Consensus and controversies about diagnosing GH deficiency: a Delphi survey by the GH research society

M C Arlien-Søborg¹, S Radovick², M C S Boguszewski³, M Bidlingmaier⁴, G Johannsson^{5

6}, A Grimberg⁷, K K Y Ho⁸, B M K Biller⁹, C S Choong¹⁰, A R Hoffman¹¹, P Backeljauw¹², C L Boguszewski¹³, J Bollerslev¹⁴, T Brue¹⁵, P Chanson¹⁶, E Christ¹⁷, S Cianfarani^{18

19}, P E Clayton²⁰, P Cohen²¹, A Dauber²², M Fleseriu²³, J Gebauer²⁴, A Giustina²⁵, C E Higham²⁶, R Horikawa²⁷, C Höybye²⁸, A Juul²⁹, M Lodish³⁰, X Luo³¹, N Mauras³², K K Miller⁹, S Melmed³³, S J C M M Neggers³⁴, N Karavitaki^{35

36

37}, R Rosenfeld³⁸, R Ross³⁹, L Savendahl⁴⁰, K Schilbach⁴, P F Collett-Solberg⁴¹, C J Strasburger⁴², N A Tritos⁹, H M van Santen⁴³, K C J Yuen⁴⁴, J O L Jorgensen⁴⁵

Affiliations

¹ Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark.
² Department of Pediatrics, Rutgers University-Robert Wood Johnson Medical School New, Brunswick, NJ, USA.
³ Department of Pediatrics, Federal University of Parana, Curitiba, Brazil.
⁴ Department of Medicine IV, LMU University Hospital, LMU Munich, München, Germany.
⁵ Department of Endocrinology, Sahlgrenska University Hospital, Göteborg, Sweden.
⁶ Department of Internal Medicine and Clinical Nutrition, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
⁷ Division of Endocrinology and Diabetes, Perelman School of Medicine, Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia, USA.
⁸ Garvan Institute of Medical Research and St. Vincent's Hospital, Sydney, NSW, Australia.
⁹ Neuroendocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
¹⁰ Department of Endocrinology, Perth Children's Hospital & School of Medicine, University of Western Australia, Crawley, WA, Australia.
¹¹ Department of Medicine, Stanford University, Stanford, CA, USA.
¹² Division of Endocrinology, Cincinnati Children's Hospital Medical Center, Cincinnati, USA.
¹³ Endocrine Division (SEMPR), Department of Internal Medicine, Federal University of Parana, Curitiba, Brazil.
¹⁴ Faculty of Medicine, University of Oslo, Oslo, Norway.
¹⁵ Department of Endocrinology, Conception University Hospital, Marseille, France.
¹⁶ Service d'Endocrinologie et des Maladies de la Reproduction, Centre de Référence des Maladies Rares de l'Hypophyse, Université Paris-Saclay, Inserm, Physiologie et Physiopathologie Endocriniennes, AP-HP, Hôpital Bicêtre, Le Kremlin-Bicêtre, France.
¹⁷ Department of Endocrinology, Diabetology and Metabolism and Endocrine and Neuroendocrine Tumor Center, University Hospital of Basel, Basel, Switzerland.
¹⁸ Department of Systems Medicine, University of Rome "Tor Vergata", Rome, Italy.
¹⁹ Endocrinology and Diabetes Unit, I.R.C.C.S. "Bambino Gesù" Children's Hospital, Rome, Italy.
²⁰ Developmental Biology & Medicine, Faculty of Biology, Medicine & Health, University of Manchester, Manchester, UK.
²¹ Leonard Davis School of Gerontology, University of Southern California, Los Angeles, CA, USA.
²² Division of Endocrinology, Children's National Hospital, Washington, DC, USA.
²³ Departments of Medicine and Neurological Surgery, Pituitary Center, Oregon Health Sciences University, Portland, OR, USA.
²⁴ Department of Internal Medicine, University Hospital Schleswig-Holstein, Lübeck, Germany.
²⁵ Vita-Salute San Raffaele University and IRCCS San Raffaele Hospital, Milan, Italy.
²⁶ Department of Endocrinology, Christie Hospital NHS Foundation Trust and Division of Cancer Sciences,, University of Manchester, Manchester, UK.
²⁷ Division of Endocrinology and Metabolism, National Center for Child Health and Development, Tokyo, Japan.
²⁸ Department of Molecular Medicine and Surgery, Karolinska Institute, Stockholm, Sweden.
²⁹ Department of Growth and Reproduction-Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
³⁰ University of California, San Francisco, CA, USA.
³¹ Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
³² Nemours Children's Health Jacksonville, Jacksonville, FL, USA.
³³ Pituitary Center, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
³⁴ Erasmus University Medical Centre, Rotterdam, The Netherlands.
³⁵ Department of Metabolism and Systems Science, College of Medicine and Health, University of Birmingham, Birmingham, UK.
³⁶ Centre for Endocrinology, Diabetes and Metabolism, Birmingham Health Partners, Birmingham, UK.
³⁷ Department of Endocrinology, Queen Elizabeth Hospital, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK.
³⁸ Department of Pediatrics, Oregon Health Science University, Portland, OR, USA.
³⁹ University of Sheffield, Sheffield, UK.
⁴⁰ Division of Pediatric Endocrinology, Karolinska University Hospital, Stockholm, Sweden.
⁴¹ Discipline of Endocrinology, Internal Medicine Department, Faculdade de Ciências Médicas, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Brazil.
⁴² Charité Universitätsmedizin, Berlin, Germany.
⁴³ Department of Pediatric Endocrinology, Wilhelmina Children's Hospital, University Medical Center and Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands.
⁴⁴ Department of Neuroendocrinology, St. Joseph's Hospital and Medical Center, University of Arizona College of Medicine and Creighton School of Medicine, Phoenix, AZ, USA.
⁴⁵ Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark. joj@clin.au.dk.

