Combined therapy with L-Thyroxine and L-Triiodothyronine compared to L-Thyroxine alone in the treatment of primary hypothyroidism

Fadeyev, V V; Моргунова, Т. Б.; Мельниченко, Г. А.; Дедов, И И

doi:10.14310/horm.2002.1274

Cited by 66 publications

(66 citation statements)

References 20 publications

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“…Such peripheral tissue function tests have been used to evaluate whether T4 + T3 therapy and T4 monotherapy differ in their effects on target tissues. In one study, in which patients were randomized already when primary hypothyroidism was diagnosed, T4 + T3 combination therapy not only resulted in more favorable changes in serum cholesterol but also in higher activation of bone resorption compared to T4 monotherapy; TSH was similar in both groups (25). Two other RCTs observed likewise a slightly better profile in some tests during treatment with T4 + T3 therapy or desiccated thyroid extract (Armour) compared to T4 monotherapy despite similar TSH values; the differences between groups in SHBG, PINP, NT-proBNp, cholesterol were however small and not always significant (26,27).…”

Section: Introductionmentioning

confidence: 99%

THERAPY OF ENDOCRINE DISEASE: T4 + T3 combination therapy: is there a true effect?

Wiersinga

2017

European Journal of Endocrinology

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About 5%-10% of hypothyroid patients on T4 replacement therapy have persistent symptoms, despite normal TSH levels. It was hoped that T4 + T3 combination therapy might provide better outcomes, but that was not observed according to a meta-analysis of 11 randomized clinical trials comparing T4 monotherapy with T4 + T3 combination therapy. However, the issue is still subject of much research because normal thyroid function tests in serum may not necessarily indicate an euthyroid state in all peripheral tissues. This review evaluates recent developments in the field of T4 + T3 combination therapy. T4 monotherapy is associated with higher serum FT4 levels than in healthy subjects, and subnormal serum FT3 and FT3/FT4 ratios are observed in about 15% and 30% respectively. T4 + T3 combination therapy may mimic more closely thyroid function tests of healthy subjects, but it has not been demonstrated that relatively low serum FT3 or FT3/FT4 ratios are linked to persistent symptoms. One study reports polymorphism Thr92Ala in DIO2 is related to lower serum FT3 levels after thyroidectomy, and that the D2-Ala mutant reduces T4 to T3 conversion in cell cultures. Peripheral tissue function tests such as serum cholesterol reflect thyroid hormone action in target tissues. Using such biochemical markers, patients who had a normal serum TSH during postoperative T4 monotherapy, were mildly hypothyroid, whereas those with a TSH 0.03-≤0.3 mU/L were closest to euthyroidism. Peripheral tissue function tests suggest euthyroidism more often in patients randomized to T4 + T3 rather than that to T4. Preference for T4 + T3 combination over T4 monotherapy was dose-dependently related to the presence of two polymorphisms in MCT10 and DIO2 in one small study. It is not known if persistent symptoms during T4 monotherapy disappear by switching to T4 + T3 combination therapy. The number of patients on T4 + T3 therapy has multiplied in the last decade, likely induced by indiscriminate statements on the internet. Patients are sometimes not just asking but rather demanding this treatment modality. It creates tensions between patients and physicians. Only continued research will answer the question whether or not T4 + T3 combination therapy has true benefits in some patients.

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Section: Introductionmentioning

confidence: 99%

THERAPY OF ENDOCRINE DISEASE: T4 + T3 combination therapy: is there a true effect?

Wiersinga

2017

European Journal of Endocrinology

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“…Indeed 80% of T4 is de-iodinated to provide 90% of the free T3 needed by tissues. Thus the management of hypothyroidism has been focused on T4 replacement [13].…”

Section: Thyroid Hormone Secretionmentioning

confidence: 99%

“…Standard treatment of hypothyroidism is with levothyroxine [13]. This is normally taken in the morning 30 min before breakfast to prevent malabsorption that may occur if taken with food [14].…”

Section: Treatmentmentioning

confidence: 99%

“…Several studies have claimed that combination therapy has a more positive effect on depression, anxiety and quality of life than levothyroxine therapy alone [29,30]. Other studies have noted a reduction in total cholesterol and LDL cholesterol [13].…”

Section: Clinical Evidence On Combination Therapy With Liothyronine Amentioning

confidence: 99%

“…It has however, been suggested that studies of levothyroxine and liothyronine combinations were not adequately powered to detect and evaluate changes in psychological well-being [37], and that the review may have compared studies with different patient groups and outcomes [13]. Larger controlled studies may therefore be required to fully understand the benefit of liothyronine in combination with levothyroxine.…”

Section: Clinical Evidence On Combination Therapy With Liothyronine Amentioning

confidence: 99%

See 2 more Smart Citations

Thyroid Replacement Therapy: The Hidden Challenges

Rahim

2013

J Endocrinol Metab

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Hypothyroidism has a gradual onset and non-specific symptoms, which might be subtle, and which might therefore be ignored or misdiagnosed. Subclinical hypothyroidism is a well-established phenomenon where a patient does not have thyroid symptoms, but shows biochemical evidences of hypothyroidism. However, diagnosis and treatment of these patients may prevent development of overt hypothyroidism and cardiovascular symptoms. Replacement therapy with levothyroxine (T4) is the treatment of choice for hypothyroidism; levothyroxine is taken daily, provides stable plasma levels and is suitable for the majority of patients. Patients with certain forms of hypothyroidism -central hypothyroidism, thyroidectomy patients and patients with "low T3 syndrome" -may benefit from treatment with liothyronine (T3), which is more potent and has a shorter onset of action. The use of liothyronine in combination with levothyroxine is controversial, but there is evidence that some patients, particularly those with deiodinase 2 and thyroid hormone transporter expression polymorphisms, may benefit from combination therapy.

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Modalities of Thyroid Hormone Administration and Correlates Between Blood and Tissue Levels

Celi

2020

Thyroid and Heart

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Combined therapy with L-Thyroxine and L-Triiodothyronine compared to L-Thyroxine alone in the treatment of primary hypothyroidism

Cited by 66 publications

References 20 publications

THERAPY OF ENDOCRINE DISEASE: T4 + T3 combination therapy: is there a true effect?

THERAPY OF ENDOCRINE DISEASE: T4 + T3 combination therapy: is there a true effect?

Thyroid Replacement Therapy: The Hidden Challenges

Modalities of Thyroid Hormone Administration and Correlates Between Blood and Tissue Levels

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