Complex relationship between free thyroxine and TSH in the regulation of thyroid function

Abstract

Objective: The present study re-evaluates the inverse log TSH-free thyroxine (fT 4 ) relationship, which has generally been assumed to characterize the thyroid pituitary hypothalamic feedback regulation in thyroid function. Design and Methods: The correlation between fT 4 and TSH was analyzed in two data sets from differing time periods involving 3223 and 6605 patients referred for thyroid testing, representing the whole range of thyroid functions from hypothyroidism to hyperthyroidism. Results: We found that the data do not support a linear log TSH-fT 4 relationship; instead, the correlation's gradient varies with thyroid function. As a consequence, an alternate model, based on the error function, was introduced. When directly comparing the models by means of curve fitting, using F-test and Akaike criteria, the alternate model results in a significantly better fit. The model was verified in the independent second set of data. Subgroup analysis of untreated patients added further proof to the non-linear model. Conclusions: We propose a refined non-linear model to describe the relationship between TSH and fT 4 . It implies that TSH response to a deviating fT 4 value may not be log-linear, but may be disproportionally related to the extent of the deviation from an optimum set point. A better understanding of the complex nature of the TSH-fT 4 relationship may further the development of more precise clinical models and aid in better defining subclinical states of thyroid dysfunction. Also, it may encourage other biological interrelations to be reconsidered in the wake of advanced measurement techniques and more powerful computerized statistical procedures.

Is pituitary TSH an adequate measure of thyroid hormone-controlled homoeostasis during thyroxine treatment?

“…This study extends an earlier publication where full details of methods were described (14). Data were obtained from a large number of unselected patients referred for thyroid testing to the Departments of Endocrinology or Nuclear Medicine of the Klinikum Ludenscheid, Germany, between October 2006 and January 2007.…”

Reply to: The TSH–free thyroxine relationship: logarithmic–linear or error function?

“…In this issue of the EJE, we publish a critical comment (1) on a previously published study by Hoermann et al (2). While the latter propose a complex relationship between thyroid hormones and TSH, Dr Leow (1) supports the classical logarithmic-linear relationship as described in another study also published here by Benhadi et al (3).…”

“…The conclusion is of a logarithmic-linear relationship observed in the group but not in individuals, presumably because of insufficient dose of thyroid hormones. In contrast, in the study by Hoermann et al (2) the population is much larger and more heterogeneous: more than 10 000 subjects, composed of patients aged between 18 and 100 years, some of them are free of treatment and some of them are on treatment with either thyroid hormones or on anti-thyroidal drugs (2). In this aspect, this work is more related to real life.…”

Diagnosis of Thyroid Disease: Principles and Problems

“…Thirdly, there is a log linear relationship between thyroxine and TSH, meaning that small changes in thyroxine will cause large changes in TSH (8). Recent data suggest that the relationship between TSH and thyroxine might be even more complex (9). However, it takes 6-12 weeks for pituitary TSH se cretion to reequilibrate to the new thyroid hormone status, when the thyroid status is changed (10).…”