Clinical characteristics, timing of peak responses and safety aspects of two dosing regimens of the glucagon stimulation test in evaluating growth hormone and cortisol secretion in adults

The GH Research Society held a Consensus Workshop in Sydney, Australia, 2007 to incorporate the important advances in the management of GH deficiency (GHD) in adults, which have taken place since the inaugural 1997 Consensus Workshop. Two commissioned review papers, previously published Consensus Statements of the Society and key questions were circulated before the Workshop, which comprised a rigorous structure of review with breakout discussion groups. A writing group transcribed the summary group reports for drafting in a plenary forum on the last day. All participants were sent a polished draft for additional comments and gave signed approval to the final revision. Testing for GHD should be extended from hypothalamic-pituitary disease and cranial irradiation to include traumatic brain injury. Testing may indicate isolated GHD; however, idiopathic isolated GHD occurring de novo in the adult is not a recognized entity. The insulin tolerance test, combined administration of GHRH with arginine or growth hormone-releasing peptide, and glucagon are validated GH stimulation tests in the adult. A low IGF-I is a reliable diagnostic indicator of GHD in the presence of hypopituitarism, but a normal IGF-I does not rule out GHD. GH status should be reevaluated in the transition age for continued treatment to complete somatic development. Interaction of GH with other axes may influence thyroid, glucocorticoid, and sex hormone requirements. Response should be assessed clinically by monitoring biochemistry, body composition, and quality of life. There is no evidence that GH replacement increases the risk of tumor recurrence or de novo malignancy.

Synergism between glucose and cAMP in the stimulation of insulin secretion has been suggested to regulate beta cells. This study assessed the importance of an interaction between glucose and cAMP in the stimulation of insulin secretion from human islet cells by investigating expression and functional activity of receptors recognising glucagon, glucagon-like peptide-1 (7-36)amide (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). Expression of the glucagon, GLP-1 and GIP receptors in human islets was investigated by northern blots and reverse transcription-polymerase chain reaction analysis. Functional activity of these receptors was assessed by the effects of peptides (agonists and antagonists) on glucose-induced insulin release. Human islet cells express transcripts encoding glucagon, GLP-1 and GIP receptors. Glucose (10 mmol/l) stimulated insulin release 4.5 +/- 0.6-fold over basal (2.5 mmol/l). This glucose effect was amplified by 10 nmol/l GLP-1, GIP or glucagon. It was reduced by 51 +/- 6% in the presence of 1 micromol/l of the glucagon-receptor antagonist des-His1-[Glu9]-glucagon-amide (n = 8; p < 0.05), indicating participation of endogenously released glucagon in the process of glucose-induced insulin release. The glucagon-receptor antagonist also suppressed the potentiation of glucose-induced insulin release by addition of 10 nmol/l glucagon. These data suggest that human beta cells express functional glucagon receptors which can, similar to incretin hormone receptors, generate synergistic signals for glucose-induced insulin secretion.

Adrenal insufficiency, first codified in 1855 by Thomas Addison, remains relevant in 2010 because of its lethal nature. Reports illuminate features of adrenal insufficiency cause, diagnosis and treatment, and the role of glucocorticoids in critical illness. Progress has been made in identifying human leukocyte antigen and major histocompatability complex alleles that predispose to the development of adrenal insufficiency in patients with antibodies to 21-hydroxylase, but their role in clinical care is not established. Reports of HIV-associated infections and medication-induced hypocortisolism are reminders that autoimmune adrenal destruction does not underlie all cases. The diagnosis is adequately established by the 250 microg adrenocortocotropin hormone stimulation test in most patients; the 1 microg test carries the risk of misdiagnosis of healthy individuals as adrenally insufficient. Glucocorticoids provide life-saving treatment, but long-term quality of life is impaired, perhaps because therapy is not given in a physiologic way. The current recommended total daily dose is lower than that often prescribed. Dehydroepiandrosterone replacement may be useful in pubertal girls with hypopituitarism, but not in adults. Supraphysiologic hydrocortisone doses may aid in the reversal of septic shock independent of underlying adrenal function.