TSH Concentration by Itself Does not Reflect Successful Treatment

Letters to the Editor regarding the article Over- and Undertreatment With Levothyroxine Findings of the Population-Based Rhineland Study by Nersi Alaeddin, Dr. Rutchanna M.S. Jongejan, and Prof. Dr. med. Julia C. Stingl, et al. in issue 42/2023

We read the results of the Population-Based Rhineland Study (1) of thyroxine (T4) treatment with great interest. The authors reported on almost 3000 participants, of whom 23% received T4 treatment. Comparison with the resultant TSH concentrations showed a high proportion of improper treatment, with 18% categorized as overtreated. We agree with the authors that this result is striking and unsatisfactory. The same applies, however, for the selected criterion for classifying treatment success, since the TSH concentration does not necessarily reflect successful treatment.

A substantial proportion—5–10% of patients having substitution treatment—complain of a sustained low quality of life on monotherapy with T4, in spite of reaching TSH reference values (2). Genetic variability in the genes for thyroid hormone transporters, receptors, and selenium dependent deiodinases, which control the metabolism of T4 and T3, are considered as potential causes (3). Negative feedback regulation of TSH, for example, is dominated primarily by the beta-isoform of the thyroid hormone receptor, whereas many peripheral organs depend on the alpha-isoform. Further to genetic variability, thyroid hormone resistance has been described in patients with chronic fatigues syndrome, which can be explained by autoimmunity against the selenium transporter and impairs the deiodination of T4 in the target organs (4).

In this setting too, the deficiency was not reflected in the TSH concentrations, which underlines that, in order to assess the success of any substitution, additional variables need to be measured, such as quality of life and alternative biomarkers for the effect of thyroid hormone. We therefore agree with the authors that overtreatment should be avoided, but TSH as the only parameter is not sufficient to classify the success of T4 substitution. This is a relevant limitation of the study, which should be mentioned and borne in mind.

DOI: 10.3238/arztebl.m2024.0012

Prof. Dr. rer. nat. Lutz Schomburg

Institut für Experimentelle Endokrinologie

Max Rubner Center (MRC) für kardiovaskuläre metabolische

renale Forschung

Charité-Universitätsmedizin Berlin

Dr. med. Helena Orfanos-Boeckel

Praxis für ganzheitliche Innere Medizin

Stoffwechselmedizin und Präventivmedizin

10629 Berlin

Conflict of interest statement

LS is in receipt of funding from the German Research Foundation (DFG); special research area CRC/TR 296 “Local control of TH action” (LocoTact, P17).

HOB declares that no conflict of interest exists.

References

1. Alaeddin N, Jongejan RMS, Stingl JC, et al.: Over- and undertreatment with levothyroxine—findings of the population-based Rhineland Study. Dtsch Arztebl Int 2023; 120: 711–8

2. Wiersinga WM: Paradigm shifts in thyroid hormone replacement therapies for hypothyroidism. Nat Rev Endocrinol 2014; 10: 164–74

3. Penna GC, Salas-Lucia F, Ribeiro MO, Bianco AC: Gene polymorphisms and thyroid hormone signaling: implication for the treatment of hypothyroidism. Endocrine 2023; doi: 10.1007/s12020–023–03528-y. Online ahead of print

4. Sun Q, Oltra E, Dijck-Brouwer DAJ, et al.: Autoantibodies to selenoprotein P in chronic fatigue syndrome suggest selenium transport impairment and acquired resistance to thyroid hormone. Redox Biol 2023; 65: 102796