ORIGINAL
ARTICLE
Impairment of Anaerobic Capacity in Adults With Growth Hormone Deficiency Viral Chikani, Ross C. Cuneo, Ingrid Hickman, and Ken K. Y. Ho Departments of Diabetes and Endocrinology (V.C., R.C.C., K.K.Y.H.) and Nutrition and Dietetics (I.H.), Princess Alexandra Hospital, Brisbane, Queensland, Australia 4102; and School of Medicine (V.C., K.K.Y.H.) and Mater Research Institute (I.H.), University of Queensland, Brisbane, Queensland, Australia 4072
Context: The anaerobic energy system underpins the initiation of all physical activities, including those of daily living. GH supplementation improves sprinting in recreational athletes, a performance measure dependent on the anaerobic energy system. The physiological and functional link between GH and the anaerobic energy system is unknown. Objective: The objective was to investigate whether anaerobic capacity is impaired in adults with GH deficiency (GHD) and to assess its functional significance. Design: This was a cross-sectional study. Participants: The participants were 13 adults with GHD and 13 age-, gender- and body mass indexmatched normal subjects. Main Outcome Measures: Anaerobic power (watts) was assessed by the 30-second Wingate test, and aerobic capacity was assessed by the VO2max (L/min) test. The functional assessment comprised the stair-climb test, chair-stand test, and 7-day pedometry. Quality of life (QoL) was assessed by the QoL-AGHDA questionnaire. Lean body mass (LBM) was quantified by dual-energy x-ray absorptiometry. Results: Mean anaerobic power (5.8 ⫾ 0.4 vs 7.1 ⫾ 0.3 W 䡠 kg LBM⫺1; P ⬍ .05) and VO2max were significantly lower in adults with GHD. The duration of the stair-climb test was longer (19.4 ⫾ 0.7 vs 16.5 ⫾ 0.7 s; P ⬍ .01) in adults with GHD and correlated negatively (R2 ⫽ 0.7; P ⬍ .0001) with mean anaerobic power. The mean number of chair-stand repetitions and daily step counts were lower, and the QoL-AGHDA score was higher in adults with GHD (P ⬍ .05). In a multiple regression analysis, age, gender, LBM, and GH status were significant predictors of mean anaerobic power. Mean anaerobic power significantly predicted stair-climb performance (P ⬍ .01) and QoL (P ⬍ .05). Conclusions: Anaerobic capacity is subnormal, and it independently predicts stair-climbing capacity and QoL in adults with GHD. We conclude that GH regulates anaerobic capacity, which determines QoL and selective aspects of physical function. (J Clin Endocrinol Metab 100: 1811–1818, 2015)
H is a major metabolic hormone regulating carbohydrate, lipid, and protein homeostasis (1). GH deficiency (GHD) leads to detrimental changes in body composition causing diminished muscle strength and endurance capacity (2). Strength and endurance are measures of muscle
G
function that depend on muscle size, muscle fiber composition, and the availability of energy to support the exercising muscle. This energy is available as ATP, which is produced by two complementary energy systems: anaerobic (oxygen independent) and aerobic (oxygen dependent) (3).
ISSN Print 0021-972X ISSN Online 1945-7197 Printed in U.S.A. Copyright © 2015 by the Endocrine Society Received January 1, 2015. Accepted February 12, 2015. First Published Online February 19, 2015
Abbreviations: BMI, body mass index; CV, coefficient of variation; GHD, GH deficiency; ICC, intraclass correlation coefficient; LBM, lean body mass; QoL, quality of life; VO2max, maximal oxygen consumption.
doi: 10.1210/jc.2015-1006
J Clin Endocrinol Metab, May 2015, 100(5):1811–1818
jcem.endojournals.org
The Endocrine Society. Downloaded from press.endocrine.org by [${individualUser.displayName}] on 11 October 2015. at 18:40 For personal use only. No other uses without permission. . All rights reserved.
