Exploring Quality of Life in Acromegaly: The Role of Gender, Psychiatric Disorders, and Comorbidities

Abstract

(1) Background: Acromegaly is a rare disease associated with multiple complications. Consequently, it has a high clinical burden, which leads to a lower quality of life (QoL). The Acromegaly Quality of Life Questionnaire (AcroQoL) is a specific tool developed to assess the impact of the disease on a patient’s physical and emotional well-being. Current research on anxiety has shown that higher levels of psychosocial factors are linked to a poorer quality of life. (2) Methods: Our study included 40 patients (26 women and 14 men) with a mean disease duration of 85.9 ± 97.7 months. Information about disease status, associated comorbidities, and clinical and paraclinical data was obtained. All patients completed the AcroQoL questionnaire. (3) Results: The lowest score was observed on the physical scale, while the least affected scale was personal relations. Biochemical parameters, biochemical control, and adenoma size were not associated with a lower QoL. Gender, age at diagnosis, and comorbidities, such as hypertension and arthropathy, were associated with a decrease in QoL. Additionally, the presence of anxiety and depression, which were mostly reported by women (30.7%), had a negative impact on the global QoL. (4) Conclusions: Early diagnosis of acromegaly can increase the QoL by preventing comorbidities, but there are also non-modifiable factors that have been associated with a decreased QoL. Preventing depression and anxiety could serve as important targets for future interventions.

1. Introduction

Acromegaly is a disease with a gradual progression associated with excess growth hormone (GH) secretion, most often from a pituitary adenoma [1]. The consequences of this hormonal secretion are physical (acral enlargement, oral changes, hyperhidrosis) and psychological [2]. Due to its slow progression, it is often diagnosed when the effects of hypersomatotropism are overt and after the occurrence of complications, such as hypertension, arthropathy, or diabetes mellitus (DM) type 2 [3]. Multimodal treatment (surgery, medical treatment, and radiotherapy) has lowered the rate of morbidity and mortality [3]. While multimodal treatment reduces morbidity, irreversible changes (e.g., prognathism, arthritis) and persistent complications (e.g., hypertension, diabetes) remain a concern [4]. Another important aspect is the variability of the remission rate after surgery [5]. A meta-analysis of 1105 patients identified that overall remission after surgery is around 55% [6]. As a consequence, the burden of this disease remains high and leads to increased mortality and morbidity, and decreased QoL [7,8]. The World Health Organization defines QoL as a “subjective evaluation of one’s perception of their reality” [9]. In 2006, a specific questionnaire for patients with acromegaly was validated [10]. AcroQoL evaluates multiple domains that are significantly modified by acromegaly, such as body image and the capacity to perform daily activities [11]. Successful surgery and pharmacological treatment lead to an increased QoL, but no correlation has been found regarding changes in GH or IGF-I [10,12]. Biochemical control is not strictly correlated with a better QoL [13]. Decreased QoL was observed among patients with active disease and cured patients [8]. Another important factor that can impair quality of life is further medical treatment, such as somatostatin analogs [14] or radiotherapy [15]. The following parameters were also associated with low QoL: high body mass index (BMI), female gender, delayed diagnosis, and employment status [16,17,18]. Comorbidities are often diagnosed in patients with acromegaly and are recognized as possible factors that influence their well-being [3]. Depression, anxiety, and arthropathy are important factors that negatively impact QoL [19,20]. Moreover, patients’ perceptions of disease can change over time, which might lead to poor QoL since the treatment received does not cure acromegaly [21]. The treatment’s end goal is to improve clinical and biochemical parameters and ensure an improvement in all aspects related to this disease.

The objective of the present study was to assess the QoL in our cohort of patients with acromegaly and determine possible correlations with clinical parameters, biochemical markers, and comorbidities. Another goal of our research was to find out how socio-demographic factors or gender might influence the well-being of acromegalic patients. We hypothesize that in patients with acromegaly, comorbidities such as hypertension, diabetes, and sleep apnea are negatively associated with quality of life (QoL), resulting in lower AcroQoL scores. Furthermore, gender differences are expected to impact QoL, with female patients reporting poorer outcomes than males.

2. Materials and Methods

The study population consisted of 40 patients over 18 years of age diagnosed with acromegaly in the Department of Endocrinology of the County Emergency Hospital in Timisoara, Romania, from 1 January 2017 to 30 April 2024.

