ORIGINAL RESEARCH

published: 14 January 2020

doi: 10.3389/fendo.2019.00899

Importance of Illness Acceptance

Among Other Factors Affecting
Quality of Life in Acromegaly
Aleksandra Jawiarczyk-Przybyłowska 1*, Dorota Szcześniak 2 , Marta Ciułkowicz 2 ,
Marek Bolanowski 1 and Joanna Rymaszewska 2
1
Department of Endocrinology, Diabetes and Isotope Therapy, Wroclaw Medical University, Wroclaw, Poland, 2 Department
of Psychiatry, Wroclaw Medical University, Wroclaw, Poland

Introduction: The aim of this study was to analyze psychological factors of patients
with acromegaly and assessment of their relationship with the quality of life (QoL) in the
context of the control of the disease.
Materials and methods: A total sample of 50 patients (62% of females; mean
age = 51.66 ± 14.5) with acromegaly underwent a comparative, cross-sectional
cohort assessment including the QoL (AcroQoL, WHOQoL-BREF), psychiatric morbidity
(GHQ-28), the acceptance of illness (AIS) as well as influence of treatment, comorbidities
Edited by:
and symptoms in the relation of disease activity. Acromegaly group was divided in
Günter Karl Stalla, two subgroups: patients with uncontrolled acromegaly (UA, n = 28) and patients with
Max Planck Institute of Psychiatry
controlled acromegaly (CA, n =22).
(MPI), Germany

Reviewed by: Results: The acromegaly groups did not differ in health-related QoL measured
Mauro Antonio Czepielewski, with AcroQoL and WHOQoL questionnaires. However, obtained results showed QoL
Federal University of Rio Grande
do Sul, Brazil
impairments in all subscales and the study participants had decreased scores compared
Przemyslaw Witek, to reference values. The interaction of the relationship between the AIS and disease
Warsaw Medical University, Poland
activity as well as the prevalence of all psychopathological symptoms and disease activity
*Correspondence:
were tested and the statistically significantly differences in the context of QoL in AcroQoL
Aleksandra Jawiarczyk-Przybyłowska
aleksandra.jawiarczyk-przybylowska@ questionnaires and its domains were observed in relation to the course of the disease.
umed.wroc.pl No difference in acromegaly symptoms as well as in number of comorbidities were found
between CA and UA but these two parameters affected the results QoL scores in AcroQol
Specialty section:
This article was submitted to questionnaires and their domains, regardless the disease activity. Similarly, the prevalence
Pituitary Endocrinology, of psychopathological symptoms (GHQ-28) contributed the level of acceptance of the
a section of the journal
disease, regardless the disease activity. The strongest predictors of QoL were related to
Frontiers in Endocrinology
the level of illness acceptance (p = 0.01) as well as serum growth hormone concentration.
Received: 08 September 2019
Accepted: 09 December 2019 Conclusion: Minding people with UA, the control of biochemical factors seemed
Published: 14 January 2020
to be more important for the QoL perception, while among CA, psychological
Citation:
Jawiarczyk-Przybyłowska A,
variables such as AIS are observed to play a fundamental role in QoL. Moreover,
Szcześniak D, Ciułkowicz M, inclusion of patient’s acceptance of the illness into clinical routine would promote
Bolanowski M and Rymaszewska J
holistic, patient-centered care and empower doctor-patient partnership where patients’
(2020) Importance of Illness
Acceptance Among Other Factors expectations and perceptions are constantly tracked. Obtaining biochemical control
Affecting Quality of Life in Acromegaly. should not be considered as the only measure of treatment success.
Front. Endocrinol. 10:899.
doi: 10.3389/fendo.2019.00899 Keywords: acromegaly, quality of life, disease activity, acceptance of illness, psychopathology

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Jawiarczyk-Przybyłowska et al. Quality of Life in Acromegaly

