Radiocontrast agents decrease T4 to T3 conversion and enhance the TSH response to TRH stimulation in the postabsorptive state. Since fasting is a condition in which T4 and T3 conversion is decreased and TSH responses are diminished, we designed the present study to determine if ipodate, a radiocontrast agent, could affect either iodothyronine levels or TSH responsiveness in this condition. It was anticipated that the use of ipodate during fasting would supply information relating to the mechanism of the fasting-induced decrement in TSH. Furthermore, the administration of physiological amounts of T3, either alone or in combination with ipodate, allowed us to examine the possibility in vivo that ipodate might block pituitary T3 uptake and subsequent biological action. Twenty-four euthyroid obese subjects were randomly allocated to one of four groups, although the general study design, consisting of 6 days of a weight-maintaining diet, followed by 9 days of fasting, was identical. TRH was administered on day 6 of the fed period and day 7 of the fasting period. The fasting portion of the protocol was as follows: group 1 (control; n = 5), fasting alone; group 2, ipodate (3 g on days 1 and 5 of fasting; n = 8); group 3, T3 (5 μg every 4 h; n = 5); and group 4, ipodate plus T3 in doses as detailed for groups 2 and 3 (n = 6). As expected, serum T3 decreased significantly from 128 ± 15 (±sem) ng/dl in the control fed group to 71 ± 11 ng/dl during fasting (P < 0.005); ipodate ingestion resulted in a greater decrement in serum T3 (120 ± 11 to 44 ± 7 μg/dl) (P < 0.05). Free T3 also decreased significantly during fasting in the control (P < 0.05) and ipodate groups (P < 0.025), while free T4 increased significantly (P < 0.025) during ipodate ingestion. TSH responses to TRH decreased from 22.1 ± 6.6 μU/ml during the fed period to 11.2 ± 3.5 μU/ml during fasting alone (group 1). However, ipodate administration abolished this fasting-induced TSH decrement, as TSH values were 12.4 ± 2.4 μU/ml during feeding and 13.9 ± 2.5 μU/ml during fasting plus ipodate treatment (group 2). T3 administration while fasting abolished the TSH rise in TRH either when given alone or with ipodate (groups 3 and 4). In summary, the present study indicates that 1) the TSH response to TRH is decreased during fasting, remains at normal fed values when ipodate is given during fasting, and is abolished when T3 is given alone or with ipodate; and 2) ipodate administration while fasting decreases total T3 levels even further than fasting alone and also is associated with increased free T4 and decreased free T3 levels. These observations do not support the hypothesis of decreased sensitivity to intrapituitary T3 during fasting, but do support the concept that intrapituitary T4 to T3 conversion plays an important role in TSH regulation in man during the fed state as well as during fasting.
ASJC Scopus subject areas
- Endocrinology, Diabetes and Metabolism
- Clinical Biochemistry
- Biochemistry, medical