2.1. Assessment of Disease Control and Relevant Hormonal Biomarkers

The diagnosis of acromegaly was established according to the Romanian guidelines [22] based on the measurement of IGF-1, nadir GH (lowest value of GH) during the oral glucose tolerance test (OGTT), or the mean value of 4 GH determinations over 24 h for patients diagnosed with DM. Pituitary function was assessed by determining serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol, progesterone, testosterone, basal cortisol, adrenocorticotrophic hormone (ACTH), thyroid-stimulating hormone (TSH), and prolactin. The pituitary hormone profile was evaluated using a chemiluminescence assay (Siemens IMMULITE 2000 xpi, Advia Centaur^® XP Immunoassay System, Tarrytown, NY, USA). Serum GH and IGF-1 concentrations were measured using a chemiluminescence assay (Siemens IMMULITE 2000 xpi, Diagnostic Products Corporation, Flanders, NJ, USA).

Disease control was defined as follows: controlled symptoms, GH level < 1 ng/mL, determined from a random sample or GH during OGTT < 0.4 ng/mL, and IGF-1 level 1–1.3 × upper limit of normal (ULN) for age and gender. The disease was uncontrolled if one of the following criteria was present: symptoms specific for acromegaly, basal serum GH > 1 ng/mL (random sample), IGF-1 > 1.3 × ULN, or tumor progression. Normal values for GH and IGF-1 were provided by the local laboratory.

2.2. Collection of Clinical and Socio-Demographic Data

Patient clinical, biochemical, magnetic resonance imaging (MRI) data, and the presence or absence of acromegaly-specific comorbidities were collected from medical records. They also completed a separate form on their socio-demographic profiles.

2.3. Inclusion Criteria

Patients older than 18 years old who were diagnosed with acromegaly and agreed to provide written consent.

2.4. Exclusion Criteria

Acute disease, end-stage disease not caused by acromegaly, known psychiatric disorder, treatment with psychiatric medications, or the absence of written consent.

2.5. The AcroQoL Scale: Methodology and Calculation Procedures

Patients filled out the Romanian version of the questionnaire (AcroQol) after a brief explanation of its content and completion method. The principal investigator was available at all times for patients who had further questions. AcroQol is a tool designed to measure Health-Related Quality of Life (HRQoL) in patients diagnosed with acromegaly. It comprises 22 items that evaluate different dimensions of the disease: “physical” and “psychological”. The latter has two subdimensions: “appearance” and “personal relationships”. Each question can be answered by selecting one of five response options provided (“strongly agree”/“always” equals 1 and “never” or “strongly disagree” equals 5) on a Likert-style scale.

The final score/score of the subdimension was calculated using the following formula: $Y=\left({\displaystyle \frac{\left(X\right)-min}{\mathrm{m}\mathrm{a}\mathrm{x}-\mathrm{m}\mathrm{i}\mathrm{n}}}\right)$ (Y = recalculated score; X = sum of all the items belonging to a specific dimension/subdimension or study score; min = minimum possible score in the study dimension; max = maximum possible score in the study dimension). The formula transforms various scores into a range from 0 to 100, with higher values indicating better QoL.

2.6. Statistical Approach and Data Analysis

Continuous variables are presented as mean +/− standard deviation (SD), and categorical variables as numbers (%). The Shapiro–Wilk test was used to assess the normality of data distribution. The only variable that did not have a normal distribution was the value of GH. The t-test was applied to compare groups when normality was present, while the Mann–Whitney U test was used when normality was absent. The Pearson correlation coefficient was used to assess the relationship between continuous variables. Fisher’s Exact Test and the Chi-Square Test were used to analyze categorical data. If any of the cell counts were less than 5, Fisher’s Exact Test (educational status) was applied; otherwise, the Chi-Square Test was used. No outliers were found in the data after applying the Interquartile Range (IQR).

Statistical analysis was performed using Microsoft Excel and JASPv16.4 programs. The significance level was set at p < 0.05 for the whole study.

2.7. Ethical Considerations

The study was approved by the Ethics Committee of the “Victor Babes” University of Medicine and Pharmacy, 88/2020, revised in February 2024.

3. Results

The study group included 40 patients: 14 men (35%) and 26 women (65%). The mean age at diagnosis was 43.8 ± 11.6 years, and the mean disease duration was 85.9 ± 97.7 months. Socio-demographic factors highlight that the majority of patients came from an urban area and had finished secondary education (

Table 1. General characteristics and socio-demographic profile of patients with acromegaly.

Parameters
Number of patients	40
Age at diagnosis of acromegaly, years, mean ± SD	43.8 ± 11.6
Age at inclusion in the study, years, mean ± SD	49.9 ± 11.2
Women n (%)	26, (65)
Men n (%)	14, (35)
Disease duration (months), mean ± SD	85.9 ± 97.7
Adenoma size at diagnosis (mm), mean ± SD	22.8 ± 15.0
BMI (kg/m2), mean ± SD	30.6 ± 6.7
Educational status
Elementary school/High school n (%)	33 (82.5)
College n (%)	7 (17.5)
Employment status
Working n (%)	20 (50)
Retired or unemployed n (%)	20 (50)
Place of residence
Urban area n (%)	30 (75)
Rural area n (%)	10 (25)

Legend: SD = standard deviation; BMI = body mass index.

