Predictors of Quality of Life in 165 Patients With Acromegaly

Results From a Single-Center Study

Ilonka Kreitschmann-Andermahr, MD; Michael Buchfelder, MD; Bernadette Kleist, CN; Johannes Kohlmann, MD; Christa Menzel, RN; Rolf Buslei, MD; Maria Kołtowska-Häggström, MD; Christian Strasburger, MD; Sonja Siegel, CP


Endocr Pract. 2017;23(1):79-88. 

In This Article


On average, 7.1 years after diagnosis and subsequent treatment of acromegaly, we found decreased physical and mental QoL in roughly one-third of the investigated patients. Other psychosocial impairments, such as moderate to severe depressive symptoms in the BDI-II and above-average to extreme embitterment in the BEI, were present in 16.6 and 18.5% of patients, respectively. This magnitude of embitterment, in comparison to the general population, places treated patients with acromegaly on the same level as patients with rheumatic disease who were receiving disability pensions.[19]

A number of factors strongly influencing different QoL dimensions in patients with acromegaly were identified in the regression analyses, some of which were surprisingly consistent for the different constructs studied. The physical QoL component, as measured by SF-36 PSC score, was explained, in almost 40% of patients, by the following factors: delay in diagnosis, BMI, number of doctors visited, and age at diagnosis. The SF-36 MCS score and the BDI-II score were strongly explained by similar factors (number of doctors visited, previous radiotherapy, and age). Furthermore, we found that unemployment was a risk factor for depression, but not for the mental component of QoL. Embitterment was predicted by similar factors as the other psychological measures (mainly number of doctors visited). Radiotherapy did not feature as a predictor in the SF-36 PCS score and embitterment status, but featured in both mental measures (SF-36 MCS and BD-II).

Similarly to our previous results from a small patient group,[8] in the present study, a delay in the provision of services emerged as a paramount factor predicting psychosocial impairment and decreased QoL in patients with acromegaly. We hypothesize that this finding could be explained, on the one hand, by the progression of comorbidities of acromegaly, such as changes in appearance, heart disease, and osteoarthritis, which develop with prolonged cumulative exposure to inadequately high GH and IGF-1 levels.[20] Additionally, other studies have shown that continued patient concern about their appearance and musculoskeletal problems reduce QoL in patients with acromegaly.[21–23] On the other hand, 18.5% of all investigated patients experienced above-average to extreme embitterment according to the BEI, which was predicted by the number of doctors visited. This result strongly indicates that the prolonged diagnostic process is indeed perceived as an unjust and humiliating life event, leading to adverse psychological sequelae. These results have profound implications for the quality of medical care in acromegaly. Efforts must be made to integrate the provision of healthcare services, in a way that enables patients to receive optimal, holistic care (including psychological assessment), irrespective of the disease stage or the specialist they first approach.

The negative effects of increased BMI and advanced age on physical well-being are expected and have been described before.[24] A good acromegaly service should, therefore, liaise closely with weight-loss services and take into account the general age-related decline in physical functioning. On the other hand, we showed that older patients experienced a better mental QoL. A similar result, albeit in a different field, was reported by Shamaskin and colleagues,[25] who found (in a large multicenter study) that older patients (>65 years) reported a better QoL, psychological adjustment, and adherence 5 years after heart transplantation. This observation is likely to reflect the higher expectation of what constitutes a happy, and fulfilling life in younger patients and/or a better adjustment to illness-related disability in older ones, which can be supposed to be a result of the response-shift phenomena.[26] It is important to recognize this age-related susceptibility and offer appropriate, targeted support to younger patients.

Affective symptoms are well-recognized side effects of cancer radiation therapy and appear independently of any cancer-related psychiatric comorbidity per se.[27] We observed a similar effect in patients receiving radiotherapy for a pituitary adenoma. Although this could be supporting a direct causative link between radiotherapy and depression, we also believe this to be due to a longer diagnostic process among patients receiving radiotherapy. Based on evidence gained by animal studies, it has been recently proposed that postcancer depression stems from a direct biologic effect, namely the inhibition of adult neurogenesis in the hippocampus through radiotherapy and chemo-therapy.[28] As modern radiotherapy regimens generally aim to spare the hippocampus,[29] and recent evidence shows no difference in number of white matter lesions and brain atrophy in patients irradiated for pituitary adenoma,[30] we do not believe this to be an exclusive explanation for our results. In any case, our findings underscore the necessity of openness in patient communication about potential psychiatric morbidity, as well as the provision of psychological and psychiatric support for recipients of radiotherapy.

Unemployment is a well-recognized contributory factor in the pathogenesis of depression,[31] frequently acting as a perpetuating factor in affected patients. Although it is a problem that is difficult to tackle within the framework of a medical service, practitioners and social workers should be well aware of the broader services for keeping or regaining employment available to patients, and should point patients in the right direction if required. Nonetheless, tackling other, more directly 'medical' issues, may yield beneficial health outcomes and lead to improved patient engagement with the social provisions available.

Interestingly, although IGF-1 levels are a well-recognized marker of mortality in acromegaly,[2] our data from the same cohort presented elsewhere suggest that biochemical control as per IGF-1 concentration does not impact QoL outcomes.[32] Broadly similar results were obtained previously, with the exception of a better psychological measure of 'appearance,' which was significantly worse in the group with elevated posttreatment IGF-1 levels.[33] A head-to-head, prospective, randomized, double-blind study demonstrated superiority of pasireotide over octreotide in the medical therapy of acromegaly but failed to show improvement in QoL with better disease control.[34] Some recent results seem to contradict this, suggesting that objectively measured disease control (e.g., IGF-1 levels) correlated to AcroQoL score.[35] However, our current evidence points to other factors being the important determinants of QoL. This is a sobering reminder that a clinically favorable outcome may still be associated with a poor outcome from the patient's perspective, if the broader context, like diagnostic delay, is not addressed appropriately.

The methods we employed led to several limitations. First, questionnaire studies are always liable to selection and reporting bias. Second, the present study was conducted at a large tertiary neurosurgical referral center with a nationwide catchment area; such a set-up provides the advantage of a large patient database but the disadvantage of the inability to track patients who relocated postsurgery and did not provide new contact details. Third, the stepwise regression model we employed resulted in the inclusion of two distinct age-related variables: age at study entry, and age at diagnosis. The SF-36 PCS score was predicted by age at diagnosis, whereas the SF-36 MCS, BDI-II and BEI scores were predicted by age at study entry. We considered these variables to be grossly interrelated; however, it should be noted that these variables represent different time points and thus should be interpreted as distinct entities. Finally, the study only included patients who had undergone neurosurgery—this criterion, however, represents the majority of patients with acromegaly.

Our results have identified several worthwhile avenues for future research, of which we feel that embitterment is of particular importance. In particular, a longitudinal study to prospectively assess the degree of embitterment throughout the patient's progress would shed light on the dynamic aspect of embitterment, and the effect intervention/s may have upon it.