1811
1812
Chikani et al
Anaerobic Capacity in Growth Hormone Deficiency
The anaerobic energy system comprises preformed ATP, stored in the form of phosphocreatine, and ATP production from anaerobic glycolysis, ie, metabolism of glucose in the absence of oxygen. The aerobic energy system generates ATP from oxidative metabolism of substrates derived from carbohydrates, lipids, and proteins in the mitochondria (3). The amount of preformed ATP present in muscle is sufficient to sustain physical activity for the first 5–10 seconds. Thereafter, anaerobic glycolysis provides energy for an additional 30 – 40 seconds when aerobic metabolism begins to take over, providing energy for sustained activity (4). The aerobic energy system supports endurance exercise, whereas the anaerobic energy system powers intensive activity of short-term duration. The anaerobic energy system underpins the initiation of all physical activities including activities of daily living, such as rising from a chair, climbing stairs, and rushing for a bus (5). Thus, it is conceivable that impairment of anaerobic capacity leads to the perception of increased fatigue during the execution of ordinary activities of daily living, a symptom commonly observed in adults with GHD (6). Muscle strength and aerobic capacity are impaired in GHD and restored by GH replacement over a period of a few months (2, 7). The question as to whether anaerobic capacity is impaired in GHD has not been studied. Two recent studies (8, 9) have provided evidence that GH regulates anaerobic metabolism. In a gene expression study, Sjögren et al (8) found that GH down-regulated the key genes activating aerobic metabolism and some genes inhibiting glycolysis in skeletal muscle from adults with GHD (8). In a study of physical performance in recreational athletes, Meinhardt et al (9) observed that GH induced a significant and selective improvement in sprinting, a measure of performance dependent on anaerobic capacity. This study was undertaken in GH-sufficient healthy adults using a supraphysiological dose of GH. The
Table 1.
J Clin Endocrinol Metab, May 2015, 100(5):1811–1818
physiological significance of the link between GH, the anaerobic energy system, and physical function is unclear. The objective of the present study was to assess whether anaerobic exercise capacity is impaired and is related to aspects of physical function in adults with GHD.
Subjects and Methods Subjects Thirteen hypopituitary adults with GHD and 13 age-, gender-, and body mass index (BMI)-matched normal adults were recruited. GHD was established by a peak GH response ⬍3 g/L to insulin-induced hypoglycemia or the presence of three or more pituitary hormone deficiencies co-existing with a subnormal IGF-1 level. Subjects with severe cardiorespiratory, liver, or renal impairment or malignancy were excluded. Most patients had coexisting anterior pituitary hormone deficiencies, and they were placed on stable replacement therapies for at least 6 months before enrollment in the study. The causes of pituitary deficiencies and hormone replacements are summarized in the Table 1. None of the hypopituitary patients had been previously replaced with GH, except for two subjects in whom GH therapy was stopped at least 3 months before recruitment.
Study design This was a cross-sectional comparison of anaerobic capacity, aerobic capacity, physical function, body composition, and quality of life (QoL). Subjects attended the test venue on 2 consecutive days for the baseline assessments, on each occasion after an overnight fast. The study was carried out in accordance with Good Clinical Practice guidelines, approved by the Metro South Human Research Ethics Committee, and signed informed consent was obtained from all subjects.
Physical performance tests The following tests to assess anaerobic and aerobic capacities were undertaken. Reproducibility of physical performance tests and function tests was assessed under standardized conditions by studying six healthy volunteers on two separate occasions, pro-
Causes of Pituitary Deficiency and Pituitary Hormone Replacement Therapies in 13 Subjects With GHD
Patient No.
Age, y
Gender
Diagnosis
Hormone Replacement
1 2 3 4 5 6 7 8 9 10 11 12 13
38 24 38 46 60 57 52 58 49 39 46 48 58
F F F F F F F M F F F F F
Cushing’s disease Septo-optic dysplasia Macroprolactinoma Silent ACTH macroadenoma Panhypopituitarism, empty sella Non-functioning macroadenoma Cushing’s disease Cushing’s disease Macroprolactinoma Glioma Cushing’s disease Non-functioning macroadenoma Rathke’s cleft cyst
H, T4, E2, D H, T4, E2 C, T4, E2, D H, T4 C, T4 T4 C, T4, E2 C, T, T4 H, T4, E2, D P, T4, E2 P, T4, E2, D H C, T4
Abbreviations: F, female; M, male; H, hydrocortisone; C, cortisone acetate; P, prednisone; T4, thyroxine; E2, estradiol; T, testosterone; D, desmopressin.
