Background : Resistance to TSH is defined as reduced sensitivity of the thyroid to TSH stimulation . High TSH , low T3 and T4 levels characterize the patients .At birth they are diagnosed as Congenital hypothyroidism based on elevated TSH in the neonatal screen.
Methods and Results
An asymptomatic male born to consanguineous parents
had TSH levels above 400 mIU/L in the newborn screen .Thyroid replacement therapy ( LT4) was initiated. he had horse shoe kidney upon ultrasound, there is family history of hypothyroidism in an adult.
Since age 5 years TSH levels increased over 100mIU/L in spite of adequate replacement therapy , with normal FT4 levels. At age 7 years his height and weight were at normal range with no tachycardia and good school performance, indicating clinical euthyroidism inspite of consistent highly elevated of TSH for several years.
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Neck ultrasound detected a residual thyroid like tissue 3mm*2mm consistent with thyroid dysgenesis.
Family members thyroid function tests were normal but the mother showed elevated TSH with normal FT4 .
Increasing the LT4 dose towards 100mcg daily resulted in partial decrease in TSH fwith unchanged normal FT 4 As the clinical and laboratory course in the current and 2 other similar cases suggest TSH resistance , DNA sequencing is pending for both TSH receptor and PAX 8 genes.
Conclusion
Chronically highly elevated TSH levels with normal FT4 levels despite adequate LT4 replacement suggests dysfunctional TSH receptor or its signaling pathway. The complete clinical euthyroidism normal growth and intelligence suggests that highly elevated TSH per-se is not majorly contributing to the detrimental symptoms of hypothyroidism and should not be a critical component in prediction of the clinical outcome of such cases. Monitoring the LT4 dosing in such cases should therefore be based specifically on FT4 levels and clinical signs.
