maandag 15 juli 2013

Aandacht voor de ingewikkelde relatie tussen TSH en vrij T4

This study aimed to determine the relationship between median fT4 and TSH in a large population and to assess effects of age and gender on the relationship over a range of fT4 levels. A subset of patients on thyroxine therapy was included in the analysis.

The relationship between TSH and free T4 is not log-linear and differs between genders and age groups
NC Hadlow, KM Rothacker, S Collier, R Wardrop, EM Lim, JP Walsh

In this large study, a complex relationship between free T4 and median TSH was found which was not inverse log linear but better described by 3 lines of different slope. The relationship between fT4 and median TSH was altered by thyroxine therapy, gender and age.

Men, (both untreated and on thyroxine) had a higher overall median TSH for fT4 compared to women. The effects of age and gender were different depending on fT4 level. When fT4 was normal, median TSH for a given fT4 was always higher in males, (up to 1.13 mU/L higher), and median TSH increased in both genders with age.

In severe hypothyroidism, the youngest (of either gender) mounted the highest TSH response and this response decreased with age. When fT4 was elevated young females suppressed TSH most whilst young males suppressed TSH least.

The relationship between serum TSH and Free T4 is not log-linear and varies by age and sex
EN Pearce, comment in Clinical Thyroidology, July 2013

In older studies, the relationship between serum TSH and free T4 appeared to be log-linear (1,2). However, in a more recent study, a complex and nonlinear relationship was seen (3). This had not previously been assessed in a very large population sample. In addition, there have been conflicting reports regarding the effects of age and sex on the relationship between TSH and free T4 (4-6).

TSH reference ranges are not one-size-fits-all

What relevance do these results have for clinical practice?

These data suggest that TSH reference ranges are not one-size-fits-all, and the use of a single TSH range for all subpopulations might result in misclassification of thyroid status in some cases, in particular the inappropriate diagnosis of subclinical hypothyroidism. The age-associated increase in serum TSH among euthyroid individuals seen in this and previous studies argues against routine treatment of mild TSH elevations in elderly patients. Age- and sex-specific TSH reference ranges might be used to more accurately classify thyroid status. Although race and ethnicity were not examined by Hadlow and colleagues, racial and ethnic variability in serum TSH values have been described previously and racial/ethnic subpopulation-specific TSH values might also be helpful in some regions.


  1. Applications of a new chemiluminometric thyrotropin assay to subnormal measurement
    Spencer CA, LoPresti JS, Patel A, Guttler RB, Eigen A, Shen D, Gray D, Nicoloff JT. J Clin Endocrinol Metab 1990;70:453-60.
  2. Replacement dose, metabolism, and bioavailability of levothyroxine in the treatment of hypothyroidism: role of triiodothyronine in pituitary feedback in humans
    Fish LH, Schwartz HL, Cavanaugh J, Steffes MW, Bantle JP, Oppenheimer JH. N Engl J Med 1987;316:764-70.
  3. Complex relationship between free thyroxine and TSH in the regulation of thyroid function
    Hoermann R, Eckl W, Hoermann C, Larisch R. Eur J Endocrinol 2010;162:1123-9. Epub March 18, 2010.
  4. Longitudinal changes in thyroid function in the oldest old and survival: the Cardiovascular Health Study All-Stars Study
    Waring AC, Arnold AM, Newman AB, Bùzková P, Hirsch C, Cappola AR. J Clin Endocrinol Metab 201;97:3944-50. Epub August 9, 2012.
  5. An approach for development of age-, gender-, and ethnicity-specific thyrotropin reference limits
    Boucai L, Hollowell JG, Surks MI. Thyroid 2011;21:5-11. Epub November 8, 2010.
  6. Thyrotropin secretion profiles are not different in men and women
    Roelfsema F, Pereira AM, Veldhuis JD, Adriaanse R, Endert E, Fliers E, Romijn JA. J Clin Endocrinol Metab 2009;94:3964-7.

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