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Smart technologies and connected health are providing opportunities for improved healthcare for chronic conditions. Acceptance by healthcare professionals (HCPs) and patients is crucial for successful implementation. Evidence-based standards, technological infrastructure and regulatory processes are needed to integrate digital tools into clinical practice. Personal health records provide continuity and aid decision-making, while machine-learning algorithms may help in optimizing therapies and improving outcomes. Digital healthcare can negate geographical barriers, enabling patients in remote areas to access specialist endocrine expertise. We review available and developing digital tools to manage care for patients requiring growth hormone (GH) therapy for growth failure conditions. GH is most often administered via daily injections over several years; continuous adherence is necessary but may become insufficient. Future development and integration of electronic platforms for GH therapy requires involvement of all stakeholders in design-thinking approaches and human-factor testing. Growzen Connect is an innovative digital ecosystem designed to increase the management and monitoring of GH therapy, comprising the easypod device and connected mobile apps. It provides a real-time overview of a patient’s therapy, including adherence and growth response, which aids decision-making by HCPs and empowers patients to engage in their therapy journey. Incorporating prediction models for adherence and growth in the ecosystem helps patients build treatment habits and allows issues to be addressed in a timely fashion. A connected ecosystem for GH therapy can enhance outcomes and empower patients, fostering a collaborative and patient-centered approach that is more proactive, beyond the traditional clinic-based approach.

IntroductionTo analyse the perspectives of healthcare professionals (HCPs) regarding the acceptance of digital health solutions for growth hormone (GH) deficiency care. This study identified factors impacting HCPs’ intent to use and recommend digital solutions supporting recombinant-human growth hormone (r-hGH) therapy in Italy and Korea with a use case of connected drug delivery system (Aluetta® with Smartdot™) integrated in a platform for GH treatment support (the Growzen™ digital health ecosystem).MethodsParticipatory workshops were conducted in Rome, Italy, and Seoul, Korea, to collect the perspectives of 22 HCPs on various predefined topics. HCPs were divided into two teams, each moderated by a facilitator. The workshops progressed in five phases: introduction of the project and experts, capturing views on the current context of digitalisation, perceived usefulness and ease of use of Aluetta® with Smartdot™, exploration of the perception of health technology evolution, and combined team recommendations. Data shared by HCPs on technology acceptance were independently analysed using thematic analysis, and relevant findings were shared and validated with experts.ResultsHCPs from both Italy and Korea perceived Aluetta® with Smartdot™ and the Growzen™ based digital health ecosystem as user-friendly, intuitive, and easy-to-use solutions. These solutions can result in increased adherence, a cost-effective healthcare system, and medication self-management. Although technology adoption and readiness may vary across countries, it was agreed that using digital solutions tailored to the needs of users may help in data-driven clinical decisions and strengthen HCP–patient relationships.ConclusionHCPs’ perspectives on the digitalisation in paediatric GH therapies suggested that digital solutions enable automatic, real-time injection data transmission to support adherence monitoring and evidence-based therapy, strengthen HCP–patient relationships, and empower patients throughout the GH treatment process.

IntroductionThis study in Argentina evaluated the impact of the growzen™ buddy smartphone app on adherence to recombinant human growth hormone (r-hGH) treatment.MethodsThe adherence data, invitation dates with a link to the app, app activation dates, and height measurements entered were extracted from the growzen™ digital health ecosystem. Patients with 12 months of adherence data, aged ≥2 years at treatment start, and aged

Worldwide regulations during COVID-19 positively and negatively impacted self-management in paediatric patients with chronic medical conditions. We investigated the impact of regulations on adherence to recombinant human growth hormone (r-hGH) therapy in paediatric patients with growth disorders, using real-world adherence data extracted March 2019–February 2020 (before COVID-19) and March 2020–February 2021 (during COVID-19) from the easypod™ connect ecosystem. Data from three measures of regulations were analysed: stringency index (SI), school closure and stay-at-home. The mean SI, and the proportion of days with required school closure or stay-at-home during COVID-19 were categorised as high versus medium/low based on the 75th percentile. Adherence was categorised as optimal (≥85%) versus suboptimal (p < 0.001). Stay-at-home requirements showed no statistically significant effect (p = 0.13). Stringent COVID-19 regulations resulted in improved adherence to r-hGH therapy in patients with growth disorders, supported by connected digital health technologies. Insights into patient behavior during this time are useful to understand potential influences and strategies to improve long-term adherence to r-hGH.