The Endocrine Society. Downloaded from press.endocrine.org by [${individualUser.displayName}] on 11 October 2015. at 18:40 For personal use only. No other uses without permission. . All rights reserved.
doi: 10.1210/jc.2015-1006
jcem.endojournals.org
1813
viding the coefficient of variation (CV) and intraclass correlation coefficient (ICC) for these tests.
analysis. The CV and ICC of the chair-stand test were 11% and 0.95, respectively.
Wingate test
Seven-day pedometry
The Wingate test was used to quantify anaerobic exercise capacity (power) as described by Bar-Or et al (10). It is one of the most widely used tests that has been validated in various groups ranging from athletes to subjects with chronic disease (10). Participants cycle on a Monark ergometer (Monark Exercise AB) for 30 seconds at maximal speed and against a constant force of 0.075 kp per kg body weight. Power output per second was recorded in watts. The power profile during a Wingate test typically reaches a peak within the first 5 seconds before declining gradually. The peak power and mean anaerobic power over 30 seconds were quantified. The CV and ICC were 4% and 0.99 for peak anaerobic power and 3% and 0.99 for mean anaerobic power, respectively.
We employed pedometry as a functional assessment of aerobic capacity. Pedometry is a simple, inexpensive, and userfriendly research tool for the objective assessment of habitual physical activity in healthy subjects and in patients with chronic disease (16, 17). A Kenz activity monitor (Kenz Lifecorder; Suzuken Co, Ltd) was used to record 7-day pedometry. It has an intramodel reliability of 0.998 and absolute accuracy of 3% (16). Participants were instructed to wear the Kenz activity monitor on their waist belt continuously for 7 days, from which the average steps per day were calculated. The CV and ICC of daily step count were 6% and 0.98, respectively.
Maximal oxygen consumption (VO2max) test The VO2max test was used to quantify aerobic exercise capacity by cycle ergometry (11). In this project, VO2max was determined using a Monark ergometer. A work rate was set at 40 W and increased by 10 W every minute until exhaustion. Subjects were encouraged verbally to maximize their effort. Oxygen consumption (VO2), carbon dioxide production (VCO2), and ventilatory volumes were measured continuously with a metabolic monitor (ParvoMedics), which uses infrared CO2, paramagnetic O2 analyzers, and a pneumotachograph. Calibration against standard gases (16% O2 and 4% CO2), volume (3 L), operating temperature, humidity, and barometric pressure was undertaken immediately before each test. VO2 values were averaged for each 15-second period, and the highest value was recorded as CHAIR-STANDmax. The CV and ICC of VO2max were 4% and 0.96, respectively.
Physical function assessments We selected the stair-climb and chair-stand tests as functional assessments of anaerobic power. Both test functional capacity from initiation to up to 30 seconds of the physical tasks.
Stair-climb test The stair-climb test is widely used for the assessment of physical function and leg muscle power (12–14). We measured the time taken to ascend four flights of stairs totaling 48 steps (step height, 17 cm). The time was recorded to the nearest 0.001 second, using a switch mat timing system (TAG Heuer HL440 Minitimer; TAGHeuer Professional Timing). The participants climbed the stairs as fast as possible, one step at a time. The test was performed three times on each occasion, separated by a rest period of 5 minutes. The best of three readings was selected for data analysis. The CV and ICC of the stair-climb test were 4% and 0.97, respectively.
Chair-stand test The chair-stand test is a validated functional test to assess lower body power (15). It measures the number of times a subject can stand up and sit down in 30 seconds from a fully seated position in a chair. The time was recorded by a stopwatch, and repetitions were counted by an electronic counter. The test was repeated three times on each occasion, separated by a 5-minute rest period, and the best reading out of three was selected for data
QoL assessment QoL was assessed by the QoL-AGHDA (Quality of Life Assessment of Growth Hormone Deficiency in Adults) questionnaire, a research tool specifically validated in adults with GHD (18, 19). The QoL-AGHDA contains 25 items with a “yes/no” response format. Each positive (yes) response is given a score of 1, allowing scores to range from 0 to 25. Higher scores indicate poorer QoL.
Body composition assessment Body composition was assessed by dual-energy x-ray absorptiometry using a Hologic absorptiometer (model QDR 4500A, software version 12.6; Hologic, Inc) to allow correction of anaerobic power and VO2max for the lean body mass (LBM). The CVs for LBM and fat mass assessed by dual-energy x-ray absorptiometry in our laboratory are 1.4 and 2.9%, respectively (20).
