Avaliação da atividade física na prática de vida diária comparada com o nível de atividade da doença em pacientes acromegálicos: impacto na percepção da qualidade de vida

Physical activities in daily life and functional capacity compared to disease activity control in acromegalic patients: impact in self-reported quality of life

ORIGINAL ARTICLE

Physical activities in daily life and functional capacity compared to disease activity control in acromegalic patients: impact in self-reported quality of life

Avaliação da atividade física na prática de vida diária comparada com o nível de atividade da doença em pacientes acromegálicos: impacto na percepção da qualidade de vida

Renata Aparecida Elias Dantas^I,II; Karine Elias Passos^I; Lara Benigno Porto^I; Juliano Coelho Oliveira Zakir^I; Marcia Cristina Reis^I; Luciana Ansaneli Naves^I

^IUnit of Endocrinology, School of Medicine, Universidade de Brasília (UnB), DF, Brazil

^IISchool of Physical Education, Centro Universitário de Brasília (UniCEUB), Brasília, DF, Brazil

^{Correspondence to}

ABSTRACT

OBJECTIVE: To evaluate the quality of life and its association with daily physical activity and disease control in acromegalic patients.

SUBJECTS AND METHODS: A cross-sectional, case series study, composed of 42 patients recruited from the Neuroendocrinology Unit of the University Hospital of Brasilia. Level of physical activity was accessed by the International Physical Activity Questionnaire (IPAQ 6-short-form), which evaluates the weekly time spent on physical activity of moderate to vigorous intensity in different contexts of life. Quality of life was evaluated by The Medical Outcome Study Questionnaire Short Form (SF-36). Data was compared to growth hormone (GH) and insulin-like growth factor (IGF-1) levels. Students' t test and Fisher test were used, p < 0.05, SPSS 17.0.

RESULTS: Twenty-two women, aged 51.33 ± 14.33 and 20 men, aged 46.2 ± 13.18 were evaluated. Arthralgia was present in 83% of cases. In men, the most common sites of pain were the knees (73%), spine (47% lumbar, and 53% thoracic and cervical segments), hands and wrists (40%). Higher scores on SF-36 were observed in patients with intermediate or high levels of physical activity, in the domains social functioning (75 CI 57.3-92.6), general health (75.5 CI 60.4-90.5), mental health (70 CI 57.8-82.1).

CONCLUSIONS: In this study, the presence and severity of physical disability and pain were not associated with initial GH and IGF-1 levels or time of exposure to GH excess. However, the patients considered controlled, with normal a normal age-adjusted IGF-1, presented higher scores in SF-36, in physical and emotional domains, compared with patients with persistent hypersomatotrophism. These findings suggest benefits of metabolic control in self-reported quality of life.

Keywords : Acromegaly; quality of life; functional capacity; activities in daily life

RESUMO

OBJETIVO: Avaliar a qualidade de vida e sua associação com a prática de vida diária e controle metabólico em pacientes portadores de acromegalia.

SUJEITOS E MÉTODOS: Estudo seccional de série de casos, composto por 42 pacientes recrutados na Unidade de Neuroendocrinologia do Hospital Universitário de Brasília. O nível de atividade física foi estimado pelo Questionário Internacional de Atividade Física (IPAQ-6), que avalia o tempo gasto semanalmente em atividades físicas que variam de intensidade em diferentes contextos de vida. A qualidade de vida foi avaliada pelo questionário SF-36. Os dados obtidos foram comparados aos níveis de hormônio do crescimento (GH) e fator de crescimento semelhante à insulina (IGF-1). Os testes t Students e Fisher foram aplicados e p < 0,05 foram considerados significativos, SPSS 17.0.

RESULTADOS: Avaliaram-se 22 mulheres com idades de 51,33 ± 14,33 e 20 homens com idades de 46,2 ±13,18. Artralgia foi relatada em 83% dos pacientes. Em homens, os sítios de dor mais comuns foram os joelhos (73%), coluna vertebral (47% lombar, 53% segmentos torácico e cervical), mãos e quadris (40%). Os maiores escores no SF-36 foram observados em pacientes com níveis intermediário ou alto de atividade física, sobretudo nos domínios social (75 CI 57,3-92,6), saúde geral (75,5 CI 60,4-90,5), saúde mental (70 CI 57,8-82,1).

CONCLUSÕES: A presença e a severidade do prejuízo no desempenho físico e dor não se associaram com Gh e IGF-1 no diagnóstico, tempo de exposição prévio à doença. Todavia, pacientes considerados controlados apresentaram melhores escores nos domínios físico e emocional, comparados com pacientes com hipersomatotrofismo persistente. Tais achados sugerem benefícios do controle metabólico na qualidade de vida.

