Effects of Long-term Growth Hormone Replacement in Adults With Growth Hormone Deficiency Following Cure of Acromegaly: A KIMS Analysis

Nicholas A Tritos; Gudmundur Johannsson; Márta Korbonits; Karen K Miller; Ulla Feldt-Rasmussen; Kevin C J Yuen; Donna King; Anders F Mattsson; Peter J Jonsson; Maria Koltowska-Haggstrom; Anne Klibanski; Beverly M K Biller

doi:10.1210/jc.2014-1013

Effects of Long-term Growth Hormone Replacement in Adults With Growth Hormone Deficiency Following Cure of Acromegaly: A KIMS Analysis

Nicholas A Tritos, Gudmundur Johannsson, Márta Korbonits, Karen K Miller, Ulla Feldt-Rasmussen, Kevin C J Yuen, Donna King, Anders F Mattsson, Peter J Jonsson, Maria Koltowska-Haggstrom, Anne Klibanski, Beverly M K Biller

Institut for Klinisk Medicin

21 Citationer (Scopus)

Abstract

CONTEXT: 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.

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

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

PATIENTS: 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).

OUTCOME MEASURES: 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.

Originalsprog	Engelsk
Tidsskrift	Endocrinology
Vol/bind	99
Udgave nummer	6
Sider (fra-til)	2018-2029
Antal sider	12
ISSN	0013-7227
DOI	https://doi.org/10.1210/jc.2014-1013
Status	Udgivet - jun. 2014

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10.1210/jc.2014-1013

Citationsformater

Tritos, N. A., Johannsson, G., Korbonits, M., Miller, K. K., Feldt-Rasmussen, U., Yuen, K. C. J., King, D., Mattsson, A. F., Jonsson, P. J., Koltowska-Haggstrom, M., Klibanski, A., & Biller, B. M. K. (2014). Effects of Long-term Growth Hormone Replacement in Adults With Growth Hormone Deficiency Following Cure of Acromegaly: A KIMS Analysis. Endocrinology, 99(6), 2018-2029. https://doi.org/10.1210/jc.2014-1013

Tritos, NA, Johannsson, G, Korbonits, M, Miller, KK, Feldt-Rasmussen, U, Yuen, KCJ, King, D, Mattsson, AF, Jonsson, PJ, Koltowska-Haggstrom, M, Klibanski, A & Biller, BMK 2014, 'Effects of Long-term Growth Hormone Replacement in Adults With Growth Hormone Deficiency Following Cure of Acromegaly: A KIMS Analysis', Endocrinology, bind 99, nr. 6, s. 2018-2029. https://doi.org/10.1210/jc.2014-1013

@article{2a1a106cd20a4817929449a4651a2cf8,

title = "Effects of Long-term Growth Hormone Replacement in Adults With Growth Hormone Deficiency Following Cure of Acromegaly: A KIMS Analysis",

abstract = "CONTEXT: 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.DESIGN: This study was a retrospective analysis of data from KIMS (Pfizer International Metabolic Database).SETTING: Data were extracted from a pharmaco-epidemiological survey of >16 000 GHD adults from 31 countries.PATIENTS: 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).OUTCOME MEASURES: 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.",

keywords = "Acromegaly, Adult, Aged, Databases, Factual, Female, Follow-Up Studies, Hormone Replacement Therapy, Human Growth Hormone, Humans, Hypopituitarism, Male, Middle Aged, Remission Induction, Retrospective Studies, Treatment Outcome, Young Adult",

author = "Tritos, {Nicholas A} and Gudmundur Johannsson and M{\'a}rta Korbonits and Miller, {Karen K} and Ulla Feldt-Rasmussen and Yuen, {Kevin C J} and Donna King and Mattsson, {Anders F} and Jonsson, {Peter J} and Maria Koltowska-Haggstrom and Anne Klibanski and Biller, {Beverly M K}",

year = "2014",

month = jun,

doi = "10.1210/jc.2014-1013",

language = "English",

volume = "99",

pages = "2018--2029",

journal = "Journal of Clinical Endocrinology and Metabolism",

issn = "0013-7227",

publisher = "Oxford University Press",

number = "6",

}

TY - JOUR

T1 - Effects of Long-term Growth Hormone Replacement in Adults With Growth Hormone Deficiency Following Cure of Acromegaly

T2 - A KIMS Analysis

AU - Tritos, Nicholas A

AU - Johannsson, Gudmundur

AU - Korbonits, Márta

AU - Miller, Karen K

AU - Feldt-Rasmussen, Ulla

AU - Yuen, Kevin C J

AU - King, Donna

AU - Mattsson, Anders F

AU - Jonsson, Peter J

AU - Koltowska-Haggstrom, Maria

AU - Klibanski, Anne

AU - Biller, Beverly M K

PY - 2014/6

Y1 - 2014/6

N2 - CONTEXT: 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.DESIGN: This study was a retrospective analysis of data from KIMS (Pfizer International Metabolic Database).SETTING: Data were extracted from a pharmaco-epidemiological survey of >16 000 GHD adults from 31 countries.PATIENTS: 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).OUTCOME MEASURES: 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.

AB - CONTEXT: 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.DESIGN: This study was a retrospective analysis of data from KIMS (Pfizer International Metabolic Database).SETTING: Data were extracted from a pharmaco-epidemiological survey of >16 000 GHD adults from 31 countries.PATIENTS: 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).OUTCOME MEASURES: 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.

KW - Acromegaly

KW - Adult

KW - Aged

KW - Databases, Factual

KW - Female

KW - Follow-Up Studies

KW - Hormone Replacement Therapy

KW - Human Growth Hormone

KW - Humans

KW - Hypopituitarism

KW - Male

KW - Middle Aged

KW - Remission Induction

KW - Retrospective Studies

KW - Treatment Outcome

KW - Young Adult

U2 - 10.1210/jc.2014-1013

DO - 10.1210/jc.2014-1013

M3 - Journal article

C2 - 24694339

SN - 0013-7227

VL - 99

SP - 2018

EP - 2029

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

IS - 6

ER -

Effects of Long-term Growth Hormone Replacement in Adults With Growth Hormone Deficiency Following Cure of Acromegaly: A KIMS Analysis

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