CONTEXT: The relationship between TSH and T₄ is thought to be inverse log-linear, but recent studies have challenged this. There are limited data regarding age and sex differences in the TSH-T₄ relationship. OBJECTIVE: The purpose of this study was to evaluate the TSH-free T₄ relationship in a large sample. METHODS: In a cross-sectional, retrospective study, we analyzed TSH and free T₄ results from 152 261 subjects collected over 12 years by a single laboratory. For each free T₄ value (in picomoles per liter), the median TSH was calculated and analyzed by sex and age (in 20-year bands). RESULTS: The relationship between log TSH and free T₄ was nonlinear. Mathematical modeling confirmed that it was described by 2 sigmoid curves with inflexion points at free T₄ concentrations of 7 and 21 pmol/L. For free T₄ within the reference range (10-20 pmol/L), median TSH was higher in men than in women (P < .001) and increased across age bands with the highest values in those 80 years and older (P < .001). In contrast, in overt hypothyroidism (n = 4403), TSH was lower in older age groups than in those aged 20-39 years (P < .001). CONCLUSIONS: The TSH-free T₄ relationship is not inverse log-linear but can be described by 2 overlapping negative sigmoid curves. At physiological free T₄ concentrations, TSH is higher in men and in older people, whereas the TSH response to hypothyroidism is more robust in younger people. These results advance understanding of the TSH-free T₄ relationship, which is central to thyroid pathophysiology and laboratory diagnosis of thyroid disease.
CONTEXT: The relationship between TSH and T₄ is thought to be inverse log-linear, but recent studies have challenged this. There are limited data regarding age and sex differences in the TSH-T₄ relationship. OBJECTIVE: The purpose of this study was to evaluate the TSH-free T₄ relationship in a large sample. METHODS: In a cross-sectional, retrospective study, we analyzed TSH and free T₄ results from 152 261 subjects collected over 12 years by a single laboratory. For each free T₄ value (in picomoles per liter), the median TSH was calculated and analyzed by sex and age (in 20-year bands). RESULTS: The relationship between log TSH and free T₄ was nonlinear. Mathematical modeling confirmed that it was described by 2 sigmoid curves with inflexion points at free T₄ concentrations of 7 and 21 pmol/L. For free T₄ within the reference range (10-20 pmol/L), median TSH was higher in men than in women (P < .001) and increased across age bands with the highest values in those 80 years and older (P < .001). In contrast, in overt hypothyroidism (n = 4403), TSH was lower in older age groups than in those aged 20-39 years (P < .001). CONCLUSIONS: The TSH-free T₄ relationship is not inverse log-linear but can be described by 2 overlapping negative sigmoid curves. At physiological free T₄ concentrations, TSH is higher in men and in older people, whereas the TSH response to hypothyroidism is more robust in younger people. These results advance understanding of the TSH-free T₄ relationship, which is central to thyroid pathophysiology and laboratory diagnosis of thyroid disease.
Authors: Jacqueline Jonklaas; Antonio C Bianco; Andrew J Bauer; Kenneth D Burman; Anne R Cappola; Francesco S Celi; David S Cooper; Brian W Kim; Robin P Peeters; M Sara Rosenthal; Anna M Sawka Journal: Thyroid Date: 2014-12 Impact factor: 6.568
Authors: Christine Baumgartner; Bruno R da Costa; Tinh-Hai Collet; Martin Feller; Carmen Floriani; Douglas C Bauer; Anne R Cappola; Susan R Heckbert; Graziano Ceresini; Jacobijn Gussekloo; Wendy P J den Elzen; Robin P Peeters; Robert Luben; Henry Völzke; Marcus Dörr; John P Walsh; Alexandra Bremner; Massimo Iacoviello; Peter Macfarlane; Jan Heeringa; David J Stott; Rudi G J Westendorp; Kay-Tee Khaw; Jared W Magnani; Drahomir Aujesky; Nicolas Rodondi Journal: Circulation Date: 2017-10-23 Impact factor: 29.690
Authors: Peter N Taylor; Diana Albrecht; Anna Scholz; Gala Gutierrez-Buey; John H Lazarus; Colin M Dayan; Onyebuchi E Okosieme Journal: Nat Rev Endocrinol Date: 2018-03-23 Impact factor: 43.330
Authors: Eleanor M Simonsick; Chee W Chia; Jennifer S Mammen; Josephine M Egan; Luigi Ferrucci Journal: J Gerontol A Biol Sci Med Sci Date: 2016-01-20 Impact factor: 6.053
Authors: C Piras; M Pibiri; V P Leoni; A Balsamo; L Tronci; N Arisci; S Mariotti; L Atzori Journal: J Endocrinol Invest Date: 2020-10-06 Impact factor: 4.256