).

In the majority of cases (67.5%), the first therapeutic line was surgery. After surgery, medical treatment was considered in 55.5% of the patients, including somatostatin analogs, GH receptor antagonists, cabergoline, or a combination of these drugs. Thirteen patients (32.5%) were newly diagnosed and had not yet received therapeutic measures. The majority of patients (67.5%) had uncontrolled disease when they were included in the study (

Table 2. Current biochemical parameters, disease status, and treatment received.

Parameters	Values
GH (ng/mL), mean ± SD	21.2 ± 55.4
IGF-1 (ng/mL) mean ± SD	387.2 ± 237.9
ULN IGF-1 (ng/mL) mean ± SD	1.63 ± 1.10
Disease status
Controlled disease n (%)	13 (32.5)
Active disease n (%)	27 (67.5)
Treatment
No treatment *, n (%)	13 (32.5)
Surgery n (%)	27 (67.5)
Medical treatment, n (%)	15 (55.5)
Radiotherapy n (%)	6 (15)

Legend: GH = growth hormone; IGF-1 = insulin-like growth factor 1; SD = standard deviation; ULN = upper limit of normal; SD = standard deviation; SSA = somatostatin analogues; *—first presentation, at diagnosis.

).

Women were significantly older than men at diagnosis and also had a higher mean disease duration (p < 0.05). They were also more prone to developing hypertension and articular complications. The most frequent pituitary insufficiency was thyrotropin deficiency. The only notable difference between genders was the diagnosis of corticotroph deficiency, which was more frequent in male patients (

Table 3. Gender differences in acromegaly.

Parameters	Female (n = 26)	Male (n = 14)	p
Age at diagnosis of acromegaly (years), mean ± SD	46.4 ± 9.6	36.7 ± 12.8	0.012
Age at inclusion in the study (years), mean ± SD	53.6 ± 9.3	42.7 ± 11.2	0.002
Disease duration (months), mean ± SD	88.6 ± 104.7	78 ± 86.61	0.746
Adenoma size at diagnosis (mm), mean ± SD	20.9 ± 14.1	26.2 ± 16.6	0.298
BMI (kg/m2), mean ± SD	31.4 ± 4.3	30.8 ± 7.5	0.770
Educational status
Elementary school/High school n (%)	22 (84.6)	11 (78.5)	0.678
College n (%)	4 (15.3)	3 (21.4)
Employment status
Working n (%)	10 (38.4)	9 (64.2)	0.185
Retired or unemployed n (%)	16 (61.5)	5 (35.7)
Place of residence
Urban area n (%)	17 (65.3)	1 (7.1)	0.000
Rural area n (%)	9 (34.6)	13 (92.8)
GH (ng/mL), mean ± SD	10.8 ± 20.5	28.0 ± 80.6	0.809
IGF-1 (ng/mL) mean ± SD	359.9 ± 218.3	441.6 ± 270.5	0.294
ULN IGF-1 (ng/mL) mean ± SD	1.9 ± 1.2	1.6 ± 1.0	0.499
Disease status
Controlled disease n (%)	9 (34.6)	3 (21.4)	0.484
Active disease n (%)	17 (65.3)	11 (78.5)
Hypertension n (%)	20 (76.9)	5 (35.7)	0.016
DM type 2 n (%)	9 (34.6)	1 (7.1)	0.069
Psychiatric complications n (%)	8 (30.7)	1 (7.1)	0.124
Articular complications, n (%)	13 (5)	2 (16.6)	0.040
Gonadotropin deficiency n (%)	10 (38.4)	9 (64.2)	0.185
Substitution treatment n (%)	1 (10)	5 (55.5)	0.057
Thyrotropin deficiency n (%)	13 (50)	9 (64.2)	0.510
Corticotropin deficiency n (%)	6 (23.0)	9 (64.2)	0.016
Benign or malignant tumors n (%)	12 (46.1)	3 (21.4)	0.176

Legend: SD = standard deviation; GH = growth hormone; IGF-1 = insulin-like growth factor 1; ULN = upper limit of normal; DM = diabetes mellitus.

