Objective: Diazoxide is first-line treatment for hyperinsulinaemic hypoglycaemia (HH) but diazoxide-induced pulmonary hypertension (PH) can occur. We aim to characterize the incidence and risk factors of diazoxide-induced PH in a large HH cohort to provide recommendations for anticipating and preventing PH in diazoxide-treated patients with HH. Design and Patients:Retrospective cohort study involving four UK regional HH centres; review of case notes of HH patients on diazoxide. Measurements:The diagnosis of PH was based on clinical and echocardiography evidence. Patient and treatment-related risk factors were analysed for association.Results: Thirteen (6 men) of 177 HH diazoxide-treated patients developed PH, an incidence of 7%. In the PH group, HH was diagnosed at median (range) of 9 (1,180) days, with diazoxide commenced 4 (0,76) days from diagnosis and reaching a maximum dose of 7 (2.5,20) mg/kg/d. The majority (8 of 13 patients) developed PH within 2 weeks of diazoxide. Complete diazoxide withdrawal, but not dose reduction, led to PH resolution at 41 (3,959) days. In three patients, PH continued beyond 12 months.Risk factors for the development of PH included the presence of congenital heart disease (CHD) (P = .008), and total fluid volume exceeding 130 mL/kg/d in the immediate 24 hours preceding diazoxide (P = .019). Conclusion:Pulmonary hypertension can occur in 7% of diazoxide-treated HH patients. Risk factors include the presence of congenital heart disease and fluid overload.Recommendations include echocardiography and fluid restriction to 130 mL/kg/d prior to diazoxide treatment and immediate discontinuation of diazoxide if PH develops. K E Y W O R D Sdiazoxide, echocardiography, hyperinsulinism, hypoglycaemia, pulmonary hypertension | 771 CHEN Et al.

Small for gestational age (SGA) children exhibiting catch-up (CU) growth have a greater risk of cardiometabolic diseases in later life compared with non-catch-up (NCU) SGA children. The aim of this study was to establish differences in metabolism and gene expression profiles between CU and NCU at age 4-9 years. CU children (n=22) had greater height, weight and body mass index standard deviation scores along with insulin-like growth factor-I (IGF-I) and fasting glucose levels but lower adiponectin values than NCU children (n=11; all P<0.05). Metabolic profiling demonstrated a fourfold decrease of urine myo-inositol in CU compared with NCU (P<0.05). There were 1558 genes differentially expressed in peripheral blood mononuclear cells between the groups (P<0.05). Integrated analysis of data identified myo-inositol related to gene clusters associated with an increase in insulin, growth factor and IGF-I signalling in CU children (P<0.05). Metabolic and transcriptomic profiles in CU SGA children showed changes that may relate to cardiometabolic risk.

Background: Recombinant human growth hormone (rhGH) is being used to promote linear growth in short children with Noonan syndrome. However, its efficacy is still controversial. Aims: To systematically determine the impact of rhGH therapy on adult height in children with Noonan syndrome. Methods: We searched the Cochrane Central Register of Controlled Trials, ISI Web of Science, MEDLINE, and the bibliographic references from all retrieved articles published until April 2014. Studies reporting adult/near-adult height in children with Noonan syndrome treated with rhGH or reporting at least a 3-year follow-up were analysed. Quality and strength of recommendation were assessed according to the Endocrine Society criteria. Results: No controlled trials reporting adult height were available. Five studies were identified reporting adult height or near adult height. Data comparison showed inter-individual variability in the response to rhGH, mean height gain standard deviation score ranging between 0.6 and 1.4 according to national standards, and between 0.6 and 2 according to Noonan standards. Significant biases affected all the studies. Conclusions: High-quality controlled trials on the impact of rhGH therapy on adult height are lacking, and the robustness of available data is not sufficient to recommend such therapy in children with Noonan syndrome.

Corticosteroids are incorporated into protocols for the treatment of acute lymphoblastic leukaemia, and hyperglycaemia is a recognised side effect. Corticosteroids exert their hyperglycaemic effect with a multifactorial mechanism. Complications of hyperglycaemia include an increased risk of infection – bacterial, viral and fungal. Approximately half of the children who develop corticosteroid‐associated hyperglycaemia are predicted to require insulin treatment, with age and obesity having found to be predictive factors. Fasting and random glucose values can be used to define hyperglycaemia. This review focuses on the published evidence for significant predictive factors for the development of corticosteroid‐induced hyperglycaemia and provides guidance on management.