Endocrine Abstracts

JOINT2238

Introduction: The high-dose hook effect is a well-described yet sometimes overlooked lab artifact when using immunoassays in the clinical laboratory. Extremely high analyte levels could produce false low or undetectable results, with potential impact on clinical decisions and treatment. We present a case of severe hyperthyroidism in which the high-dose hook effect played a central role in the diagnostic work-up.

Case Report: A 36-year-old female was referred for worsening thyrotoxicosis, diagnosed 11 weeks prior after presenting with hematuria and urinary retention, caused by a pelvic mass. Her medical history included endometriosis and a complete molar pregnancy, successfully treated with chemotherapy. At presentation the patient had a sore throat, suggesting viral thyroiditis, due to absence of thyroid-stimulating hormone (TSH) receptor and thyroid peroxidase antibodies and a normal thyroid ultrasound. Thyrotoxicosis persisted despite initial therapy with thyrostatics (methimazole 30mg daily) and subsequent corticosteroids (methylprednisolone 32mg daily, tapered down to 12mg over 4 weeks). One week prior to referral, scintigraphy revealed high technetium uptake, possibly indicating antibody-negative Graves’ disease, and methimazole was resumed. Further investigation identified the pelvic mass as malignant gestational trophoblastic disease, characterized by high human chorionic gonadotropin (hCG) levels, which were initially valued at 6.769 IU/l. hCG can however, due to structural similarities and at high doses, cross-activate the TSH receptor, causing hyperthyroidism with high isotope uptake, similar to Graves’. Upon initiating chemotherapy, hCG levels unexpectedly rose to >1.000.000 IU/l, a paradoxical increase instated due to high-dose hook effect. Dilution of the pre-chemotherapy sample revealed much higher hCG levels (2.883.000 IU/l). As chemotherapy progressed, hCG levels decreased, improving thyroid function and resolving thyrotoxicosis.

Conclusion: This case underscores the impact of hCG on thyroid function and especially its ability to stimulate thyroid activity when circulating in high levels. Although rare, measuring hCG in unexplained thyrotoxicosis cases is advisable. Furthermore, in case of immunoassay diagnostic testing for hCG, the potential impact of high-dose hook effect must be considered in situations where one would clinically expect extremely elevated levels of hCG, despite being (falsely) low on the lab report. Recognizing this phenomenon is crucial for accurate interpretation of immunoassay results in similar clinical contexts.