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Growth hormone deficiency (GHD) describes the impairment of growth hormone (GH) secretion by the pituitary somatotroph cells. GHD may be congenital, with causes, including genetic alterations and structural brain malformations, or acquired, including midline tumours, cranial irradiation, traumatic brain injury, central nervous system infections and inflammatory conditions. GHD in children is characterised by short stature, delayed bone maturation and abnormalities in substrate metabolism, body composition, physical and psychosocial functioning, all of which improve with recombinant human GH (rhGH) therapy. The diagnosis of GHD is based on clinical signs and symptoms, biochemistry and imaging. Although GH stimulation tests are considered the mainstay of diagnostic investigations, the results must be interpreted with caution owing to the variability in cut-off values and reproducibility. Transition refers to the physical and psychosocial changes in adolescent patients during the mid-teens to late teens (usually 15–18 years of age) until about 6–7 years after achievement of adult height. During the transition age, only a small residual capacity of longitudinal growth is left, but body maturity is not yet complete. Discontinuation of rhGH treatment at the end of longitudinal growth in adolescents with permanent GHD is associated with decreased muscle strength and mass, increased body fat (mainly in the abdomen), the arrest or reversal of muscle mass and bone mass density (BMD) gain and lipid profile deterioration. For these reasons, patients whose GHD persists during the transition age need to continue rhGH treatment to obtain full somatic maturation and normalisation of body composition, BMD, quality of life (QoL) and lipid metabolism. There is some evidence that rhGH treatment during transition may result in improved growth and bone health, as well as a better prognosis for metabolic and cardiovascular risks in the long term. Since these patients need to continue treatment to complete their body development, a multidisciplinary approach is required to ensure continuity of care during the transfer from paediatric to adult endocrinology services. Guidelines for the diagnosis and treatment of young adults with GHD have been published by the American Association of Clinical Endocrinologists (AACE), American College of Endocrinology (ACE), Endocrine Society, European Society of Paediatric Endocrinology (ESPE), Lawson Wilkins Society, European Society of Endocrinology, Japan Endocrine Society and Endocrine Society of Australia. However, clinical practice lacks uniformity in terms of diagnosis and treatment of transition-age patients, the impact of GH replacement during transition has not been adequately assessed in randomised clinical trials (RCTs), validated questionnaires to assess QoL in patients on rhGH treatment in the transition period are not available and there is still uncertainty about the multidisciplinary approach during transition [8]. Hence, a structured transition protocol is essential to establish the best practice for transitioning adolescents with GHD to adult care. A study in Italy in 2015 identified a low level of awareness of these issues in clinical practice and real-world gaps in the management of GHD patients during transition. To address these gaps and assist endocrinologists (adult and paediatric) in the diagnosis and treatment of GHD in transition-age patients, a Delphi consensus process was undertaken to develop clinically relevant recommendations. The current consensus statements address the diagnosis of GHD, benefits of treatment, monitoring and management of transition-age patients with GHD, along with treatment adherence and safety concerns.