). Type 2 DM and psychiatric disorders (anxiety and depression) were more prevalent in women, but did not reach statistical significance. GH, IGF-1, and disease control did not differ between female and male patients. Socio-demographic factors were similar between groups, except for the place of residence. Gonadotropic deficiency was comparable between groups, but substitution treatment was administered more frequently in male patients than in premenopausal and menopausal female patients (five patients versus one patient). Women who were diagnosed at menopausal age (older than 45 years old) did not receive substitutive treatment with estroprogestatives. Ten women were diagnosed before the age of menopause (younger than 45 years old), and four of them had gonadotroph insufficiency. One patient received treatment, while the other three women either refused the treatment or had contraindications for estroprogestatives, e.g., epilepsy. Male patients who did not receive replacement therapy with testosterone were diagnosed when they were included in the study.

Women were also more prone to being diagnosed with comorbidities than men (Table 3). In our group, 90% of the patients were diagnosed with three or more complications associated with acromegaly.

Females are six times more likely to have hypertension and articular complications compared with males. These findings suggest that gender may play a role in the prevalence of these complications. The odds ratio of 0.166 suggests that males are approximately six times more likely to have corticotropin deficiency than females. This indicates that being female may be associated with a lower likelihood of corticotropin deficiency (

Table 4. Association between comorbidities and AcroQoL, according to gender.

	OR	95% CI
Hypertension	6	1.4 to 24.9
Articular complications	6	1.1 to 32.2
Corticotropin deficiency	0.166	0.040 to 0.692

OR = odds ratio; CI = confidence interval.

).

Women had lower global scores, as well as lower scores in all subdimensions of AcroQoL, compared with men. BMI, educational status, and place of residence did not influence QoL, while patients who were employed had better scores in all domains of the questionnaire (

Table 5. Differences in QoL regarding gender, disease activity, BMI, and sociodemographic factors.

AcroQoL Score	Men (n = 14)	Women (n = 26)	p	Cohen’s d
Physical score	70.7 ± 22.2	48.9 ± 23.6	0.007	0.95
Psychological score	75.8 ± 11.7	55.2 ± 23.6	0.004	1.11
Appearance	69.1 ± 17.6	50.7 ± 25.4	0.021	0.84
Personal relations	82.7 ± 14.4	63.1 ± 23.0	0.002	1.02
Total score	74.0 ± 14.1	54.1 ± 22.0	0.004	1.08
AcroQoL score	BMI < 30 kg/m2 (n = 20)	BMI > 30 kg/m2 (n = 20)
Physical score	58.1 ± 20.6	54.9 ± 29.4	0.700
Psychological score	66.0 ± 20.4	58.9 ± 24.3	0.320
Appearance	58.2 ± 24.7	56.1 ± 24.8	0.785
Personal relations	74.0 ± 20.1	66.0 ± 24.2	0.266
Total score	63.1 ± 19.2	58.4 ± 23.5	0.487
AcroQoL score	Elementary school/High school (n = 33)	College (n = 7)
Physical score	55.7 ± 26.5	60.2 ± 18.4	0.673
Psychological score	61.2 ± 23.8	68.3 ± 14.1	0.453
Appearance	55.7 ± 24.9	63.7 ± 22.6	0.440
Personal relations	69.4 ± 23.5	72.7 ± 16.6	0.731
Total score	59.8 ± 22.5	65.4 ± 15.1	0.535
AcroQoL score	Working (n = 20)	Retired or unemployed (n = 17)
Physical score	69.5 ± 16.4	38.4 ± 23.6	<0.000	1.55
Psychological score	72.5 ± 16.0	47.6 ± 22.5	0.000	1.29
Appearance	65.5 ± 20.8	43.8 ± 23.8	0.005	0.98
Personal relations	79.6 ± 14.7	56.7 ± 23.9	0.002	1.18
Total score	71.4 ± 14.3	45.3 ± 20.2	<0.000	1.51
AcroQoL score	Urban area (n = 30)	Rural area (n = 10)
Physical score	58.6 ± 24.3	50.3 ± 27.8	0.371
Psychological score	66.4 ± 19.3	50.7 ± 27.7	0.054
Appearance	61.1 ± 21.9	45.4 ± 28.9	0.079
Personal relations	71.8 ± 21.2	64.6 ± 25.9	0.384
Total score	63.5 ± 19.8	52.3 ± 24.6	0.153
AcroQoL score	Active disease (n = 27)	Controlled disease (n = 13)	p
Physical score	54.5 ± 25.9	60.8 ± 23.9	0.465
Psychological score	60.7 ± 24.9	66.2 ± 16.5	0.475
Appearance	56.9 ± 25.4	57.6 ± 23.2	0.930
Personal relations	67.9 ± 24.4	74.4 ± 17.4	0.395
Total score	59.1 ± 22.9	64.2 ± 18.0	0.485

Legend: AcroQoL = Acromegaly Quality of Life Questionnaire; BMI = body mass index.