INTRODUCTION things considered, literature on the factors modulating QoL of

patients with acromegaly suggests that further research is still
Acromegaly is a rare disease, predominantly associated with required to provide them with patient-tailored assessment and
growth hormone-secreting pituitary adenoma. The total therapeutic interventions.
prevalence ranges between 2.8 and 13.7 cases per 100,000 people The aim of this study was to analyze the psychological factors
(1). Increased level of growth hormone (GH) results in extensive of patients living with acromegaly and to assess their relationship
peripheral secretion of insulin-like growth factor-1 (IGF-1), with the perceived QoL in the context of the control of the course
both of which in a long term are in charge of unique set of of the disease.
problems such as alterations in body and facial appearance and
defect of major organs. Effective treatment reduces the severity
of symptoms resulting from the GH excess, such as increased MATERIALS AND METHODS
sweating or soft tissue swelling. On the other hand, some changes
A comparative, cross-sectional cohort study was conducted at the
are permanent, for example changes in facial appearance or
Department of Endocrinology, Diabetes and Isotope Therapy,
destruction of bones and cartilages (2). It is estimated that the Wroclaw Medical University during the years 2012–2015.
treatment of 50% of the patients is considered to be suboptimal Fifty participants were enrolled in the study. The study was
which means they deal with consequences of long-term approved by the local ethical committee. All the participants
uncontrolled course of the disease, some of the symptoms are signed an informed consent before entering the study. The
at least reversible with successful treatment (3). What is more, sample consisted of group of acromegaly patients (A), n = 50.
the reduction of GH to the desirable level and normalization Acromegaly group was divided in two subgroups: patients
of IGF-1 (defined as GH concentration < 2.5 ng/ml and IGF-1 with uncontrolled acromegaly (UA, n = 28) and those with
within normal range) not always guarantee disappearance of controlled disease (CA, n = 22). Demographic characteristics
accompanying symptoms such as headache, which significantly and medical history, which included the history of treatment
diminish quality of life (QoL) (4). Managing satisfying QoL (surgery, radiotherapy, pharmacological treatment), disease
is, in turn, listed guidelines among normalization of hormone duration, and pituitary function were assessed in all patients.
levels as a tool to assess the effectiveness of treatment (5, 6). The GH concentrations were measured by a chemiluminescent
Additionally, in the light of multisystem-associated morbidities, immunometric method (Immulite 2000, Siemens, USA or
optimal disease management seems to be crucial to prevent Germany). Serum IGF-1 level was assessed by radioimmunologic
major side effects that may in turn lead to premature morbidity assay using an IGF-I-D-RIT-CT kit (BioSource S.A., Nivelles,
(3, 7). In the study by Liu et al. almost half of the patients with Belgium), normal range: according to the sex and age. The levels
acromegaly presented with 5 or more comorbidities, the most of GH and IGF-1 were measured during the recruitment for
common of which was depression at 56.6%. Moreover, 83.6% current analysis and based on which patients were qualified to
reported that symptoms interfere with their daily life and work the appropriate groups (UA vs. CA). Acromegaly was confirmed
(8). What is interesting, the appearance seems to be the most by nadir serum GH during an oral glucose tolerance test
affected dimension while assessing QoL (9). According to a (OGTT) > 0.4 ng/ml and elevated IGF-1 for age and gender.
Dutch study, even after a long-term biochemical remission, Age and gender normalized levels of IGF-1, associated with nadir
the self-consciousness about appearance occurs. The face was serum GH during OGTT < 0.4 ng/ml after surgery or random
indicated as the most prominent source of this anxiety (10). GH < 1.0 ng/ml when treated with somatostatin analogs were
Complex system of manifestations that influence each other taken as criterion of cure or good disease control (19).
and may persist or even worsen regardless treatment requires
continuous multi-specialty approach. The necessary attention
should be given to provide psychological and psychiatric support
Instruments
The following instruments were used in the patients’ groups:
with respect of the adequate assessment of the psychosocial and
emotional consequences of the illness. It is also worth to noting 1. A sociodemographic profile sheet.
that delay in diagnosis has been associated with psychosocial 2. Clinical profile sheet consisted of the following details:
impairment, including depression, body image distortion, and disease onset and duration, delay of diagnosis, first
social withdrawal (11, 12). As the course of the disease is the symptoms, treatment, co-morbidities, and hormonal
rather insidious chronic and slowly progressing, many patients and biochemical measurement.
experience a prolonged diagnostic process, to the extent of 7–10 3. The 26-item Polish version of the WHO Quality of Life Scale-
years which strongly negatively affects receiving appropriate BREF (WHOQoL-BREF). It profiles the subjective evaluation
interventions in a timely manner (1, 2). of the QoL in the past 2 weeks within 4 domains: physical
The effect of GH and IGF-1 normalization on patient’s health (PhyHealth), psychological health (PsyHealth), social
self-reported well-being is still questionable suggests though relationship (SocRel), and environment (Enviro).
that QoL in patients with acromegaly is a multifactorial issue 4. The AcroQoL-Polish version for assessing the QoL in patients
requiring individualized approach and points out (13–16). It with acromegaly was used after obtaining permission by
is also known that other factors may be important, such as the authors. It consists of 22 items of QoL (AcroTotal).
duration of the disease, age, disease activity, gender which The questionnaire is divided into 2 scales that measure
playing the main role and correlates with QoL (4, 17, 18). All physical (AcroPhy) and psychological aspects (AcroPsy). The

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Jawiarczyk-Przybyłowska et al. Quality of Life in Acromegaly