PMID: 40335774
DOI: 10.1007/s11102-025-01526-z

Review

Consensus and controversies about diagnosing GH deficiency: a Delphi survey by the GH research society

M C Arlien-Søborg et al. Pituitary. 2025.

. 2025 May 7;28(3):57.

doi: 10.1007/s11102-025-01526-z.

Authors

Affiliations

¹ Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark.
² Department of Pediatrics, Rutgers University-Robert Wood Johnson Medical School New, Brunswick, NJ, USA.
³ Department of Pediatrics, Federal University of Parana, Curitiba, Brazil.
⁴ Department of Medicine IV, LMU University Hospital, LMU Munich, München, Germany.
⁵ Department of Endocrinology, Sahlgrenska University Hospital, Göteborg, Sweden.
⁶ Department of Internal Medicine and Clinical Nutrition, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
⁷ Division of Endocrinology and Diabetes, Perelman School of Medicine, Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia, USA.
⁸ Garvan Institute of Medical Research and St. Vincent's Hospital, Sydney, NSW, Australia.
⁹ Neuroendocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
¹⁰ Department of Endocrinology, Perth Children's Hospital & School of Medicine, University of Western Australia, Crawley, WA, Australia.
¹¹ Department of Medicine, Stanford University, Stanford, CA, USA.
¹² Division of Endocrinology, Cincinnati Children's Hospital Medical Center, Cincinnati, USA.
¹³ Endocrine Division (SEMPR), Department of Internal Medicine, Federal University of Parana, Curitiba, Brazil.
¹⁴ Faculty of Medicine, University of Oslo, Oslo, Norway.
¹⁵ Department of Endocrinology, Conception University Hospital, Marseille, France.
¹⁶ Service d'Endocrinologie et des Maladies de la Reproduction, Centre de Référence des Maladies Rares de l'Hypophyse, Université Paris-Saclay, Inserm, Physiologie et Physiopathologie Endocriniennes, AP-HP, Hôpital Bicêtre, Le Kremlin-Bicêtre, France.
¹⁷ Department of Endocrinology, Diabetology and Metabolism and Endocrine and Neuroendocrine Tumor Center, University Hospital of Basel, Basel, Switzerland.
¹⁸ Department of Systems Medicine, University of Rome "Tor Vergata", Rome, Italy.
¹⁹ Endocrinology and Diabetes Unit, I.R.C.C.S. "Bambino Gesù" Children's Hospital, Rome, Italy.
²⁰ Developmental Biology & Medicine, Faculty of Biology, Medicine & Health, University of Manchester, Manchester, UK.
²¹ Leonard Davis School of Gerontology, University of Southern California, Los Angeles, CA, USA.
²² Division of Endocrinology, Children's National Hospital, Washington, DC, USA.
²³ Departments of Medicine and Neurological Surgery, Pituitary Center, Oregon Health Sciences University, Portland, OR, USA.
²⁴ Department of Internal Medicine, University Hospital Schleswig-Holstein, Lübeck, Germany.
²⁵ Vita-Salute San Raffaele University and IRCCS San Raffaele Hospital, Milan, Italy.
²⁶ Department of Endocrinology, Christie Hospital NHS Foundation Trust and Division of Cancer Sciences,, University of Manchester, Manchester, UK.
²⁷ Division of Endocrinology and Metabolism, National Center for Child Health and Development, Tokyo, Japan.
²⁸ Department of Molecular Medicine and Surgery, Karolinska Institute, Stockholm, Sweden.
²⁹ Department of Growth and Reproduction-Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
