Consensus guidelines for the diagnosis and treatment of adults with growth hormone deficiency: Summary statement of the growth hormone research society workshop on adult growth hormone deficiency

Based on the increasing body of evidence that adults with GH deficiency (somatotropin deficiency) have impaired health that improves with GH replacement, many countries have already approved the use of GH for replacement therapy in adults with GH deficiency. To ensure that patients are appropriately identified and treated, the Growth Hormone Research Society (GRS) convened a workshop on April 14–17, 1997, in Port Stephens, Australia, to formulate consensus guidelines for the diagnosis and treatment of adults with GH deficiency. The GRS invited scientists with expertise in the field, representatives from industry involved in the manufacture of recombinant human GH, and representatives from health authorities from a number of countries to attend the workshop, all of whom contributed to the consensus guidelines as detailed below

Consensus guidelines for the diagnosis and treatment of growth hormone (GH) deficiency in childhood and adolescence: Summary statement of the GH research society

The diagnosis and treatment of GH deficiency (GHD) during childhood and adolescence have been the subject of much controversy (1–3). To insure that patients are appropriately identified and treated, the GH Research Society (GRS) convened a workshop, on October 17–21 1999, in Eilat, Israel. The objectives of this workshop were to formulate consensus guidelines for the diagnosis and treatment of children and adolescents with GHD. The GRS invited clinicians and scientists with expertise in the field, representatives from industries involved in the manufacturing of recombinant GH, and representatives from health authorities from a number of countries to attend the workshop. All of them contributed to the consensus guidelines as detailed below

Growth Hormone Research Society perspective on the development of long-acting growth hormone preparations

Objective The Growth Hormone (GH) Research Society (GRS) convened a workshop to address important issues regarding trial design, efficacy, and safety of long-acting growth hormone preparations (LAGH). Participants A closed meeting of 55 international scientists with expertise in GH, including pediatric and adult endocrinologists, basic scientists, regulatory scientists, and participants from the pharmaceutical industry. Evidence Current literature was reviewed for gaps in knowledge. Expert opinion was used to suggest studies required to address potential safety and efficacy issues. Consensus process Following plenary presentations summarizing the literature, breakout groups discussed questions framed by the planning committee. Attendees reconvened after each breakout session to share group reports. A writing team compiled the breakout session reports into a draft document that was discussed and revised in an open forum on the concluding day. This was edited further and then circulated to attendees from academic institutions for review after the meeting. Participants from pharmaceutical companies did not participate in the planning, writing, or in the discussions and text revision on the final day of the workshop. Scientists from industry and regulatory agencies reviewed the manuscript to identify any factual errors. Conclusions LAGH compounds may represent an advance over daily GH injections because of increased convenience and differing phamacodynamic properties, providing the potential for improved adherence and outcomes. Better methods to assess adherence must be developed and validated. Long-term surveillance registries that include assessment of efficacy, cost-benefit, disease burden, quality of life, and safety are essential for understanding the impact of sustained exposure to LAGH preparations

Diagnosis, Genetics, and Therapy of Short Stature in Children: A Growth Hormone Research Society International Perspective

The Growth Hormone Research Society (GRS) convened a Workshop in March 2019 to evaluate the diagnosis and therapy of short stature in children. Forty-six international experts participated at the invitation of GRS including clinicians, basic scientists, and representatives from regulatory agencies and the pharmaceutical industry. Following plenary presentations addressing the current diagnosis and therapy of short stature in children, breakout groups discussed questions produced in advance by the planning committee and reconvened to share the group reports. A writing team assembled one document that was subsequently discussed and revised by participants. Participants from regulatory agencies and pharmaceutical companies were not part of the writing process. Short stature is the most common reason for referral to the pediatric endocrinologist. History, physical examination, and auxology remain the most important methods for understanding the reasons for the short stature. While some long-standing topics of controversy continue to generate debate, including in whom, and how, to perform and interpret growth hormone stimulation tests, new research areas are changing the clinical landscape, such as the genetics of short stature, selection of patients for genetic testing, and interpretation of genetic tests in the clinical setting. What dose of growth hormone to start, how to adjust the dose, and how to identify and manage a suboptimal response are still topics to debate. Additional areas that are expected to transform the growth field include the development of long-acting growth hormone preparations and other new therapeutics and diagnostics that may increase adult height or aid in the diagnosis of growth hormone deficiency.info:eu-repo/semantics/publishedVersio

Pituitary Stalk Interruption Syndrome: Diagnostic Delay and Sensitivity of the Auxological Criteria of the Growth Hormone Research Society