Diagnosis and management of individuals who have differences of sex development (DSD) due to numerical or structural variations of sex chromosomes (NSVSC) remains challenging. Girls who have Turner syndrome (45X) may present with varying phenotypic features, from classical/severe to minor, and some remain undiagnosed. Boys and girls who have 45,X/46,XY chromosomal mosaicism may have Turner syndrome-like features and short stature; therefore, unexplained short stature during childhood requires karyotype analysis in both sexes, particularly if characteristic features or atypical genitalia are present. Many individuals with Klinefelter syndrome (47XXY) remain undiagnosed or are only diagnosed as adults due to fertility problems. Newborn screening by heel prick tests could potentially identify sex chromosome variations but would have ethical and financial implications, and in-depth cost-benefit analyses are needed before nationwide screening can be introduced. Most individuals who have NSVSC have lifelong co-morbidities and healthcare should be holistic, personalized and centralized, with a focus on information, psychosocial support and shared decision-making. Fertility potential should be assessed individually and discussed at an appropriate age. Oocyte or ovarian tissue cryopreservation is possible in some women who have Turner syndrome and live births have been reported following assisted reproductive technology (ART). Testicular sperm cell extraction (TESE) is possible in some men who have 45,X/46,XY mosaicism, but there is no established protocol and no reported fathering of children. Some men with Klinefelter syndrome can now father a child following TESE and ART, with multiple reports of healthy live births. Children who have NSVSC, their parents and DSD team members need to address possibilities and ethical questions relating to potential fertility preservation, with guidelines and international studies still needed.

Abstract Background Our aim was to develop a machine learning model, using real-world data captured from a connected auto-injector device and from early indicators from the first 3 months of treatment, to predict sub-optimal adherence to recombinant human growth hormone (r-hGH) in patients with growth disorders. Methods Adherence to r-hGH treatment was assessed in children (aged

BackgroundChildren with growth hormone deficiency face the prospect of long-term recombinant human growth hormone (r-hGH) treatment requiring daily injections. Adherence to treatment is important, especially at treatment initiation, to achieve positive health outcomes. Historically, telenursing services embedded in patient support programs (PSPs) have been a valid approach to support r-hGH treatment initiation and patient education and facilitate adherence by identifying and optimizing appropriate injection techniques. The development of mobile phones with augmented reality (AR) capabilities offers nurses new tools to support patient education. ObjectiveTo investigate experiences among nurses of a new mobile phone app developed to support patient training with a phone-based PSP for r-hGH treatment. MethodsIn 2020, the Easypod AR mobile app was launched to support nurse-driven telehealth education for patients initiating r-hGH therapy with the Easypod electromechanical auto-injector device. Nurses who were part of PSPs in countries where the Easypod AR app had been launched or where training was provided as part of an anticipated future launch of the app were invited to participate in an online survey based on the Mobile App Rating Scale to capture their feedback after using the app. ResultsIn total, 23 nurses completed the online questionnaire. They positively rated the quality of the app across multiple dimensions. The highest mean scores were 4.0 for engagement (ie, adaptation to the target group; SD 0.74), 4.1 (SD 0.79) for functionality (navigation) and 4.1 (SD 0.67) for aesthetics (graphics). Responses indicated the potential positive impact of such a tool on enhancing patient education, patient support, and communication between patients and PSP nurses. Some participants also suggested enhancements to the app, including gamification techniques that they felt have the potential to support the formation of positive treatment behaviors and habits. ConclusionsThis study highlights the potential for new digital health solutions to reinforce PSP nurse services, including patient education. Future studies could explore possible correlations between any behavioral and clinical benefits that patients may derive from the use of such apps and how they may contribute to support improved patient experiences and treatment outcomes.