Descritores: Acromegalia; qualidade de vida; capacidade funcional; atividades da vida diária

INTRODUCTION

A cromegaly is a rare chronic disease, due to growth hormone (GH) and insulin-like growth factor (IGF-1) oversecretion (1). The estimated prevalence is 40-70 patients for one million inhabitants, and the age of diagnosis occurs in most cases in the third to fifth decade of life. The disease is associated with reduced expectancy of life and high mortality related to cardiovascular and metabolic co-morbidities. (2,3).

The disease results in most cases from a somatotropic pituitary tumor (4), but is rarely associated to neuroendocrine ectopic tumors and uncommon genetic familial syndromes (5,6). The behavior is insidious and the delay in diagnosis may be more than 10 years after the tumor development (7).

The most prevalent clinical manifestations are soft tissue enlargement, organomegaly, and metabolic complications. The cardiovascular disease is related to more than 60% of mortality in acromegalic patients (8). Hypertension occurs in more than 46% of patients with acromegaly and a higher frequency of classic and non-classic cardiovascular risk factors was described (9,10).

The articular manifestations are frequent and may be present as the earliest symptom of acromegaly (11). Arthropathy can affect both axial and peripheral joints; the most involved are hips, shoulders, knees, hands, and elbows. It is frequently irreversible despite treatment, and may contribute to decreased quality of life (Qol) (12). Musculoskeletal impairment is related to articular damage and its prevalence and severity worsens with the duration of uncontrolled disease, resulting in significant physical disability (13).

Some studies compared the quality of life in patients with several types of pituitary tumors, treated for long periods of time, using questionnaires to evaluate Qol, anxiety and depression. The authors concluded that patients treated for acromegaly reported more impairment in physical ability and more pain compared to patients treated for nonfunctioning macroadenomas and prolactinomas (14). The questionnaire SF-36 has been described as an important tool to evaluate the self-reported quality of life, and may be useful in patients with acromegaly (15-17).

The impairment in quality of life in acromegalic patients may be related to depression, poor self-image, pain, mood swings, impaired physical activity and mental health (15,18). This study evaluated postural defects, physical disability in daily life activities, and the consequences in quality of life in a cohort of Brazilian acromegalic patients.

AIM OF THIS STUDY

The aims of this study were to describe the impairment in physical ability for daily life activities and functioning, and compare it with the quality of life and its relation with the type of treatment and activity of the disease in acromegalic patients.

SUBJECTS AND METHODS

This is a cross-sectional, case series study that enrolled 42 patients with confirmed diagnosis of acromegaly (19,20), recruited from outpatient clinics of the Neuroendocrine Unit of the University Hospital of Brasilia. Before beginning the study, a structured anamnesis, medical record review, physical evaluation of each participant were put together to document symptoms, co-morbidities, current medications, and previous treatments. All patients were submitted to GH and IGF-1 determinations, using standardized chemiluminescence methods (Immulite 2000-IS 98/574). The patients were categorized by gender, tumor size and invasiveness, previous treatments (surgery, radiotherapy, medical treatment), and activity of disease (controlled and not controlled). All patients answered specific questionnaires to evaluate the level of physical activity and quality of life. All procedures used in this study were in accordance with the resolution 196/96 from the Brazilian Ministry of Health, and were approved by the ethics committee from our institution. All patients signed an informed consent form before the inclusion in the study.

Evaluation of level of physical activity and quality of life

The level of physical activity was evaluated by the International Physical Activity Questionnaire (IPAQ 6- short-form), which measures the weekly time spent on physical activity, from mild to vigorous intensity, in different contexts of life, such as work, housekeeping, transportation, and leisure (21).

The Qol was evaluated by The Medical Outcome Study Questionnaire Short Form (SF-36), which is a dimensionless questionnaire to measure generic quality of life, translated and validated for Brazil (18). This questionnaire is composed of 36 items, grouped in eight health domains: functional capacity, physical aspects, pain, general health, vitality, social functioning, emotional aspects and mental health, and self-reported health status (18,22).

Clinical anamnesis and evaluation of pain

Clinical anamnesis was performed and an interview in the form of a questionnaire was used to assess the patients' perception of the presence and intensity of headaches and osteoarticular pain. In this instrument, a map demonstrating a human figure to show sites of discomfort by a Visual Analogue Scale for pain was presented to each patient (23). All patients were photographed in front of a white background, at a distance of 3 meters, in anterior, posterior, right, and left position as proposed by Kendall (24). All patients were using bathing suits, and were in orthostatic position with the body relaxed. The data was inserted in the software Physical Test 6.3-Terrazul.

