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.

Quality of life, daily functioning, and symptoms in hypothyroid patients on thyroid replacement therapy: A Dutch survey

“…Low serum FT3 levels and low FT3/FT4 ratios with LT4 treatment would suggest tissue hypothyroidism, which could - at least in part - explain persisting hypothyroid symptoms and would contradict the hypothesis that local deiodinases always convert T4 into sufficient T3 levels [30] , [45] . Several authors believe that, although LT4 replacement restores (hypothalamic) TSH concentrations, it may in fact not fully restore euthyroidism at the tissue or receptor level [30] , [41] , [46] , [47] , [48] , [49] . Our data might fit with this ‘low T3 ' hypothesis to explain persisting symptoms, since low serum FT3 concentrations were reported concurrent with low FT3/FT4 ratios.…”

Thyroid disorders and gastrointestinal dysmotility: an old association

“…Other studies observed delayed gastric emptying ( Pfaffenbach et al, 1997 ; Gharahbaghian et al, 2007 ). Euthyroidism restoration results in slightly increased gastric emptying rate ( Jonklaas, 2022 ). Hyperthyroidism treatment may improve abnormal myoelectrical activity and GI symptoms ( Gunsar et al, 2003 ).…”

“…Data indicate that L-thyroxine therapy can improve the symptoms of gastric dysmotility that are apparent in the subclinical hypothyroidism (SCH) state. Hypothyroid patients are routinely treated worldwide with levothyroxine sodium monotherapy in replacement mode ( Jonklaas, 2022 ). There has been strong suggestion for an individually tailored dose ( Yin and Chen, 2013 ).…”

“…There has been strong suggestion for an individually tailored dose ( Yin and Chen, 2013 ). Unfortunately, a high number of patients do not respond clinically or biochemically to thyroxine and only a large thyroxine dose is required to get the optimum concentration of serum TSH ( Jonklaas, 2022 ). Also, suboptimal treatments for longer period adversely affect body homeostasis ( Ettleson et al, 2022 ).…”

Impaired autonomic function and somatosensory disturbance in patients with treated autoimmune thyroiditis

“…This enigmatic condition, also referred to as “syndrome T” 5 , 8 or “syndrome of residual symptoms of hypothyroidism on T4” (SORSHOT) 9 affects about 0.5% of the inhabitants of developed countries 2 . A plethora of possible underlying mechanisms have been suggested, including psychological factors, the presence of other autoimmunity diseases, thyroid autoimmunity, insufficient dosage, hysteresis effects, the modality of therapy with levothyroxine (potentially resulting in abnormal T3 generation) and polymorphic variants of deiodinase genes 2 , 10 – 12 .…”