DIMINISHED TSH SECRETION ASSOCIATED WITH NEONATAL THYROTOXICOSIS

Abstract

We report 3 1/2 year old twin boys with prolonged neonatal thyrotoxicosis and persistently low TSH secretion manifested by a diminished TSH response to hypothyroxinemia and to TRH stimulation. Features of neonatal thyrotoxicosis included: intrauterine growth retardation, microcephaly with ventriculomegaly, poor weight gain, hyperphagia, irritability, diarrhea, exophthalmos, tachycardia, hepatosplenomegaly, and direct hyperbilirubinemia. However, there was no goiter or history of maternal thyroid disease and diagnosis was delayed until 11 weeks of age (T4<29 ug/dl, T3>580 ng/dl). By age 6 mo., on propylthiouricil (PTU) 25 mg b.i.d., both infants had TSH levels <2 uU/ml (normal N=0.4-4.5) despite T4 levels <1 and 3.1 ug/dl (N=7.2-15.6) and free T4 (FT4) levels of 0.3 and 0.5 ng/dl (N=0.8-1.9). At 3 4/12 years, while on PTU 50 mg q.i.d., they again became hypothyroid withi FT4s of <0.2 and T3RIA of 47 and 43 ng/dl (N=80-220) with a TSH of 3.5. A TRH stimulation test revealed baseline TSH values of 8.5 and 11 and maximal stimulation values of 11 and 14. Normal hGH responses to L-Dopa (8.7 and 13.1 ng/ml), fasting A.M. cortisols (12.6 and 14.1 ug/dl), and normal genitalia make other pituitary hormone deficiencies unlikely. The diminished TSH responses to hypothyroxinemia and TRH stimulation indicate that the capacity to synthesize TSH, or the set point for pituitary-thyroid feedback control, may be altered by excess thyroid hormone concentrations during a critical stage of development.