psychological scale is further divided into 2 subscales, the WHOQoL-BREF scale study participants with uncontrolled
appearance (AcroApp) and personal relationships (AcroRel). course of disease showed slightly worse scores in psychical,
5. The 28-item version of the General Health Questionnaire psychological, and environmental domain and better scores in
(20) in Polish adaptation was used (21). The scale allows social relation but the difference was not statistically significant.
to measure general health status and its four components In the same scale the whole study group obtained the lowest
(each consists of 7 questions): A—GHQ-somatic symptoms, scores in social relation (a = 11.64 ± 2.3) and the highest in
B—GHQ-anxiety and insomnia, C—GHQ-social dysfunction, environmental domain (a = 29.68 ± 4.68). The acromegaly
and D—GHQ-severe depression. Higher scores indicate a groups (controlled and uncontrolled) did not differ in health-
greater probability of psychiatric distress. related QoL measured with AcroQoL questionnaires. However,
6. The standardized Acceptance of Illness Scale (AIS) in obtained results showed QoL impairments in all subscale,
Polish adaptation (22) consists of 8 questions describing the especially in appearance among the total study sample. The
consequences of poor health condition. Higher scores indicate study participants had decreased AcroQoL scores compared to
a better acceptance of the illness. reference values.
There were no significant differences in prevalence of
Statistical Analysis psychopathological symptoms among CA and UA groups, but the
The analysis of differences between the group with controlled and worst disturbances were observed in anxiety and insomnia scale
uncontrolled acromegaly was performed using Fisher’s test for in the whole group as well as in both study subgroups separately
qualitative variables or the Mann-Whitney test for quantitative (Table 2).
variables. The values of variables are presented by specifying The level of AIS was similar in UA and CA subgroups and
the mean value ± standard deviation. Analysis of the impact of indicated moderate AIS. There was no significant difference as
quantitative variables (for example GHQ-28, AIS, etc.) including long as acceptance of acromegaly is considered in controlled and
the division into groups of acromegaly was performed using a uncontrolled group.
multifactorial regression analysis with an element of interaction. Moreover, the interaction of the relationship between the AIS
Similarly, differences in the QoL when divided by the acromegaly and disease activity was tested and a statistically significantly
group and qualitative variables (for example surgery etc.) were difference in the context of QoL in AcroQoL questionnaires
examined using two-way ANOVA analysis. The independent and its domains was observed in relation to the course of the
impact of variables on QoL was performed using multifactorial disease. In the both groups of participants the higher the level
regression analysis. As statistically significant, p value on the level of acceptance of the disease, the higher scores in AcroQoL
below < 0.5 was used. The analysis was performed in the R for was observed, but in uncontrolled group the size effect was
windows software (version 3.6.1) (23). significantly smaller (r = 0.885 vs. r = 0.432, respectively).
Similar relationships were observed in three domains of AcroQol.
RESULTS In both groups, the higher acceptance of the disease, the
higher scores in Physical Dimension, Psychological Dimension,
A total of 50 patients with acromegaly were assessed: 31 females and Personal Relationship were observed but the size effect
and 19 males, mean age was 51.66 ± 14.5 years, with a mean was significantly smaller in uncontrolled group (r = 0.857 vs.
disease duration of 8.4 ± 8.77 years. A group of 36 patients r = 0.482; r = 0.831 vs. r = 0.367; r = 0.874 vs. r = 0.139,
underwent pituitary adenoma surgery, 6 of them had additional respectively). Moreover, the level of acceptance of the disease
radiotherapy. Only 10 patients were successfully treated with affected perception of appearance, regardless the disease activity
operation and required no additional medical interventions. (CAG and UAG) (r = 0.58 vs. r = 0.41, respectively) (Table 3).
Twenty six patients were treated with somatostatin analogs (SA). Additionally, the interaction of the relationship between
Among the whole study group, 22 patients were qualified to CA these two variables (AIS and disease activity) is statistically
group (10 with successfully treated with operation and 12 well- significantly different in the context of social relations in
controlled with SA) and 28 patients were certified as UA (14 WHOQoL questionnaires. In the group of participants with
with newly recognized acromegaly and 14 with non-successfully controlled acromegaly, the higher the level of acceptance of
treatment such as operation, radiotherapy, and actually treatment the disease, the higher scores in social relations were observed.
with SA). The sociodemographic profiles in terms of gender, And in the group of participants with uncontrolled acromegaly,
education, place of residence and marital status did not vary the relationship was negatively correlated, but the size effect
significantly between groups. Statistical significance was obtained was much smaller (r = 0.7178 vs. r = −0.1528, respectively).
regarding age and duration of the disease. Controlled acromegaly What is more, the level of acceptance of the disease affected
group was older compared to UA group (p = 0.003). Duration environmental domain, regardless the disease activity (CA and
of the disease since time of diagnosis was higher in UA UA) (r = 0.543 vs. r = 0.120) (Table 3).
compared to CA (p = 0.0015). The levels of IGF-1 and GH were No difference in acromegaly symptoms as well as in number
statistically significantly higher in patients with UA compared to of comorbidities were found between CA and UA but these
CA which confirmed correct division of groups. The study groups two parameters affected the results QoL scores in AcroQol
characteristics was presented in Table 1. questionnaires and their domains, regardless the disease activity.
The comparison of the QoL among CA and UA subgroup The number of comorbidities, not disease activity, was important
is presented in Table 2 (WHOQol-BREF and AcroQoL). In for the results in AcroTotal (CA vs. UA (r = −0.54 vs. r = −0.40,

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Jawiarczyk-Przybyłowska et al. Quality of Life in Acromegaly

TABLE 1 | Demographic characteristics of the acromegaly groups.

Acromegaly group Controlled acromegaly Uncontrolled acromegaly p-value

(A) N = 50 subgroup (CA), N = 22 subgroup (UA) N = 28

Gender (females) n (%) 31 (62%) 15 (68.2%) 16 (57.1%)

Age (mean years ± SD) 51.66 ± 14.5 57.91 ± 14.11 46.75 ± 13.10 CA vs. UA
p = 0.003
Education n (%)
Basic 4 (8.1%) 3 (13.6%) 1 (3.5%)
Medium 20 (40.8%) 12 (54.5%) 8 (29.6%)
High 14 (28.6%) 3 (13.7%) 11 (40.7%)
Vocational 11 (22%) 4 (18.2%) 7 (25.9%)
Unknown 1 (0.5%) 1
Locality of living n (%)
City 35 (70%) 13 (59.09%) 22 (78.57%)
Country 15 (30%) 9 (40.91%) 6 (21.43%)
Time since diagnosis 8.4 ± 8.77 12.13 ± 8.7 5.20 ± 7.66 CA vs. UA
(in years) p = 0.0015
Marital status n (%)
Married 34 (69.39%) 18 (81.82%) 16 (59.26%)
Single 15 (30.61%) 4 (18.18%) 11 (40.74%)
Occupation n (%)
Employed 21 (43.7%) 7 (31.81%) 14 (53.84%)
Unemployed 1 (2.08%) 0 1 (3.84%)
Sickness benefit 12 (25%) 5 (22.72%) 7 (26.92%)
Retirement 14 (29.16%) 10 (45.45%) 4 (15.38%)
IGF-1 (ng/ml) (mean ± 434.5 ± 291.6 217 ± 137.5 618.6 ± 259.0 CA vs. UA
SD) p = 0.000
GH (ng/ml) (mean ± 6.32 ± 8.81 1.53 ± 1.28 9.86 ± 10.28 CA vs. UA
SD) p = 0.000

