Physical and Cardiovascular Performance in Cases with Acromegaly after Regular Short-Term Exercise

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This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1111/cen.12708 This article is protected by copyright. All rights reserved.

Article Type: 2 Original Article - Europe, excluding UK

Physical and Cardiovascular Performance in Cases with Acromegaly after Regular Short-Term Exercise

Running Title: Exercise in Acromegaly

Esra Hatipoglu1, Nuri Topsakal2, Oya Erkut Atilgan2, Asiye Filiz Camliguney2, Baris Ikitimur3, Serdal

Ugurlu4, Mutlu Niyazoglu1, Hasan Birol Cotuk2, Pinar Kadioglu1

1Division of Endocrinology and Metabolism, Department of Internal Medicine, Cerrahpasa Medical

School, Istanbul University, Istanbul, Turkey

2 Marmara University School of Physical Education and Sports, Istanbul, Turkey

3 Department of Cardiology, Cerrahpasa Medical School, Istanbul University, Istanbul, Turkey

4Division of Rheumatology, Department of Internal Medicine, Cerrahpasa Medical School, Istanbul

University, Istanbul, Turkey

Corresponding author and reprint request:

Dr. Pinar Kadioglu

Address: Cerrahpasa Tip Fakültesi, Ic Hastalıkları Anabilim Dali, Endokrinoloji-Metabolizma ve Diyabet Bilim

Dali, 34303 Cerrahpasa, Istanbul, Turkey

Telephone number: 90-532-404 10 40 Fax number: 90-212- 233 38 06

E-mail: [email protected]

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This article is protected by copyright. All rights reserved.

Key words: Acromegaly, exercise, physical performance, functional capacity, muscle, body composition

Acknowledgment: None

Funding: The study was supported by the Research Fund of the University of Istanbul. Istanbul, Turkey, Project

No. 22561.

Conflict of interest: The authors declare that they have no conflict of interest.

Abstract

Objective: Impaired physical performance is a disturbing complication of acromegaly. We aimed to evaluate the

role of regular exercise in amelioration of the impaired physical performance in acromegaly.

Methods: Patients with acromegaly were divided into two groups according to their participation in a

prescheduled program of exercise. Participants in the study group exercised 3 days a week for 3 consecutive

months. Exercise tolerance was evaluated by maximal oxygen consumption (VO2max) and time (T) taken to

complete the Bruce protocol, muscle flexibility by the sit and reach test (SRT) and muscle strength by the hand

grip strength test (HGST). Concomitantly, anthropometric assessment was done using body mass index (BMI),

waist to hip ratio (WHR) , skinfold measurements from 8 points, percentage body fat (PBF), fat mass (FM) and

lean body mass (LBM).

Results: After 3 months of exercise VO2max and T were higher in cases that exercised than in cases that did not

(p=0.004 and p=0.001). Over 3 months, within the exercise group, VO2max and T of the Bruce protocol

increased (p=0.003 and p=0.004) and heart rate during warming decreased (p=0.04). SRT increased within the

exercise group after 3 months (p=0.004). HGSRT did not change significantly (right p=0.06 and left p=0.2). The

sum of skinfolds, BMI, WHR and LBM remained stable over the study period (p=0.1, p=0.08, p=0.3 and

p=0.09). PBF decreased slightly and FM decreased significantly over 3 months (p=0.05 and p=0.03).

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Conclusion: Even short-term exercise may improve impaired physical performance, muscle activity and

disturbed body fat composition in acromegaly.

Introduction

Acromegaly is a chronic condition of excessive growth hormone (GH) and insulin-like growth factor-1 (IGF-1)

secretion, mostly originating from a pituitary adenoma 1. It has a wide range of systemic involvement, varying

from soft tissue and skin to cardiovascular changes 2. Consequently, it has detrimental effects on both the

functional performance and psychosocial status of the cases involved 3-5. Although acromegaly is amenable to

treatment, not all complications are reversible and even after remission, quality of life may not be restored 2, 6 .

In a previous study, we demonstrated that the self esteem and body perception of the persons with acromegaly

improved significantly with exercise 7. However, there are limited data on physical performance in cases of

acromegaly and preventive measures, other than the control of the disease activity, has not yet been evaluated.

