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

Background: Subclinical 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 presentation: An 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 mu IU/mL and 5.47 mu IU/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 mu IU/mL (5.65-1.50 mu IU/mL measured; a decrease of 75%) and 1.26 mu IU/mL (5.47-1.26 mu IU/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%. Conclusions: The 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 mu IU/mL without hypothyroidism symptoms or who require a higher levothyroxine replacement dose than expected to make them euthyroid.