Effects of long-term growth hormone replacement in adults with growth hormone deficiency following cure of acromegaly: a KIMS analysis.
BACKGROUND
GH deficiency (GHD) may occur in adults with cured acromegaly (acroGHD).


OBJECTIVE
Our objective was to examine the effectiveness and safety of GH replacement in acroGHD.


METHODS
This study was a retrospective analysis of data from KIMS (Pfizer International Metabolic Database).


METHODS
Data were extracted from a pharmaco-epidemiological survey of >16 000 GHD adults from 31 countries.


METHODS
The effectiveness population included 115 adults with acroGHD and 142 age-, gender-, and body mass index-matched GHD adults with nonfunctioning pituitary adenoma (NFPA) followed up to 5 years on GH. The safety population included 164 adults with acroGHD and 2469 with NFPA, all GH-replaced. Both acroGHD and NFPA were compared with several cohorts from the general population (including the World Health Organization Global Burden of Disease).


METHODS
Outcome measures included quality of life (QoL-AGHDA), lipids, serious adverse events, and additional safety endpoints.


RESULTS
Median GH dose was 0.3 mg/d in acroGHD and NFPA at 5 years. There were comparable improvements in QoL-AGHDA and total and low-density lipoprotein cholesterol in acroGHD and NFPA. High-density lipoprotein cholesterol increased only in acroGHD. Cardiovascular mortality was increased in acroGHD vs NFPA (standardized mortality ratio = 3.03, P = .02). All-cause mortality was similar in acroGHD (ratio between observed/expected cases [95% confidence interval] = 1.32 [0.70-2.25]) and lower in NFPA [observed/expected = 0.58 [0.48-0.70]) in comparison with the general population. There was no difference in incidence of all cancers, benign or malignant brain tumors, or diabetes mellitus between acroGHD and NFPA.


CONCLUSIONS
GH replacement has comparable effects on quality of life and lipids in acroGHD and NFPA. Further investigation is needed to examine whether the increased cardiovascular mortality may be attributed to the history of previous GH excess in acroGHD.
Neuroendocrine Unit (N.A.T., K.K.M., A.K., B.M.K.B.), Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114; Department of Endocrinology (G.J.), Sahlgrenska University Hospital (A.F.M.), Gothenburg, Sweden SE-41345; Department of Endocrinology (M.K.), Barts and the London School of Medicine, Queen Mary University of London, London, United Kingdom EC1M 6BQ; Department of Medical Endocrinology (U.F.-R.), Rigshospitalet, National University Hospital, Copenhagen University, Copenhagen, Denmark DK-2100; Division of Endocrinology, Diabetes, and Clinical Nutrition (K.C.J.Y.), Oregon Health and Science University, Portland, Oregon 97239; Pfizer, Inc (D.K.), New York, New York 10017; and Pfizer Endocrine Care (P.J.J., M.K.-H.), Sollentuna, Sweden SE-19091.
Nicholas A
NA
Tritos
Gudmundur
G
Johannsson
Márta
M
Korbonits
Karen K
KK
Miller
Ulla
U
Feldt-Rasmussen
Kevin C J
KC
Yuen
Donna
D
King
Anders F
AF
Mattsson
Peter J
PJ
Jonsson
Maria
M
Koltowska-Haggstrom
Anne
A
Klibanski
Beverly M K
BM
Biller
D000172:Acromegaly / Q000453:epidemiology / Q000628:therapy*; D000328:Adult; D000368:Aged; D016208:Databases, Factual / Q000706:statistics & numerical data; D005260:Female; D005500:Follow-Up Studies; D020249:Hormone Replacement Therapy / Q000009:adverse effects / Q000706:statistics & numerical data; D019382:Human Growth Hormone / Q000172:deficiency / Q000627:therapeutic use*; D006801:Humans; D007018:Hypopituitarism / Q000188:drug therapy* / Q000453:epidemiology / Q000209:etiology; D008297:Male; D008875:Middle Aged; D012074:Remission Induction; D012189:Retrospective Studies; D016896:Treatment Outcome; D055815:Young Adult
D019382:Human Growth Hormone