New reference intervals for thyrotropin and thyroid hormones based on National Academy of Clinical Biochemistry criteria and regular ultrasonography of the thyroid

Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, Institute of Transfusion Medicines, Clinics for Nuclear Medicine, University Hospital Leipzig, Germany.
Clinical Chemistry (Impact Factor: 7.91). 09/2005; 51(8):1480-6. DOI: 10.1373/clinchem.2004.047399
Source: PubMed


The aim of our present study was to establish new reference intervals for thyrotropin (TSH) and thyroid hormones based on National Academy of Clinical Biochemistry (NACB) criteria and regular thyroid ultrasonography. We also assessed the effect of potentially confounding factors to modulate the limits of these intervals.
We investigated 870 apparently healthy persons and excluded, step by step, those with a family history of thyroid disease, pathologic thyroid ultrasonography results, and increased anti-thyroid peroxidase or anti-thyroglobulin antibodies. Accordingly, only 453 of the 870 persons in the entire group were finally included as reference collective. We measured serum concentrations of TSH, total and free thyroxine (T(4) and FT(4)), and total and free triiodothyronine (T(3) and FT(3)) of the whole and the reference collective on the ELECSYS system assays (Roche Diagnostics) and calculated the 2.5th and 97.5th percentiles for comparison.
The calculated lower limit for TSH differed significantly between the reference intervals for healthy persons with an assessed normal thyroid gland vs the nonselected group of healthy blood donors. Age was the only independent factor and was significantly inversely associated with TSH (P <0.0001). Use of oral contraceptives was a significant predictor for variation in T(4) concentrations (P <0.001). Age and oral contraceptives were independently associated with T(3) variations (P <0.05). For FT(4) vs FT(3) variation, gender and (inversely) age (P <0.01) were independent modulating factors.
The selection of healthy persons according to NACB criteria combined with sonographic confirmation of a normal thyroid gland provide a valid basis for the reference interval for TSH. Factors indicating a preclinical disease state, such as family history, pathologic ultrasonography result, or increased anti-thyroid peroxidase and anti-thyroglobulin antibodies, can be associated with normal hormone concentrations. Additionally, patient age and gender as well as use of contraceptives should be considered in diagnostic evaluation of thyroid diseases.

