A rare cause of subclinical hypothyroidism: macro-thyroid-stimulating hormone

Abstract

BackgroundSubclinical hypothyroidism is a situation in which the thyroid-stimulating hormone (TSH) value exceeds the upper limit of normal, but the free triiodothyronine (T3) and thyroxine (T4) values are within the normal range. The etiology is similar to overt hypothyroidism.Case presentationAn 18-year-old female patient was referred to our endocrinology clinic due to elevated TSH levels detected during a routine examination. She was clinically euthyroid and had a normal thyroid ultrasound pattern. The TSH concentration was measured twice independently, giving values of 5.65 μIU/mL and 5.47 μIU/mL. The polyethylene glycol (PEG) method for TSH measurement was used to determine the concentration of macro-TSH (m-TSH), a macromolecule formed between TSH and immunoglobulin (Ig). Using the same blood samples for which the TSH levels were found to be high, the PEG method found TSH levels to be within a normal range, with values of 1.50 μIU/mL (5.65–1.50 μIU/mL measured; a decrease of 75%) and 1.26 μIU/mL (5.47–1.26 μIU/mL measured; a decrease of 77%), respectively. The TSH values determined by the PEG precipitation test were markedly low, with PEG-precipitable TSH ratios greater than 75%.ConclusionsThe cause of 55% of subclinical hypothyroidism is chronic autoimmune thyroiditis. However, it is necessary to exclude other TSH-elevated conditions for diagnosis. One of these conditions is m-TSH, which should be kept in mind even though it is rarely seen. m-TSH should be considered especially in patients who have a TSH value above 10 μIU/mL without hypothyroidism symptoms or who require a higher levothyroxine replacement dose than expected to make them euthyroid.

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

“…As a result, TSH concentration was determined by a Polyethylene Glycol precipitation test (PEG-6000) at 25%, similar to the macroprolactin study [21], and a highly reduced percentage was obtained (TSH in controls was 87.70 ± 3.23 % and in the samples of our patients 31.66 ± 6.31 %) (Table 4). Today, the most commonly used technique for detecting macro TSH [18].…”

“…Viral infection causes a significant generalized inflammatory response and a considerable increase in the levels of circulating cytokines (mainly IL-2, IL-7, TNF-α, IFN-α, IFN-γ, NF-κB, and IL-6) [8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23]26,27], which may cause pulmonary [3] and thyroid damage in patients suffering from this infection.…”

“…Polyethylene glycol (PEG) precipitation: For determining the presence of macro-TSH, all samples were subjected to the traditional method of immune complex precipitation with Polyethylene Glycol ([PEG] Merck® PEG-6000 at 25%); which is typically used for macroprolactinemia screening, described by Hattori et al [21] and validated by Fahie-Wilson [22] and Olukoga [23,24,16]. In brief, serum samples (200 μl) were treated with 200 μl of 25% PEG (final concentration of PEG; 12.5%) to precipitate γ-globulin fractions and followed by free TSH determination in the supernatant.…”

“…One of the rare causes of an elevated TSH concentration is macro-TSH. Macro-TSH is a macromolecule that includes TSH and an anti-TSH antibody [16][17][18][19][20].…”

“…The definitive test to detect the macro-TSH is gel filtration chromatography, but this technique was not used because it is expensive and is not available in most centers [18]. Currently, the most widely used technique to detect macro-TSH is polyethylene glycol precipitation.…”