Three weekly injections (TWI) of low-dose growth hormone (GH) restore low normal circulating IGF-I concentrations and reverse cardiac abnormalities associated with adult onset GH deficiency (GHD)

A. I. Pincelli, R. Bragato, M. Scacchi, G. Branzi, G. Osculati, R. Viarengo, G. Leonetti, Francesco Cavagnini

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

GH replacement therapy given 3 times weekly (TWI) and adjusted to allow serum IGF-I concentrations in the mid-normal range for sex and age has been shown to be as effective as the daily regimen in improving lipid profile, body composition, bone mass and turnover in adult GH deficient (GHD) patients. Only one study has investigated so far the short-term (6 months) effect of a fixed weight-based TWI dosing schedule on heart structure and function in childhood onset (CO) GHD patients, whereas such a schedule in adult onset (AO) GHD patients has not been studied as yet. Aim of this study was to investigate whether a 1-yr low-dose titrated TWI GH-replacement regimen aimed at achieving and maintaining IGF-I levels within the low normal limits for age and sex is able to affect cardiovascular and heart parameters in a group of AO GHD patients. Eight adult patients (4 women and 4 men, age 35.8±3.37 yr, body mass index, BMI, 28.7±2.62 kg/m2) with AO GHD were included in the study, along with 10 healthy subjects, matched for age, sex, BMI and physical activity (6 women and 4 men, age 35.2±4.05 yr, BMI 28.4±2.34 kg/m2). M- and B- mode ecocardiography and pulsed doppler examination of transmitral flow were performed in GHD patients at baseline and after 3 and 12 months of GH therapy (mean GH dose 6.7±0.8 μg/kg/day given thrice a week), while normal subjects were studied once. Treatment with GH for 1 yr induced a significant increase in left ventricular (LV) diastolic and systolic volumes (+11.1 and +16.5%, respectively). Systolic LV posterior wall thickness and LV mass were increased (+10.2 and +7.7%, respectively) by GH administration. Systemic vascular resistance was significantly decreased by 1-yr GH therapy (-13.8% after 1 yr), while stroke volume, cardiac output and cardiac index were increased (+9.4, +11.6 and +11.9%, respectively). LV end-systolic stress was decreased at the end of GH therapy (-11.2%). E and A wave, significantly reduced at baseline, were increased by 1 yr of GH therapy (+23.3% and +28.1%, respectively); likewise, the abnormally high E peak deceleration time was partially reversed by GH administration (-10.7%). Our study, though conducted in a small sample size, demonstrates that a TWI GH treatment schedule is able to reverse the cardiovascular abnormalities in AO GHD patients and to improve body composition and lipid profile. The maintenance of circulating IGF-I concentrations within the low normal range allows to avoid most of the side-effects reported with higher GH doses while being cost-effective and improving the patient's compliance.

Original languageEnglish
Pages (from-to)420-428
Number of pages9
JournalJournal of Endocrinological Investigation
Volume26
Issue number5
Publication statusPublished - May 2003

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Insulin-Like Growth Factor I
Growth Hormone
Injections
Appointments and Schedules
Body Composition
Reference Values
Therapeutics
Cardiovascular Abnormalities
Lipids
Deceleration
Bone Remodeling
Hormone Replacement Therapy
Patient Compliance
Cardiac Output
Vascular Resistance
Stroke Volume
Sample Size
Healthy Volunteers
Body Mass Index
Maintenance

Keywords

  • Adult onset GH deficiency
  • Body composition
  • Echocardiography
  • Heart
  • Thrice-a-week GH replacement therapy

