The finding of increased thyroxine (T4) and tri-iodothyronine (T3) levels in a 
patient with normal or increased thyroid-stimulating hormone is unexpected and 
presents a differential diagnosis between a thyroid-stimulating 
hormone-secreting pituitary adenoma, generalized resistance to thyroid hormone 
(RTH) and laboratory artefact. Without careful clinical and biochemical 
evaluation, errors may occur in patient diagnosis and treatment. In the case of 
RTH, mutation of the thyroid hormone receptor beta gene results in generalized 
tissue resistance to thyroid hormone. As the pituitary gland shares in this 
tissue resistance, euthyroidism with a normal thyroid-stimulating hormone is 
usually maintained by increased thyroid hormones. To date, we have identified 
eight pedigrees in New Zealand with mutations in the thyroid hormone receptor 
beta gene, including two novel mutations. Mutational analysis of the thyroid 
hormone receptor beta gene allows definitive diagnosis of RTH, potentially 
avoiding the need for protracted and expensive pituitary function testing and 
imaging. Mutational analysis also enables family screening and may help to avoid 
potential misdiagnosis and inappropriate treatment.