TY - JOUR

T1 - Growth Hormone Research Society perspective on biomarkers of GH action in children and adults

AU - Johannsson, Gudmundur

AU - Bidlingmaier, Martin

AU - Biller, Beverly M K

AU - Boguszewski, Margaret

AU - Casanueva, Felipe F

AU - Chanson, Philippe

AU - Clayton, Peter E

AU - Choong, Catherine S

AU - Clemmons, David

AU - Dattani, Mehul

AU - Frystyk, Jan

AU - Ho, Ken

AU - Hoffman, Andrew R

AU - Horikawa, Reiko

AU - Juul, Anders

AU - Kopchick, John J

AU - Luo, Xiaoping

AU - Neggers, Sebastian

AU - Netchine, Irene

AU - Olsson, Daniel S

AU - Radovick, Sally

AU - Rosenfeld, Ron

AU - Ross, Richard J

AU - Schilbach, Katharina

AU - Solberg, Paulo

AU - Strasburger, Christian

AU - Trainer, Peter

AU - Yuen, Kevin C J

AU - Wickstrom, Kerstin

AU - Jorgensen, Jens O L

AU - Growth Hormone Research Society

N1 - © 2018 Growth Hormone Research Society.

PY - 2018

Y1 - 2018

N2 - 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.

AB - 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.

U2 - 10.1530/EC-18-0047

DO - 10.1530/EC-18-0047

M3 - Review

C2 - 29483159

VL - 7

SP - R126-R134

JO - Endocrine Connections

JF - Endocrine Connections

SN - 2049-3614

IS - 3

ER -