The prevalence of macro TSH in patients with subclinical hypothyroidism: experience of a single centre

Background: Subclinical hypothyroidism (SH) is a frequent clinical condition with a prevalence of 3–15% in general population. It is defined by elevated TSH levels with normal thyroid hormones [free thyroxine (FT4) and free triiodothyronine (FT3)]. Similar to prolactin, high TSH levels may be caused by macroTSH, a large molecular sized TSH with a low bioactivity. The aim of the study was to assess the prevalence of macroTSH in patients with subclinical hypothyroidism. Subjects and methods: Blood samples were obtained from 500 adult patients with subclinical hypothyroidism (TSH>5 mUI/ml and FT4 within the reference interval: 8–17 ng/l) between September 2017 and September 2018. The presence of macroTSH was assessed by precipitating 250 μl of serum treated with 250 μl of 25% polyethylene glycol (PEG). The precipitable TSH (%) was calculated using the formula: [1-(2* post-PEG TSH/pre-PEG TSH)*100]. Samples with a precipitable TSH >75% were considered as macroTSH positives. Results: Of 500 patients (mean age 53±18 years), 366 (73%) were females. The median of pre-PEG TSH was 6.5 mUI/ml (IQR: 5.5-8.5) with a mean FT4 of 11.6±1.85 ng/l. The median post-PEG TSH was 3.1 mUI/ml (IQR: 2.4-4.2) with a mean precipitable TSH of 53±12%. Three patients (0.6%) had macroTSH and 26 (5.2%) a borderline precipitable TSH between 70 and 74%. MacroTSH positive patients were all young females, aged between 31 and 41 years with negative antithyroid antibodies [antithyroglobulin (AbTg) and antithyroidperoxidase (AbTPO)] and not receiving any related thyroid therapy. Pre-PEG TSH levels ranged between 5.7 and 12.9 mUI/ml, whereas the post-PEG TSH ranged between 0.98 and 3 mUI/ml. Regarding 26 patients with borderline precipitable TSH, 20 (77%) were females with a mean age of 58±16.3 years. Evaluation of AbTg and AbTPO was available in 13 patients: 12 out of them (92%) had at least one positive antibody and 11/13 was receiving thyroid substitutive therapy. The median pre-PEG TSH was 6.2 mUI/ml g(IQR: 5.4-7.9), while the median post-PEG TSH was 1.77 mUI/ml (IQR: 1.5-2.3). Conclusion and discussion: The prevalence of macroTSH in our cohort of patients with SH was 0.6%. This result is in line with other previous studies that reported a prevalence between 0.6 and 1.62%. Despite the low prevalence, the assessment of macroTSH could be useful in patients with subclinical hypothyroidism and negative antithyroid antibodies in order to better evaluate the need of a chronic substitutive therapy

The European Biological Variation Study (EuBIVAS): weekly biological variation of cardiac troponin I estimated by the use of two different high-sensitivity cardiac troponin I assays

Background Cardiac troponins (cTn) are specific markers for cardiac damage and acute coronary syndromes. The availability of new high-sensitivity assays allows cTn detection in healthy people, thus permitting the estimation of biological variation (BV) of cTn. The knowledge of BV is important to define analytical performance specifications (APS) and reference change values (RCVs). The aim of this study was to estimate the within- and between-subject weekly BV (CVI, CVG) of cTnI applying two high-sensitivity cTnI assays, using European Biological Variation Study (EuBIVAS) specimens. Methods Thirty-eight men and 53 women underwent weekly fasting blood drawings for 10 consecutive weeks. Duplicate measurements were performed with Singulex Clarity (Singulex, USA) and Siemens Atellica (Siemens Healthineers, Germany). Results cTnI was measurable in 99.4% and 74.3% of the samples with Singulex and Atellica assays, respectively. Concentrations were significantly higher in men than in women with both methods. The CVI estimates with 95% confidence interval (CI) were for Singulex 16.6% (15.6–17.7) and for Atellica 13.8% (12.7–15.0), with the observed difference likely being caused by the different number of measurable samples. No significant CVI differences were observed between men and women. The CVG estimates for women were 40.3% and 36.3%, and for men 65.3% and 36.5% for Singulex and Atellica, respectively. The resulting APS and RCVs were similar for the two methods. Conclusions This is the first study able to estimate cTnI BV for such a large cohort of well-characterized healthy individuals deriving objective APS and RCV values for detecting significant variations in cTnI serial measurements, even within the 99th percentile