Restoration of euthyroidism with levothyroxine: implications of etiology of hypothyroidism and the degree of residual endogenous thyroid function

Abstract

There are many thyroid-related factors that combine with non-thyroid-related factors in order to affect the patient response to treatment of hypothyroidism, in terms of their satisfaction with therapy. Some of the thyroid-derived factors include the etiology of the hypothyroidism and the amount of residual thyroid function that the patient retains. These two factors may be intertwined and affected by a third influence, the presence of thyroid peroxidase antibodies. The downstream consequences of the interactions between these three factors may influence both free thyroxine and free triiodothyronine levels, TSH concentrations, and various thyroid biomarkers. Evidence of the widespread importance of thyroid hormones can be inferred from the multiple genes that are regulated, with their regulation affecting multiple serum biomarkers. Thyroid biomarkers may extend from various well-known serum markers such as lipids and sex hormone-binding globulin to serum levels of thyroid hormone metabolites. Moreover, the interplay between thyroid hormones and biomarkers and their relative ratios may be different depending on the hypothyroidism etiology and degree of residual thyroid function. The ultimate significance of these relationships and their effect on determining patient-reported outcomes, quality of life, and patient satisfaction is, as yet, poorly understood. However, identification of better biomarkers of thyroid function would advance the field. These biomarkers could be studied and correlated with patient-reported outcomes in future prospective studies comparing the impact of various thyroid hormone therapies.

Keywords: biomarkers; etiology; patient satisfaction; quality of life; residual thyroid function; thyroid hormones.

Figure 1

(A) Potential explanations offered for impaired quality of life despite treatment of hypothyroidism that may be thyroid-related. (B) Potential explanations offered for impaired quality of life despite treatment of hypothyroidism that may be thyroid-unrelated.

Figure 2

Hypothetical interaction between residual thyroid function and etiology of hypothyroidism.

Figure 3

Predicted steady state serum T3, T4, and TSH concentrations versus residual thyroid function (RTF) values. Untreated obese, normal and underweight patients were simulated for 50 days. The final steady state T3, T4, and TSH simulation values are shown on the abscissa for each RTF value on the ordinate axis, separated into female (left hand side) and male (right hand side) plots. (From Cruz-Loya et al., Ref 45).