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OBJECTIVE: To determine whether insulin tolerance tests (ITTs), arginine stimulation tests (ASTs), and glucagon stimulation tests (GST) identify patients who have similar clinical features of growth hormone (GH) deficiency when a diagnostic GH threshold of 3 μg/L is used. METHODS: Data were obtained from the KIMS database (Pfizer International Metabolic Database). Comparisons were made between patients who underwent ITT, AST, or GST for GH peak, body mass index, lipids, waist circumference, waist-to-hip ratio, and quality of life. RESULTS: A total of 5453 tests were available from 4867 patients registered in the database (ITT = 3111, AST = 1390, GST = 952). Significant (P

It has been suggested that the immune-endocrine communication plays an important role in development and progression of multiple sclerosis (MS). Interferon beta (IFN beta-1b) treatment is the therapy of choice in patients suffering from relapsing remitting or secondary chronic progressive multiple sclerosis. While typical adverse events of IFN beta-1b treatment such as flu-like symptoms or fatigue are well studied, little is known about the acute changes in the immune and neuroendocrine system. Therefore, we analyzed the short-term effects of IFN beta-1b on cortisol, epinephrine, norepinephrine, prolactin and growth hormone (GH) plasma levels before and 4, 8 and 24 h after IFN beta-1b administration in healthy subjects. Moreover, we determined heart rate, blood pressure, body temperature, leukocyte and lymphocyte subsets and plasma levels of interleukin (IL)-1 beta, IL-6, IL-10 and tumor necrosis factor (TNF)-alpha. IFN beta-1b led to an increase in body temperature and heart rate, and in parallel, elevated cortisol, prolactin and GH plasma levels at 4 and 8 h after IFN beta-1b injection. There were no significant alterations in blood pressure, norepinephrine or epinephrine plasma levels. Simultaneously, IFN beta-1b injection led to an immediate granulocytosis while concomitantly decreasing peripheral lymphocytes, especially natural killer (NK) cells. At the same time, IL-6, IL-10 and TNF-alpha plasma levels showed an overall increase. Overall, cytokine administration exerts strong stimulatory effects on the hypothalamic-pituitary-adrenal (HPA)-axis that may contribute to the side effects of IFN beta-1b therapy and affect the efficacy of IFN beta-1b treatment.

Thyroxine-binding globulin (TBG) is the major serum transport protein for iodothyronines in most of the large, omni- or herbivorous mammals. Characterization of human TBG (hTBG), including its 20 known natural variants, allowed the identification of the ligand-binding site and a correlation of diminished synthesis or loss of function with mutations in the TBG gene. Further refinement of the structure-function correlation, especially the high binding affinity and heat stability, requires characterization of other mammalian TBGs, of which only rat and sheep TBG were available. We now present some of the chemical and physical properties of bovine TBG (bTBG) and porcine TBG (pTBG) and their primary structures deduced from their cDNA sequences. The serum concentrations of bTBG and pTBG estimated by Scatchard analysis of T(4)-binding were similar to hTBG. The T(4)-binding affinity of human, bovine and porcine TBGs were all similar, at 1.2x10(10) M(-1). However, heat stability of the animal TBGs was reduced, with a half life of denaturation of 7 min (bTBG) and 5 min (pTBG) at 55 degreeC, compared with 21 min for hTBG. Nucleotide alignment revealed identity with hTBG of 85.5% (bTBG) and 83.7% (pTBG) and amino acid identity of 82.8% (bTBG) and 82.6% (pTBG). As expected, the relevant parts of the ligand-binding domain (amino acids 215-291, and 363-395) were highly conserved at more than 95% similarity. Comparison of the five known mammalian TBGs allows focusing of future mutagenesis experiments to further characterize the properties of the molecule.

levels did not differ (patients vs. controls: 701±87 vs. 572±33mg/l, P =0.17), whereas bioactive IGF-I tended to be lower in patients (5.37±0.55 vs. 6.63±0.25mg/l, P < 0.06). Conclusion: The baseline findings of elevated free GH and low bioactive IGF-I support the concept of GH resistance in uremic hemodialysis patients. Using high dose rhGH treatment it was possible to obtain normal responses in total and bioactive IGF-I levels, showing that the GH resistance may be overcome. Nevertheless, our data imply that the response of bioactive IGF-I to GH is subnormal in hemodialysis patients.