Two thyroid tests for subclinical hypothyroidism made by two different manufacturers performed differently in a side-by-side comparison analysis. If taken to determine a subclinical hypothyroidism diagnosis, the results of the tests—thyroid stimulating hormone (TSH) and free thyroxine (fT4) made by Roche Diagnostics and Abbott Laboratories—may be vastly different and impact the diagnosis and management of disease.

The study found the diagnostic results for a subclinical hypothyroidism (SCH) diagnosis with Roche’s thyroid stimulating hormone (TSH) and free thyroxine (fT4) assays were significantly higher compared with results from thyroid assays made by Abbot Laboratories.

The study, which was published last month in Clinical Endocrinology, also found the diagnosis and management of subclinical hypothyroidism was ultimately “strikingly different” depending on which assays were used to derive at a diagnosis. The implications are potentially significant as approximately 75% of laboratories in the UK use these assays.


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“Clinicians and laboratorians should be aware that between assay differences and variations in reference ranges will directly impact the diagnosis and management of subclinical hypothyroidism,” wrote the authors who were led by Tejas Kalaria, MBBS, MD MRCP, of the Royal Wolverhampton NHS Trust in the United Kingdom.

Mild to moderate thyroid failure is defined as a when TSH levels reach above 10 mlU/L with a normal level of serum free thyroxine (fT4). The condition affects approximately 10% of the general population and 90% of patients with subclinical hypothyroidism have a TSH of less than 10 mIU/L.

TSH assay results can be affected by age, comorbidities, medications, supplements, gender, ethnicity, iodine status, time of day the test is taken and a host of other many physiological and pathological factors. It is known that results from the two assays, and reference ranges, can vary greatly, but there is little evidence that explains how the results can impact a diagnosis and treatment. Patients are subject to the possibility of over diagnosis and treatment or under diagnosis and treatment.

Subclinical hypothyroidism, which indicates mild to moderate thyroid failure, is defined as a serum thyroid-stimulating hormone (TSH) level above the upper reference limit with a normal level of serum free thyroxine (fT4). The condition affects approximately 10% of the general population and 90% of patients with subclinical hypothyroidism have a TSH of less than 10 mIU/L.

For patients who are symptomatic or with TSH of ≥ 10 mIU/L, levothyroxine replacement is recommended.

The study included consecutive samples from 93 primary care patients with subclinical hypothyroidism that exhibited increased TSH <10 mIU/L and a normal fT4. Samples were obtained from 2 laboratories using either the Roche or Abbott thyroid assays.

Manufacturer-provided reference ranges included 0.35 to 4.94 mIU/L and 9.0 to 19.0 pmol/L for the Abbott TSH and fT4 assays, respectively, and 0.27 to 4. 2 mIU/L and 12.0 to 22.0 pmol/L for Roche’s assays. Positive samples for SCH were analyzed, and researchers measured TSH and fT4 in duplicate on each sample at both sites.

Roche TSH (40±15%) and fT4 (16±7%) results were significantly higher than Abbott results (P <.001). Among all 93 patients, approximately 44% were concordant for subclinical hypothyroidism using both assay methods. In the 53 patients who underwent Roche assays, 75.5% exhibited normal thyroid function, while 24.5% had subclinical hypothyroidism when tested on the Abbott assays.

In contrast, 70% of the 40 patients with subclinical hypothyroidism on the Abbott assays had SCH, while 30% had results indicative for levothyroxine replacement therapy according to the Roche assays. Of the 12 patients who had results indicative for replacement therapy on the Roche assays, a total of 4 had TSH >10 mIU/L, 5 had low fT4, and 3 had both TSH >10 mIU/L and low fT4.

Limitations of this study included its small sample size as well as the lack of a randomized design.

Reference

Kalaria T, Sanders A, Fenn J, et al. The diagnosis and management of subclinical hypothyroidism is assay-dependent- Implications for clinical practice. Published online January 21, 2021. Clin Endocrinol (Oxf). doi:10.1111/cen.14423