). Disease activity was not correlated with worse QoL, but patients who achieved disease control had higher scores than those who remained uncontrolled (Table 5). Although the p-value was statistically significant (p < 0.05), Cohen’s d values indicate a large effect size for employment status.

Biochemical markers of acromegaly were not associated with lower AcroQoL scores (

Table 6. Correlation between age, disease duration, adenoma size, biochemical parameters, and QoL.

Parameter	AcroQoL	r	p
GH (ng/mL)	Physical score	−0.040	0.806
	Psychological score	−0.046	0.774
	Appearance	−0.067	0.677
	Personal relations	0.108	0.504
	Total score	−0.241	0.278
Parameter	AcroQoL	r	p
IGF-1 (ng/mL)	Physical score	0.004	0.971
	Psychological score	0.014	0.927
	Appearance	−0.126	0.435
	Personal relations	0.024	0.880
	Total score	−0.010	0.948
Parameter	AcroQoL	r	p
ULN IGF-1	Physical score	−0.048	0.767
	Psychological score	−0.014	0.929
	Appearance	−0.185	0.251
	Personal relations	−0.019	0.904
	Total score	−0.025	0.877
Parameter	AcroQoL	r	p
Age at diagnosis, years	Physical score	−0.191	0.237
	Psychological score	0.172	0.288
	Appearance	−0.017	0.915
	Personal relations	−0.337	0.033
	Total score	−0.328	0.038
Parameter	AcroQoL	r	p
Age at inclusion in the study, years	Physical score	−0.362	0.021
	Psychological score	−0.514	0.000
	Appearance	−0.394	0.011
	Personal relations	−0.410	0.008
	Total score	−0.462	0.002
Parameter	AcroQoL	r	p
Disease duration, months	Physical score	−0.194	0.229
	Psychological score	−0.046	0.774
	Appearance	0.092	0.568
	Personal relations	−0.095	0.557
	Total score	−0.090	0.578
Parameter	AcroQoL	r	p
Tumor size at diagnosis, mm	Physical score	0.039	0.810
	Psychological score	0.031	0.849
	Appearance	−0.111	0.499
	Personal relations	−0.187	0.252
	Total score	−0.061	0.710

Legend: AcroQoL = Acromegaly Quality of Life Questionnaire; GH = growth hormone; IGF-1 = insulin-like growth factor 1; ULN = upper limit of normal; SD = standard deviation.

). Age at diagnosis was negatively correlated with AcroQol total score and the personal relationship sub-domain, while disease duration had no impact on QoL. Age at inclusion in the study was negatively correlated with all the questionnaire domains, with the strongest correlation observed in the psychological score (r coefficient = −0.514). No statistically significant association was found between adenoma size and QoL (Table 6).

Regarding comorbidities, hypertension had a significant impact on QoL in all domains, while type 2 DM impacted only the psychological scale. Psychiatric disorders (anxiety and depression) and articular complications were predominantly diagnosed in women and had an important effect on all aspects of QoL. Lower scores were also observed in patients who were diagnosed with tumors and sleep apnea, but they failed to reach statistical significance. Pituitary insufficiency did not significantly influence the QoL, except for thyrotropin insufficiency, which was associated with lower scores in the sub-domain appearance (p < 0.05) (

Table 7. QoL and its association with complications associated with acromegaly.