BackgroundGrowth hormone deficiency (GHD) is a rare disorder characterized by inadequate secretion of growth hormone (GH) from the anterior pituitary gland. One of the challenges in optimizing GH therapy is improving adherence. Using digital interventions may overcome barriers to optimum treatment delivery. Massive open online courses (MOOCs), first introduced in 2008, are courses made available over the internet without charge to a large number of people. Here, we describe a MOOC aiming to improve digital health literacy among healthcare professionals managing patients with GHD. Based on pre- and post-course assessments, we evaluate the improvement in participants’ knowledge upon completion of the MOOC.MethodsThe MOOC entitled ‘Telemedicine: Tools to Support Growth Disorders in a Post-COVID Era’ was launched in 2021. It was designed to cover 4 weeks of online learning with an expected commitment of 2 h per week, and with two courses running per year. Learners’ knowledge was assessed using pre- and post-course surveys via the FutureLearn platform.ResultsOut of 219 learners enrolled in the MOOC, 31 completed both the pre- and post-course assessments. Of the evaluated learners, 74% showed improved scores in the post-course assessment, resulting in a mean score increase of 21.3%. No learner achieved 100% in the pre-course assessment, compared with 12 learners (40%) who achieved 100% in the post-course assessment. The highest score increase comparing the pre- and the post-course assessments was 40%, observed in 16% of learners. There was a statistically significant improvement in post-course assessment scores from 58.1 ± 18.9% to 72.6 ± 22.4% reflecting an improvement of 14.5% (p

IntroductionThe appropriate use of recombinant human growth hormone (r-hGH) treatment provides an opportunity to improve growth outcomes among pediatric patients with growth hormone deficiency (GHD). However, a major challenge in clinical practice is to adequately recognize and address factors that negatively affect treatment adherence. TUITEK® patient support program (PSP) was designed to help caregivers of children diagnosed with GHD to personalize the care pathway, improve adherence, and achieve better outcomes. Effectiveness of TUITEK® PSP has been demonstrated previously in a smaller sample (n = 31) in Taiwanese population. Here, we present the results from Argentina.MethodsTUITEK® PSP was piloted among 76 caregivers of children with GHD administering r-hGH using easypod™ (Merck KGaA, Darmstadt, Germany) auto-injector device in Argentina. Based on TUITEK® personalization questionnaire, caregivers were assigned to high- and low-risk groups across four categories that may influence adherence, including disease and treatment coherence (DTC), self-administration (SA), treatment-related anxiety (TRA), and emotional burden (EB). The caregivers who were included in atleast one high-risk group had the provision of telephone calls with a nurse practitioner every 2 weeks for 3 months. The Wilcoxon signed-rank test was employed to assess changes in questionnaire-based scoring patterns between baseline and follow-up evaluations.ResultsStatistically significant changes (p < 0.05) in questionnaire scores between baseline and follow-up evaluations were observed across the four categories. The mean/median DTC (n = 11) and SA (n = 23) scores changed from 2.45/3 and 2.17/2, respectively, to 4/4, with all the caregivers moving to low-risk group following program completion (100%) for both categories. The mean/median TRA score (n = 40) changed from 3.58/3 to 2.5/2 and 67.5% of patients (27/40) moved to low-risk group. The mean/median EB score (n = 32) changed from 3.69/3 to 3.13/3 however, none of the caregivers moved to low-risk group (0%).ConclusionTUITEK® PSP is a simple, practical, and time-efficient interventional tool that can be used to address key adherence-related issues among caregivers of children with GHD and provide personalized adherence support. Our findings demonstrate that TUITEK® PSP has the potential to improve treatment adherence and self-management, thereby improving growth outcomes in Argentina.

