Inappropriate TSH secretion. Paradoxical rise in serum TSH in response to thyroxine therapy

Serum thytropin (TSH) in a 45-year-old woman suffering from Hashimoto's thyroiditis and hypothyroidism rose over a period of 8 months from 23 to 98 muU/ml while on 0.15 mg of thyroxine daily. A significant pituitary tumor was excluded and the response of other anterior pituitary hormones to provocative stimuli were normal. The TSH response to thyrotropin releasing hormone (TRH) carried out after a year of therapy and while on 0.15 mg T4 was exaggerated and required 100 mug of triiodothyronine (T3) daily in addition to the thyroxine replacement to suppress it. After the completion of the T3 suppression test and while on 0.2 mg thyroxine, serum TSH rose from less than 0.5 to 27 muU/ml when seen last. It is postulated that in this patient there exists a partial selective resistance of the thyrotrophs to T4 and that the paradoxical increase in serum TSH associated with thyroxine therapy results from T4 dependent increase in the synthesis and secretion of endogenous TRH. Other possibilities include an as yet undetected pituitary microadenoma or a pituitary defect in the deiodination of T4.