AcroQoL Score	Hypertension		p	Cohen’s d
	Yes (n = 25, 62.5%)	No (n = 15)
Physical score	49.4 ± 24.8	68.3 ± 21.6	0.019	0.81
Psychological score	53.9 ± 22.9	76.7 ± 12.3	0.000	1.24
Appearance	49.6 ± 24.6	69.7 ± 18.7	0.009	0.92
Personal relations	61.7 ± 22.6	83.9 ± 13.5	0.000	1.19
Total score	53.0 ± 21.3	73.7 ± 14.2	0.002	1.14
AcroQoL score	DM type 2
	Yes (n = 10, 25%)	No (n = 30)
Physical score	49.6 ± 26.5	58.8 ± 24.7	0.324
Psychological score	48.9 ± 27.1	67.0 ± 19.0	0.025	0.77
Appearance	46.8 ± 28.7	60.6 ± 22.3	0.125
Personal relations	59.6 ± 25.6	73.5 ± 20.4	0.089
Total score	51.0 ± 25.0	64.0 ± 19.7	0.095
AcroQoL score	Benign or malignant tumors
	Yes (n = 15, 37.5%)	No(n = 25)
Physical score	51.8 ± 27.0	59.3 ± 24.0	0.368
Psychological score	63.0 ± 23.5	62.1 ± 22.2	0.898
Appearance	58.6 ± 25.0	56.3 ± 24.5	0.776
Personal relations	67.3 ± 25.3	71.6 ± 20.7	0.565
Total score	59.0 ± 23.6	61.8 ± 20.3	0.688
AcroQoL score	Articular complications
	Yes (n = 15, 37.5%)	No (n = 25)
Physical score	39.1 ± 20.6	66.9 ± 21.8	0.000	1.30
Psychological score	47.6 ± 21.1	71.4 ± 18.3	0.000	1.20
Appearance	42.6 ± 24.0	65.8 ± 20.6	0.002	1.03
Personal relations	58.3 ± 20.9	77.0 ± 20.4	0.008	0.90
Total score	45.7 ± 17.3	69.8 ± 18.4	0.000	1.34
AcroQoL score	Psychiatric disorders
	Yes (n = 9, 22.5%)	No (n = 31)
Physical score	37.1 ± 21.5	62.1 ± 23.5	0.006	1.11
Psychological score	43.8 ± 24.6	67.9 ± 18.9	0.003	1.09
Appearance	46.9 ± 28.8	60.1 ± 22.7	0.155
Personal relations	50.3 ± 25.4	75.7 ± 18.1	0.001	1.15
Total score	43.4 ± 20.4	65.8 ± 19.1	0.004	1.13
AcroQoL score	Obstructive sleep apnea syndrome
	Yes (n = 27, 67.5%)	No (n = 13)
Physical score	53.1 ± 27.0	63.7 ± 19.6	0.217
Psychological score	59.5 ± 23.3	68.6 ± 20.0	0.231
Appearance	53.6 ± 27.3	64.5 ± 15.3	0.189
Personal relations	65.4 ± 23.4	79.6 ± 16.8	0.058
Total score	57.1 ± 23.4	68.2 ± 14.4	0.074
AcroQoL score	Gonadotropin deficiency
	Yes (n = 19, 47.5%)	No (n = 21)
Physical score	56.7 ± 26.0	56.3 ± 25.0	0.966
Psychological score	60.0 ± 24.3	64.7 ± 20.9	0.519
Appearance	56.4 ± 25.0	57.8 ± 24.5	0.856
Personal relations	68.2 ± 23.7	71.6 ± 21.4	0.631
Total score	59.8 ± 22.1	61.8 ± 21.1	0.785
AcroQoL score	Thyrotropin deficiency
	Yes (n = 21, 52.5%)	No (n = 19)
Physical score	58.7 ± 27.9	54.1 ± 22.1	0.564	0.67
Psychological score	64.6 ± 23.5	60.1 ± 21.5	0.535
Appearance	64.6 ± 24.2	48.9 ± 22.5	0.040
Personal relations	68.5 ± 21.8	71.7 ± 23.4	0.658
Total score	63.3 ± 22.1	57.9 ± 20.7	0.431
AcroQoL score	Corticotropin deficiency
	Yes (n = 15, 37.5%)	No (n = 25)
Physical score	61.0 ± 26.7	53.8 ± 24.3	0.390
Psychological score	68.9 ± 20.9	58.6 ± 22.8	0.163
Appearance	62.6 ± 24.2	53.8 ± 24.4	0.276
Personal relations	75.2 ± 22.2	66.9 ± 22.3	0.261
Total score	66.0 ± 21.6	57.6 ± 21.0	0.232

Legend: AcroQoL = Acromegaly Quality of Life Questionnaire; n = number.

). Cohen’s d values indicate that comorbidities have a meaningful impact on QoL (Table 7).

In order to assess the importance of gender as a predictor of QoL, we have used two statistical models. The first model (M₁) uses only gender as a predictor of QoL, and the second model (M₂) uses gender and comorbidities (

Table 8. Comparison of linear regression models.

Variable	Model	Unstandardized Coefficient (b)	Standard Error	β Standardized	t	p
Intercept	Gender Model	53.667	3.771	-	14.233	<0.001
Gender	Gender Model	20.355	6.374	0.460	3.194	0.003
Intercept	Gender + Comorbidities	35.827	9.073	-	3.949	<0.001
Gender	Gender + Comorbidities	10.066	7.672	0.229	1.312	0.200
Gonadotropin deficiency	Gender + Comorbidities	11.945	7.040	0.283	1.697	0.101
Thyrotropin deficiency	Gender + Comorbidities	−3.708	6.492	−0.087	−0.571	0.572
Corticotropin deficiency	Gender + Comorbidities	−4.111	6.839	−0.095	−0.601	0.553
Sleep apnea	Gender + Comorbidities	5.230	6.719	0.117	0.778	0.443
Hypertension	Gender + Comorbidities	10.289	6.961	0.237	1.478	0.151
Tumors	Gender + Comorbidities	2.108	6.552	0.049	0.322	0.750
Diabetes mellitus	Gender + Comorbidities	−5.400	8.601	−0.112	−0.628	0.535
Arthropathy	Gender + Comorbidities	11.421	7.477	0.259	1.527	0.138
Psychiatric complications	Gender + Comorbidities	12.645	7.823	0.252	1.616	0.117

).