Curve matching may be used to predict growth outcomes using data of patients whose growth curves resemble those of a new patient with growth hormone deficiency (GHD) and those born small for gestational age (SGA). We aimed to investigate the validity of curve matching to predict growth in patients with GHD and those born SGA receiving recombinant human growth hormone (r-hGH). Height data collected between 0–48 months of treatment were extracted from the easypod™ connect ecosystem and the easypod™ connect observational study. Selected patients with height standard deviation scores (HSDS) [-4,

Assessment and management of children with growth failure has improved greatly over recent years. However, there remains a strong potential for further improvements by using novel digital techniques. A panel of experts discussed developments in digitalization of a number of important tools used by pediatric endocrinologists at the third 360° European Meeting on Growth and Endocrine Disorders, funded by Merck KGaA, Germany, and this review is based on those discussions. It was reported that electronic monitoring and new algorithms have been devised that are providing more sensitive referral for short stature. In addition, computer programs have improved ways in which diagnoses are coded for use by various groups including healthcare providers and government health systems. Innovative cranial imaging techniques have been devised that are considered safer than using gadolinium contrast agents and are also more sensitive and accurate. Deep-learning neural networks are changing the way that bone age and bone health are assessed, which are more objective than standard methodologies. Models for prediction of growth response to growth hormone (GH) treatment are being improved by applying novel artificial intelligence methods that can identify non-linear and linear factors that relate to response, providing more accurate predictions. Determination and interpretation of insulin-like growth factor-1 (IGF-1) levels are becoming more standardized and consistent, for evaluation across different patient groups, and computer-learning models indicate that baseline IGF-1 standard deviation score is among the most important indicators of GH therapy response. While physicians involved in child growth and treatment of disorders resulting in growth failure need to be aware of, and keep abreast of, these latest developments, treatment decisions and management should continue to be based on clinical decisions. New digital technologies and advancements in the field should be aimed at improving clinical decisions, making greater standardization of assessment and facilitating patient-centered approaches.

Abstract Background A range of factors can reduce the effectiveness of treatment prescribed for the long-term management of chronic health conditions, such as growth disorders. In particular, prescription medications may not achieve the positive outcomes expected because approximately half of patients adhere poorly to the prescribed treatment regimen. Methods Adherence to treatment has previously been assessed using relatively unreliable subjective methods, such as patient self-reporting during clinical follow-up, or counting prescriptions filled or vials returned by patients. Here, we report on a new approach, the use of electronically recorded objective evidence of date, time, and dose taken which was obtained through a comprehensive eHealth ecosystem, based around the easypod™ electromechanical auto-injection device and web-based connect software. The benefits of this eHealth approach are also illustrated here by two case studies, selected from the Finnish cohort of the easypod™ Connect Observational Study (ECOS), a 5-year, open-label, observational study that enrolled children from 24 countries who were being treated with growth hormone (GH) via the auto-injection device. Results Analyses of data from 9314 records from the easypod™ connect database showed that, at each time point studied, a significantly greater proportion of female patients had high adherence (≥ 85%) than male patients (2849/3867 [74%] vs 3879/5447 [71%]; P

Digital health has seen rapid advancements over the last few years in helping patients and their healthcare professionals better manage treatment for a variety of illnesses, including growth hormone (GH) therapy for growth disorders in children and adolescents. For children and adolescents requiring such therapy, as well as for their parents, the treatment is longitudinal and often involves daily injections plus close progress monitoring; a sometimes daunting task when young children are involved. Here, we describe our experience in offering devices and digital health tools to support GH therapy across some 40 countries. We also discuss how this ecosystem of care has evolved over the years based on learnings and advances in technology. Finally, we offer a glimpse of future planned enhancements and directions for digital health to play a bigger role in better managing conditions treated with GH therapy, as well as model development for adherence prediction. The continued aim of these technologies is to improve clinical decision making and support for GH-treated patients, leading to better outcomes.

