SAT-401 - Human Anti-Mouse Antibody Interference Resulting in False TSH Elevation

Hypothyroidism is commonly monitored using serum thyroid-stimulating hormone (TSH) levels, with levothyroxine dose adjustments guided by biochemical measurements. However, immunoassay interference can lead to misleading laboratory results and inappropriate management. We present the case of a 54-year-old woman with a 10-year history of primary hypothyroidism who was treated with progressively escalating doses of levothyroxine due to persistently elevated TSH levels despite reported adherence.

Over the course of several years, her primary care physician increased her levothyroxine dose multiple times in response to elevated TSH values. Despite supratherapeutic dosing, repeat laboratory testing consistently demonstrated markedly elevated TSH with elevated free thyroxine (FT4) levels and free triiodothyronine (FT3) levels. The patient also had elevated alkaline phosphatase suggestive of thyrotoxicosis and exhibited mixed symptoms of hyper- and hypothyroidism, including palpitations, anxiety, dry skin, forgetfulness, and fatigue, prompting referral to endocrinology for further evaluation.

Comprehensive review of her laboratory results revealed persistent TSH elevation with free thyroid hormone levels that were not consistent with the expected biochemical profile of hypothyroidism. Serum TSH was measured using an enzyme-linked immunosorbent assay (ELISA), which is susceptible to interference from heterophile antibodies such as human anti-mouse antibodies. Further evaluation identified the presence of human anti-mouse antibodies (HAMA), resulting in falsely elevated TSH measurements due to assay interference.

Following identification of HAMA interference, levothyroxine dosing was adjusted based on free T4 and free T3 levels, leading to resolution of hyperthyroid symptoms. Follow-up testing demonstrated persistently elevated TSH with normalization of free thyroid hormone levels, raising concern for ongoing assay-related TSH elevation. Further evaluation is planned to clarify the patient’s underlying thyroid status.

This case highlights the importance of recognizing immunoassay interference as a cause of persistently abnormal laboratory values that do not reflect true thyroid status. Awareness of HAMA-related assay interference may help prevent unnecessary medication escalation, iatrogenic thyrotoxicosis, and prolonged diagnostic delays.

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