In the M₁ model, gender is a significant predictor (p = 0.003), but in the M₂ model, the gender coefficient becomes non-significant (p = 0.200). The inclusion of comorbidities introduces several new predictors, though most of them are not statistically significant. This finding suggests that the effect of gender diminishes when other comorbidities are considered. Adding comorbidities significantly improves the R², suggesting that comorbidities collectively explain more variance in the dependent variable. However, individual comorbidities have less statistically significant effects than gender alone, which suggests that comorbidities contribute to the model but not strongly enough to influence the outcome as much as gender. Overall, M₂ provides a more comprehensive explanation of the dependent variable and explains variance up to 51.7% (Table 8).

4. Discussion

This study evaluated the overall QoL in patients diagnosed with acromegaly and searched for factors that decreased the QoL. The mean total score in our cohort of patients was 38.6, which was lower than the mean scores found by other studies conducted on Romanian patients with acromegaly—77 and 60.3, respectively, in [23,24]. The lowest mean score was observed on the physical scale, which is contrary to studies in the literature, where the lowest score was noted in the appearance subdimension; the highest score was noted in the personal relationship sub-scale, which is in concordance with current published data [24,25,26,27]. These results might be associated with the heterogeneity of the acromegalic population included in these studies. Factors such as age, gender, socio-economic status, and number of comorbidities vary and might influence the results. Complications such as hypertension, arthropathy, and sleep apnea were frequently diagnosed (62.5%, 37.5%, 67.5%) in our cohort of patients, and 90% of the patients had at least three distinct comorbidities. These factors may affect energy levels, which can result in reduced physical activity and, consequently, lower QoL. Our linear regression model, M2, which included comorbidities, influenced QoL.

It should also be noted that the number of comorbidities was associated with poor disease prognosis, lower QoL, and lower scores in the physical sub-domain [28].

Socio-economic factors and BMI did not have an important impact on QoL. A few research papers noted a negative relationship between QoL and higher BMI, lower educational status, and living in the countryside [23,25,29]. A significant relationship was observed between employment status and QoL. Unemployment is frequent among patients with acromegaly and is more common in those with decreased QoL and an increased number of comorbidities [28,30]. In our study, we observed that patients with better scores were more likely to be employed. Motor disability was correlated with decreased QoL and work productivity, which can be a consequence of arthropathy [20].

Results of studies on the importance of gender in acromegaly are contradictory. Some report a minor sex difference [31], while others underline that women who are diagnosed with acromegaly are older and have an increased delay in diagnosis [32]. This is probably because some of the symptoms, such as headache, sweating, and weight gain, are also common in premenopausal and menopausal women [33]. In our study, the female gender was predominant (65%) and was significantly older, both at diagnosis (mean age 46.4 versus 36.7) and when included in the study (mean age 53.6 versus 42.7) compared with men. Biochemical parameters, adenoma size, and disease control were similar between these groups. These results are concordant with the literature, except for the lower IGF-1 levels noted in female patients, most likely due to the inhibitory effects of estrogen on hepatic IGF-1 [31,32]. In our study, women were older and had lower estrogen levels, which may account for the absence of significant differences in IGF-1 values between men and women. Comorbidities were more commonly diagnosed in the female group. QoL was significantly lower in women than in men in all scales of the questionnaire. The lowest score for women was noted in the physical scale, while the lowest score for men was noted in the appearance sub-scale. Our results might be explained by the fact that women suffered from physical disabilities as a consequence of acromegaly and older age, while men were more prone to experience morphological changes as a consequence of younger age and fewer comorbidities. It should also be noted that morphological changes, such as edema and hand enlargement, might affect men more because they are more commonly engaged in manual labor. Age has a significant impact on physical function and might influence motivation, energy levels, and pain perception [34].

Gender differences in QoL and associations between lower AcroQol scores and anxiety or depression have been observed in multiple studies [17,34,35]. Psychiatric complications were noted in 22.5% of acromegalic patients and had a strong correlation with lower QoL in all scales except appearance. We also noted that female patients suffered from psychiatric diseases more often than men. Studies have shown that psychological changes are associated with lower QoL and are more predictive of QoL than biochemical control [19,36]. A Polish study underlined that the level of illness acceptance is a strong predictor of QoL [37]. Higher prevalences of depression and anxiety scores were observed in acromegaly, mostly in female patients, which was associated with lower AcroQol scores [29,38]. In patients with controlled disease, higher levels of psychiatric distress were associated with lower scores in the personal relationship domain [37]. Anagnostis et al. also observed that patients with acromegaly were more prone to developing depression and anger compared with healthy controls [35]. Female patients suffered more from anxiety, depression, and fatigue [35]. Hypertension and articular complications were significantly more frequent in women (p < 0.005). Our analysis revealed a significant association between gender and complications, with an odds ratio of six, suggesting that the female sex has a higher risk of developing hypertension and articular complications.