Herein, we aimed to assess the impact of exercise on physical and cardiovascular performance, which are known

to be impaired in cases with acromegaly.

Methods

A total of 120 patients with acromegaly, who were being monitored and treated at the Department of

Endocrinology and Metabolism at Cerrahpasa Faculty of Medicine, were asked to participate in the study. Of the

35 patients, who agreed to participate, only 11 completed the full course of the exercise program, 11

discontinued and 13 did not attend any course. Those who exercised regularly were included in the study group.

From patients not attending any course, 11 were randomly matched for age and gender to comprise the control

group.

Those in the study group exercised 3 days a week for 3 consecutive months. Each exercise session lasted 75

minutes while the participants were supervised. An exercise session consisted of warming up, cardio, strength,

balance and stretching. Strength exercises were done using the body-circuit method involving all the muscle

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groups. Each session concluded with stretching exercises. At the end of each month, the performance level of the

exercises was increased, but the subjectively perceived exertion assessed by the Borg scale remained stable at a

“light” level during the entire training period 8. To be included in the study group, attendance at each session was

mandatory. None of the control group cases participated in the exercise sessions.

A diagnosis of acromegaly was initially determined on the basis of clinical findings, which included failure to

suppress nadir GH level to less than 1 ng/dl during the oral glucose tolerance test (OGTT) and high levels of

IGF-1 adjusted for age and gender. Status of remission was assessed by using levels of GH and IGF-1 obtained

in the morning. At study entry, rheumatologic and cardiologic examinations were performed for each case by a

rheumatologist and cardiologist to ensure there was no obstacle to exercising. Two main visits were performed at

study entry (month-0) and after 3 months of the study period (month-3). Fasting blood glucose (FBG), insulin,

HbA1C, total cholesterol (T-chol), HDL cholesterol (HDL), LDL cholesterol (LDL), and triglyceride (TG)

levels were also measured at each visit for each case in both groups. HOMA-IR was used to assess status of

insulin resistance 9. Age-adjusted IGF-1 values were calculated by using age-specific reference ranges for our

IGF-1 assay (xULN IGF-1= patient’s IGF-1/age-specific upper limit). Bilateral systolic and diastolic blood

pressures (SBP and DBP) were also recorded.

For each attendant, both at the beginning and after 3 months, resting transthoracic echocardiography was

performed with GE Vivid 3 (General Electric, USA) equipment and 2.5 MHZ transducer, according to the

recommendations of the American Society of Echocardiography 10. All measurements were performed by same

cardiologist and at the same hour of the day. The following measurements were obtained with echocardiography

for each participant: interventricular septum thickness (IVST), left ventricular internal end-systolic and diastolic

diameters (LVID), left ventricular posterior wall thickness during diastole (LVPWd), Left atrium diameter

(LAd), left ventricular mass index (LVMI), and left ventricular ejection fraction (EF). Additionally, transmitral

velocities during early and late filling (E and A) and tissue Doppler velocities during early and late filling (E’

and A’) were obtained. Left ventricular mass (LVM) was calculated based on the Devereux and Reishek

Formula [LVM= 1.04x(LVID + IVST + LVPWd)3-13.6]. Left ventricular mass index was calculated by the

ratio of LVM to body surface area 11.

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At each visit, to evaluate effort-induced changes in cardiac function, both groups were subjected to graded

exercise testing using the Bruce protocol 12. The total time of the test, heart rate (HR) during warming and when

the maximal level was reached were recorded during the protocol. Maximal oxygen consumption (VO2max) for

female cases was calculated using the formula VO2 max = 4.38 × T - 3.9 and for male cases VO2 max = 14.8 -

(1.379 × T) + (0.451 × T²) - (0.012 × T³), where T is the total time of the test expressed in minutes and fractions

of a minute 13, 14 . The estimated maximum heart rate was calculated based on the formula (220-age).The

protocol was ended when the cases began to experience fatigue or reached the estimated maximum heart rate.

