CONTEXT: Pegvisomant is a GH antagonist, which is used for the treatment of acromegalic patients. It effectively blocks the hepatic and peripheral effects of GH, but transient elevations in circulating liver enzymes of unknown pathogenesis may occur, which seems to be more prevalent when the treatment is combined with a somatostatin analog (SA). Accumulation of intrahepatic lipid is a known cause of elevated liver enzymes, and there is evidence to suggest that GH impacts lipid content in liver and skeletal muscle. OBJECTIVE: Our objective was to measure lipid content in liver and skeletal muscle in acromegalic patients before and after cotreatment with pegvisomant and SA as compared with SA monotherapy. DESIGN:Eighteen acromegalic patients well controlled on SA monotherapy were randomized in a parallel study over 24 wk to 1) unchanged SA monotherapy, or 2) cotreatment with pegvisomant (15-30 mg twice a week) and SA (half the usual dosage). SETTING: This was an investigator-initiated study in a single tertiary referral center. MAIN OUTCOME MEASURES: Intrahepatic lipid (IHL) and intramyocellular lipid (IMCL) was assessed by ¹H magnetic resonance spectroscopy. RESULTS:IHL increased in the cotreatment group compared with SA only (P = 0.002). The increase was positively correlated to weekly pegvisomant dose (r² = 0.52; P = 0.01). By contrast, IMCL decreased in the cotreatment group compared with SA only (P = 0.01). These changes related neither to insulin sensitivity nor inflammatory markers. CONCLUSION: Cotreatment with pegvisomant and a reduced SA dose increase IHL and decrease IMCL compared with SA monotherapy. The clinical implications remain unclear, but increased IHL may be causally linked to the transient elevations in liver enzymes observed during pegvisomant treatment.
RCT Entities:
CONTEXT: Pegvisomant is a GH antagonist, which is used for the treatment of acromegalicpatients. It effectively blocks the hepatic and peripheral effects of GH, but transient elevations in circulating liver enzymes of unknown pathogenesis may occur, which seems to be more prevalent when the treatment is combined with a somatostatin analog (SA). Accumulation of intrahepaticlipid is a known cause of elevated liver enzymes, and there is evidence to suggest that GH impacts lipid content in liver and skeletal muscle. OBJECTIVE: Our objective was to measure lipid content in liver and skeletal muscle in acromegalicpatients before and after cotreatment with pegvisomant and SA as compared with SA monotherapy. DESIGN: Eighteen acromegalicpatients well controlled on SA monotherapy were randomized in a parallel study over 24 wk to 1) unchanged SA monotherapy, or 2) cotreatment with pegvisomant (15-30 mg twice a week) and SA (half the usual dosage). SETTING: This was an investigator-initiated study in a single tertiary referral center. MAIN OUTCOME MEASURES: Intrahepaticlipid (IHL) and intramyocellular lipid (IMCL) was assessed by ¹H magnetic resonance spectroscopy. RESULTS: IHL increased in the cotreatment group compared with SA only (P = 0.002). The increase was positively correlated to weekly pegvisomant dose (r² = 0.52; P = 0.01). By contrast, IMCL decreased in the cotreatment group compared with SA only (P = 0.01). These changes related neither to insulin sensitivity nor inflammatory markers. CONCLUSION: Cotreatment with pegvisomant and a reduced SA dose increase IHL and decrease IMCL compared with SA monotherapy. The clinical implications remain unclear, but increased IHL may be causally linked to the transient elevations in liver enzymes observed during pegvisomant treatment.
Authors: Carlos M Reyes-Vidal; Hamed Mojahed; Wei Shen; Zhezhen Jin; Fernando Arias-Mendoza; Jean Carlos Fernandez; Dympna Gallagher; Jeffrey N Bruce; Kalmon D Post; Pamela U Freda Journal: J Clin Endocrinol Metab Date: 2015-06-02 Impact factor: 5.958
Authors: Miriam A Bredella; Melanie Schorr; Laura E Dichtel; Anu V Gerweck; Brian J Young; Whitney W Woodmansee; Brooke Swearingen; Karen K Miller Journal: J Clin Endocrinol Metab Date: 2017-11-01 Impact factor: 5.958
Authors: Jose Cordoba-Chacon; Andre Sarmento-Cabral; Mercedes Del Rio-Moreno; Alberto Diaz-Ruiz; Papasani V Subbaiah; Rhonda D Kineman Journal: Endocrinology Date: 2018-11-01 Impact factor: 4.736
Authors: Jose Cordoba-Chacon; Neena Majumdar; Edward O List; Alberto Diaz-Ruiz; Stuart J Frank; Anna Manzano; Ramon Bartrons; Michelle Puchowicz; John J Kopchick; Rhonda D Kineman Journal: Diabetes Date: 2015-05-26 Impact factor: 9.461
Authors: Cheol Ryong Ku; Eun Yeong Choe; Jae Won Hong; Eui Hyun Kim; Se Hee Park; Sun Ho Kim; Eun Jig Lee Journal: Medicine (Baltimore) Date: 2016-06 Impact factor: 1.889