OBJECTIVES: To study the diagnostic delay for pituitary stalk interruption syndrome (PSIS) with growth hormone deficiency (GHD) and the sensitivity of the auxological criteria of the Growth Hormone Research Society (GHRS) consensus guidelines. METHODS: A single-center retrospective case-cohort study covering records from January 2000 through December 2007 evaluated the performance of each GHRS auxological criterion for patients with GHD and PSIS. Diagnostic delay was calculated as the difference between the age at which the earliest GHRS criterion could have been observed and the age at diagnosis of PSIS with GHD. A diagnostic delay exceeding one year was defined as late diagnosis. RESULTS: The study included 21 patients, 16 (76%) of whom had isolated GHD and 5 (24%) multiple pituitary hormone deficiencies. The median age at diagnosis was 3.6 years (interquartile range, IQR, 2.6-5.5). The median diagnostic delay was 2.3 years (range 0-12.6; IQR 1.5-3.6), with late diagnosis for 17 patients (81%). Height more than 1.5 SDS below target height was the most effective criterion: 90% of the patients met the criterion before diagnosis at a median age of 1 year, and it was the first criterion to be fulfilled for 84%. CONCLUSION: In our cohort, the delay for diagnosis of PSIS with GHD was long and could have been reduced by using the GHRS criteria, in particular, height more than 1.5 SDS below the target height. The specificity of such a strategy needs to be tested in healthy populations

Growth Hormone Research Society perspective on biomarkers of GH action in children and adults

Objective The Growth Hormone Research Society (GRS) convened a Workshop in 2017 to evaluate clinical endpoints, surrogate endpoints and biomarkers during GH treatment of children and adults and in patients with acromegaly. Participants GRS invited 34 international experts including clinicians, basic scientists, a regulatory scientist and physicians from the pharmaceutical industry. Evidence Current literature was reviewed and expert opinion was utilized to establish the state of the art and identify current gaps and unmet needs. Consensus process Following plenary presentations, breakout groups discussed questions framed by the planning committee. The attendees re-convened after each breakout session to share the group reports. A writing team compiled the breakout session reports into a document that was subsequently discussed and revised by participants. This was edited further and circulated for final review after the meeting. Participants from pharmaceutical companies were not part of the writing process. Conclusions The clinical endpoint in paediatric GH treatment is adult height with height velocity as a surrogate endpoint. Increased life expectancy is the ideal but unfeasible clinical endpoint of GH treatment in adult GH-deficient patients (GHDA) and in patients with acromegaly. The pragmatic clinical endpoints in GHDA include normalization of body composition and quality of life, whereas symptom relief and reversal of comorbidities are used in acromegaly. Serum IGF-I is widely used as a biomarker, even though it correlates weakly with clinical endpoints in GH treatment, whereas in acromegaly, normalization of IGF-I may be related to improvement in mortality. There is an unmet need for novel biomarkers that capture the pleiotropic actions of GH in relation to GH treatment and in patients with acromegaly

Labordiagnostik bei Wachstumshormon-assoziierten Erkrankungen/Biochemical diagnosis of growth hormone related diseases

The symptoms of growth hormone deficiency and growth hormone excess manifest themselves clinically in different ways, before and after the completion of longitudinal growth. Always, however, biochemical diagnostics is based on the measurement of circulating concentrations of growth hormone and insulin-like growth factor I (IGF-I). Immunoassays are practical, sensitive, and mostly specific methods for measuring either hormone. Still, there are serious discrepancies between the measured results of different assays. These discrepancies are mainly due to differences in the isoform specificity of assays, the use of different standard preparations, as well as the interference of binding proteins. The method-related differences in measured results make the general application of published diagnostic decision limits more difficult. At an interdisciplinary consensus conference, with the participation of the Growth Hormone Research Society, the IGF Society, and the International Federal of Clinical Chemistry and Laboratory Medicine (IFCC), the existing problems were analyzed and possible strategies were highlighted to improve the comparability of the measured results of different GH and IFG-I assays. Currently, however, the use of method-specific reference ranges obtained from well-characterized cohorts continues to be essential in clinical practice.Die Krankheitsbilder des Wachstumshormonmangels und des Wachstumshormonexzesses imponieren klinisch unterschiedlich vor und nach dem Abschluss des Längenwachstums. Stets jedoch bilden die Messung der zirkulierenden Konzentrationen von Wachstumshormon und Insulinartigem Wachstumsfaktor I (Insulin-like growth-factor I, IGF-I) die Basis der laborchemischen Diagnostik. Mit den Immunoassays stehen praktikable, sensitive und meist auch spezifische Methoden zur Messung beider Hormone zur Verfügung. Trotzdem bestehen nach wie vor gravierende Diskrepanzen zwischen den Messergebnissen verschiedener Assays. Diese Diskrepanzen sind vor allem bedingt durch Unterschiede in der Isoformspezifität der Assays, die Verwendung unterschiedlicher Standardpräparationen sowie die Interferenz von Bindungsproteinen. Die methodenbedingten Unterschiede in den Messergebnissen erschweren die allgemeine Anwendung publizierter diagnostischer Entscheidungsgrenzen. Auf einer interdisziplinären Konsensuskonferenz unter Beteiligung der Growth Hormone Research Society, der IGF Society, und der International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) wurden die bestehenden Probleme analysiert und mögliche Strategien zu einer Verbesserung der Vergleichbarkeit der Messergebnisse verschiedener GH- und IGF-I-Assays aufgezeigt. Derzeit bleibt jedoch in der klinischen Praxis die Anwendung methodenspezifischer, an gut charakterisierten Kollektiven gewonnener Referenzbereiche unabdingba