ASJC Scopus subject areas

  • Endocrinology

Cite this

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title = "Three weekly injections (TWI) of low-dose growth hormone (GH) restore low normal circulating IGF-I concentrations and reverse cardiac abnormalities associated with adult onset GH deficiency (GHD)",
abstract = "GH replacement therapy given 3 times weekly (TWI) and adjusted to allow serum IGF-I concentrations in the mid-normal range for sex and age has been shown to be as effective as the daily regimen in improving lipid profile, body composition, bone mass and turnover in adult GH deficient (GHD) patients. Only one study has investigated so far the short-term (6 months) effect of a fixed weight-based TWI dosing schedule on heart structure and function in childhood onset (CO) GHD patients, whereas such a schedule in adult onset (AO) GHD patients has not been studied as yet. Aim of this study was to investigate whether a 1-yr low-dose titrated TWI GH-replacement regimen aimed at achieving and maintaining IGF-I levels within the low normal limits for age and sex is able to affect cardiovascular and heart parameters in a group of AO GHD patients. Eight adult patients (4 women and 4 men, age 35.8±3.37 yr, body mass index, BMI, 28.7±2.62 kg/m2) with AO GHD were included in the study, along with 10 healthy subjects, matched for age, sex, BMI and physical activity (6 women and 4 men, age 35.2±4.05 yr, BMI 28.4±2.34 kg/m2). M- and B- mode ecocardiography and pulsed doppler examination of transmitral flow were performed in GHD patients at baseline and after 3 and 12 months of GH therapy (mean GH dose 6.7±0.8 μg/kg/day given thrice a week), while normal subjects were studied once. Treatment with GH for 1 yr induced a significant increase in left ventricular (LV) diastolic and systolic volumes (+11.1 and +16.5{\%}, respectively). Systolic LV posterior wall thickness and LV mass were increased (+10.2 and +7.7{\%}, respectively) by GH administration. Systemic vascular resistance was significantly decreased by 1-yr GH therapy (-13.8{\%} after 1 yr), while stroke volume, cardiac output and cardiac index were increased (+9.4, +11.6 and +11.9{\%}, respectively). LV end-systolic stress was decreased at the end of GH therapy (-11.2{\%}). E and A wave, significantly reduced at baseline, were increased by 1 yr of GH therapy (+23.3{\%} and +28.1{\%}, respectively); likewise, the abnormally high E peak deceleration time was partially reversed by GH administration (-10.7{\%}). Our study, though conducted in a small sample size, demonstrates that a TWI GH treatment schedule is able to reverse the cardiovascular abnormalities in AO GHD patients and to improve body composition and lipid profile. The maintenance of circulating IGF-I concentrations within the low normal range allows to avoid most of the side-effects reported with higher GH doses while being cost-effective and improving the patient's compliance.",
keywords = "Adult onset GH deficiency, Body composition, Echocardiography, Heart, Thrice-a-week GH replacement therapy",
author = "Pincelli, {A. I.} and R. Bragato and M. Scacchi and G. Branzi and G. Osculati and R. Viarengo and G. Leonetti and Francesco Cavagnini",
year = "2003",
month = "5",
language = "English",
volume = "26",
pages = "420--428",
journal = "Journal of Endocrinological Investigation",
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T1 - Three weekly injections (TWI) of low-dose growth hormone (GH) restore low normal circulating IGF-I concentrations and reverse cardiac abnormalities associated with adult onset GH deficiency (GHD)

AU - Pincelli, A. I.

AU - Bragato, R.

AU - Scacchi, M.

AU - Branzi, G.

AU - Osculati, G.

AU - Viarengo, R.

AU - Leonetti, G.

