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Sensitivity and specificity of the macimorelin test for diagnosis of AGHD

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 perfo...

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Autores principales: Garcia, Jose M, Biller, Beverly M K, Korbonits, Márta, Popovic, Vera, Luger, Anton, Strasburger, Christian J, Chanson, Philippe, Swerdloff, Ronald, Wang, Christina, Fleming, Rosa Rosanna, Cohen, Fredric, Ammer, Nicola, Mueller, Gilbert, Kelepouris, Nicky, Strobl, Frank, Ostrow, Vlady, Yuen, Kevin C J
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Bioscientifica Ltd 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7923131/
https://www.ncbi.nlm.nih.gov/pubmed/33320108
http://dx.doi.org/10.1530/EC-20-0491
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author Garcia, Jose M
Biller, Beverly M K
Korbonits, Márta
Popovic, Vera
Luger, Anton
Strasburger, Christian J
Chanson, Philippe
Swerdloff, Ronald
Wang, Christina
Fleming, Rosa Rosanna
Cohen, Fredric
Ammer, Nicola
Mueller, Gilbert
Kelepouris, Nicky
Strobl, Frank
Ostrow, Vlady
Yuen, Kevin C J
author_facet Garcia, Jose M
Biller, Beverly M K
Korbonits, Márta
Popovic, Vera
Luger, Anton
Strasburger, Christian J
Chanson, Philippe
Swerdloff, Ronald
Wang, Christina
Fleming, Rosa Rosanna
Cohen, Fredric
Ammer, Nicola
Mueller, Gilbert
Kelepouris, Nicky
Strobl, Frank
Ostrow, Vlady
Yuen, Kevin C J
author_sort Garcia, Jose M
collection PubMed
description 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, 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/m(2) 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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spelling pubmed-79231312021-03-05 Sensitivity and specificity of the macimorelin test for diagnosis of AGHD Garcia, Jose M Biller, Beverly M K Korbonits, Márta Popovic, Vera Luger, Anton Strasburger, Christian J Chanson, Philippe Swerdloff, Ronald Wang, Christina Fleming, Rosa Rosanna Cohen, Fredric Ammer, Nicola Mueller, Gilbert Kelepouris, Nicky Strobl, Frank Ostrow, Vlady Yuen, Kevin C J Endocr Connect Research 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, 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/m(2) 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%). Bioscientifica Ltd 2020-12-14 /pmc/articles/PMC7923131/ /pubmed/33320108 http://dx.doi.org/10.1530/EC-20-0491 Text en © 2021 The authors http://creativecommons.org/licenses/by-nc/4.0/ This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. (http://creativecommons.org/licenses/by-nc/4.0/)
spellingShingle Research
Garcia, Jose M
Biller, Beverly M K
Korbonits, Márta
Popovic, Vera
Luger, Anton
Strasburger, Christian J
Chanson, Philippe
Swerdloff, Ronald
Wang, Christina
Fleming, Rosa Rosanna
Cohen, Fredric
Ammer, Nicola
Mueller, Gilbert
Kelepouris, Nicky
Strobl, Frank
Ostrow, Vlady
Yuen, Kevin C J
Sensitivity and specificity of the macimorelin test for diagnosis of AGHD
title Sensitivity and specificity of the macimorelin test for diagnosis of AGHD
title_full Sensitivity and specificity of the macimorelin test for diagnosis of AGHD
title_fullStr Sensitivity and specificity of the macimorelin test for diagnosis of AGHD
title_full_unstemmed Sensitivity and specificity of the macimorelin test for diagnosis of AGHD
title_short Sensitivity and specificity of the macimorelin test for diagnosis of AGHD
title_sort sensitivity and specificity of the macimorelin test for diagnosis of aghd
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7923131/
https://www.ncbi.nlm.nih.gov/pubmed/33320108
http://dx.doi.org/10.1530/EC-20-0491
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