Hamstring and low back flexibility were assessed by using the sit and reach test (SRT). Better scores implicated

a higher degree of hip and trunk flexibility 15. The hand grip strength test (HGST) for both hands was used to

evaluate muscle strength by using a hand-held isometric dynamometry (Jamar hand dynamometer, Lafayette

Instrument Company, USA). The mean of 3 measurements taken at one-minute intervals was used for each case.

Body mass index (BMI =weight/height2) and waist-to-hip ratio were recorded at the beginning and at the end of

the study. To evaluate the interface between morphology of body parts and movement capacity of the cases,

eight skinfold (biceps, chest, triceps, subscapular, suprailiac, abdominal, thigh and medial calf) thicknesses were

measured in accordance of International Society for Advancement of Kinanthropometry (ISAK) international

procedures, using Harpenden skinfold calipers (Holtain, UK). The sum of the 8 skinfolds was taken and the

percentage body fat (PBF), fat mass (FM), lean body mass (LBM) were calculated as body composition

variables.

The study protocol was approved by the Ethics Committee of Cerrahpasa Faculty of Medicine at Istanbul

University. All the patients read and signed the informed consent forms before enrolling in the study.

Data were statistically analyzed with the SPSS 21.0 package program. The results are presented as medians and

interquartile ranges [IQR]. The Mann-Whitney U test was used to compare independent variables whereas the

Wilcoxon test was used to compare related variables. Spearman's correlation coefficient was used to calculate

associations between variables. The χ² and McNemar’s tests were used for categorical variables. P <0.05 was

considered statistically significant.

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Results

The mean age of the acromegaly patients in the exercise and non-exercise control groups was 45.6 + 8.1 years

and 43.6 + 4.9 years, respectively (p = 0.5). The Female/Male distribution was 9/2 in the exercise group and 8/3

in the control group (p=0.6). Additional demographic data of both groups are presented in Table 1.

At the beginning of the study, baseline HbA1c and TG levels were slightly higher in the control group than in

the exercise group (p=0.04 and p=0.02). There were no additional differences between initial laboratory values

of the 2 groups. After 3 months, there was no difference between the groups in HbA1c and TG levels (p=0.4 and

p=0.2). None of the metabolic parameters changed significantly after 3 months of exercise in the group that

exercised. Comparison of the laboratory findings at month-0 and at month-3 within exercise and control groups

are presented in Table 2.

The baseline SBP of the exercise group was 130 [IQR: 110-130] mmHg while that of the control group was 134

[IQR: 120-150] mmHg (p=0.2). The baseline DBP of the exercise and control groups were 90 [IQR: 88-103]

mmHg and 90 [IQR: 84-106] mmHg, respectively (p=0.9). Three months later, the SBP was 130 [IQR: 120-140]

mmHg in the exercise group and the control group 130 [IQR: 120-140] mmHg (p=0.7). DBP 80 [IQR: 80-84]

mmHg in the exercise group and 80 [IQR: 75-100] mmHg in the control group (p=0.5). SBP did not change

significantly over the 3 months in either the exercise group or the control group (in exercise group p= 0.5, in

control group p= 0.3). After 3 months, DBP decreased significantly within both groups (in exercise group

p=0.01 and in control group p= 0.04).

Echocardiography

At the beginning of the study, EF was higher in the exercise group than in the control group. However, at the end

of 3 months, EF of the two groups was similar (p=0.008 and p=0.7). There was no difference between the two

groups with respect to other echocardiographic findings. A comparison of the echocardiographic findings at

month-0 and at month-3 within the exercise and control groups is presented in Table 3.

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Physical performance

At the start of the study, baselineT and VO2max of the two groups were similar (p=0.1 and p=0.2), whereas after

3 months both were higher in in the exercise group than in the control group (p=0.004 and p=0.001). The

VO2max of the exercise group at month-3 was higher than the basal VO2max at month-0 (p=0.003). In contrast,

it remained stable in the control group (p=0.5). Additionally, the T of the Bruce protocol increased in the

exercise after short-term regular exercise while it remained stable in the control group ( p=0.004 and p=0.9)

(Figure 1).

