Benefit of Combined Triiodothyronine (LT3) and Thyroxine (LT4) Treatment in Athyreotic Patients Unresponsive to LT4 Alone

Abstract

Despite some reports, the usefulness of levothyroxine (LT(4)) and levotriiodothyronine (LT(3)) combination therapy in hypothyroidism remains controversial. The objective of this paper is to study a benefit of additional LT(3) in athyreotic patients who failed to normalize TSH on LT(4) alone even with hyperthyroid serum T(4) values. In a survey of 200 athyreotic patients treated between 2006 and 2009, about 7% failed to normalize serum TSH levels following treatment with LT(4), though serum T(4) values in the hyperthyroid range were achieved. These patients (characterized by serum T(4)≥160 nmol/L and TSH≥5.0 mIU/L), were additionally treated with 10 μg b. i. d LT(3). LT(3) and LT(4) combination therapy resulted in decreased serum TSH levels into the normal range (12.8 vs. 1.22 mIU/L; p<0.01) and reduced LT(4) dose (153.3 vs. 117.5 μg; p<0.01) required for normalization of serum T(4) values (170.6 vs. 123.3 nmol/L; p<0.01). Serum T(3) values were higher (1.3 vs. 2.26 nmol/L; p<0.01) than those during monotherapy with LT(4). Our results indicate a subpopulation of athyreotic patients that could significantly benefit from combined LT(4) + LT(3) therapy in restoring normal TSH and thyroid hormone patterns. Further research should be undertaken to provide a genetic basis for these findings.

Homeostatic Control of the Thyroid–Pituitary Axis: Perspectives for Diagnosis and Treatment

“…Three remarkable phenomena have been observed in l -T4-treated patients, (1) a dissociation between FT3 and FT4, (2) a disjoint between TSH and FT3, and (3) an l -T4-related conversion inefficiency ( 121 , 123 ). Hence, l -T4 dose escalation may not invariably remedy T3 deficiency but could actually hinder its attainment ( 121 , 201 ). In addition to substrate inhibition and an inhibitory action of reverse T3 on the enzyme activity of deiodinase type 2, experimental studies in the rat elaborate on molecular details involving ubiquitination that may explain a lack of effect of increasing T4 dose in this condition ( 64 ).…”

Relational Stability in the Expression of Normality, Variation, and Control of Thyroid Function

“…While LT4 dose escalation or the use of liquid formulations effectively control elevated TSH levels in various conditions including gastric problems, intestinal malabsorption, or drug interference (103, 104), this situation is different, as low FT3 concentrations persist in these patients despite suppressed TSH levels and elevated FT4 concentrations (102). Apparently, a minority of patients on LT4 still fail to concomitantly raise their serum FT3 concentrations as the T4 excess itself impairs T3–T4 conversion (102, 105). The clinical relevance was recently confirmed as euthyroid TSH targets could not adequately raise resting energy expenditure (REE) adjusted for lean body mass in LT4-treated women, compared to healthy controls, only FT3 levels being positively correlated with REE (106).…”

Triiodothyronine alongside levothyroxine in the management of hypothyroidism?

“…Observational data from these patients suggested that the addition of T3 reduced TSH and FT4 and increased FT3. 57 Real world evidence is used increasingly by regulators and other clinical experts to evaluate the effects of therapeutic interventions in the routine clinical setting outside the restrictions of randomised clinical trials. Such studies are inherently prone to bias, however, and their results should be interpreted with caution.…”