³⁰ University of California, San Francisco, CA, USA.
³¹ Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
³² Nemours Children's Health Jacksonville, Jacksonville, FL, USA.
³³ Pituitary Center, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
³⁴ Erasmus University Medical Centre, Rotterdam, The Netherlands.
³⁵ Department of Metabolism and Systems Science, College of Medicine and Health, University of Birmingham, Birmingham, UK.
³⁶ Centre for Endocrinology, Diabetes and Metabolism, Birmingham Health Partners, Birmingham, UK.
³⁷ Department of Endocrinology, Queen Elizabeth Hospital, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK.
³⁸ Department of Pediatrics, Oregon Health Science University, Portland, OR, USA.
³⁹ University of Sheffield, Sheffield, UK.
⁴⁰ Division of Pediatric Endocrinology, Karolinska University Hospital, Stockholm, Sweden.
⁴¹ Discipline of Endocrinology, Internal Medicine Department, Faculdade de Ciências Médicas, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Brazil.
⁴² Charité Universitätsmedizin, Berlin, Germany.
⁴³ Department of Pediatric Endocrinology, Wilhelmina Children's Hospital, University Medical Center and Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands.
⁴⁴ Department of Neuroendocrinology, St. Joseph's Hospital and Medical Center, University of Arizona College of Medicine and Creighton School of Medicine, Phoenix, AZ, USA.
⁴⁵ Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark. joj@clin.au.dk.

PMID: 40335774
DOI: 10.1007/s11102-025-01526-z

Abstract

Purpose: Biochemical tests are required for diagnosing GH-deficiency in children and adults, but controversies remain regarding diagnostic criteria and type of biochemical tests. The aim of the study is to map the clinical practices of GHD diagnosis in children and adults.

Methods: The Growth Hormone Research Society members initiated a Delphi survey of the diagnosis of GHD in children and adults. Pediatric (n = 18) and adult (n = 25) endocrinologists from 14 countries participated and rated their extent of agreement with 61 statements using a Likert-type-scale (1-7). Consensus was predefined as ≥ 80% of panelists rating their agreement unidirectionally as either ≥ 5 (agreement) or ≤ 3 (disagreement).

Results: The pediatric panel reached consensus on 17 of 29 (59%) statements on diagnosis in children, whereas the adult panel reached consensus on 28 of 32 (88%) statements on adult patients. There was general agreement to test for GHD in an appropriate clinical context and also on the timing of testing for GHD in both children and adults. A subnormal IGF-I level was considered diagnostic in both children and adults with panhypopituitarism. In children, there was consensus to recommend the arginine stimulation test and the glucagon test. The insulin tolerance test (ITT) was considered gold standard in adults and there was also consensus to recommend the macimorelin test. A stimulated GH cut-off < 5μg/l was consistent with severe GHD in children, whereas test-specific cut-offs were recommended in adults.

Conclusion: Consensus on the GHD diagnosis was lower in pediatric practice, mainly with respect to choice and interpretation of GH stimulation tests.