PurposePoor adherence to recombinant human growth hormone (r-hGH) treatment presents a significant barrier to achieving optimal growth outcomes. It is important to identify and address the treatment adherence-related needs of children prescribed r-hGH treatment, and develop new approaches to improve adherence. We aimed to measure the impact of the TUITEK® patient support programme, a multi-component personalized service intervention, on caregivers’ knowledge, beliefs, and perceptions of short stature and adherence to its treatment.Patients and MethodsThe evaluation of the TUITEK® patient support programme was conducted among 31 caregivers of children with short stature and receiving r-hGH treatment via the easypod™ auto-injector device in Taiwan. Caregivers within the ‘high risk’ category for knowledge, beliefs and perception factors influencing adherence to r-hGH treatment (disease and treatment coherence, emotional burden, self-administration, and treatment-related anxiety) were identified via the TUITEK® personalization questionnaire and followed up with bi-weekly telephone calls by a nurse practitioner over a 3-month period. A Wilcoxon signed-rank test was used to compare changes in questionnaire-based scoring patterns between baseline and follow-up.ResultsBetween baseline and follow-up, the percentage of caregivers scoring as ‘high risk’ for emotional burden reduced by 37%; there was an improvement in confidence of self-administration by 57% and the percentage of caregivers scoring as ‘high risk’ for treatment-related anxiety reduced by 52%. At follow-up, all caregivers classified as ‘high risk’ within the disease and treatment coherence item at baseline moved into the ‘low risk’ category. Statistically significant changes in questionnaire scores between baseline and follow-up for disease and treatment understanding, emotional burden, self-administration, and treatment-related anxiety were also observed.ConclusionThese findings indicate that the TUITEK® patient support programme can positively address disease and treatment-related barriers amongst caregivers regarding optimal adherence of their children to r-hGH treatment, which has the potential to positively impact on adherence levels and patient clinical health outcomes.

Abstract Background Poor adherence to long-term recombinant human growth hormone (r-hGH) treatment can lead to suboptimal clinical outcomes; consequently, supporting and monitoring adherence is a crucial part of patient management. We assessed adherence to r-hGH treatment in children with growth disorders over 48 months using a connected monitoring device (easypod™), which automatically transmits adherence data via an online portal (easypod™ connect); both sit within an adherence decision support system (ADSS). We also investigated the effect of age and sex on adherence. Methods Data from children transmitting over 10 injections between January 2007 and February 2019 were analyzed. Adherence (mg injected/mg prescribed) was categorized as high (≥85%), intermediate (> 56–84%) or low (≤56%) and assessed at seven time points from the start of treatment up to 48 months. Adherence was investigated over time and stratified by puberty status and sex. Mean transmission rate in each adherence category (total number of transmissions/total number of children) at each time point was calculated as a proxy measure of engagement in disease and treatment management. Descriptive analyses were performed. Results Longitudinal records were available for 13,553 children. Overall, 71% (n = 9578) had high adherence, 22% (n = 2989) intermediate and 7% (n = 986) low. The proportion of children with high adherence decreased over time from 87% (n = 12,964) to 65% (n = 957) and was higher in pre-pubertal than pubertal children (girls: 80% [n = 1270] vs 70% [n = 4496]; boys 79% [n = 2573] vs 65% [n = 5214]). Children with high adherence had a higher mean number of transmissions (12.5 [SD 24.9]) than children with intermediate (7.2 [SD 15.3]) or low (3.5 [SD 5.7]) adherence. Conclusions High adherence was seen in patients administering r-hGH using the connected device. Children with high adherence were most likely to regularly transmit data. Pubertal children showed lower adherence. We show the potential to develop an ADSS to analyze trends in real-world adherence data. This may prove useful to direct interventions to improve adherence while the ability to readily share data with healthcare professionals may itself improve adherence.