Statistical analysis

Student's t test was performed for the comparative analysis of quantitative variables. Fisher exact test was used to compare frequencies and determine associations between categorical variables. The distributions of all continuous variables were reviewed for normality using the Kolmogorov-Smirnov test. Relationships between continuous variables were accessed by Spearman Rank or Pearson correlations. All statistical analyses were conducted using the Statistical Package for Social Sciences (SPSS 17.0) and p values < 0.05 were considered statistically significant.

RESULTS

Characteristics of the sample

The group was composed of 22 women and 20 men aged 53.63 ± 14.3 and 46.35 ± 13.18 years old, respectively. The delay between the first symptoms and diagnosis for the whole cohort was 5.43 years, but no statistically significant differences were found between genders (p = 0.92). The women presented a tendency to have higher mean age at diagnosis than men at the inclusion in the study, but no statistical difference was found (Table 1).

Tumor size

By the time of diagnosis, 89.4% of women had macroadenomas (17.05 mm; CI 95% 12.77-21.33), 36.8% with supra and parasellar invasion to cavernous sinus and carotids (Table 2). In men, 13.04% had microadenomas and the frequency of invasive macroadenomas was 43.47% (21.35 mm; CI 95% 16.52-26.18) (p = 0.18 calculated by test t for difference between genders).

Frequency of symptoms reported at the diagnosis

The frequency of symptoms was categorized by gender (Table 3). Enlargement of soft tissue was the most prevalent complaint in both genders. Arthralgia was present in 84.21% of women and 82.61% of men. Sudoresis and cephalea were very frequent, with no statistically significant differences between genders.

Treatment before the inclusion in the study

All patients were submitted to previous treatments, 76.19% were submitted to one surgery, 23.6% to two surgeries, and 34.37% of the operated patients were submitted to further radiotherapy. Primary treatment with somatostatin analogs was prescribed to 23.80% of patients and 11.30% of them was treated by combined cabergoline and octreotide.

Metabolic control at inclusion

Considering the current criteria for cure and control of Acromegaly (19,20), 26.32% of women and 4.35% of men were considered cured, 68.42% of women and 60.87% of men were considered controlled by medical treatment (p = 0.85), and the other patients were considered with uncontrolled disease, despite the previous and current treatments as surgery, radiotherapy, and somatostatin analogs (p = 0.11).

Distribution, frequency and intensity of pain symptoms

More than 80% of patients complained of arthralgia by time of inclusion in the study. In men, the most common sites of pain were the knees (73%), spine (47%), hands and wrists (40%). Most of the women presented multiple sites of pain. The most frequent site was the spine (47% lumbar, and 53% thoracic and cervical segments). The intensity of pain was evaluated by a Visual Analogue Scale and was reported as intense by 33.3% of women and 22.2% of men, moderate by 46.7% of women and 48.1% of men, and mild in 20% of women and 29.6% of men. Pain of severe intensity was reported more frequently on shoulders and spine. The frequency of pain was described as 3 to 5 days per week, in 53.3% of women and 7.4% of men, but 44.4% of men reported daily pain. There was no association between severity of pain and number of surgeries (r = 0.25, p = 0.19), or time to achieve metabolic control (r = 0.01, p = 0.08).

Postural defects

The analysis of the frequency of postural defects showed that 53% of men and 45% of women presented Genu varus, and Genu valgus was observed in 18% of women and 9% of men (Figure 1). Spine deviations (scoliosis, kyphosis or lordosis) were noted on 90% of patients, and 80% presented more than two deviations as asymmetry, scoliosis, cervical or lumbar lordosis, or hyperkyphosis (Figure 2). It was noted that 58% of patients had abdominal protrusions. Shoulder deviations were frequent, and more than two deviations (unilateral or bilateral asymmetry, internal rotation) were observed in 35% of men and 45% of women (Figure 3). There was no correlation between postural defects and disease activity (r = 0.6 p = 0.12), nor between postural defects and time of exposure to growth hormone hypersecretion (r = 0.3 p = 0.47).

Level of physical activity and quality of life

The level of Physical Activity is expressed by weekly time spent on physical activity, from mild to vigorous intensity, in different contexts of life, and was compared with functional capacity score and emotional aspects. In patients with intermediate or high levels of physical activity, we observed a tendency to present higher scores on SF-36 (Table 4), concerning the domains social functioning (75 CI 57.3-92.6), general health (75.5 CI 60.4-90.5), and mental health (70 CI 57.8-82.1), although no significant statistical differences were observed comparing to patients with low physical activity level (p = 0.23, p = 0.11, p = 0.62, respectively).

