IMPAIRED TSH SECRETION DURING SUSTAINED HYPERGLUCAGONEMIA IN ANESTHETIZED DOGS

We previously demonstrated that hyperglucagonemia may be responsible f or thyroid hormone alterations noted in some nonthyroidal illnesses, S ince TSH secretion is also known to be altered in many subjects with s everal nonthyroidal illnesses, we assessed the influence of sustained hyperglucagonemia on TSH secretory pattern in 5 anesthetized dogs, Ser um TSH concentrations were determined after a 16-h fast and again at i ntervals of 15 min during sustained hyperglucagonemia (515-645 pg/mL) induced by iv bolus administration of glucagon. 0.1 mg followed by a c ontinuous glucagon infusion 3 ng/kg/min for 3 h, TRH (200 mu g) was ad ministered iv at 60 min to assess the influence of sustained hypergluc agonemia on the hypothalamic pituitary thyrotroph axis during the stud y, A control study was also conducted using normal saline instead of g lucagon, and both studies were performed in a randomized sequence, Bas al TSH levels were not significantly different during both studies, Ho wever, serum TSH declined significantly during sustained hyperglucagon emia prior to TRH administration (Delta TSH, pre-TRH, -0.86 +/- 0.24 v s 0.02 +/- 0.07 ng/mL for normal saline, p < 0.01). Furthermore, TSH r esponse to iv TRH administration was significantly blunted during gluc agon infusion alone as expressed by both the absolute rise (Delta TSH, post-TRH, 1.1 +/- 0.5 vs 5.9 +/- 1.7 ng/ml for normal saline, p < 0.0 1) as well as an integrated response over a 2-h period (Sigma TSH, pos t-TRH, 4.0 +/- 1.1 vs 11.7 +/- 3.5 ng/min/ml, p < 0.001). Therefore, t his study demonstrates that sustained hyperglucagonemia inhibits basal TSH secretion as well as TSH response to iv TRH administration, a TSH secretory pattern similar to that noted at the peak of many nonthyroi dal illnesses.