Sensitivity and specificity of the macimorelin test for diagnosis of AGHD

in Endocrine Connections
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  • 1 J Garcia, GRECC VA Puget Sound HCS/University of Washington, Seattle, United States
  • 2 B Biller, Neuroendocrine Unit, Massachusetts General Hospital, Boston, United States
  • 3 M Korbonits, Endocrinology, Barts and the London School of Medicine, Queen Mary University of London, London, United Kingdom of Great Britain and Northern Ireland
  • 4 V Popovic, Medical Faculty, University of Belgrade, Belgrade, Serbia
  • 5 A Luger, Div. Endocrinology and Metabolism, Medical University, General Hospital, Vienna, Austria
  • 6 C Strasburger, Clinical Endocrinology CCM, Charité Universitätsmedizin Berlin, Berlin, 10117, Germany
  • 7 P Chanson, Signalisation Hormonale Physiopathologie Endocrinienne et Métabolique, Assistance Publique-Hôpitaux de Paris, Hôpital de Bicêtre, Service d’Endocrinologie et des Maladies de la Reproduction, Centre de Référence des Maladies Rares de l’Hypophyse, and Université Paris-Saclay, Univ. Paris-Sud, Inserm, Le Kremlin-Bicêtre, France
  • 8 R Swerdloff, The Lundquist Institute at Harbor-UCLA Medical Center, Torrance, United States
  • 9 C Wang, The Lundquist Institute at Harbor-UCLA Medical Center, Torrance, United States
  • 10 R Fleming, Strongbridge Biopharma, Trevose, United States
  • 11 F Cohen, Strongbridge Biopharma, Trevose, United States
  • 12 N Ammer, Aeterna Zentaris GmbH, Frankfurt, Germany
  • 13 G Mueller, Aeterna Zentaris GmbH, Frankfurt, Germany
  • 14 N Kelepouris, Novo Nordisk Inc, Plainsboro, United States
  • 15 F Strobl, Novo Nordisk Inc, Plainsboro, United States
  • 16 V Ostrow, Inc., Novo Nordisk, Plainsboro, United States
  • 17 K Yuen, Barrow Pituitary Center, Barrow Neurological Institute, University of Arizona College of Medicine and Creighton School of Medicine, Phoenix, United States

Correspondence: Nicky Kelepouris, Email: nlkp@novonordisk.com

Objective: The macimorelin test is approved for the diagnosis of adult growth hormone deficiency (AGHD) based on its efficacy vs the insulin tolerance test (ITT). Macimorelin has a significant advantage over ITT in avoiding hypoglycemia. Analyses were conducted to determine whether macimorelin performance is affected by age, body mass index (BMI), or sex, and evaluate its performance vs ITT over a range of GH cutpoints.

Design: Post hoc analyses of data from a previous randomized phase 3 study included participants aged 18-66 years with BMI <37 kg/m2 and high (Group A), intermediate (Group B), or low (Group C) likelihood for AGHD based on pituitary history, and matched controls (Group D).

Methods: Probability of AGHD was estimated using unadjusted, age-adjusted, BMI-adjusted, and sex-adjusted logistic models. Area under the curve (AUC) of the estimated receiver operating characteristic (ROC) curve (range, 0-1; 1=perfect) was compared for adjusted vs unadjusted models. Separate analyses evaluated agreement, sensitivity, and specificity for macimorelin and ITT using cutpoints of 2.8, 4.0, 5.1, and 6.5 ng/mL.

Results: For participants in Group A (n=41) and Group D (n=29), unadjusted, age-adjusted, BMI-adjusted, and sex-adjusted models had ROC AUCs (95% CIs) of 0.9924 (0.9807-1), 0.9924 (0.9807-1), 0.9916 (0.9786-1), and 0.9950 (0.9861-1), respectively.

Conclusions: Macimorelin performance was not meaningfully affected by age, BMI, or sex, indicating robustness for AGHD diagnosis. Of the 4 GH cutpoints evaluated, the cutpoint of 5.1 ng/mL provided maximal specificity (96%) and high sensitivity (92%) and was in good overall agreement with the ITT at the same cutpoint (87%).

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