The effect of short-term hypothyroidism on growth hormone secretory responses to growth hormone-releasing hormone (1-29) and insulin-induced hypoglycemia

Introduction: Hypothyroidism is frequently associated with growth failure. In long-standing hypothyroidism the growth hormone (GH) secretory responses to growth hormone-releasing hormone (GRH) and insulin-induced hypoglycemia are decreased. Methods: To investigate whether hypothyroidism of short duration affects pituitary GH release, we measured the serum GH response to synthetic GRH (1-29), 1g/kg body weight, given IV to six athyreotic patients during thyroxine (T4) treatment and one month after stopping T4 (short-term hypothyroid state). This served as a direct measure of pituitary somatotroph function .We also assessed the serum GH response to insulin-induced hypoglycemia in three patients as an indirect assessment of hypothalamic function. Results: We found that basal GH levels remained the same both during (euthyroid state) and after stopping T4 therapy (hypothyroid state). Peak serum GH response to GRH was significantly greater in patients while they were hypothyroid than during T4 therapy when they were euthyroid (p< 0.01). There was no difference in the peak serum GH response to hypoglycemia during and after stopping T4 replacement (30.3 + 8.9 g/L euthyroid-state versus 45 + 14.5 g/L short term hypothyroid-state). Discussion: These results suggest that, in contrast to long standing hypothyroidism, thyroid hormone deficiency of short duration increases somatotroph sensitivity to GRH, perhaps as a result of decreased endogenous hypothalamic IGF-1 release and/or tone.

Profound Hypothermia Provides Neuroprotection Following Hypothermic Circulatory Arrest: Ultrastructural Observations.

Objective: To assess whether cooling to 10°C can reduce neurological injury during 75 minutes of hypothermic circulatory arrest (HCA) compared to cooling to 18°C. Methods: Twelve domestic swine were used for this prospective blind randomized study. The animals were divided into 2 groups: Group A (n=6) underwent hypothermic circulatory arrest at 18oC for 75 min, and Group B (n=6) underwent hypothermic circulatory arrest at 10oC for 75 min. At the end of the experiment, the brains were removed and immersed in paraformaldehyde. All brains were dissected in the sagital plane. Tissue blocks from the left hemisphere were cut to encompass the sensory neocortex. Results: The selected area was identified with a dissecting microscope. Samples were examined in a blind fashion using electron microscope. Two investigators were instructed to find 10 representative neurons and analyze electron micrographs of these neurons for evidence of nuclear and cytoplasmic changes. Similarly, each investigator was instructed to examine the perinuclear neuronal mitochondria for abnormalities in mitochondrial distribution. Significant differences were observed between the 2 groups in mitochondria and rough endoplasmic reticulum (RER). In 5 of the 6 animals treated with 18oC HCA, neurons had slightly dilated RER, Golgi apparatus and mitochondria. In all 6 animals treated with 10oC HCA, the structure of the cytoplasmic organelles was intact, with no apparent dilatation (p=0.015). Conclusion: This study adds further support that hypothermia at 10oC exerts better cellular protection than hypothermia at 18oC, as evidenced by these electron microscopy findings.