Macro-TSH in Covid-19 Patients with an Underlying Thyroid Condition: A Case Series and Literature Review

Abstract

Introduction: The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) that began in Wuhan (China), that spread rapidly worldwide, seriously affecting the population leading to a public health emergency declared by the World Health Organization. It is unknown how SARS-CoV-2 infection can affect thyroid function. In this study, we describe the characteristics of an unusual analytical interference that may explain the false detection of hypothyroidism in patients with SARS-CoV-2 infection. This is the first time that a phenomenon of this nature has been described in patients with COVID-19 and underlying thyroid dysfunction. Material and Methods: Observational study of patients admitted for severe COVID-19 infection and underlying thyroid disease. Results: TSH levels presented an atypical pattern different from that of Euthyroid Sick Syndrome (ESS), confirmed by the lack of response to substitution treatment. We develop different studies to confirm or eliminate potential interferences, being diagnosed of a possible macro-TSH. Conclusion: It is important to consider that in patients with COVID-19 and high concentrations of TSH and thyroid hormones within reference ranges with lack of response to treatment, one of the possible causes to consider is the presence of macro-TSH. The presence of macro-TSH interference in COVID-19 patients requires extreme precautions to avoid errors in diagnosis or treatment (replacement dose adjustment) in patients with hypothyroidism secondary to an underlying disease.

Pars Distalis and Pars Tuberalis Thyroid-Stimulating Hormones and Their Roles in Macro-Thyroid-Stimulating Hormone Formation

“…After PEG precipitation and applying the cut-off levels of >80%, only 3.1% of samples from thyroid cancer patients contained macro-TSH. This prevalence was higher than values reported for SCH from other groups, e.g., 0.79-1.6% [72,76]. Due to this relatively high background precipitation rate, macro-TSH is only suspected when the signal decreases by more than 75% of the initial value.…”

“…In patients with SCH, 0.79-1.6% of the samples contained macro-TSH [72,76]. Other studies report prevalence in a similar range in these patients: 1.6% as verified with gel filtration chromatography (GFC) and 0.8% upon the exclusion of HAMA [76]. In patients with thyroid cancer, 3.1% of the samples contained macro-TSH [77].…”

“…Macro-TSH was reported with a prevalence of 0.6% in individuals with TSH concentrations > 10 mIU/L [75]. In patients with SCH, 0.79-1.6% of the samples contained macro-TSH [72,76]. Other studies report prevalence in a similar range in these patients: 1.6% as verified with gel filtration chromatography (GFC) and 0.8% upon the exclusion of HAMA [76].…”

“…Upon addition of the IgA-binding lectin Jacalin, IgA also can be adequately precipitated [66]. In one study, TSH concentrations decreased after precipitation with PEG in 30-40% of patients without thyroid disease or thyroid cancer and in 63% of patients with SCH according to another study [76]. The precipitation method as an indication for the presence of macro-TSH is somewhat controversial because increased concentrations of globulins in the blood may also augment the fraction of precipitated TSH [39].…”