SAT-560 Real or Not Real? An Elevated TSH

Abstract M.E. Sevilla-Alsina: None. A. Salvat: None. M. Saiful Islam: None. J. Yang: None. M.J. McPhaul: None. R.E. Weiss: None. Macro-thyroid-stimulating hormone (macro-TSH) is a rare, under-recognized cause of elevated thyroid-stimulating hormone (TSH) in presence of normal free T4 and T3 concentrations. The binding of glycoproteins, particularly antibodies, to TSH results in the formation of inactive macromolecular complexes, resulting in a falsely elevated TSH. Macro-TSH has very low biological activity but can represent a diagnostic challenge due to its measurement by TSH immunoassays. In many cases, it can be misdiagnosed as subclinical hypothyroidism or other causes of euthyroid hyperthyrotopinemia. As a consequence, patients may receive unnecessary treatment. We present a case with macro-TSH to guide the diagnostic approach and awareness of the condition. A 19-year-old male undergoing a “routine workup” was found to have a serum TSH of 85 mIU/l (Reference interval [RI] 0.36-4.0) measured by immunoassay (IA), with no specific symptoms and normal free T3 and T4. The patient was taking biotin supplements for hair growth. He was referred for endocrine evaluation and had suspended the biotin supplement several weeks prior to visit. He denied hypothyroid symptoms except for mild fatigue and chronic constipation. He was clinically euthyroid with an unremarkable physical exam, and the following test results were obtained: TSH 94.7 mUI/L (RI 0.40-4.50), Free T4 1.36 ng/dL (RI 0.8-1.8)., Total T3 93 ng/dL (RI 76-181), negative TPO, and thyroglobulin antibodies. Additional testing revealed a serum Free T4 direct by dialysis 1.3 ng/dL (RI 0.9-2.2), Alpha-Subunit 0.2 ng/mL (RI 0.1-0.5), Prolactin 11.5 ng/mL, cortisol 7.5 mcg/dL, and ACTH 13 pg/mL. Sequencing of the THRB gene was negative and ruled out resistance to thyroid hormone beta. Human anti-mouse IgG antibody (HAMA) testing identified no interference. The presence of TSH antibodies was assessed by demonstrating the presence of antibodies capable of immunoprecipitating radiolabeled TSH, absent from control serum. The positive TSH antibody test suggested the elevated TSH was due to macro-TSH. Gel filtration chromatography with a 23 x 3 cm Sephadex G-100 column demonstrated that a large proportion of the circulating TSH was contained within large molecular weight complexes, consistent with macro-TSH. The biochemical findings were discussed with the patient, avoiding initiating unnecessary treatment. Macro-TSH is an uncommon condition with a prevalence of 0.6-1.6%. Elevated TSH with normal free thyroid hormones in an asymptomatic patient raises the suspicion macro-TSH. Size fractionation chromatography of TSH is the gold standard method to confirm macro-TSH. Unfortunately, this test is unavailable commercially. The use of a TSH antibody test (available commercially at Quest Diagnostics), can help to identify immunoglobulins causing of macro-TSH, as presented in this case, preventing unnecessary medical intervention. Saturday, June 1, 2024