Thyrotropin-releasing hormone degradation in patients with insulin dependent diabetes mellitus. Effects of metabolic control.

We investigated thyrotropin releasing hormone (TRH) degradation in terms of half-life (t1/2) and metabolic clearance rate (MCR) in eight subjects with insulin dependent diabetes mellitus (IDDM) before and after strict metabolic control. The results were compared with those of six healthy control subjects. The basal plasma TRH-IR levels (31 +/- 9 fmoles/ml) were on the lowest normal limit in the IDDM patients and were not considerably changed (24 +/- 10) after strict metabolic control. The basal and delta max rise of TSH to TRH (200 micrograms i.v.) were not significantly different before or after improved metabolic control in IDDM and as compared to controls. The TRH-degradation curves showed similar exponential decay before and after improvement of metabolic control (t1/2: 7.6 +/- 0.4 min and 7.3 +/- 0.3 respectively; 6.5 +/- 0.4 min for the controls). The MCR of exogenously administered TRH in IDDM before (65.5 +/- 8.6 l/m2/day) and after (65.0 +/- 8.9) control was not different compared to the normals (76.5 +/- 9.6). The area under the plasma concentration-time curve (AUC) in IDDM before (52.193 +/- 6.773 fmoles.ml-1.min) and after improvement of metabolic control (53.186 +/- 7.856) was slightly higher than in the healthy subjects (40.151 +/- 3.741, n.s.). These findings demonstrate that a) the degradation of exogenous TRH is not dependent on the glucose metabolic state, b) insulin deficient diabetes mellitus does not affect the enzymatic system responsible for TRH degradation and, c) the hypothalamic-pituitary axis appears to be intact in IDDM.