Growth Hormone Research Society perspective on the development of long-acting growth hormone preparations: Table 1

The Growth Hormone (GH) Research Society (GRS) convened a workshop to address important issues regarding trial design, efficacy, and safety of long-acting growth hormone preparations (LAGH)

Management of the child born small for gestational age through to adulthood: A consensus statement of the international societies of pediatric endocrinology and the Growth Hormone Research Society

Objective: Low birth weight remains a major cause of morbidity and mortality in early infancy and childhood. It is associated with an increased risk of health problems later in life, particularly coronary heart disease and stroke. A meeting was convened to identify the key health issues facing a child born small for gestational age (SGA) and to propose management strategies. Participants: There were 42 participants chosen for their expertise in obstetrics, peri- and neonatal medicine, pediatrics, pediatric and adult endocrinology, epidemiology, and pharmacology. Evidence: Written materials were exchanged, reviewed, revised, and then made available to all. This formed the basis for discussions at the meeting. Where published data were not available or adequate, discussion was based on expert clinical opinions. Consensus Process: Each set of questions was considered by all and then discussed in plenary sessions with consensus and unresolved issues identified. The consensus statement was prepared in plenary sessions and then edited by the group chairs and shared with all participants. Conclusions: The diagnosis of SGA should be based on accurate anthropometry at birth including weight, length, and head circumference. We recommend early surveillance in a growth clinic for those without catch-up. Early neurodevelopment evaluation and interventions are warranted in at-risk children. Endocrine and metabolic disturbances in the SGA child are recognized but infrequent. For the 10% who lack catch-up, GH treatment can increase linear growth. Early intervention with GH for those with severe growth retardation (height SD score, < -2.5; age, 2-4 yr) should be considered at a dose of 35-70 mu g/kg center dot d. Long-term surveillance of treated patients is essential. The associations at a population level between low birth weight, including SGA, and coronary heart disease and stroke in later life are recognized, but there is inadequate evidence to recommend routine health surveillance of all adults born SGA outside of normal clinical practice

Pituitary Neoplasm Nomenclature Workshop: Does Adenoma Stand the Test of Time?

The WHO Classification of Endocrine Tumours designates pituitary neoplasms as adenomas. A proposed nomenclature change to pituitary neuroendocrine tumors (PitNETs) has been met with concern by some stakeholder groups. The Pituitary Society coordinated the Pituitary Neoplasm Nomenclature (PANOMEN) workshop to address the topic. Experts in pituitary developmental biology, pathology, neurosurgery, endocrinology, and oncology, including representatives nominated by the Endocrine Society, European Society of Endocrinology, European Neuroendocrine Association, Growth Hormone Research Society, and International Society of Pituitary Surgeons. Clinical epidemiology, disease phenotype, management, and prognosis of pituitary adenomas differ from that of most NETs. The vast majority of pituitary adenomas are benign and do not adversely impact life expectancy. A nomenclature change to PitNET does not address the main challenge of prognostic prediction, assigns an uncertain malignancy designation to benign pituitary adenomas, and may adversely affect patients. Due to pandemic restrictions, the workshop was conducted virtually, with audiovisual lectures and written précis on each topic provided to all participants. Feedback was collated and summarized by Content Chairs and discussed during a virtual writing meeting moderated by Session Chairs, which yielded an evidence-based draft document sent to all participants for review and approval. There is not yet a case for adopting the PitNET nomenclature. The PANOMEN Workshop recommends that the term adenoma be retained and that the topic be revisited as new evidence on pituitary neoplasm biology emerges