Warming HR decreased over 3 months in the exercise group warming HR whereas it remained stable within the

control group (p=0.04 and p=0.2). During Bruce protocol at month-0, 6 (55%) and at month-3, 9 (82%) of the 11

cases in the exercise group reached the estimated maximum HR (p=0.2). Of the cases in the control group, the

number reaching the estimated maximum HR was 8 (73%) at month-0 and 6 (55%) at month-3 (p=0.5).

Although there was no difference between the two groups in SRT at the study entry and at the end of study

period (p=0.7 and p=0.5), it significantly increased within the exercise group after 3 months (p=0.004). HGST

results did not show a significant change during the study period. More data on physical performance of the

groups are presented in Table 4.

Body composition and anthropometric assessment

BMI was similar between the groups both at both the beginning and end of the study (p=0.2 and p=0.4).

Although the percentage body fat was similar in the groups (at the beginning of the study p=0.2 and at the end

p=0.1), within the exercise group it had slightly decreased by month-3 compared to the value observed at month-

0 (p=0.05). Similarly, there was no difference between the groups in FM (at the beginning of the study, p=0.3,

and at the end, p=0.3) and decreased within the exercise group over 3 months (p=0.03). Total skin fold thickness,

BMI and LBM did not change significantly within either group over the study period (for the sum of the skin

folds: in exercise group p=0.1 and control group p=0.1; for BMI: in exercise group p=0.08 and control group

p=0.09; for LBM: in exercise group p=0. 9 and control group p=0.9) (Table 5).

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Correlations

At the end of 3 months, the maximum HR reached during Bruce protocol was in the exercise group negatively

correlated with the duration between onset of symptoms and the diagnosis of acromegaly (r= - 0.6, p=0.05). At

the end of the study period, maximum HR reached during Bruce protocol in the non-exercise group was

negatively correlated with GH levels (r= -0.6, p=0.03); in contrast, this correlation was not detected in exercise

group (p=0.2).

Both right and left sided HGST in the exercise group were negatively correlated with GH level (for right r= -0.6,

p=0.04 and for left r= - 0.6, p=0.04) at the start of the study. This correlation did not exist at the end of 3 months.

In control group, IGF-1 levels and XULN IGF-1 were correlated with PBF at study entry (r=0.7, p=0.02 and

r=0.7, p=0.02). FM at the end of study period was significantly correlated with IGF-1 levels, however

correlation with xULN IGF-1 was less significant ( r=0.7, p=0.03, r=0.6, p=0.06). In the exercise group, LBM

was negatively correlated with GH levels (at study entry r= -0.8, p=0.004 and at the end r= -0.7, p=0.03). LBM

was also negatively correlated with the time elapsed since diagnosis (r= -0.6, p=0.04).

There were no additional significant correlations between the variables included in the study (data not shown).

Discussion

In the study, the total time the cases could run during the Bruce protocol and the calculated maximal oxygen

consumption increased in by the end of a 3-month program of exercise, both compared to the participants’ own

initial values at study entry and to the scores of the participants in the non-exercise group. This means that even

short-term exercise can improve functional capacity. In addition, the heart rate during warm-up declined in the

exercise group during the study period. The decrease in warming heart rate shows the demand on the heart

decreased so heart was able to work with less effort during exercise. Moreover, the sit and reach test, showing

muscle flexibility, performed after exercise improved in the exercise group. On the other hand, muscle strength,

as measured by the hand grip strength test, did not change over the study period.

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Acromegaly is a chronic disorder which, in addition to metabolic and cardiovascular impairment, is well-known

for its detrimental effects on functional capacity, sense of well being and fatigue 2, 3, 5 . Previously, we showed

that exercise may lessen the negative self-image people with acromegaly 7. A limited number of studies have

also shown decreased exertional capacity and impaired cardiac performance during and/or in response to

exercise in cases with acromegaly 5, 16, 17 . Previous studies have mostly dealt with the impact of medical

treatment on exercise-related changes in acromegaly or acute cardiovascular changes during exercise 4, 5, 16, 17.

However, none has shown prospectively whether or not regular exercise has an improving effect on impaired

functional and cardiovascular performance in cases with acromegaly.