Download full-text


Available from: Georg Martin Fiedler,
  • Source
    • "By design, the study represents a retrospective analysis of prospectively collected data. To be included in the study, patients had to have angiographic CAD (coronary stenosis with ≥50% lumen obstruction in ≥ one of the major coronary arteries) and a TSH level within reference range (0.3 mU/L to 4.0 mU/L) [22]. Patients with prior or current thyroid gland disease (including prior history, surgery or drug therapy for thyroid gland disease) and those with acute infections, advanced renal disease (serum creatinine level ≥ 2 mg/dL), known malignancies or those receiving dopamine or dopamine agonists on admission were excluded. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Thyroid-stimulating hormone (TSH) in the upper part of reference range is associated with cardio-metabolic disorders. The association of TSH within reference range with prognosis of patients with coronary artery disease (CAD) after percutaneous coronary intervention (PCI) remains poorly investigated. The study included 8010 consecutive patients with CAD who were treated with PCI. All patients had a TSH level within reference range (0.3 to 4.0mU/L). The primary outcome was 3-year all-cause mortality. TSH tertiles were: 1st tertile (0.3mU/L to <1.02mU/L; n=2694), 2nd tertile (1.02mU/L to <1.67mU/L; n=2654) and 3rd tertile (1.67mU/L to 4.00mU/L; n=2662). The primary outcome (3-year mortality) occurred in 753 patients: 240 deaths in the 1st, 227 deaths in the 2nd and 286 deaths in the 3rd TSH tertile (Kaplan-Meier estimates of mortality 10.2%, 9.8% and 12.3%; adjusted hazard ratio [HR]=1.31, 95% confidence interval [CI] 1.04-1.66 for each tertile increase). TSH level was associated with 30-day mortality (mortality estimates, 1.6% in the 1st, 1.6% in the 2nd and 3.5% in the 3rd TSH tertile; adjusted HR=2.30 [1.33-3.97] for each tertile increase) but not with 30-day to 3-year mortality (mortality estimates, 8.6% in the 1st, 8.2% in the 2nd and 8.8% in the 3rd TSH tertile; P=0.603). The incidence of cardiogenic shock or peri-PCI bleeding was increased in patients in the upper TSH tertile. In patients with CAD undergoing PCI, TSH level in the upper part of reference range was associated with increased risk of mortality after PCI. Copyright © 2015. Published by Elsevier Inc.
    Metabolism: clinical and experimental 07/2015; 64(10). DOI:10.1016/j.metabol.2015.07.009 · 3.89 Impact Factor
  • Source
    • "This observation might be explained by the fact that our study sample has various potential risk factors of thyroid dysfunction, associated with clinical diagnosis and resulting from treatment. On the other hand, our results are consistent with results of the German study, which show that age was the only independent factor and was significantly inversely associated with TSH [21]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: The aim of this study is to investigate differences in thyroid-stimulating hormone (TSH) level in patients with acute schizophrenia, unipolar depression, bipolar depression and bipolar mania. Serum level of TSH was measured in 1,685 Caucasian patients (1,064 women, 63.1 %; mean age 46.4). Mean serum TSH concentration was: schizophrenia (n = 769) 1.71 μIU/mL, unipolar depression (n = 651) 1.63 μIU/mL, bipolar disorder (n = 264) 1.86 μIU/mL, bipolar depression (n = 203) 2.00 μIU/mL, bipolar mania (n = 61) 1.38 μIU/mL (H = 11.58, p = 0.009). Depending on the normal range used, the overall rate of being above or below the normal range was 7.9-22.3 % for schizophrenia, 13.9-26.0 % for unipolar depression, 10.8-27.6 % for bipolar disorder, 12.2-28.5 % for bipolar depression, and 11.4-24.5 % for bipolar mania. We have also found differences in TSH levels between the age groups (≤20, >20 years and ≤40, >40 years and ≤60 years and >60 years). TSH level was negatively correlated with age (r = - 0.23, p < 0.001). Weak correlations with age have been found in the schizophrenia (r = - 0.21, p < 0.001), unipolar depression (r = - 0.23, p < 0.001), bipolar depression (r = - 0.25, p = 0.002) and bipolar disorder (r = - 0.21, p = 0.005) groups. Our results confirm that there may be a higher prevalence of thyroid dysfunctions in patients with mood disorders (both unipolar and bipolar) and that these two diagnostic groups differ in terms of direction and frequency of thyroid dysfunctions.
    Neurochemical Research 04/2014; 39(7). DOI:10.1007/s11064-014-1305-3 · 2.59 Impact Factor
  • Source
    • "In subjects younger than 60, the value of z pointed that FT4 is lower in males than in females. A study of Kratzsch et al. also reports lower FT4 in males than in females [29]. However, as in our study, z result (3.0249) is very close to the cutoff point we consider that in the clinical routine, it is appropriate to use the same RI to both genders, the same way as in older subjects. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Studies based on laboratory data about thyroid stimulating hormone (TSH) and free thyroxine (FT4) reference interval (RI) show conflicting results regarding the importance of using specific values by age groups with advancing age. Retrospective laboratory data or non-specific criteria in the selection of subjects to be studied may be factors leading to no clear conclusions. The aim of this study is to test the hypothesis that TSH and FT4 have specific RI for subjects over 60 to 80 years. We evaluated prospectively 1200 subjects of both sexes stratified by age groups, initially submitted to a questionnaire to do the first selection to exclude those with factors that could interfere in TSH or FT4 levels. Then, we excluded those subjects with goiter or other abnormalities on physical examination, positive thyroid peroxidase antibodies (TPOAb), thyroglobulin antibodies (TGAb), and other laboratory abnormalities. TSH increased with age in the whole group. There was no statistical difference in the analysis of these independent subgroups: 20-49 versus 50-59 years old (p > 0.05), and 60-69 versus 70-79 years old (p > 0.05). Consequently, we achieved different TSH RI for the three major age groups, 20 to 59 years old: 0.4 - 4.3 mU/L, 60 to 79 years old: 0.4 - 5.8 mU/L and 80 years or more: 0.4 - 6.7 mU/L. Conversely, FT4 progressively decreases significantly with age, but the independent comparison test between the sub-groups showed that after age 60 the same RI was obtained (0.7 - 1.7 ng/dL) although the minimum value was smaller than that defined by manufacturer. In the comparison between TSH data obtained by this study and those defined by the manufacturer (without segmentation by age) 6.5% of subjects between 60 and 79 years and 12.5% with 80 years or more would have a misdiagnosis of elevated TSH. TSH normal reference range increases with age, justifying the use of different RI in subjects 60 years old and over, while FT4 decreases with age. Using specific-age RI, a significant percentage of elderly will not be misdiagnosed as having subclinical hipothyroidism.
    Thyroid Research 12/2013; 6(1):13. DOI:10.1186/1756-6614-6-13
Show more