EFFECTS OF GROWTH HORMONE (GH) REPLACEMENT FOR UP TO 5 YEARS IN GH DEFICIENT (GHD) ADULTS WITH ACROMEGALY IN REMISSION A KIMS (PFIZER INTERNATIONAL METABOLIC DATABASE) CASE-CONTROL ANALYSIS

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: SAT 109-133-GHRH, GH & IGF Biology & Signaling
Bench to Bedside
Saturday, June 15, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board SAT-121
Nicholas A Tritos*1, Gudmundur Johannsson2, Marta Korbonits3, Karen Klahr Miller1, Ulla Feldt-Rasmussen4, Donna King5, Peter J. Jonsson6, Ann-Charlotte Akerblad6, Maria Koltowska-Haggstrom6, Anne Klibanski1 and Beverly MK Biller7
1Massachusetts General Hospital/Harvard Medical School, Boston, MA, 2Sahlgrenska Academy, Gothenburg, 3Barts and the London School of Medicine, London, United Kingdom, 4Copenhagen University Hospital, Rigshospitalet, 5Pfizer Inc, Lawrenceville, NJ, 6Pfizer, Endocrine Care, Sollentuna, Sweden, 7Massachusetts General Hospital, Boston, MA
Objective: Patients with acromegaly (ACRO) in remission are at risk for GHD. The efficacy and safety of GH replacement in this population has not been well characterized.

Methods: To this end, KIMS was searched for ACRO in remission and stringently defined GHD. Controls were patients with non-functioning pituitary adenoma (NFPA), matched for age, gender and BMI.

Results: This search identified 115 ACRO {71 women (62%) and 44 men (38%); aged [median (10th percentile, 90th percentile)]:  51.7 yr (35.7, 66.4)} and 142 NFPA {79 women (56%) and 63 men (44%); aged: 53.5 yr (40.6, 65.8)}, naïve to GH replacement at entry. At baseline, 40% of ACRO and 23% of NFPA had insulin-like growth factor 1 (IGF-1) standard deviation score (SDS) < -2 (p=0.002 between groups). Most patients had ≥3 additional pituitary hormone deficits (62% of ACRO and 59% of NFPA).

Subgroups received GH replacement for up to 5 years, at which time GH dose and IGF-1 SDS were comparable. Quality of life (AGHDA) improved (decreased score) in both groups [AGHDA change: ACRO: -4.0 (-10.0, 1.0), p=0.0001; NFPA: -2.0 (-15.0, 6.0), p=0.017]. Total cholesterol (TC) decreased [TC change: ACRO: -0.8 mmol/l (-2.1, 0.5), p=0.0005; NFPA: -0.5 mmol/l (-2.3, 0.8), p=0.0021] and LDL cholesterol (LDLC) decreased [LDLC change: ACRO: -0.9 mmol/l (-2.2, 0.4), p=0.0003; NFPA: -0.7 mmol/l (-2.6, 0.4), p=0.0001] in both groups. HDL cholesterol (HDLC) increased in ACRO [HDLC change: ACRO: 0.1 mmol/l (-0.1, 0.4), p=0.0456; NFPA: 0.0 mmol/l (-0.5, 0.4), p=NS]. On subgroup analysis at 5 years, TC and LDLC decreased only in ACRO with baseline IGF-1 SDS < -2.

Plasma glucose (PG) increased [PG change: ACRO: 0.7 mmol/l (-0.6, 1.9), p=0.0001; NFPA: 0.3 mmol/l (-0.4, 1.6), p=0.0011]; HbA1c increased in ACRO [HbA1c change: ACRO: 0.2% (-0.6, 1.0), p=0.0194; NFPA: 0.2% (-0.5, 1.0), p=0.0672]. At 5 years, HbA1c values were 5.4% (4.4, 6.6) in ACRO and 5.4% (4.5, 6.2) in NFPA. (p=NS between groups).

There were 83 serious adverse events (SAEs) (7 GH-related) reported in 39 ACRO and 70 SAEs (14 GH-related) in 44 NFPA. GH was discontinued secondary to SAEs in 13 ACRO and 14 NFPA. There were 10 deaths in ACRO (including 2 related to heart disease and 3 to tumors) and 1 death in NFPA. New or worsening diabetes mellitus was reported in 3 ACRO and 1 NFPA.

Conclusions: GH replacement for up to 5 years in ACRO in remission may improve quality of life and lipids. The safety of GH replacement in this population requires further study.

Disclosure: NAT: Principal Investigator, Pfizer, Inc., Investigator, Ipsen, Medical Advisory Board Member, Corcept, , Pfizer, Inc.. GJ: Advisory Group Member, Pfizer, Inc., Investigator, Pfizer, Inc., Investigator, Novo Nordisk. MK: Principal Investigator, Pfizer, Inc., Principal Investigator, Syntaxin, Principal Investigator, Chiasma. KKM: Principal Investigator, Pfizer, Inc.. UF: Advisory Group Member, Pfizer Global R&D, Speaker, Novo Nordisk, Investigator, Novo Nordisk. DK: Employee, Pfizer, Inc.. PJJ: Employee, Pfizer, Inc.. ACA: Employee, Pfizer, Inc.. MK: Employee, Pfizer, Inc.. BMB: Investigator, Novartis Pharmaceuticals, Consultant, Novartis Pharmaceuticals, Investigator, Novo Nordisk, Consultant, Novo Nordisk, Consultant, Pfizer, Inc.. Nothing to Disclose: AK

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm