T4 monotherapy results in relatively low serum 3,5,3′-triiodothyronine (T3) and high serum thyroxine/T3 (T4/T3) ratio.3

Conclusion

In conclusion, the present studies revealed that D2 ubiquitination is not universal in all tissues and that an inability of the hypothalamus to drive D2 ubiquitination is a pivotal element in the TRH/TSH negative-feedback regulation. This allows circulating thyroid hormone to function as a regulatory signal for hypophysiotropic TRH, and perhaps also for the control of appetite/satiety centers in the hypothalamus. Even in tissues where D2 is ubiquitinated and inactivated by exposure to T4, dependence on WSB-1 is not universal as well. Avoiding a higher serum T4/T3 ratio through chronic combination therapy with L-T4 and L-T3 through slow-release subcutaneous pellets was key to normalize thyroid hormone–dependent biological parameters in the brain, liver, and skeletal muscle.

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Maternal Thyroid Deficiency during Pregnancy and Subsequent Neuropsychological Development of the Child

A study on hypothyroid pregnant women who took thyroid medication compared to hypothyroid women who didn't. Those women who took thyroid medication had children with higher IQ scores when the children were tested at ages 7-9.4

Conclusion

We conclude that systematic screening for hypothyroidism early in pregnancy may be worthwhile, even when the degree of deficiency is mild and does not cause immediate clinical manifestations in the woman. If routine screening were to be introduced, the most conservative policy would be to perform testing at the first prenatal visit, preferably in the first trimester. Follow-up of women with positive screening results would need to be prompt, so that treatment could begin quickly.

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Effects of Thyroxine as Compared with Thyroxine plus Triiodothyronine in Patients with Hypothyroidism

A study that looks at mood and depression. The patients on both T4 and T3 medication reported more energy, improved concentration and overall felt better.5

Conclusion

We conclude that in patients with hypothyroidism, partial substitution of triiodothyronine for thyroxine may have more salutary effects on the brain and perhaps other tissues than those of an equivalent amount of thyroxine, as determined by their effects on thyrotropin secretion. This finding suggests that thyroidal secretion of triiodothyronine is physiologically important.

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Effect of combination therapy with thyroxine (T4) and 3,5,3′-triiodothyronine versus T4 monotherapy in patients with hypothyroidism, a double-blind, randomised cross-over study

50% of the patients preferred the T4/T3 combo. Only 15% preferred T4 alone. Patients on T4/T3 combo reported improved quality of life. T4/T3 had no more side effect than T4 alone. This study reported that the T4 only caused more side effects that the T4/T3 combo.6

Conclusion

In a study design, where morning TSH levels were unaltered between groups combination therapy, (treated with T3 20 μg once daily) was superior to monotherapy by evaluating several QOL, depression and anxiety rating scales as well as patients own preference.

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Sources:

1. Thanh D. Hoang, Cara H. Olsen, Vinh Q. Mai, Patrick W. Clyde, Mohamed K. M. Shakir; Desiccated Thyroid Extract Compared With Levothyroxine in the Treatment of Hypothyroidism: A Randomized, Double-Blind, Crossover Study. J Clin Endocrinol Metab 2013; 98 (5): 1982-1990. doi: 10.1210/jc.2012-4107

2. Gullo D, Latina A, Frasca F, Le Moli R, Pellegriti G, Vigneri R. Levothyroxine Monotherapy Cannot Guarantee Euthyroidism in All Athyreotic Patients. Ludgate M, ed. PLoS ONE. 2011;6(8):e22552. doi:10.1371/journal.pone.0022552.

3. Werneck de Castro JP, Fonseca TL, Ueta CB, et al. Differences in hypothalamic type 2 deiodinase ubiquitination explain localized sensitivity to thyroxine. The Journal of Clinical Investigation. 2015;125(2):769-781. doi:10.1172/JCI77588.

4. Haddow, James E., Glenn E. Palomaki, Walter C. Allan, Josephine R. Williams, George J. Knight, June Gagnon, Cheryl E. O'heir, Marvin L. Mitchell, Rosalie J. Hermos, Susan E. Waisbren, James D. Faix, and Robert Z. Klein. "Maternal Thyroid Deficiency during Pregnancy and Subsequent Neuropsychological Development of the Child." New England Journal of Medicine 341.8 (1999): 549-55.

5. Bunevicius, Robertas, Gintautas Kazanavicius, Rimas Zalinkevicius, and Arthur J. Prange. "Effects of Thyroxine as Compared with Thyroxine plus Triiodothyronine in Patients with Hypothyroidism." New England Journal of Medicine 340.6 (1999): 424-29.

6. Nygaard B, Jensen EW, Kvetny J, Jarlov A, Faber J. Effect of combination therapy with thyroxine (T4) and 3,5,3′-triiodothyronine versus T4 monotherapy in patients with hypothyroidism, a double-blind, randomised cross-over study. Eur J Endocrinol. 2009;161:895-902. doi:10.1530/EJE-09-0542.