BackgroundRecombinant human growth hormone (rhGH) therapy is an effective treatment for children with growth disorders. However, poor outcomes are often associated with suboptimal adherence to treatment. ObjectiveThe easypod connected injection device records and transmits injection settings and dose data from patients receiving rhGH. In this study, we evaluated adherence to rhGH treatment, and associated growth outcomes, in Latin American patients. MethodsAdherence and growth data from patients aged 2-18 years from 12 Latin American countries were analyzed. Adherence data were available for 6207 patients with 2,449,879 injections, and growth data were available for 497 patients with 2232 measurements. Adherence was categorized, based on milligrams of rhGH injected versus milligrams of rhGH prescribed, as high (≥85%), intermediate (>56%-

It is over sixty years since the first administration of human growth hormone (GH) to children with GH deficiency, and over thirty years since recombinant human GH has been available for treatment of GH deficiency and a wider range of non-GH deficiency disorders. From a diagnostic perspective, genetic analysis, using single gene or Sanger sequencing and more recently next generation or whole exome sequencing, has brought advances in the diagnosis of specific causes of short stature, which has enabled therapy to be targeted more accurately. Genetic discoveries have ranged from defects of pituitary development and GH action to abnormalities in intracellular mechanisms, paracrine regulation and cartilage matrix formation. The strategy of GH therapy using standard doses has evolved to individualised GH dosing, depending on diagnosis and predictors of growth response. Evidence of efficacy of GH in GH deficiency, Turner syndrome and short children born small for gestational age is reviewed. The importance of critical assessment of growth response is discussed, together with the recognition and management of a poor or unsatisfactory growth response and the organisational issues related to prevention, detection and intervention regarding suboptimal adherence to GH therapy.

Digitalization of healthcare delivery is rapidly fostering development of precision medicine. Multiple digital technologies, known as telehealth or eHealth tools, are guiding individualized diagnosis and treatment for patients, and can contribute significantly to the objectives of precision medicine. From a basis of “one-size-fits-all” healthcare, precision medicine provides a paradigm shift to deliver a more nuanced and personalized approach. Genomic medicine utilizing new technologies can provide precision analysis of causative mutations, with personalized understanding of mechanisms and effective therapy. Education is fundamental to the telehealth process, with artificial intelligence (AI) enhancing learning for healthcare professionals and empowering patients to contribute to their care. The Gulf Cooperation Council (GCC) region is rapidly implementing telehealth strategies at all levels and a workshop was convened to discuss aspirations of precision medicine in the context of pediatric endocrinology, including diabetes and growth disorders, with this paper based on those discussions. GCC regional investment in AI, bioinformatics and genomic medicine, is rapidly providing healthcare benefits. However, embracing precision medicine is presenting some major new design, installation and skills challenges. Genomic medicine is enabling precision and personalization of diagnosis and therapy of endocrine conditions. Digital education and communication tools in the field of endocrinology include chatbots, interactive robots and augmented reality. Obesity and diabetes are a major challenge in the GCC region and eHealth tools are increasingly being used for management of care. With regard to growth failure, digital technologies for growth hormone (GH) administration are being shown to enhance adherence and response outcomes. While technical innovations become more affordable with increasing adoption, we should be aware of sustainability, design and implementation costs, training of HCPs and prediction of overall healthcare benefits, which are essential for precision medicine to develop and for its objectives to be achieved.

