Appropriate management of growth hormone deficiency during the age of transition: an Italian Delphi consensus statement

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.