Endocrine Abstracts

JOINT1638

Background: Thyroid function test discrepancies often cause diagnostic delays and sometimes lead to unnecessary treatments. Thyroid hormone resistance syndrome is rare (1/40,000 births), affecting both sexes equally, with autosomal dominant inheritance. Diagnosis relies on excluding other causes of hyperthyroxinemia and genetic analysis of the thyroid hormone receptor (THR) beta subunit. Clinical symptoms are usually minimal. The primary differential diagnosis is with TSH-producing tumors and analytical laboratory system discrepancies.

Methods: A 22-year-old woman presented with discordant thyroid function tests since 2023, showing elevated or normal TSH and elevated free T4 and free T3 levels. No family history of thyroid dysfunction. Diagnosed with polycystic ovary syndrome, grade 1 obesity, and mild hyperprolactinemia. Previous tests from another hospital and ours (with a different system) revealed subclinical hypothyroidism with normal free T4 levels (2022 and earlier). No clear symptoms of hyperthyroidism or hypothyroidism. Treated with progesterone only and no supplements. Physical examination showed no goiter, tachycardia, or ophthalmopathy. Anti-thyroid antibodies (anti-peroxidase and anti-thyroglobulin) were positive, TSI negative. Free alpha subunit and SHBG levels were normal. Pituitary MRI was normal. Thyroid ultrasound showed no nodules. Blood samples on other platforms (Vitros ECiQ and Architect i2000SR) showed similar results to our hospital (Cobas e801 Roche). Other studies were negative, including antibodies (antinuclear, heterophile, anti-thyroxine), rheumatoid factor, and no macro TSH or macro free T4. Genetic study for familial dysalbuminemic hyperthyroxinemia was negative. Serum selenium levels were normal. T3 suppression test (100 mg for 8 days) showed TSH 0.094 mIU/ml on day 8 (normal response). Octreotide LAR test (20 mg/28 days) showed no TSH decrease after one month. Genetic study for thyroid hormone resistance syndrome identified missense variant of the THRB gene c.749T>C (p.Ile250Thr) variant associated with OMIM #188570, autosomal dominant inheritance from her mother, with her two siblings also affected.

Conclusions: A previously normal phenotype did not raise suspicion for thyroid hormone resistance syndrome. Routine tests (TSH only) can overlook family history of thyroid discordant study. Genetic testing was key to diagnosis in this case. It is relevant that this case involves a woman of childbearing age, due to the therapeutic considerations for a future pregnancy.