Endocrine Abstracts

Introduction: Resistance to thyroid hormone (RTH) is a rare autosomal dominant (AD) condition caused by mutations of the Thyroid Hormone Receptor Beta (TR-β) gene, resulting in generalized tissue resistance to thyroid hormone. Euthyroidism is usually maintained at the expense of increased levels of thyroid hormones and with non-supressed TSH.

Case report: A 61 year-old-woman was evaluated for increased free T4 index: 2.29 ng/dl (normal, 0.9–2.1) and free T3 index: 4.59 pg/ml (normal, 2.57–4.43) and normal TSH levels:3.22 μUI/ml (normal, 0.3–5)). Analysis were repeated and laboratory error was excluded. The patient was asymptomatic. A physical examination detected a moderate diffuse goitre and a normal resting heart rate. Thyroid antibodies were negative. Sex hormone binding globulin and gonadotrophin α-subunit were within the normal range and pituitary magnetic resonance imaging ruled out a pituitary adenoma. Thyroid ultrasound showed a multinodular goitre with micronodules (<6 mm size). Thyroid scintigraphy demonstrated a diffuse goitre with increased technetium uptake. A diagnosis of RTH was suspected. Molecular genetic studies showed a change in exon 10 of the TR-β gene: p.L450F (c.C1633T). Later, our patient’s daughter was also diagnosed of RTH and AD inheritance was demonstrated in family segregation studies.

Conclusions: The rare finding of increased thyroid hormones (T3 and T4) with normal or increased TSH level presents a differential diagnosis between a TSH secreting pituitary adenoma and RTH. Mutational analysis of the TR-β gene enables both definitive diagnosis of RTH and family screening. We present a novel mutation of this gene that has not been previously reported. Although, there have been reported mutations affecting another aminoacid substitution at this position (L450P) in cases of RTH.