respectively) as well as for its domains (AcroPhy: r = −0.54 difference in the context of QoL in AcroQoL questionnaires
vs. r = −0.53; AcroPsy: r = −0.50 vs. r = −0.12; AcroApp: and its domains was observed in relation to the course of the
r = −0.013 vs. r = −0.43; AcroRel: r = −0.44 vs. r = −0.18, disease. In both groups of participants, the higher prevalence of
respectively). Similarly, symptoms of acromegaly contributed the psychopathological symptoms (GHQ-28), the worse QoL scores
results in AcroTotal (CA vs. UAG (r = −0.46 vs. r = −0.37, was observed but in uncontrolled group the size effect was
respectively) and its three domains (AcroPhy: r = −0.39 vs. significantly smaller in AcroTotal (CA vs. AU) (r = −0.61,
r = −0.25; AcroPsy: r = −0.47 vs. r = −0.33; AcroRel: r = −0.40 r = −0.16, respectively) as well as in AcroPhy (r = −0.63 vs.
vs. r = −0.42, respectively), independently of disease activity r = 0.432, respectively) and AcroPsy (r = −0.54 vs. r = −0.1,
(Table 3). respectively). Moreover, in the subgroup of participants with
Besides, the prevalence of psychopathological symptoms controlled acromegaly, the more psychiatric distress, the lower
(GHQ-28) contributed the level of acceptance of the disease, scores in personal relationship domain was observed. And in
regardless the disease activity (CA vs. UA) (r = −0.55 vs. the subgroup of participants with uncontrolled acromegaly, the
r = −0.30, respectively). Similarly, somatic symptoms (GHQ-A), relationship was positively correlated, but the size effect was
anxiety and insomnia (GHQ-B) and social dysfunction (GHQ-C) much smaller (r = −0.51 vs. r = 0.01, respectively). What is
affected the level of acceptance of the disease, independently of more, the prevalence of psychopathological symptoms affected
disease activity (CA vs. AU) (r = −0.53 vs. r = −0.20; r = −0.55 perception of appearance, irrespective of the disease activity (CA
vs. r = −0.31; r = −0.52 vs. r = −0.21, respectively). What is vs. UA) (r = −0.43 vs. r = −0.15). Otherwise, the interaction of
more, the duration of illness had an impact on AIS, irrespective the relationship between somatic symptoms (GHQ-A), anxiety
of the disease activity (r = −0.47, r = −0.21, respectively). The and insomnia (GHQ-B) and social dysfunction (GHQ-C) with
AIS seems to be not affected by participants’ age, number of the disease activity was also a statistically significantly different
comorbidities and symptoms (Table 4). in the context of QoL, in relation to the course of the disease.
In addition, the interaction of the relationship between In the both analyzed groups the higher incidence of somatic
the prevalence of all psychopathological symptoms (GHQ-28) symptoms, the worse QoL scores was observed in AcroTotal
and disease activity was tested and a statistically significantly (CA vs. UA) (r = −0.59 vs. r = −0.14, respectively) as well as

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Jawiarczyk-Przybyłowska et al. Quality of Life in Acromegaly

TABLE 2 | Quality of life and psychopathological status of acromegaly group. TABLE 3 | Linear mixed model analysis—interaction effect between
WHOQoL-BREF scores and AcroQoL with AIS, comorbidities, and number of
A (n = 50) CA (n = 22) UA (n = 28) p-value symptoms in study groups.
Mean ± SD Mean ± SD Mean ± SD
Tool Interaction Estimate Std p-value
WHOQoL-BREF description error
Physical health 55.28 ± 9.6 55.32 ± 11.63 55.25 ± 7.87 0.93
WHOQoL D3 UA 67.90 17.94 0.00*
Psychological health 63.98 ± 10.85 66.23 ± 10.76 62.21 ± 10.78 0.25
AIS 1.60 0.36 0.00*
Social relation 69.4 ± 17.84 65.64 ± 20.4 72.36 ± 15.64 0.28 UA × AIS −1.93 0.54 0.00*
Environmental 69 ± 14.7 71.23 ± 16.26 68.71 ± 13.56 0.70 WHOQoL D4 UA 21.21 16.39 0.20
AcroQoL total (min 71.92 ± 14.11 70.95 ± 18.39 72.68 ± 9.85 0.80 AIS 0.98 0.33 0.00*
22–max 110) UA × AIS −0.76 0.39 0.13
Physical dimension 25.22 ± 6.39 24.41 ± 8.23 25.86 ± 4.54 1 AcroQoL UA 39.92 10.58 0.00*
(min 8–max 40) All AIS 1.82 0.21 0.00*
Psychological 46.6 ± 8.74 46.55 ± 11.09 46.64 ± 6.53 0.57 UA × AIS −1.2 0.32 0.00*
dimension (min Physical UA 16.48 4.95 0.00*
14–max 70) dimension AIS 0.79 0.10 0.00*
Appearance (min 19.68 ± 5.57 20.64 ± 6.77 18.93 ± 4.40 0.32 UA × AIS −0.48 0.15 0.00*
7–max 35) Psychological UA 21.78 7.40 0.00*
Personal relationship 26.96 ± 4.63 25.91 ± 5.98 27.79 ± 3.08 0.49 dimension AIS 1.03 0.15 0.00*
(min 7–max 35) UA × AIS −0.70 0.22 0.00*
GHO-28 (total) 5.5 ± 5.81 5.5 ± 6.37 5.5 ± 5.45 0.87 Appearance UA 4.10 5.69 0.47
AIS 0.44 0.11 0.00*
A—somatic symptoms 1.6 ± 2.1 1.68 ± 2.25 1.53 ± 2.02 0.93
UA × AIS −0.19 0.11 0.27
B—anxiety and 2.16 ± 2.1 2.27 ± 2.22 2.10 ± 1.89 0.95
Personal UA 18.34 3.61 0.00*
insomnia
relationship AIS 0.58 0.07 0.00*
C—social dysfunction 1.10 ± 1.63 1.27 ± 1.77 1.0 ± 1.54 0.84 UA × AIS −0.52 0.10 0.00*
D—severe depression 0.62 ± 1.2 0.36 ± 0.65 0.82 ± 1.46 0.50 AcroQoL UA −6.59 5.97 0.27
All Comorbidities −4.31 1.17 0.00*
UA × Comorbidities 1.61 1.99 0.42
Physical UA −1.39 2.64 0.60
in AcroPhy (r = −0.58 vs. r = −0.18, respectively), AcroPsy dimension Comorbidities −1.90 0.51 0.00*
(r = −0.54 vs. r = −0.1, respectively) and AcroRel (r = −0.31 UA × Comorbidities 0.27 0.88 0.75
vs. r = −0.02, respectively), but the size effect was significantly Psychological UA −5.52 3.87 0.16
dimension Comorbidities −2.40 0.75 0.00*
smaller in UA. Also, in the both group of participants, the more
UA × Comorbidities 1.40 1.29 0.28
frequent occurrence of anxiety and insomnia, the lower QoL in
Appearance UA −4.63 2.52 0.07
AcroTotal (CA vs. UA) (r = −0.58 vs. r = −0.27, respectively) as Comorbidities −1.27 0.49 0.01*
well as in AcroPhy (r = −0.62 vs. r = −0.23, respectively) and UA × Comorbidities 0.72 0.84 0.39
AcroRel (r = −0.53 vs. r = −0.06, respectively) were observed Personal UA −0.88 2.06 0.66
and size effect again was significantly smaller in uncontrolled relationship Comorbidities −1.13 0.40 0.00*
group. Further, the prevalence of anxiety and insomnia had an UA × Comorbidities 0.74 0.68 0.29
impact on psychological dimension (CA vs. UA) (r = −0.51 AcroQoL UA −20.47 13.17 0.12
All Symptoms −3.9 1.31 0.00*
vs. r = −0.26, respectively) and appearance (r = −0.36 vs.
UA × Symptoms 2.72 1.54 0.08
r = −0.39, respectively), independently of disease activity.
Physical UA −1.39 2.64 0.60
Equally, in CA and in UA, the higher incidence of pathological dimension Symptoms −1.90 0.51 0.00*
symptoms in terms of social relation, the poorer QoL scores UA × Symptoms 0.27 0.88 0.75
in physical domain were obtained (r = −0.58 vs. r = −0.03, Psychological UA −5.52 3.87 0.16
respectively). Moreover, in the subgroup of participants with dimension Symptoms −2.40 0.75 0.00*
controlled acromegaly, the more psychiatric distress in terms UA × Symptoms 1.40 1.29 0.28
of social relations, the lower scores in QoL was observed in Appearance UA −4.63 2.52 0.07
Symptoms −1.27 0.49 0.01*
AcroTotal and in AcroPsy. And in the subgroup of participants
UA × Symptoms 0.72 0.84 0.39
with uncontrolled acromegaly, the relationship was positively
Personal UA −0.88 2.06 0.66
correlated, but the size effect was very weak and much smaller relationship Symptoms −1.13 0.40 0.00*
(CA vs. UA) (r = −0.54 vs. r = 0.02 and r = −0.47 vs. UA × Symptoms 0.72 0.68 0.29
r = 0.02, respectively).
*p < 0.05, statistically significant.
The prevalence of psychopathological symptoms affected
environmental domain of the WHOQoL-BREF, regardless the
disease activity (CA vs. UA) (r = −0.30 vs. r = −0.34). regardless the disease activity (CA vs. UA) (r = −0.36 vs.
Additionally, the psychiatric distress in terms of social relation r = −0.28; r = −0.26 vs. r = −0.36, respectively). What
affected physical health as well as environmental domain, is more and very interesting, depressive symptoms had an

