Combined Thyroxine and Triiodothyronine for Thyroid Replacement Therapy

Taylor, Selwyn; Kapur, M. M.; Adie, Ross

doi:10.1136/bmj.2.5704.270

Cited by 38 publications

(23 citation statements)

References 4 publications

(2 reference statements)

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“…Repeat estimations of serum T-3 after a longer period on T-4 might, therefore, show normal serum T-3 concentrations in all these subjects-and some preliminary studies suggest that this may well be the case. It is clear, in any event, that replacement with T-3 is not required, nor is there anything to recommend replacement with tablets containing mixtures of T-4 and T-3 as has been previously suggested (Taylor et al, 1970). It is also clear that a raised P.B.I.…”

Section: Discussionmentioning

confidence: 93%

Treatment of Hypothyroidism: A Reappraisal of Thyroxine Therapy

Evered¹,

Young²,

Ormston³

et al. 1973

BMJ

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SummaryTwenty-two subjects with hypothyroidism have been studied in detail before and during replacement therapy with L-thyroxine (T4). All subjects were stabilized on the minimum dose of T-4 which was necessary to suppress their serum thyroid-stimulating hormone (TSH) concentration to normal, and on this dose most subjects had a normal or impaired TSH response to thyrotrophinreleasing hormone (TRH). The daily dose of T-4 required to suppress TSH was 01 mg (13 subjects), 015 mg (six subjects), and 0 2 mg (three subjects). It was shown that all subjects were euthyroid on these doses and, using a range of thyroid function tests, that they were normal in all respects when compared with a group of euthyroid controls, with the exception of a smaIl group who had a marginally raised serum triiodo-L-thyronine (T-3) concentration. It has been shown that those subjects who required the larger doses of T-4 had a more advanced degree of thyroid failure than those who were stabilized on 0 1 mg T-4 daily. It is concluded that conventional doses of T-4 (0 2-0 4 mg daily) are often associated with subclinical hyperthyroidism.

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Section: Discussionmentioning

confidence: 93%

Treatment of Hypothyroidism: A Reappraisal of Thyroxine Therapy

Evered¹,

Young²,

Ormston³

et al. 1973

BMJ

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“…6 However, we now understand that ~12% of all patients treated with levothyroxine are biochemically euthyroid (that is, they have normal serum levels of TSH) but continue to experience residual symptoms of hypothyroidism, including psychological 7–9 and metabolic effects. 10,11 This finding represents a major public-health concern given the high prevalence of hypothyroidism and the fact that not all parameters are restored by levothyroxine monotherapy.…”

Section: Introductionmentioning

confidence: 99%

Scope and limitations of iodothyronine deiodinases in hypothyroidism

et al. 2015

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The coordinated expression and activity of the iodothyronine deiodinases regulate thyroid hormone levels in hypothyroidism. Once heralded as the pathway underpinning adequate thyroid-hormone replacement therapy with levothyroxine, the role of these enzymes has come into question as they have been implicated in both an inability to normalize serum levels of tri-iodothyronine (T3) and the incomplete resolution of hypothyroid symptoms. These observations, some of which were validated in animal models of levothyroxine monotherapy, challenge the paradigm that tissue levels of T3 and thyroid-hormone signalling can be fully restored by administration of levothyroxine alone. The low serum levels of T3 observed among patients receiving levothyroxine monotherapy occur as a consequence of type 2 iodothyronine deiodinase (DIO2) in the hypothalamus being fairly insensitive to ubiquitination. In addition, residual symptoms of hypothyroidism have been linked to a prevalent polymorphism in the DIO2 gene that might be a risk factor for neurodegenerative disease. Here, we discuss how these novel findings underscore the clinical importance of iodothyronine deiodinases in hypothyroidism and how an improved understanding of these enzymes might translate to therapeutic advances in the care of millions of patients with this condition.

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“…It has been suggested that the addition of T 3 to T 4 replacement therapy may improve mood, cognitive function, and general sense of well-being (11)(12)(13)(14)(15). Furthermore, T 3 has been reported to augment the effect of antidepressant treatment in depressed patients who are already receiving levothyroxine replacement therapy (16,17).…”

mentioning

confidence: 98%

Does a Combination Regimen of Thyroxine (T₄) and 3,5,3′-Triiodothyronine Improve Depressive Symptoms Better Than T₄Alone in Patients with Hypothyroidism? Results of a Double-Blind, Randomized, Controlled Trial

Sawka

Gerstein

Marriott

et al. 2003

The Journal of Clinical Endocrinology & Metabolism

152

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Some hypothyroid patients receiving levothyroxine replacement therapy complain of depressive symptoms despite normal TSH measurements. It is not known whether adding T(3) can reverse such symptoms. We randomized 40 individuals with depressive symptoms who were taking a stable dose of levothyroxine for treatment of hypothyroidism (excluding those who underwent thyroidectomy or radioactive iodine ablation of the thyroid) to receive T(4) plus placebo or the combination of T(4) plus T(3) in a double-blind manner for 15 wk. Participants receiving combination therapy had their prestudy dose of T(4) dropped by 50%, and T(3) was started at a dose of 12.5 micro g, twice daily. T(4) and T(3) doses were adjusted to keep goal TSH concentrations within the normal range. Compared with the group taking T(4) alone, the group taking both T(4) plus T(3) did not report any improvement in self-rated mood and well-being scores that included all subscales of the Symptom Check-List-90, the Comprehensive Epidemiological Screen for Depression, and the Multiple Outcome Study (P > 0.05 for all indexes). In conclusion, the current data do not support the routine use of combined T(3) and T(4) therapy in hypothyroid patients with depressive symptoms.

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Combined Thyroxine and Triiodothyronine for Thyroid Replacement Therapy

Cited by 38 publications

References 4 publications

Treatment of Hypothyroidism: A Reappraisal of Thyroxine Therapy

Treatment of Hypothyroidism: A Reappraisal of Thyroxine Therapy

Scope and limitations of iodothyronine deiodinases in hypothyroidism

Does a Combination Regimen of Thyroxine (T₄) and 3,5,3′-Triiodothyronine Improve Depressive Symptoms Better Than T₄Alone in Patients with Hypothyroidism? Results of a Double-Blind, Randomized, Controlled Trial

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Combined Thyroxine and Triiodothyronine for Thyroid Replacement Therapy

Cited by 38 publications

References 4 publications

Treatment of Hypothyroidism: A Reappraisal of Thyroxine Therapy

Treatment of Hypothyroidism: A Reappraisal of Thyroxine Therapy

Scope and limitations of iodothyronine deiodinases in hypothyroidism

Does a Combination Regimen of Thyroxine (T4) and 3,5,3′-Triiodothyronine Improve Depressive Symptoms Better Than T4Alone in Patients with Hypothyroidism? Results of a Double-Blind, Randomized, Controlled Trial

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Does a Combination Regimen of Thyroxine (T₄) and 3,5,3′-Triiodothyronine Improve Depressive Symptoms Better Than T₄Alone in Patients with Hypothyroidism? Results of a Double-Blind, Randomized, Controlled Trial