Statistical analysis Statistical analysis was performed with IBM SPSS statistics software (version 22). Results are reported as mean ⫾ SEM. Comparisons between normal and GH-deficient groups were performed with the unpaired t test. Associations were explored with simple linear regressions. Multiple regression analyses were used to determine the independent predictors of physical performance measures and functional measures. In the analysis for physical performance measures, independent variables included age, gender, LBM, and GHD; and for functional measures, independent variables included peak and mean anaerobic power, VO2max, age, gender, LBM, and GHD. A P value ⬍.05 was considered statistically significant.
Results Age, weight, gender, and BMI of 13 normal and 13 GHdeficient adults are shown in Table 2. There were no significant differences in age, weight, and BMI between the two groups. Mean fat mass tended to be higher and LBM lower in adults with GHD, but the differences were not statistically significant. The mean IGF-1 concentration was 9.0 ⫾ 1.6 nmol/L (reference range, 7–32 nmol/L). LBM significantly correlated with peak and mean anaerobic power and with VO2max in the combined groups
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Chikani et al
Anaerobic Capacity in Growth Hormone Deficiency
J Clin Endocrinol Metab, May 2015, 100(5):1811–1818
Table 2. Baseline Characteristics, Performance Tests, Functional Measures, and QoL in 13 Adults With GHD and 13 Normal Subjects
Males:females Age, y BMI, kg/m2 LBM, kg Fat mass, kg Peak anaerobic power, W Peak anaerobic power, W 䡠 kg LBM⫺1 Mean anaerobic power, W Mean anaerobic power, W 䡠 kg LBM⫺1 VO2max, L 䡠 min⫺1 VO2max, mL 䡠 min⫺1 䡠 kg LBM⫺1 Stair-climb test, s Chair-stand test repetitions, n Pedometry, steps/d QoL-AGHDA score
GHD
Normal
P Value
1:12 45.3 ⫾ 3.2 27.0 ⫾ 1.4 41.8 ⫾ 1.9 26.8 ⫾ 2.3 424 ⫾ 33 10.0 ⫾ 0.4 246 ⫾ 22 5.8 ⫾ 0.4 1.6 ⫾ 0.1 37.2 ⫾ 1.5 19.4 ⫾ 0.7 19.2 ⫾ 1.2 6655 ⫾ 634 16.6 ⫾ 1.6
1:12 43.7 ⫾ 3.1 26.0 ⫾ 1.1 44.1 ⫾ 1.5 21.9 ⫾ 2.1 473 ⫾ 22 10.7 ⫾ 0.3 312 ⫾ 17 7.1 ⫾ 0.3 2.1 ⫾ 0.1 46.7 ⫾ 2.9 16.5 ⫾ 0.7 25.5 ⫾ 2.1 9565 ⫾ 668 2.1 ⫾ 0.8
NS NS NS NS NS NS ⬍.05 ⬍.05 ⬍.01 ⬍.01 ⬍.01 ⬍.01 ⬍.01 ⬍.0001
Abbreviation: LBM, lean body mass; NS, not significant; QoL, quality of life; VO2max, maximal oxygen consumption. All values are shown as the mean ⫾ SEM.
VO2max were 18 and 20% lower in GH-deficient adults, respectively.
of normal subjects and adults with GHD (Figure 1). For data analysis, peak and mean anaerobic power and VO2max are corrected for LBM and expressed as W 䡠 kg LBM⫺1 and mL 䡠 kg LBM⫺1 䡠 min⫺1, respectively.
