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

M C Arlien-Søborg; S Radovick; M C S Boguszewski; M Bidlingmaier; G Johannsson; A Grimberg; K K Y Ho; B M K Biller; C S Choong; A R Hoffman; P Backeljauw; C L Boguszewski; J Bollerslev; T Brue; P Chanson; E Christ; S Cianfarani; P E Clayton; P Cohen; A Dauber; M Fleseriu; J Gebauer; A Giustina; C E Higham; R Horikawa; C Höybye; A Juul; M Lodish; X Luo; N Mauras; K K Miller; S Melmed; S J C M M Neggers; N Karavitaki; R Rosenfeld; R Ross; L Savendahl; K Schilbach; P F Collett-Solberg; C J Strasburger; N A Tritos; H M van Santen; K C J Yuen; J O L Jorgensen

doi:10.1007/s11102-025-01526-z

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

Pituitary. 2025 May 7;28(3):57. doi: 10.1007/s11102-025-01526-z.

Authors

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

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.

Publication types

Review

MeSH terms

Adult
Child
Consensus
Delphi Technique
Female
Human Growth Hormone* / deficiency
Humans
Insulin-Like Growth Factor I / metabolism
Male

Substances

Human Growth Hormone
Insulin-Like Growth Factor I