Children born small for gestational age (SGA) comprise a heterogeneous group due to the varied nature of the cause. Approximately 85–90% have catch-up growth within the first 4 postnatal years, while the remainder remain short. In later life, children born SGA have an increased risk to develop metabolic abnormalities, including visceral adiposity, insulin resistance, and cardiovascular problems, and may have impaired pubertal onset and growth. The third “360° European Meeting on Growth and Endocrine Disorders” in Rome, Italy, in February 2018, funded by Merck KGaA, Germany, included a session that examined aspects of short children born SGA, with three presentations followed by a discussion period, on which this report is based. Children born SGA who remain short are eligible for GH treatment, which is an approved indication. GH treatment increases linear growth and can also improve some metabolic abnormalities. After stopping GH at near-adult height, metabolic parameters normalize, but pharmacological effects on lean body mass and fat mass are lost; continued monitoring of body composition and metabolic changes may be necessary. Guidelines have been published on diagnosis and management of children with Silver-Russell syndrome, who comprise a specific group of those born SGA; these children rarely have catch-up growth and GH treatment initiation as early as possible is recommended. Early and moderate pubertal growth spurt can occur in children born SGA, including those with Silver-Russell syndrome, and reduce adult height. Treatments that delay puberty, specifically metformin and gonadotropin releasing hormone analogs in combination with GH, have been proposed, but are used off-label, currently lack replication of data, and require further studies of efficacy and safety.

Objective: The easypod connect observational study (ECOS) assessed treatment adherence among paediatric patients receiving growth hormone (GH) via the easypod electronic injection device. Design: ECOS was an open-label, observational, longitudinal study conducted in 24 countries between 2010 and 2016, enrolling children treated with GH. Methods: The primary endpoint was the rate of treatment adherence during 5 years of follow-up. Impact of adherence on growth outcomes was assessed using Spearman’s product–moment correlations. Results and conclusions: Overall, 1190 patients had easypod data available for ≥3 months; most patients had GH deficiency (75%); 606 of these patients were GH naïve at baseline. Over the first year of monitoring, the median rate of adherence was 93.7% among patients overall and >93.0% in GH-naïve patients, irrespective of the treatment indication. Clinically meaningful improvements in growth rates were observed after 1 year of treatment across all GH indications. Adherence decreased with increasing treatment duration, but the overall median adherence rate remained high after 3 years of follow-up: 87.2% (n = 409), 75.5% after 4 years (n = 143) and 70.2% after 5 years (n = 43). Statistically significant correlations between adherence and 1-year change in height standard deviation score (P < 0.001 for patients overall) and height velocity (P < 0.001) were observed. Conclusions: ECOS produced accurate, real-time adherence data in a large population of GH-treated children over 5 years of follow-up. Using the easypod connect system, physicians can potentially identify patients with inadequate adherence and poor response to treatment, enabling them to take appropriate action to help them maximise the benefits of GH treatment.

The growth hormone (GH)–insulin-like growth factor (IGF)-I axis is a key endocrine mechanism regulating linear growth in children. While paediatricians have a good knowledge of GH secretion and assessment, understanding and use of measurements of the components of the IGF system are less current in clinical practice. The physiological function of this axis is to increase the anabolic cellular processes of protein synthesis and mitosis, and reduction of apoptosis, with each being regulated in the appropriate target tissue. Measurement of serum IGF-I and IGF-binding protein (IGFBP)-3 concentrations can complement assessment of GH status in the investigation of short stature and contribute to prediction of growth response during GH therapy. IGF-I monitoring during GH therapy also informs the clinician about adherence and provides a safety reference to avoid over-dosing during long-term management.

BACKGROUND:Quantifying the association between adherence and the growth response to growth hormone (GH) treatment is hampered by suboptimal methods of measuring adherence, confounders associated with the growth response, and restriction of the outcome parameters to yearly growth velocities. AIM:To investigate the effect of adherence on the two-year growth response to GH treatment in prepubertal children with idiopathic isolated growth hormone deficiency (GHD) participating in the easypod connect observational study (ECOS), a 5-year, Phase IV open-label study to continuously assess real-world adherence via the easypod electronic drug-delivery device. PATIENTS AND METHODS:Outcome measures were change in height standard deviation score (ΔHSDS), index of responsiveness (IoR), and parameters of two catch-up growth (CUG) curve functions (monomolecular growth curve and second degree polynomial) with adj-HSDS (HSDS minus Target height (TH) SDS) as dependent variable. Inclusion criteria were GHD, naïve to GH treatment, known TH, age