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Jawiarczyk-Przybyłowska et al. Quality of Life in Acromegaly

TABLE 4 | Linear mixed model analysis—interaction effect between AcroQoL TABLE 4 | Continued
scores and AIS with GHQ-28 scores and duration of the disease in clinical groups.
Tool Interaction Estimate Std p-value
Tool Interaction Estimate Std p-value description error
description error
AIS UA −1.41 3.05 0.64
AcroQoL UA −6.36 4.84 0.19 GHQ-B −2.25 0.71 0.00*
All GHQ-28 −1.76 0.42 0.00* UA × GHQ-B 1.01 1.03 0.33
UA × GHQ-28 1.47 0.60 0.01* AIS UA −1.03 2.57 0.68
Physical UA −2.13 2.15 0.33 GHQ-C −2.62 0.91 0.00*
dimension GHQ-28 −0.81 0.18 0.00* UA × GHQ-B 1.42 1.30 0.28
UA × GHQ-28 0.65 0.27 0.02* AIS UA −3.52 3.13 0.26
Psychological UA −4.39 3.14 0.16 Duration of −0.49 0.17 0.00*
dimension GHQ-28 −0.94 0.27 0.00* disease 0.31 0.25 0.22
UA × GHQ-28 0.81 0.39 0.04* UA × Duration
Personal UA −0.83 1.64 0.61 of disease
relationship GHQ-28 −0.48 0.14 0.00*
UA × GHQ-28 0.49 0.20 0.02* *p < 0.05, statistically significant.