Aim: To investigate the potential association among Craniopharyngioma (CP), chronotypes and metabolic risk profile. Subjects and Methods: The study population included 28 patients (46.4% males; 42.6 ± 15.8 years) and 28 controls, age, gender and BMI matched (46.4% males; 46.5 ± 12.9 years). In this study sample, we evaluated: anthropometric measurements (waist circumference, WC; BMI), plasma glucose, lipid profile, and systolic (SBP) and diastolic (DBP) blood pressure. Morningness-Eveningness was measured with the Horne-Ostberg Morningness-Eveningness Questionnaire (MEQ), which included 19 questions about preferred sleep time and daily performance. Results: in both patients and controls grade I obesity was detected in 15 subjects (53.6%), grade II obesity in 13 subjects (46.4%). In the patient group, the mean score of chronotype was 47.8 ± 12.6. In particular, 9 patients (32.1%) exhibited the morning chronotype, 6 (21.4%) the intermediate chronotype and 13 (46.4.%) the evening chronotype. No significant difference was found in gender and age among the chronotype categories. Patients with the evening chronotype had higher blood pressure values and worse metabolic parameters than those with the morning chronotype. In the control group, the mean score of the chronotype was 57.6 ± 9.5. In particular, 16 (57.1%) subjects exhibited the morning chronotype, 10 (35.7%) the intermediate chronotype and only 2 (7.1.%) the evening chronotype. The prevalence of intermediate and evening chronotypes was higher in females than males (p = 0.021), while males have a higher prevalence of the morning chronotype. Subjects with intermediate and evening chronotypes had worse metabolic parameters than those with the morning chronotype. In patients, the chronotype score was inversely correlated to WC, BMI, SBP, DBP, plasma glucose, total cholesterol, triglycerides, LDL cholesterol and positively correlated with HDL cholesterol. No correlation was found between age and chronotype. In controls, the chronotype score was inversely correlated to WC, BMI, plasma glucose, total cholesterol, LDL cholesterol. No correlation was found among chronotype and age, blood pressure, triglycerides, HDL cholesterol. Considering the whole population of the study (patients and controls), at logistic regression the chronotype score was significantly associated with the presence of CP. Conclusions: for the first time thus far, our study puts the light on the association of the CP with chronotypes and metabolic alterations in this disease, which are the main determinants of the reduced quality of life, higher morbidity and mortality in this setting of patients. This finding suggests that alterations of chronotype might represent an adjunctive risk for CP patients and a possible target for their integrate management.

Growing body of scientific evidence points to link between fibroblast growth factor-23 (FGF-23) and unfavourable metabolic profile (obesity, insulin resistance, hyperglycemia) and all-cause mortality in general population with normal kidney function. On the other hand, there is little information about metabolic profile in situations characterized by pathophysiologically high FGF-23 such as chronic kidney disease and X-linked hypophosphatemia (XLH). The aim of the present longitudinal observational study was to investigate anthropometric parameters of obesity and metabolic profile on large cohort of children with XLH. Methods: Among 263 XLH-patients registered in our centre we selected 168 children of 5-20 years (108 girls/60 boys). Total period of FU was divided in five sub-periods according age (group 0: birth, N=168; group 1: 5-7 years, N=122; group 2: 7-10 years, N=86; group 3: 10-15 years, N=89; group 4: 15-20 years, N=49). Anthropometric parameters (weight, height, BMI) were collected from birth (group 0) and for every point of FU (group 1-4). In each group, subjects were classified based on International Obesity Taskforce (IOTF) cut off values of BMI for age and sex as overweight or obese (IOTF 25-30 or ≥30 kg/m2, respectively). Metabolic parameters (total cholesterol, triglycerides, HDL, LDL, fasting glycemia and insulinemia, HOMA-IR) were measured at one point of FU in some patients (N=40). Results: In each group of FU (1,2,3,4) almost 1/3 of patients were classified as overweight or obese (29.5% vs 29.4% vs 28.1% vs 36.7%, respectively). Even without reaching statistical significance (p=0.75), there was a tendency of higher number of overweight or obese patients in group 4 (15-20 years) (36.7%) compared to group 1,2,3, which was explained by gender differences (higher number of overweight or obese girls compared to boys (42.4% vs 25%, respectively, p=0.35). There were no differences in BMI z-score (SDS) and BMI-IOTF between groups 1,2,3,4 during FU (BMI-SDS: 0.9±1.1 vs 0.7±1.0 vs 0.6±1.1 vs 0.6±0.9, respectively, p=0.45; BMI-IOTF: 23.5±4.4 vs 23.5±4.1 vs 23.7±4.2 vs 24.3±3.6, respectively, p=0.72). As regard other metabolic parameters, only 1 patient was diagnosed with diabetes mellitus at age 10. No other alterations were found. In each group of FU, no correlation was found between FGF-23 and BMI, total cholesterol, triglycerides, HDL, LDL, fasting glycemia, insulinemia, HOMA-IR. In conclusion, 1/3 of XLH children have phenotypically unfavourable metabolic profile expressed as overweight or obesity which is higher compared to general paediatric population. This phenomenon has increasing tendency after puberty, especially in girls, and requires strict follow-up of BMI in XLH patients. In order to understand the further development of metabolic parameters, the studies on adult XLH population are needed.