In the current study, we were able to assess impact of exercise as an adjunctive measure, since we made no

changes to the medical treatments the cases were receiving or to life style other than exercise. We did not find

significant metabolic improvement or cardiovascular changes based on echocardiography at rest as a result of the

exercise. It is obvious that short-term adjunctive measures of any type would not be sufficient to overcome the

long-term consequences of a chronic disorder. In athletes, systolic function does not change when measured at

rest or during exercise and, left ventricular diastolic function is enhanced not at rest but during exercise 18.

Previous studies on acromegaly have also evaluated cardiac findings of echocardiography during exercise 16, 17.

However, we aimed to evaluate chronic changes; therefore, we performed an echocardiographic evaluation at a

3-month interval and at rest. If we had performed echocardiography during or just after exercise, we might have

obtained results similar to previous studies.

One of the most striking findings of the current study is the increased total time the cases could run during the

Bruce protocol. After 3 months, the subjects in exercise group could spend more time on the treadmill than the

subjects in the non-exercise group could. Moreover, this time increased over the 3-month period. In addition, the

number of the cases able to reach ≥85% of the estimated maximum HR before stopping the Bruce protocol

increased from 55% to 82% in the exercise group; the increment, however, was not statistically significant.

Overall, this shows that even after a short period of regular exercise, these subjects with acromegaly were able to

exercise longer before they began to feel tired or reached their estimated maximum HR. Furthermore, calculated

VO2max, reflecting the physical capacity of the individuals during prolonged, sub-maximal exercise, improved

after 3 months of exercise both compared to their VO2max at study entry and VO2max of the non-exercise

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group. Taken together, these findings show the recuperative power of exercise on impaired physical performance

in acromegaly.

The athlete’s heart is associated with decreased heart rate at rest or minimal exercise 18, 19. Similarly, in this

study, HR at warming in the exercise group decreased over the 3 months of exercise. This shows that exercise

may decrease demand on the heart at rest or with minimal exercise even in acromegaly. Maximum heart rate in

athletes does not vary with exercise but with age 19. In our study, the maximum HR reached during the Bruce

protocol decreased with as the time between the onset of symptoms and the diagnosis of acromegaly grew in the

exercise group and, with higher GH levels in the control group. These data may indirectly show that acromegaly

may cause certain alterations in exercise-induced changes of cardiac autonomic modulation.

Acromegaly is also associated with lower muscle strength despite muscular hypertrophy 20, 21. In the exercise

group of this study, muscle strength, measured using HGST, decreased with higher GH levels at study entry but

it did not change with exercise. Nevertheless, muscle flexibility, reflected by SRT, improved over 3 months of

exercise. Therefore, we may conclude that regular exercise may reverse some of the muscular changes related to

acromegaly while other muscular changes, namely strength, may be more resistant to change.

Within the exercise group, at the end of the 3-month period of exercise, BMI, WHR and LBM scores did not

change, FM decreased significantly and PBF decreased slightly. There were no differences between the exercise

and control groups either at the beginning or the end of the study. It is possible that the differences would be

more evident after a more prolonged course of exercise. Nevertheless, the decrease in FM and PBF within the

exercise group is a major finding, reflecting the impact of exercise on fatty tissue in acromegaly patients. GH is

known to decrease FM and increase LBM due to its lipolytic and anabolic effects and, treatment of acromegaly

increases FM 22, 23. The decline in FM and PBF with exercise may counterbalance this negative effect of

treatment. Therefore, exercise may not only be auxiliary for prevention of complications but also for certain

undesired effects of treatment in acromegaly. Why IGF-1 was correlated with FM and PBF and, LBM was

negatively correlated with GH and the time elapsed since diagnosis is inconclusive. Our study design did not

allow for a direct and certain evaluation of correlation between hormonal status and exercise effects.

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This study was not without certain limitations. First, the duration of the course of exercise was one limiting

factor; a more prolonged course may have produced more significant effects. Second, number of the participants

who attended the exercise sessions was small. We had strict criteria and included only those who attended all

sessions, therefore number of the cases in the study group dropped further. Third, we did not change any

medications, including beta blockers and calcium channel blockers, that patients were receiving for hypertension

and this may have distorted the findings on HR at some point. Also, we did not measure VO2max but calculated

it. Also medications used for treatment of acromegaly were not changed and cases were not selected based on

their disease activity; therefore, the impact of hormonal or disease status was not a primary outcome as per study

design.