Physical function (Table 2) The functional relevance of anaerobic capacity was assessed by tasks that were completed over 15 to 30 seconds, the time course of physical activity that is mainly subserved by the anaerobic energy system. In the stair-climb test, GH-deficient adults took a significantly longer time (P ⬍ .01) to complete the task of climbing four flights of stairs than normal adults. In the chair-stand test, the number of repetitions performed in 30 seconds was approximately 30% lower (P ⬍ .01) in adults with GHD. To assess the functional relevance of aerobic capacity, 7-day pedometry was performed. The average daily step count in adults with GHD was R2=0.4 p
ARTICLE
Impairment of Anaerobic Capacity in Adults With Growth Hormone Deficiency Viral Chikani, Ross C. Cuneo, Ingrid Hickman, and Ken K. Y. Ho Departments of Diabetes and Endocrinology (V.C., R.C.C., K.K.Y.H.) and Nutrition and Dietetics (I.H.), Princess Alexandra Hospital, Brisbane, Queensland, Australia 4102; and School of Medicine (V.C., K.K.Y.H.) and Mater Research Institute (I.H.), University of Queensland, Brisbane, Queensland, Australia 4072
Context: The anaerobic energy system underpins the initiation of all physical activities, including those of daily living. GH supplementation improves sprinting in recreational athletes, a performance measure dependent on the anaerobic energy system. The physiological and functional link between GH and the anaerobic energy system is unknown. Objective: The objective was to investigate whether anaerobic capacity is impaired in adults with GH deficiency (GHD) and to assess its functional significance. Design: This was a cross-sectional study. Participants: The participants were 13 adults with GHD and 13 age-, gender- and body mass indexmatched normal subjects. Main Outcome Measures: Anaerobic power (watts) was assessed by the 30-second Wingate test, and aerobic capacity was assessed by the VO2max (L/min) test. The functional assessment comprised the stair-climb test, chair-stand test, and 7-day pedometry. Quality of life (QoL) was assessed by the QoL-AGHDA questionnaire. Lean body mass (LBM) was quantified by dual-energy x-ray absorptiometry. Results: Mean anaerobic power (5.8 ⫾ 0.4 vs 7.1 ⫾ 0.3 W 䡠 kg LBM⫺1; P ⬍ .05) and VO2max were significantly lower in adults with GHD. The duration of the stair-climb test was longer (19.4 ⫾ 0.7 vs 16.5 ⫾ 0.7 s; P ⬍ .01) in adults with GHD and correlated negatively (R2 ⫽ 0.7; P ⬍ .0001) with mean anaerobic power. The mean number of chair-stand repetitions and daily step counts were lower, and the QoL-AGHDA score was higher in adults with GHD (P ⬍ .05). In a multiple regression analysis, age, gender, LBM, and GH status were significant predictors of mean anaerobic power. Mean anaerobic power significantly predicted stair-climb performance (P ⬍ .01) and QoL (P ⬍ .05). Conclusions: Anaerobic capacity is subnormal, and it independently predicts stair-climbing capacity and QoL in adults with GHD. We conclude that GH regulates anaerobic capacity, which determines QoL and selective aspects of physical function. (J Clin Endocrinol Metab 100: 1811–1818, 2015)
H is a major metabolic hormone regulating carbohydrate, lipid, and protein homeostasis (1). GH deficiency (GHD) leads to detrimental changes in body composition causing diminished muscle strength and endurance capacity (2). Strength and endurance are measures of muscle
G
function that depend on muscle size, muscle fiber composition, and the availability of energy to support the exercising muscle. This energy is available as ATP, which is produced by two complementary energy systems: anaerobic (oxygen independent) and aerobic (oxygen dependent) (3).
ISSN Print 0021-972X ISSN Online 1945-7197 Printed in U.S.A. Copyright © 2015 by the Endocrine Society Received January 1, 2015. Accepted February 12, 2015. First Published Online February 19, 2015
Abbreviations: BMI, body mass index; CV, coefficient of variation; GHD, GH deficiency; ICC, intraclass correlation coefficient; LBM, lean body mass; QoL, quality of life; VO2max, maximal oxygen consumption.
doi: 10.1210/jc.2015-1006
J Clin Endocrinol Metab, May 2015, 100(5):1811–1818
jcem.endojournals.org
The Endocrine Society. Downloaded from press.endocrine.org by [${individualUser.displayName}] on 11 October 2015. at 18:40 For personal use only. No other uses without permission. . All rights reserved.