AU - Cavagnini, Francesco

PY - 2003/5

Y1 - 2003/5

N2 - GH replacement therapy given 3 times weekly (TWI) and adjusted to allow serum IGF-I concentrations in the mid-normal range for sex and age has been shown to be as effective as the daily regimen in improving lipid profile, body composition, bone mass and turnover in adult GH deficient (GHD) patients. Only one study has investigated so far the short-term (6 months) effect of a fixed weight-based TWI dosing schedule on heart structure and function in childhood onset (CO) GHD patients, whereas such a schedule in adult onset (AO) GHD patients has not been studied as yet. Aim of this study was to investigate whether a 1-yr low-dose titrated TWI GH-replacement regimen aimed at achieving and maintaining IGF-I levels within the low normal limits for age and sex is able to affect cardiovascular and heart parameters in a group of AO GHD patients. Eight adult patients (4 women and 4 men, age 35.8±3.37 yr, body mass index, BMI, 28.7±2.62 kg/m2) with AO GHD were included in the study, along with 10 healthy subjects, matched for age, sex, BMI and physical activity (6 women and 4 men, age 35.2±4.05 yr, BMI 28.4±2.34 kg/m2). M- and B- mode ecocardiography and pulsed doppler examination of transmitral flow were performed in GHD patients at baseline and after 3 and 12 months of GH therapy (mean GH dose 6.7±0.8 μg/kg/day given thrice a week), while normal subjects were studied once. Treatment with GH for 1 yr induced a significant increase in left ventricular (LV) diastolic and systolic volumes (+11.1 and +16.5%, respectively). Systolic LV posterior wall thickness and LV mass were increased (+10.2 and +7.7%, respectively) by GH administration. Systemic vascular resistance was significantly decreased by 1-yr GH therapy (-13.8% after 1 yr), while stroke volume, cardiac output and cardiac index were increased (+9.4, +11.6 and +11.9%, respectively). LV end-systolic stress was decreased at the end of GH therapy (-11.2%). E and A wave, significantly reduced at baseline, were increased by 1 yr of GH therapy (+23.3% and +28.1%, respectively); likewise, the abnormally high E peak deceleration time was partially reversed by GH administration (-10.7%). Our study, though conducted in a small sample size, demonstrates that a TWI GH treatment schedule is able to reverse the cardiovascular abnormalities in AO GHD patients and to improve body composition and lipid profile. The maintenance of circulating IGF-I concentrations within the low normal range allows to avoid most of the side-effects reported with higher GH doses while being cost-effective and improving the patient's compliance.

AB - GH replacement therapy given 3 times weekly (TWI) and adjusted to allow serum IGF-I concentrations in the mid-normal range for sex and age has been shown to be as effective as the daily regimen in improving lipid profile, body composition, bone mass and turnover in adult GH deficient (GHD) patients. Only one study has investigated so far the short-term (6 months) effect of a fixed weight-based TWI dosing schedule on heart structure and function in childhood onset (CO) GHD patients, whereas such a schedule in adult onset (AO) GHD patients has not been studied as yet. Aim of this study was to investigate whether a 1-yr low-dose titrated TWI GH-replacement regimen aimed at achieving and maintaining IGF-I levels within the low normal limits for age and sex is able to affect cardiovascular and heart parameters in a group of AO GHD patients. Eight adult patients (4 women and 4 men, age 35.8±3.37 yr, body mass index, BMI, 28.7±2.62 kg/m2) with AO GHD were included in the study, along with 10 healthy subjects, matched for age, sex, BMI and physical activity (6 women and 4 men, age 35.2±4.05 yr, BMI 28.4±2.34 kg/m2). M- and B- mode ecocardiography and pulsed doppler examination of transmitral flow were performed in GHD patients at baseline and after 3 and 12 months of GH therapy (mean GH dose 6.7±0.8 μg/kg/day given thrice a week), while normal subjects were studied once. Treatment with GH for 1 yr induced a significant increase in left ventricular (LV) diastolic and systolic volumes (+11.1 and +16.5%, respectively). Systolic LV posterior wall thickness and LV mass were increased (+10.2 and +7.7%, respectively) by GH administration. Systemic vascular resistance was significantly decreased by 1-yr GH therapy (-13.8% after 1 yr), while stroke volume, cardiac output and cardiac index were increased (+9.4, +11.6 and +11.9%, respectively). LV end-systolic stress was decreased at the end of GH therapy (-11.2%). E and A wave, significantly reduced at baseline, were increased by 1 yr of GH therapy (+23.3% and +28.1%, respectively); likewise, the abnormally high E peak deceleration time was partially reversed by GH administration (-10.7%). Our study, though conducted in a small sample size, demonstrates that a TWI GH treatment schedule is able to reverse the cardiovascular abnormalities in AO GHD patients and to improve body composition and lipid profile. The maintenance of circulating IGF-I concentrations within the low normal range allows to avoid most of the side-effects reported with higher GH doses while being cost-effective and improving the patient's compliance.

KW - Adult onset GH deficiency

KW - Body composition

KW - Echocardiography

KW - Heart

KW - Thrice-a-week GH replacement therapy

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M3 - Article

VL - 26

SP - 420

EP - 428

JO - Journal of Endocrinological Investigation

JF - Journal of Endocrinological Investigation

SN - 0391-4097

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