Keywords: Adult endocrinology; Consensus guideline; Diagnosis; GH stimulation tests; Growth hormone deficiency; Pediatric endocrinology.

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Conflict of interest statement

Declarations. Competing interests: MCAS has received lecture fees from Pfizer. MB has served as speaker and/or consultant for Sandoz-Hexal, NovoNordisk, Pfizer, Roche, IDS, ConsilientHealth and Pharmanovia. GJ has served as a consultant for Novo Nordisk, Shire, and Astra Zeneca and has received lecture fees from Novo Nordisk, Shire/Takeda, Pfizer and Pharmanova. AG received lecture fees from Pfizer, Ascendis Pharma and Novo Nordisk. BB has served as an occasional consultant for Ascendis, Novo Nordisk and as PI of a research grant to Massachusetts General Hospital from Ascendis. CCS received speaker fees from Novo Nordisk. AH has served as a consultant for Ascendis. PB is a consultant for, and has received honoraria from Novo Nordisk, Ascendis Pharma, BioMarin Pharmaceutical, Cavalry Biosciences, Ipsen Biopharmaceuticals, and Upsher-Smith Laboratories. PC has received unrestricted research and educational grants from Ipsen, Novo-Nordisk, and Pfizer on behalf of the Service of Endocrinology and Reproductive Diseases, Hôpitaux Universitaires Paris-Saclay and Association Recherche Endocrinologie Bicêtre, has served as principal investigator for clinical trials funded by Prolor Biotech and Æterna Zentaris, has been on advisory boards for Æterna Zentaris and Pharmanovia and gave lectures for Ipsen, Pfizer and Consilient Health. All the fees and honoraria are paid to his Institution or Research Association. EC has received grants and lecture and consulting fees from Novo Nordisk and Pfizer. SC has served as a consultant for Crinetics, Novo-Nordisk and Sandoz, and has received lecture fees from Sanofi. PEC has served as a consultant to Lumos Pharma US and has received grants from Novo Nordisk and lecture fees from Merck. MF has received research support to the Oregon Health Sciences University from Ascendis and consulting fees from Novo Nordisk for occasional scientific consulting. GA is editor-in-chief of Pituitary, CH has received lecture fees from Sandoz, Pfizer and Novo Nordisk. AJ received speaker fees from Novo Nordisk, IPSEN and Sandoz, and received unrestricted grant support from Novo Nordisk and Lundbeck. KKM has received study medication and investigator-initiated research grants from Amgen and has equity in Bristol-Myers Squibb (BMS), GE Healthcare Technologies, Boston Scientific, and Becton Dickinson. SM has served as a consultant for Novo Nordisk. SJCMMN has occasionally served as speaker or consultant for Novo- Nordisk, Pfizer and Pharmanovia. NK has served as a speaker, investigator and Scientific Advisory Board for Pfizer. LS has served as speaker and/or consultant for Sandoz-Hexal, Novo Nordisk, Merck, and Pfizer. KS has received lecture fees from Pfizer and Novo Nordisk and has served as a consultant for Pharmanovia and Novo Nordisk. PFCS has received travel grants and speaker fees from Pfizer, Merck-Serono, Novo Nordisk, Sandoz and Biomarin. CJS has occasionally served as speaker or consultant for Sandoz-Hexal, Novo Nordisk, Ascendis, Pfizer, Consilient Health and Pharmanovia. HVS has received an investigator-initiated research grant from Pfizer and Rhythm and has served as a consultant for Rhythm. KCJY has received research grants to Barrow Neurological Institute from Ascendis, received lecture fees from Novo Nordisk and Ascendis and served as an occasional advisory board member for Novo Nordisk and Ascendis. JOLJ has received grants and consulting fees from Novo Nordisk and Pfizer and has been on an advisory board for Pharmanovia. In addition, JOLJ is an associate Editor for The Journal of Clinical Endocrinology & Metabolism and played no role in the Journal’s evaluation of the manuscript. The other authors have nothing to declare.

References

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Consensus and controversies about diagnosing GH deficiency: a Delphi survey by the GH research society

Affiliations

Consensus and controversies about diagnosing GH deficiency: a Delphi survey by the GH research society

Authors

Affiliations

Abstract

Conflict of interest statement

References

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