1811
1812
Chikani et al
Anaerobic Capacity in Growth Hormone Deficiency
The anaerobic energy system comprises preformed ATP, stored in the form of phosphocreatine, and ATP production from anaerobic glycolysis, ie, metabolism of glucose in the absence of oxygen. The aerobic energy system generates ATP from oxidative metabolism of substrates derived from carbohydrates, lipids, and proteins in the mitochondria (3). The amount of preformed ATP present in muscle is sufficient to sustain physical activity for the first 5–10 seconds. Thereafter, anaerobic glycolysis provides energy for an additional 30 – 40 seconds when aerobic metabolism begins to take over, providing energy for sustained activity (4). The aerobic energy system supports endurance exercise, whereas the anaerobic energy system powers intensive activity of short-term duration. The anaerobic energy system underpins the initiation of all physical activities including activities of daily living, such as rising from a chair, climbing stairs, and rushing for a bus (5). Thus, it is conceivable that impairment of anaerobic capacity leads to the perception of increased fatigue during the execution of ordinary activities of daily living, a symptom commonly observed in adults with GHD (6). Muscle strength and aerobic capacity are impaired in GHD and restored by GH replacement over a period of a few months (2, 7). The question as to whether anaerobic capacity is impaired in GHD has not been studied. Two recent studies (8, 9) have provided evidence that GH regulates anaerobic metabolism. In a gene expression study, Sjögren et al (8) found that GH down-regulated the key genes activating aerobic metabolism and some genes inhibiting glycolysis in skeletal muscle from adults with GHD (8). In a study of physical performance in recreational athletes, Meinhardt et al (9) observed that GH induced a significant and selective improvement in sprinting, a measure of performance dependent on anaerobic capacity. This study was undertaken in GH-sufficient healthy adults using a supraphysiological dose of GH. The
Table 1.
J Clin Endocrinol Metab, May 2015, 100(5):1811–1818
physiological significance of the link between GH, the anaerobic energy system, and physical function is unclear. The objective of the present study was to assess whether anaerobic exercise capacity is impaired and is related to aspects of physical function in adults with GHD.
Subjects and Methods Subjects Thirteen hypopituitary adults with GHD and 13 age-, gender-, and body mass index (BMI)-matched normal adults were recruited. GHD was established by a peak GH response ⬍3 g/L to insulin-induced hypoglycemia or the presence of three or more pituitary hormone deficiencies co-existing with a subnormal IGF-1 level. Subjects with severe cardiorespiratory, liver, or renal impairment or malignancy were excluded. Most patients had coexisting anterior pituitary hormone deficiencies, and they were placed on stable replacement therapies for at least 6 months before enrollment in the study. The causes of pituitary deficiencies and hormone replacements are summarized in the Table 1. None of the hypopituitary patients had been previously replaced with GH, except for two subjects in whom GH therapy was stopped at least 3 months before recruitment.
Study design This was a cross-sectional comparison of anaerobic capacity, aerobic capacity, physical function, body composition, and quality of life (QoL). Subjects attended the test venue on 2 consecutive days for the baseline assessments, on each occasion after an overnight fast. The study was carried out in accordance with Good Clinical Practice guidelines, approved by the Metro South Human Research Ethics Committee, and signed informed consent was obtained from all subjects.
Physical performance tests The following tests to assess anaerobic and aerobic capacities were undertaken. Reproducibility of physical performance tests and function tests was assessed under standardized conditions by studying six healthy volunteers on two separate occasions, pro-
Causes of Pituitary Deficiency and Pituitary Hormone Replacement Therapies in 13 Subjects With GHD
Patient No.
Age, y
Gender
Diagnosis
Hormone Replacement
1 2 3 4 5 6 7 8 9 10 11 12 13
38 24 38 46 60 57 52 58 49 39 46 48 58
F F F F F F F M F F F F F
Cushing’s disease Septo-optic dysplasia Macroprolactinoma Silent ACTH macroadenoma Panhypopituitarism, empty sella Non-functioning macroadenoma Cushing’s disease Cushing’s disease Macroprolactinoma Glioma Cushing’s disease Non-functioning macroadenoma Rathke’s cleft cyst
H, T4, E2, D H, T4, E2 C, T4, E2, D H, T4 C, T4 T4 C, T4, E2 C, T, T4 H, T4, E2, D P, T4, E2 P, T4, E2, D H C, T4
Abbreviations: F, female; M, male; H, hydrocortisone; C, cortisone acetate; P, prednisone; T4, thyroxine; E2, estradiol; T, testosterone; D, desmopressin.