AcroQoL UA −5.27 4.49 0.24

All GHQ-A −4.82 1.21 0.00*
impact on environmental domain, irrespective of disease activity
UA × GHQ-A 4.09 1.69 0.01*
(r = −0.22 vs. r = −0.38, respectively) (Table 4). However,
Physical UA −1.54 2.03 0.45
dimension GHQ-A −2.14 0.54 0.00* there was no relation between QoL in AcroQoL and incidence
UA × GHQ-A 1.74 0.76 0.02* of depressive symptoms.
Psychological UA −3.87 2.88 0.18 Moreover, the level of GH had an impact of QoL results
dimension GHQ-A −2.67 0.77 0.00* in AcroQol, regardless disease activity. These influences were
UA × GHQ-A 2.33 1.08 0.03* observed in scores of AcroTotal (CA vs. UA) (r = −0.13 vs.
Personal UA −0.35 1.50 0.80 r = −0.54) as well as in AcroPsy (r = −0.12 vs. r = −0.51). Also,
relationship GHQ-A −1.36 0.40 0.00*
UA × GHQ-A 1.33 0.56 0.02*
the level of GH affected the prevalence of somatic symptoms
AcroQoL UA −6.14 5.18 0.24
(GHQ-A), independently of disease activity (CA vs. UA) (r = 0.09
All GHQ-B −4.87 1.22 0.00* vs. r = 0.6). Similarly, the level of IGF-1 contributed the
UA × GHQ-B 3.45 1.75 0.05 prevalence of psychopathological symptoms (GHQ-28) and
Physical UA −2.55 2.30 0.27 psychiatric distress in relation of social dysfunction, irrespective
dimension GHQ-B −2.32 0.54 0.00* of disease activity (CA vs. UA) (r = 0.07 vs. 0.48; r = 0.23 vs. 0.51,
UA × GHQ-B 1.76 0.77 0.02*
respectively). However, what should be pointed out in each of the
Psychological UA −3.66 3.37 0.28
described cases, size effect was larger in the group of uncontrolled
dimension GHQ-B −2.55 0.79 0.00*
UA × GHQ-B 1.62 1.14 0.15 acromegaly, despite the fact that this difference did not meet the
Appearance UA −2.22 2.20 0.31 criterion of statistical significance.
GHQ-B −1.09 0.51 0.03* A multivariate linear regression with interaction term
UA × GHQ-B 0.18 0.74 0.80 gathering the most important factors was calculated in order
Personal UA −1.58 1.72 0.36 to find essential elements of QoL among patients living with
relationship GHQ-B −1.44 0.40 0.00* acromegaly (Table 5). The strongest predictors of QoL were
UA × GHQ-B 1.56 0.58 0.01*
related to the level of illness acceptance (p = 0.01) as well as the
AcroQoL UA −5.29 4.44 0.23
All GHQ-C −5.71 1.58 0.00*
growth hormone level in the serum (p = 0.04). Disease activity
UA × GHQ-C 5.72 2.25 0.01* was close to statistical significance (p = 0.06) in the described
Physical UA −1.79 1.97 0.36 model. The model explained 60% of the variance of health-related
dimension GHQ-C −2.71 0.70 0.00* QoL measured with AcroQol.
UA × GHQ-C 2.62 1.00 0.01
Psychological UA −3.69 2.86 0.20
dimension GHQ-C −2.99 1.02 0.00* DISCUSSION
UA × GHQ-C 3.11 1.45 0.03
Personal UA −3.78 1.84 0.04* In this paper psychological factors of patients harboring
relationship GHQ-C −1.65 0.65 0.01* acromegaly and assessment of their relationship with the
UA × GHQ-C 1.70 0.93 0.07
perceived QoL in the context of controlled or uncontrolled
AIS UA −1.06 2.87 0.71
course of the disease were analyzed. The connections between
GHQ-28 −0.77 0.25 0.00*
UA × GHQ-28 0.37 0.35 0.30
acromegaly and QoL are very complex and still a matter of debate.
Optimization the disease control, a core ambition of medical
AIS UA −1.44 2.68 0.59
GHQ-A −2.10 0.72 0.00* interventions, contributes to restoring life expectancy, lowering
UA × GHQ-A 1.38 1.01 0.18 morbidity rates as well as costs reduction (2) but successful
treatment in the terms of establishing biochemical control is
(Continued) controversial (3, 16–19, 24). As recalled in a paper by Matta

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Jawiarczyk-Przybyłowska et al. Quality of Life in Acromegaly