The “360° GH in Europe” meeting, which examined various aspects of GH diseases, was held in Lisbon, Portugal, in June 2016. The Merck KGaA (Germany) funded meeting comprised three sessions entitled “Short Stature Diagnosis and Referral,” “Optimizing Patient Management,” and “Managing Transition.” Each session had three speaker presentations, followed by a discussion period, and is reported as a manuscript, authored by the speakers. The first session examined current processes of diagnosis and referral by endocrine specialists for pediatric patients with short stature. Requirements for referral vary widely, by country and by patient characteristics such as age. A balance must be made to ensure eligible patients get referred while healthcare systems are not over-burdened by excessive referrals. Late referral and diagnosis of non-GH deficiency conditions can result in increased morbidity and mortality. The consequent delays in making a diagnosis may compromise the effectiveness of GH treatment. Algorithms for growth monitoring and evaluation of skeletal disproportions can improve identification of non-GH deficiency conditions. Performance and validation of guidelines for diagnosis of GH deficiency have not been sufficiently tested. Provocative tests for investigation of GH deficiency remain equivocal, with insufficient information on variations due to patient characteristics, and cutoff values for definition differ not only by country but also by the assay used. When referring and diagnosing causes of short stature in pediatric patients, clinicians need to rely on many factors, but the most essential is clinical experience.

Growth hormone (GH) promotes growth in children, but is also essential for bone strength, body composition, metabolic factors, such as lipid profile, and maintenance of quality of life. The Merck KGaA (Germany) funded “360° GH in Europe” meeting, held in Lisbon, Portugal, in June 2016, comprised three sessions entitled “Short Stature Diagnosis and Referral,” “Optimizing Patient Management and Adherence,” and “Managing Transition.” The scientific program covered all stages of pediatric GH treatment, and reported here are the outcomes of the third session of the meeting, which considered transition from pediatric GH treatment to teenage and young adult GH therapy. A large number of patients with chronic diseases, including GH deficiency, drop out of therapy during the transition period. Multiple factors are associated with this, such as lack of understanding of the disease process, insufficient knowledge of treatment options, the patient becoming more independent, and requirement for interaction with a new set of health-care workers. Education regarding disease management and treatment options should be provided from an early age and right through the transition period. However, endocrine specialists will view the transition period differently, depending on whether they are pediatric endocrinologists who mainly deal with congenital diseases, in which auxology is important, or adult endocrinologists who are more concerned with body composition and metabolic factors. View points of both a pediatric and an adult endocrine specialist are presented, together with a case study outlining practical aspects of transition. It was noted in the meeting discussion that having one person to guide a patient through transition from an early age is important, but may be constrained by various factors such as finances, and options will differ by country.

In clinical practice, every year approximately 150,000 children are referred with short stature (SS) based on a cut-off of fifth percentile. The most important endocrine and treatable cause of SS is growth hormone deficiency (GHD). The lack of reliable data on the prevalence of GHD in India limits estimation of the magnitude of this problem. The diagnosis and treatment of GHD are hurdled with various challenges, restricting the availability of growth hormone (GH) therapy to only a very limited segment of the children in India. This review will firstly summarize the gaps and challenges in diagnosis and treatment of GHD based on literature analysis. Subsequently, it presents suggestions from the members at advisory board meetings to overcome these challenges. The advisory board suggested that early initiation of the therapy could better the chances of achieving final adult height within the normal range for the population. Education and awareness about growth disorders among parents, regular training for physicians, and more emphasis on using the Indian growth charts for growth monitoring would help improve the diagnosis and treatment of children with GHD. Availability of an easy-to-use therapy delivery system could also be beneficial in improving adherence and achieving satisfactory outcomes.