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doi: 10.1210/jc.2015-1006
jcem.endojournals.org
1813
viding the coefficient of variation (CV) and intraclass correlation coefficient (ICC) for these tests.
analysis. The CV and ICC of the chair-stand test were 11% and 0.95, respectively.
Wingate test
Seven-day pedometry
The Wingate test was used to quantify anaerobic exercise capacity (power) as described by Bar-Or et al (10). It is one of the most widely used tests that has been validated in various groups ranging from athletes to subjects with chronic disease (10). Participants cycle on a Monark ergometer (Monark Exercise AB) for 30 seconds at maximal speed and against a constant force of 0.075 kp per kg body weight. Power output per second was recorded in watts. The power profile during a Wingate test typically reaches a peak within the first 5 seconds before declining gradually. The peak power and mean anaerobic power over 30 seconds were quantified. The CV and ICC were 4% and 0.99 for peak anaerobic power and 3% and 0.99 for mean anaerobic power, respectively.
We employed pedometry as a functional assessment of aerobic capacity. Pedometry is a simple, inexpensive, and userfriendly research tool for the objective assessment of habitual physical activity in healthy subjects and in patients with chronic disease (16, 17). A Kenz activity monitor (Kenz Lifecorder; Suzuken Co, Ltd) was used to record 7-day pedometry. It has an intramodel reliability of 0.998 and absolute accuracy of 3% (16). Participants were instructed to wear the Kenz activity monitor on their waist belt continuously for 7 days, from which the average steps per day were calculated. The CV and ICC of daily step count were 6% and 0.98, respectively.
Maximal oxygen consumption (VO2max) test The VO2max test was used to quantify aerobic exercise capacity by cycle ergometry (11). In this project, VO2max was determined using a Monark ergometer. A work rate was set at 40 W and increased by 10 W every minute until exhaustion. Subjects were encouraged verbally to maximize their effort. Oxygen consumption (VO2), carbon dioxide production (VCO2), and ventilatory volumes were measured continuously with a metabolic monitor (ParvoMedics), which uses infrared CO2, paramagnetic O2 analyzers, and a pneumotachograph. Calibration against standard gases (16% O2 and 4% CO2), volume (3 L), operating temperature, humidity, and barometric pressure was undertaken immediately before each test. VO2 values were averaged for each 15-second period, and the highest value was recorded as CHAIR-STANDmax. The CV and ICC of VO2max were 4% and 0.96, respectively.
Physical function assessments We selected the stair-climb and chair-stand tests as functional assessments of anaerobic power. Both test functional capacity from initiation to up to 30 seconds of the physical tasks.
Stair-climb test The stair-climb test is widely used for the assessment of physical function and leg muscle power (12–14). We measured the time taken to ascend four flights of stairs totaling 48 steps (step height, 17 cm). The time was recorded to the nearest 0.001 second, using a switch mat timing system (TAG Heuer HL440 Minitimer; TAGHeuer Professional Timing). The participants climbed the stairs as fast as possible, one step at a time. The test was performed three times on each occasion, separated by a rest period of 5 minutes. The best of three readings was selected for data analysis. The CV and ICC of the stair-climb test were 4% and 0.97, respectively.
Chair-stand test The chair-stand test is a validated functional test to assess lower body power (15). It measures the number of times a subject can stand up and sit down in 30 seconds from a fully seated position in a chair. The time was recorded by a stopwatch, and repetitions were counted by an electronic counter. The test was repeated three times on each occasion, separated by a 5-minute rest period, and the best reading out of three was selected for data
QoL assessment QoL was assessed by the QoL-AGHDA (Quality of Life Assessment of Growth Hormone Deficiency in Adults) questionnaire, a research tool specifically validated in adults with GHD (18, 19). The QoL-AGHDA contains 25 items with a “yes/no” response format. Each positive (yes) response is given a score of 1, allowing scores to range from 0 to 25. Higher scores indicate poorer QoL.
Body composition assessment Body composition was assessed by dual-energy x-ray absorptiometry using a Hologic absorptiometer (model QDR 4500A, software version 12.6; Hologic, Inc) to allow correction of anaerobic power and VO2max for the lean body mass (LBM). The CVs for LBM and fat mass assessed by dual-energy x-ray absorptiometry in our laboratory are 1.4 and 2.9%, respectively (20).