In conclusion, cases with acromegaly are in need of adjunctive measures to overcome chronic complications and

their consequences. Deterioration in physical activity has been shown long before in acromegaly and exercise,

by improving functional capacity and performance of the cases, may be one of the preventive measures.

Moreover, exercise may also reverse undesired consequences that occur with treatment, i.e., disturbance in body

fat composition that may occur with treatment of acromegaly.

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Figure Legends

ure 1 The change in VO2max and the total time of Bruce protocol over the study period

Table 1. Demographic findings of the exercise and control groups

Table 2. Comparison of laboratory values at month 0 and month 3

Table 3. Comparison of the echocardiographic findings at month 0 and month 3

Table 4. Physical performance at month 0 and month 3

Table 5. Body composition and anthropometric measurements at month 0 and month 3

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Table 1. Demographic findings of the exercise and control groups

Exercise group Control group p (n = 11) (n = 11) Duration between 4 [2.6-6.3] 3 [1.5-10] 0.7 symptom onset and diagnosis (years)¶ Time elapsed 4 [2-12] 12 [5-14] 0.1 since diagnosis (years) ¶ Treatment (n,%) Surgery 10 (91) 10 (91) 1 Medical 0.06 Octreotid-LAR

10 mg 2 (25) (–) 20 mg 3 (38) 4 (36) 30 mg 2 (25) 4 (36)

Lanreotide 60 mg 1 (13) (–) 90 mg (–) 2 (18) 120 mg (–) 1 (9)

Cabergoline 3 (27) 5 (46)

Radiotherapy 0.8 CRT 1 (13) 2 (18) GKR 1 (13) 1 (13)

Remission 7 (64) 9 (82) 0.3 Hipopituitarism (n,%)* 1 Thyroid axis 3 (27) 4 (36) Steroid axis 1 (13) 1 (13)

Gonadal axis 0 1 (13) Comorbidities (n,%) 0.5 Hypertension 7 (64) 5 (46)

Diabetes 2 (25) 5 (46) Sleep apnea syndrome 3 (27) 1 (13) CRT conventional radiotherapy, GKR Gamma-knife radiosurgery ¶ Data were expressed as median and IQR. * All cases with pituitary hormone deficiencies were on adequate replacement therapy.

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Table 2. Comparison of laboratory values at month 0 and month 3

Exercise Group p value Control Group p value

Month 0 Month3 Month 0 Month3

GH 1 0.6 0.4 0.7 0.95 0.2 (ng/ml) [0.2-1.7] [0.2-1.8] [0.5-0.9] [0.7-1.1] IGF-1 215 178 0.1 223 220 0.3 (ng/ml) [165-290] [164-230] [175-300] [150-285] xULN IGF-1 0.9 0.7 0.09 0.8 0.8 0.3 [0.6-1.1] [0.5-0.8] [0.7-1.1] [0.6-1] FBG 88 96 0.07 90 93 1 (mg/dl) [76-96] [88-111] [88-114] [88-106] Insulin 6 4.4 0.2 7 3.1 0.1 (IU/ml) [5-9] [2-9] [4-12] [1-6.1] HOMA-IR 1.4 0.9 0.5 1.2 0.9 0.1 [1-2] [0.3-2.6] [0.9-4.8] [0.3-1.4] HbA1c 5.7 5.8 0.1 6.1 5.7 0.5 (%) [5.3-5.8] [5.4-5.9] [5.6-6.6] [5.6-6.9] T-chol 218 214.5 0.8 199 212.5 0.9 (mg/dl) [181-244] [184-236] [187-230] [189-228] LDL 136 136 0.9 133 140 0.3 (mg/dl) [123-171] [119-153] [116-154] [112-173] HDL 56 53 0.2 49 44 0.3 (mg/dl) [41-75] [43-79] [43-57] [38-51] TG 91 99 0.8 126 150 0.8 (mg/dl) [63-121] [77-136] [111-228] [80-266]

The results are presented as median and interquartile range [IQR]