TABLE 5 | Multivariate linear regression model with interaction term of consequently worse QoL perception. Taking different point
health-related QoL. of view, as shown in our study, the more acceptance, the
Estimate Std error p-value better QoL measured with AcroQoL and WHOQOL-BREF was
recorded in both studied groups especially in environmental
AcroQol total (Intercept) 50.2357 18.0537 0.009 and social domains of the latter scale. However, it should
UCA −8.6614 4.4240 0.06 be emphasized that the relationship between the level of
Duration of the disease −0.1219 0.2422 0.6 acceptance of the disease and the QoL domains seemed to
Age −0.1588 0.1187 0.2 be more significant in the controlled acromegaly subgroup
Comorbidities −1.5082 0.9362 0.1 where the size effect of the correlations was much bigger.
Symptoms −0.6575 0.8209 0.4 The importance of perception of the illness and emotional
GH −0.4957 0.2341 0.04 representation of symptoms that could result in the level of
IGF-1 0.0154 0.0096 0.1 acceptance affects self-perceived QoL (24, 26) thus should not
GHQ-28 −0.4671 0.3640 0.2 be ignored by health providers, rather treated as a starting point
AIS 9.8826 0.3320 0.01 of conversation. However, biochemical normalization cannot be
simply translated as lessening acromegaly burden of concomitant
Bold values indicate p < 0.05, statistically significant.
diseases, thus biochemical control does not equal clinical control
which is more complex and multidimensional. This statement
et al. it may have positive, neutral or even negative relation could be backed with our observation that controlled and
to patient’s QoL (9). Some authors have not observed better uncontrolled groups did not differ in number of symptoms and
AcroQoL outcomes in controlled group (24) and, surprisingly, comorbidities, but these factors turned out to alter AcroQoL
proved higher scores in active period of disease (18). outcomes. Moreover, higher number of symptoms attributed
In our research, growth hormone level in the serum turned to acromegaly was parallel with lower outcomes of used QoL
out to be one of the predictors of self-perceived QoL regardless questionnaires. Additionally, the research showed similar trend
disease activity. However, the size effect was larger in the group when number of comorbidities is considered in both, controlled
of uncontrolled acromegaly, despite the fact that this difference and uncontrolled, groups. Similar tendency was recognized in
did not meet the criterion of statistical significance. Observation relation to presence psychopathological symptoms in controlled
on the importance of that particular hormone concentration is and uncontrolled acromegalic patients, where no remarkable
consistent with data published by (25) suggesting IGF-1 and differences were detected. However, higher prevalence of mental
GH control may mediate AcroQoL scores in different ways. distress turned out to be connected with worse outcome in
According to that study duration of IGF-1 normalization was the terms of QoL but in uncontrolled group the size effect
positively related to total and all subscale scores while duration was significantly smaller. What is more, the worst disturbances
of GH control affected positively total AcroQoL as well as were observed in anxiety and insomnia scale. Regardless of
appearance, personal relationships subscales (25). Notably, the disease activity the presence of mentioned psychopathological
need of GH lowering therapy in line with duration of biochemical manifestations affected environmental domain of WHOQoL-
control were described as the crucial aspects affecting patients’ BREF, similarly to depressive symptoms in both controlled
QoL (25). and uncontrolled subgroups. This suggests that the presence of
It also seems fair to emphasize that no matter what treatment depression could be a modifiable factor when pursuing better
modality was used, 22 of 50 patients’ biochemical profile in our QoL in the terms of this questionnaire. Remarkably, our results
study was assessed as controlled which is consistent with recent suggest that depressive symptoms do not alter QoL measured
research as recalled in (3) that states than <50% is to achieve with AcroQoL These observations somewhat contrast with the
disease control understood as hormone levels normalization. In outcome of the research carried out by Geraedts et al. that
a line with mentioned growth hormone level, AIS emerged as proved that the presence and intensity of depressive and anxiety
fundamental factor affecting QoL. In both groups considered, symptoms can remarkably predict QoL tested with AcroQoL
our results indicated on moderate AIS. Interestingly, there in acromegalic patients and concluded that the bigger amount
was a trend to note higher scores in uncontrolled subgroup. of psychopathology, the bigger impairment in QoL can be
The difference, however, was not significant. One of possible expected (27). Nonetheless, data suggesting no relation between
explanations of such observations could be patients’ expectations depressive symptoms and evolution of QoL in time also can
and perceptions that as long as excessive hormone secretion, a be found (27). Intercorrelation between acromegaly, presence of
biochemical stigma of acromegaly, is to be normalized, there depressive symptoms and satisfaction of patients was also found
is still hope that perceived symptoms attributed to the disease by Kepicoglu et al. (16). This being said, psychopathology is
would be reduced. At the time when hormone levels control suggested not only to be an independent factor modifying QoL
is obtained and disease manifestations are persistent, patient (15, 26, 27), but also superior to biochemical control and other
could have a sensation that all the management options were factors. Proper consideration of the role of psychopathology plays
already made used of and feel confronted with their irreversibility a major role in holistic attitude toward such patients. There is
of physical changes, a constant need for medical attention or significant amount of factors that could also contribute to QoL
illness perceptions and ineffective coping strategies (24). This, of patients living with acromegaly such as age, duration of the
in turn, could result in worse acceptance of the illness and disease, gender, and treatment modalities. Longer duration of

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Jawiarczyk-Przybyłowska et al. Quality of Life in Acromegaly

the disease along with older age were more prevalent in an improved by 6 months post-operation (32). Similarly, Mangupli
uncontrolled group in our research and are affirmed to be a et al. observed a significant improvement in the AcroQoL scores
negatively influencing considerations for the outcomes of used after disease control with octreotide LAR (4). On the other
questionnaires. Additionally, the longer time of experiencing hand, Hua et al. showed negative correlation between treatment
disease in patients with acromegaly correlated with the lower with lanreotide-controlled patients and QoL (17). In 26 of 50
AIS in the both groups. Duration can be considered in a three- participants of our study pharmacological treatment was applied.
way manner—duration of the disease, duration of biochemical A group of 6 patients that were operated on needed adjuvant
control, and duration of remission. Duration of biochemical radiotherapy sessions which could be caused by exceptionally
control in the line with the need GH lowering therapy aggressive course of the disease or treatment resistance. This
were described as the predominant factors negatively affecting treatment modality proved to have a seriously affect AcroQoL
patients’ QoL (25). Interestingly, Vandeva et al. stated that rates and result in worse QoL (13) which is explained by the
longer duration of disease remission negatively affected personal risk of, among others, long-term neurocognitive impairment
relations score measured with AcroQoL with likelihood of worse (33) or development of hypopituitarism (34). Nevertheless, such
total and psychological rates (13). Additionally, researchers trend was not present in our study. In turn, lack of impairment
suggest that QoL tend to decrease with time, with no significant of anterior pituitary axis is said to result in better scores in
role of biochemical control and age. Similar conclusions on domain of the appearance and have borderline significance on the
personal relations scores could be found in series of papers total AcroQoL improvement prospectively (13). Analysis of this
(15, 28). Possible explanations for such outcome could be the study revealed no correlation between prior radiotherapy and
presence of irreversible physical changes, a constant need for QoL scores. Biermasz et al. observed that hypopituitarism was
medical attention or illness perceptions and ineffective coping significantly more frequent when radiotherapy due to acromegaly
strategies in mentioned group (24). Kyriakakis et al. points out was performed (15). Interestingly, T’Sjoen et al. pointed out
that impaired psychosocial well-being is secondary to diminished that it was not radiotherapy itself but deficiency in at least one
physical function (25). Moreover, older age may predict worse pituitary axis that affected significantly psychological dimension
AcroQoL scores of all scales, in both controlled and uncontrolled of the AcroQol (28). Similarly, hypopituitarism as a result of
groups, apart from appearance score in controlled patients (13). surgery was proved not affect QoL as measured with AcroQoL in
Additionally, according to mentioned paper, age had borderline both primary controlled and uncontrolled acromegalic patients
influence as a predictor of better scores in physical scale when in at least 3-month post-operation observation as long as proper
baseline and prospective group of patients were compared. Data hormone replacement therapy was introduced (9). However,
on relations between gender of acromegalic patients and their patients requiring hormone replacement therapy perceived their
QoL is not consistent. According to Psaras et al. both genders treatment as less controlled (24). What is more important and
are affected by long-lasting consequences of acromegaly, but was decline in previous studies the degree of hypopituitarism
interestingly, comorbidities varied in frequency between males may play an important role in its association with QoL (27).
and females and affected them differently in matters of QoL However, it needs to be emphasized that AcroQoL may not be
(29). There could also be sex-related variations in perceptions as a suitable tool in mentioned group of patients (35).
well as response to therapy (30). Meanwhile, in cross-sectional
study carried out by Vandeva et al. active disease in men was CONCLUSIONS
related to better outcome of all scales when compared to woman
(13). It needs to be mentioned that there is a body of data As hormones concentrations are well-known and recognized
that claims contrary (15, 16, 31). In the paper by Kyriakakis factors to monitor the course of disease, more attention should
et al. women were characterized by higher QoL measured with be paid to AIS and modalities that contribute to it. The difference
AcroQoL in physical subscale (25). However, mentioned female in the perceptions of patients with controlled and uncontrolled
gender as negative independent predictor of QoL, especially acromegaly emerges as the most remarkable conclusion from this
when biochemical control was not obtained, in all scales apart study. Even though no significant differences in the variables
from the appearance subscale (13). Our results showed that analyzed individually in our study were identified, situation
gender as well as treatment modalities did not affect the QoL. In changes as relationships between variables are taken into
our study 36 out of 50 patients underwent surgical intervention consideration. Minding people with uncontrolled acromegaly,
but only 10 did not require additional medical treatment after the control of biochemical factors seemed to be more important
the operation. Literature data on the association of QoL and for the QoL perception, while among patients with controlled
biochemical disease control in patients with acromegaly are acromegaly, psychological variables such as acceptance of the
unclear. Data on diverse influence of particular types of drugs disease are observed to play a fundamental role in QoL.
used on HRQoL can be found but is still controversial (13). Moreover, inclusion of patient’s acceptance of the illness
Matta et al. points out that in patients who underwent operation into clinical routine would promote holistic, patient-centered
persistent pituitary hormones hypersecretion is characterized care and empower doctor-patient partnership where patients’
by lower IGF-1 scores and therefore better performance in expectations and perceptions are constantly tracked. Obtaining
psychological subscale appearance score than in uncontrolled biochemical control should not be considered as the only
patients treated medically (9). Ishikawa et al. claims that QoL measure of treatment success. The presence of psychopathology
where endoscopic transsphenoidal approach is hired, could be also needs to be emphasized, in contrast to age, gender, or