Table 5

The scores obtained on SF-36 domains were compared with the normal population, and were lower than Jenkinson and cols. data for all domains (35). In Role Physical and Pain, the study population obtained scores 56.67 ± 40.44 and 55.67 ± 23.59, but previously published data showed that in the healthy population, the scores were respectively 80.1 ± 34,9 and 84.8 ± 31.3 (Table 6). Patients with intermediate or high levels of physical activity frequently reported pain in anamnesis, but presented a tendency to have higher mean score in the domain pain on SF-36 (65.5, 48.61 ± 82.39) than patients with mild level of physical activity (52.27, 41.60 ± 62.95) (p = 0.06).

Domains of SF-36 categorized by level of disease activity

The patients were categorized in two groups by the level of activity of disease: controlled, when GH and IGF-1 were normal for age and gender; and uncontrolled, when GH or IGF-1 were higher than reference ranges. The scores for all domains of SF-36 presented a tendency to be higher in patients with controlled levels of GH and IGF-1, and statistical differences were found in the domains Role Physical (p = 0.02), Pain (p = 0.03), Vitality (p = 0.02), Role Emotional (p = 0.03) (Figure 4).

DISCUSSION

This is an original study evaluating the severity of impairment of daily life activities and clinical aspects in patients with acromegaly. The data showed a high percentage of postural defects in one or more regions in this cohort of patients. The patients reported pain in different muscle and joint groups and the most affected regions were knees and upper spine. The complaints about pain were daily in almost half of patients, and were proportional and more severe in patients with higher levels of physical activity. These results are in agreement with other authors and may be related to the overload in joints that may worsen previous articular disease (16,17,25).

The assessment of perception of the presence and intensity of pain was previously evaluated by a Visual Analogue Scale of discomfort, in other groups of subjects without chronic diseases, as healthy students (29), and women (31) submitted to mild or intermediate and high levels of physical activities. The group of acromegalic patients in our study reported multiple sites of discomfort, and also greater intensity of pain than normal subjects published in other studies (24,27,31).

The chronic exposure to GH oversecretion can be associated with osteoarticular damage and may lead to disability in daily life activities (DLA), with consequences in time spent on physical activities and quality of life. The patients evaluated in this study presented lower level of physical activities than age-matched control subjects, and data published in elderly populations. The problem can be worsened by the daily life activities, with constant changes in posture and the adoption of antalgic positions, postural errors and habits over time (32,33).

The pathogenesis of arthropathy in acromegaly may involve two mechanisms: initial endocrine and subsequent mechanical changes (12,13). At the initial stage, GH and IGF-1 lead to hyperfunction of articular chondrocytes and increased matrix synthesis, resulting in growth of periarticular structures. Synovial hypertrophy further exacerbates the abnormal mechanical loading in the joints, which is reversible by hormone control. In advanced cases, the ulceration of the joint cartilage promotes the osteoarthritis, which cannot be improved by GH and IGF-1 normalization (26).

Some authors have previously described that the influence of GH and IGF-1 in the osteoarticular system exposes the morphofunctional structure of the individual to possible hazards (16,17). In this study, the presence and severity of physical disability and pain were not correlated to initial GH and IGF-1 levels, time of previous exposure to GH excess, nor to metabolic control by the inclusion. A recent study investigated the clinical course of arthropathy and its relationship with radiographic progression in long-term controlled acromegaly patients, and suggested that joint function deteriorates during prolonged follow-up, despite biochemical control of the disease (36). It is currently unknown whether GH and IGF-1 control can reverse arthropathy in patients with acromegaly. However, improvement in signs and symptoms was demonstrated (34).

In our cohort, the patients considered controlled, with normal a normal age-adjusted IGF-1, presented higher scores in SF-36 in physical and emotional domains compared with patients with persistent hypersomatotrophism despite previous treatments and use of somatostatin analogs or dopamine agonists. These findings suggest benefits of metabolic control in quality of life. Studies have been published seeking to demonstrate that the improvement or possible extinction of chronic pain could improve the quality of life in different diseases (14,25,32). Other authors described that the impairment of quality of life may persist despite successful treatment in endocrine diseases (17,36).

In conclusion, the impairment in physical ability for daily life activities was shown in our study, and was not related to the type of treatment and activity of the disease in acromegalic patients. The data suggests benefits of acromegaly disease control in quality of life, based on better scores regarding emotional and physical domains of SF-36. Many unanswered questions about the benefits of controlled compared with uncontrolled disease regarding reversibility of articular co-morbidities have to be better evaluated in further studies.

Acknowledgements: we would like to acknowledge the Instituto and Laboratorio Sabin-Brasilia, that performed all hormonal tests and UniCEUB for all support.

Received on Nov/2/2012

Accepted on Mar/25/2013

Disclosure: no potential conflict of interest relevant to this article was reported.

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Datas de Publicação

• Publicação nesta coleção
  12 Nov 2013
• Data do Fascículo
  Out 2013

Histórico

• Recebido
  02 Nov 2012
• Aceito
  25 Mar 2013