Figure 1-Risk of nocturnal hypoglycemia correlated to bedtime glucose.

Context Copeptin is a surrogate marker for arginine vasopressin (AVP) release in response to hyperosmolal stimuli such as diabetic ketoacidosis (DKA). Objective Characterize kinetics of copeptin and osmolality, and their dynamic relationship during rehydration and insulin therapy in children with type 1 diabetes (T1D) and DKA. Design and Setting Prospective observational multi-centre study. Patients and Intervention Children with T1D admitted for DKA underwent serial serum copeptin and osmolality measurements from start of rehydration at 14 time points during 72 hours. Main Outcome Measures Temporal course of copeptin and osmolality (kinetics), relationship between both (dynamics), associated between-subject variability [CV%]. Results Twenty-eight children (20 newly diagnosed T1D) aged 1 to 16 years were included. Copeptin decreased from 95pmol/L (95%CI: 55-136) [CV%: 158%] to 9.7pmol/L (8.1-11.4) [31%] with a 50% recovery time (t1/2) of 7.1 (5.1-11.5) [114%] h. Serum osmolality decreased from 321mOsm/kg (315-327) [4%] to 294mOsm/kg (292-296) [1%] with t1/2 of 4.3 (3.0-5.6) [64%] h. Copeptin levels doubled with each osmolality increase by 15mOsm/kg (10-21) [59%], from 9.8pmol/L (7.3-12.3) [48%] at 280mOsm/kg. Copeptin kinetics differed between newly diagnosed and known T1D patients (P=0.0001), and less between mild versus moderate-severe DKA (P=0.044). Conclusions First, this study characterized for the first time copeptin kinetics and dynamics in the high hyperosmolar range in children with DKA. Second, it revealed significant differences in copeptin kinetics between newly diagnosed and known T1D patients that may be explained by changes at the osmoreceptor and renal AVP receptor level due to longstanding osmotic diuresis and DKA.

Patients with CO-GHD should be retested after discontinuation of therapy to identify those who may profit from further replacement therapy. Patients with organic or genetic GHD or MPHD are likely to have persistent GHD, whereas 75% of our patients with idiopathic GHD showed normalization of growth hormone secretion. IGF-I levels alone are not reliable in the diagnosis of adult GHD in many cases. The best sensitivity and specificity scores were found when a GH cut-off level below 5.0 ng/ml was used in patients with GHD in the transition from childhood to adulthood.

Prader-Labhart-Willi syndrome (PWS) is the most frequent form of syndromal obesity. Its main features are associated with hypothalamic dysfunction, which has not yet been comprehensively described. The aim of this review is to present arguments to define the presence of genuine growth hormone (GH) deficiency (GHD) in these patients. Decreasing growth velocity despite the onset of obesity, reduced lean body mass in the presence of adiposity, small hands and feet, relatively low insulin-like growth factor-I and low insulin levels, as well as the dramatic effect of GH treatment on growth, support the presence of hypothalamic GHD in PWS. Even though it might be difficult to ultimately prove GHD in PWS because of the obesity-induced counterregulation, the hormonal situation differs from that in simple obesity. The effects of long-term therapies with GH on body composition in these patients are summarized. GH therapy dramatically changes the phenotype of PWS in childhood: height and weight become normal and there is a sustained impact on the net loss of body fat. We conclude that GHD may account for several features of PWS.