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Jawiarczyk-Przybyłowska et al. Quality of Life in Acromegaly

duration of the disease, is potentially modifiable and could be management of uncontrolled acromegaly is said to be higher
targeted with suitable treatment. when contrasted with controlled patients and treatment of
coexistent diseases could enhance this trend. There is a need
to determine and describe links between given factors (serum
STRENGTHS AND LIMITATIONS levels, duration, age, gender, acceptance, etc.) to conclude which
Among strengths and limitations of this research, a few are crucial and could be monitored in order to improve QoL
things deserve to be emphasized. Studied population could in clinical environment. The stress should be put on modifiable
be considered as small from the perspective of cross-sectional considerations. Moreover, we are also still lacking data on more
study design. On the other hand, the numerousness of the “global level” to support relations between biochemical control,
group seems to be adequate and sufficient, when compared to treatment and better QoL (27).
current literature, minding the fact that acromegaly is a relatively
rare disease. Moreover, the groups’ sociodemographic profiles DATA AVAILABILITY STATEMENT
were homogeneous in the terms of gender, education, place of
All datasets generated for this study are included in the
residence, and marital status but differed statistically significantly
article/supplementary material.
in terms of age and duration of the disease. Percentage of the
patients who improved and used treatment modalities were
similar when contrasted with (remaining) data found in the ETHICS STATEMENT
literature. One of the limitations of current paper may be the lack
This study was carried out in accordance with the
of a control group in the analyzes presented. However, it should
recommendations of local Bioethics Committee Medical
be mentioned that such study design is not accidental. This paper
University, Wroclaw. The protocol was approved by the local
was aimed at detailed comparative analyzes between two groups
Bioethics Committee of Medical University, Wroclaw, Poland.
of patients living with acromegaly differing in disease activity,
All subjects gave written informed consent in accordance with
and not analyzing individual variables compared to the group of
the Declaration of Helsinki.
healthy participants who do not have to face the consequences
resulting from illness or their level of acceptance. Results on the
QoL between different clinical groups and healthy participants AUTHOR CONTRIBUTIONS
were presented in another paper in details (26).
AJ-P and DS designed the project, the main conceptual ideas
and proof outline, conducted study, interpretation of the results,
PRACTICAL IMPLICATIONS OF THE complied the literature sources, wrote manuscript, and checked
STUDY/FUTURE INTERESTS the references. MC complied the literature sources, wrote
manuscript, and reference checking. MB and JR contributed
To the best of our knowledge this is study to highlight the conception and design of the study, helped in the interpretation
complex interaction between QoL concept and the acceptance date, and reference checking. All authors contributed to the final
of diseases phenomenon in relation to the biochemical course version of the manuscript and approved it for publication.
of acromegaly. There is more and more attention paid to the
vital importance of self-perceived QoL in chronic diseases in FUNDING
research but keeping it at a certain level should be perceived as
one of the crucial goals of the everyday therapy. Pursuing optimal The project was conducted within the framework of research
comorbidity management as soon as possible as prophylaxis of aimed at promoting young scientist, funded by Minister of
their possible irreversible consequences, could result in better Science and Higher Education (Registration number Pbmn 118).
QoL in acromegaly patients. Minding psychiatric symptoms This study was also supported by Statutory Activities by
is not to be underappreciated as independent, potentially minister of Science and Higher Education (grant number
modifiable contributors to QoL. Noteworthy, total cost of ST.CT120.18.006).

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Affected illness perceptions and the association with impaired quality of life reproduction is permitted which does not comply with these terms.

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