Statistical analysis Statistical analysis was performed with IBM SPSS statistics software (version 22). Results are reported as mean ⫾ SEM. Comparisons between normal and GH-deficient groups were performed with the unpaired t test. Associations were explored with simple linear regressions. Multiple regression analyses were used to determine the independent predictors of physical performance measures and functional measures. In the analysis for physical performance measures, independent variables included age, gender, LBM, and GHD; and for functional measures, independent variables included peak and mean anaerobic power, VO2max, age, gender, LBM, and GHD. A P value ⬍.05 was considered statistically significant.
Results Age, weight, gender, and BMI of 13 normal and 13 GHdeficient adults are shown in Table 2. There were no significant differences in age, weight, and BMI between the two groups. Mean fat mass tended to be higher and LBM lower in adults with GHD, but the differences were not statistically significant. The mean IGF-1 concentration was 9.0 ⫾ 1.6 nmol/L (reference range, 7–32 nmol/L). LBM significantly correlated with peak and mean anaerobic power and with VO2max in the combined groups
The Endocrine Society. Downloaded from press.endocrine.org by [${individualUser.displayName}] on 11 October 2015. at 18:40 For personal use only. No other uses without permission. . All rights reserved.
1814
Chikani et al
Anaerobic Capacity in Growth Hormone Deficiency
J Clin Endocrinol Metab, May 2015, 100(5):1811–1818
Table 2. Baseline Characteristics, Performance Tests, Functional Measures, and QoL in 13 Adults With GHD and 13 Normal Subjects
Males:females Age, y BMI, kg/m2 LBM, kg Fat mass, kg Peak anaerobic power, W Peak anaerobic power, W 䡠 kg LBM⫺1 Mean anaerobic power, W Mean anaerobic power, W 䡠 kg LBM⫺1 VO2max, L 䡠 min⫺1 VO2max, mL 䡠 min⫺1 䡠 kg LBM⫺1 Stair-climb test, s Chair-stand test repetitions, n Pedometry, steps/d QoL-AGHDA score
GHD
Normal
P Value
1:12 45.3 ⫾ 3.2 27.0 ⫾ 1.4 41.8 ⫾ 1.9 26.8 ⫾ 2.3 424 ⫾ 33 10.0 ⫾ 0.4 246 ⫾ 22 5.8 ⫾ 0.4 1.6 ⫾ 0.1 37.2 ⫾ 1.5 19.4 ⫾ 0.7 19.2 ⫾ 1.2 6655 ⫾ 634 16.6 ⫾ 1.6
1:12 43.7 ⫾ 3.1 26.0 ⫾ 1.1 44.1 ⫾ 1.5 21.9 ⫾ 2.1 473 ⫾ 22 10.7 ⫾ 0.3 312 ⫾ 17 7.1 ⫾ 0.3 2.1 ⫾ 0.1 46.7 ⫾ 2.9 16.5 ⫾ 0.7 25.5 ⫾ 2.1 9565 ⫾ 668 2.1 ⫾ 0.8
NS NS NS NS NS NS ⬍.05 ⬍.05 ⬍.01 ⬍.01 ⬍.01 ⬍.01 ⬍.01 ⬍.0001
Abbreviation: LBM, lean body mass; NS, not significant; QoL, quality of life; VO2max, maximal oxygen consumption. All values are shown as the mean ⫾ SEM.
VO2max were 18 and 20% lower in GH-deficient adults, respectively.
of normal subjects and adults with GHD (Figure 1). For data analysis, peak and mean anaerobic power and VO2max are corrected for LBM and expressed as W 䡠 kg LBM⫺1 and mL 䡠 kg LBM⫺1 䡠 min⫺1, respectively.
Physical function (Table 2) The functional relevance of anaerobic capacity was assessed by tasks that were completed over 15 to 30 seconds, the time course of physical activity that is mainly subserved by the anaerobic energy system. In the stair-climb test, GH-deficient adults took a significantly longer time (P ⬍ .01) to complete the task of climbing four flights of stairs than normal adults. In the chair-stand test, the number of repetitions performed in 30 seconds was approximately 30% lower (P ⬍ .01) in adults with GHD. To assess the functional relevance of aerobic capacity, 7-day pedometry was performed. The average daily step count in adults with GHD was R2=0.4 p