These results were observed in older studies, which found probabilities of increased mortality in women [39,40]. Cardiovascular and articular complications negatively impacted overall QoL; this was also noted in other studies [23,41]. Type 2 DM only impacted the psychological scale. These results are similar to those of Ballesteros-Herrera et al., who found lower scores for the sub-scales of appearance and relationship [38].

An increase in the number of comorbidities is associated with lower QoL [37]. The female patients in our study were older at diagnosis, were less likely to receive estrogen substitution due to reaching the age of menopause, and were more likely to be diagnosed with cardiovascular and articular complications. These factors may have resulted in lower QoL.

Age at inclusion in the study was associated with lower scores for all scales of the questionnaire, consistent with current published data [18]. In comparison, age at diagnosis was associated with lower total and personal relationship sub-scale scores, most likely as a consequence of the morphological changes associated with the disease and the impact of the disease on family and friends dynamics. Younger age seems to be associated with a better QoL [16]. Older age was correlated with a decreased physical function score and was associated with reduced motivation and activity, as well as an increased number of comorbidities [34,42]. Arthropathy was also associated with a poorer QoL in older acromegalic patients, while in younger patients, factors such as treatment modalities and the size of the tumor were better predictors of QoL [43]. A decline in the QoL due to aging was associated with heart disease, joint deformities, type 2 DM, dementia, and cancer [44].

There was no correlation between disease duration and biochemical parameters. Even though disease control is the main focus of the endocrinologist, it seems that its correlation with QoL is rather weak. Surgery or medical treatment was associated with improvement in perceived QoL after treatment, but without reaching normal scores [10,34,45]. The most significant change was observed in the first year after treatment, and men had better scores than women [46].

QoL was not negatively affected by pituitary insufficiency, except for lower scores in the appearance sub-scale, which were observed in patients with thyrotropin deficiency. Our results are in concordance with most studies, which did not find a correlation between QoL and pituitary insufficiency [10,34,35,37]. On the other hand, it was observed that at least one pituitary deficit could lower the scores in the relationship sub-scale [26].

Applying the findings from AcroQoL in clinical practice can enhance patient care and ensure a more holistic approach to managing acromegaly. By tracking the QoL scores, clinicians can identify areas where patients may be struggling, such as emotional well-being or physical limitations, and address them promptly. For patients who reported lower scores in psychological or emotional domains (such as anxiety, depression, or body image concerns), clinicians can refer patients to mental health professionals for counseling or therapy. For patients reporting significant physical impairment, medical professionals may recommend physical therapy or pain management strategies. Clinicians could encourage family counseling or social support groups where patients can share their experiences with others facing similar challenges. Healthcare providers could also facilitate connections with patient advocacy groups or local resources for social support with the aim of reducing social isolation. For patients who express concerns over facial changes due to acromegaly, a healthcare provider can offer strategies for coping with changes in appearance and provide resources on available cosmetic treatments if needed.

Our study emphasizes the growing body of published literature on the influence of comorbidities on AcroQoL in patients with acromegaly. Previous research has highlighted that comorbidities, such as cardiovascular diseases, diabetes, and joint disorders, significantly affect the quality of life of these individuals [47]. Our findings align with these studies, reaffirming the relationship between comorbid conditions and lower AcroQoL scores. Our results further emphasize the need for early therapeutic interventions against acromegaly. This approach reduces the risk of developing comorbidities, which significantly impair quality of life. Achieving optimal disease control in the shortest possible time is also essential.

Our study has certain limitations. It is a cross-sectional study, which lowers the statistical power. Additionally, we were unable to evaluate the impact of medical treatment and radiotherapy on QoL due to the low number of patients. However, our study has its strengths, such as the uniform evaluation of the patients.

5. Conclusions

Acromegaly is associated with significant changes in QoL. Even though disease control is achieved in treated patients, the QoL does not usually return to normal. The most affected scale was the physical one, while the best score was noted in the personal relationship sub-scale. Female gender, unemployment, and age at diagnosis are predictive of a lower QoL. History of hypertension and articular and psychiatric complications are associated with decreased scores in all AcroQoL scales. Early diagnosis of acromegaly to prevent the emergence of complications remains the most important goal. Including the assessment of QoL in daily practice can lead to better management of acromegaly.