Months 0 and 3 were compared by Wilcoxon signed ranks test

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Table 3. Comparison of the echocardiographic findings at month 0 and month 3


Month 0 Month 3 Month 0 Month 3

EF (%) 65[60-68] 62 [61-65] 0.3 60 [57-63] 62 [59-66] 0.07 LAd (mm) 36 [35-40] 36 [35-40] 0.9 37 [34-40] 37 [35-40] 0.7 LVMI (g/m2) 93 [70-106] 93 [70-106] 0.2 105[86-125] 103[86-125.4] 1 E (m/sn) 0.8 [0.7-0.9] 0.9 [0.8-1.1] 0.05 0.8 [0.7-0.9] 0.8 [0.7-0.9] 1 A (m/sn) 0.7 [0.6-0.9] 0.8 [0.7-0.9] 0.5 0.7 [0.6-0.8] 0.7 [0.6-0.8] 1 E/A 1.1 [0.9-1.3] 1.2 [1.1-1.4] 0.3 1.1 [1-1.5] 1.1 [1-1.5] 1 E’(cm/sn) 8 [7-11] 7 [5-10] 0.5 9 [7-12] 9 [7-12] 1

A’(cm/sn) 11 [8-14] 9 [8-12] 0.6 12 [8-13] 12 [8-13] 1 E’/A’ 0.7 [0.6-1.6] 0.8 [0.6-1.1] 0.5 0.8 [0.6-1.3] 0.8 [0.6-1.3] 1



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Table 4. Physical performance at month 0 and month 3


Month 0 Month3 Month 0 Month3

T 6.6 8.9 0.004* 7.05 6.4 0.9 (min) [6.3-9.5] [8.2-9.8] [5.4-7.3] [6.3-7.2] Warming HR 98.1 87.8 0.04* 91.6 87.7 0.2 (beats/min) [92.6-102.7] [85.1-94.5] [83.6-108.5] [83.9-95.8] Maximum HR 152.7 166.7 0.3 160 145.9 0.3 (beats/min) [134.5-180.2] [145.6-176.5] [139.2-168.1] [136.4-169.9] VO2max 25.8 34.8 0.003* 23.7 24.1 0.5 (mls/kg-1/min-1) [21.6-32.1] [30.6-38.3] [18.1-26.9] [23.7-26.9] SRT 25.5 29.1 0.004* 24 24.5 0.8 (cm) [16.5-32] [22-36.7] [20.5-37] [19.6-36] HGST-Right 30 33 0.06 28 28 0.8 (kg) [24-40] [23-45] [26-44] [26-42] HGST-Left 28 32 0.2 30 29 0.9 (kg) [20-39] [23-38] [22-44] [26-42]

T total time of the test (Bruce protocol), HR heart rate, VO2max maximal oxygen consumption, SRT sit and

reach test, HGST hand grip strength test.



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Table 5. Body composition and anthropometric measurements at month 0 and month 3

Exercise Group p value Control Group p value Month 0 Month3 Month 0 Month3 BMI 33 33 0.08 30 29.7 0.09 (kg/m2) [30-36] [29-36] [27-35] [26.1-35] Waist-Hip Ratio 0.8 0.8 0.3 0.9 0.9 0.3 (cm) [0.8-0.9] [0.8-0.9] [0.8-0.9] [0.8-0.9] Sum of skinfolds 269.2 245.4 0.1 207.6 205 0.1 (mm) [191.2-312.6] [218-281.2] [170.4-259.6] [160.6-236.2] PBF 27 25.3 0.05 23.9 23.9 0.2 (%) [22.6-31.5] [22.3-27.9] [20.3-28.2] [20.4-25.2] FM 23.3 20.7 0.03* 19.6 18.8 0.06 (kg) [18.3-30.5] [19.2-26.2] [14.3-26.8] [14.7-22.8] LBM 64.4 61.2 0.9 64 65.1 0.9 (kg) [59.2-69.3] [59.2-72.9] [56.3-74.6] [54.4-74.1]

BMI body mass index, PBF percentage body fat, FM fat mass, LBM lean body mass



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Physical and Cardiovascular Performance in Cases with Acromegaly after Regular Short-Term Exercise