In our series of patients with acromegaly the prevalence of AIMS questionnaires-derived depression was particularly high (28%). The comparison with data from literature [21] reporting rheumatologic patients without major motor disability, showed a significantly worse psychologic condition in acromegalic subjects. When comparing our patients with those carrying more disabling rheumatological diseases, the only significant difference was observed in comparison with subjects with OA of the hip/knee. This finding, if on the one hand confirms an overall increased depression in our cohort, on the other hand cannot fully clarify whether this is mainly due to the disabling arthropathy or it is independent of it. The first hypothesis is suggested by the strict association between psychological status and the severity of arthropathy emerged in our series. In any case, the report of two suicides among subjects with acromegaly scoring more than 4/10 in AIMS depression questionnaire, even if not significant per-se, requires further investigations in other large cohorts of subjects for longer periods. On a whole these data suggest this questionnaire as an inexpensive tool to screen severe depression in acromegaly.
Apart from the already quoted association of psychological status with arthropathy, the only statistically significant correlation found when evaluating the factors associated with depression and anxiety was female sex. Differently from what we found studying acromegalic arthropathy[4], BMI, standardized IGF1 levels, and diabetes mellitus showed no correlation with anxiety and depression, as measured with our tools, and do not seem to be major determinants of this condition. On the contrary, the lack of association of psychological status with pituitary hormonal defects is possibly due to replacement therapies started in all patients receiving a diagnosis of hypopituitarism. All the results were confirmed adjusting for possible confounders. Our findings showed to be independent from concomitant therapies with SSRI and benzodiazepines. However, given the cross-sectional design of the study, we cannot exclude a role of these treatments in modulating anxiety and depression in patients affected with acromegaly, and prospective studies as well as clinical trials, are needed to provide this information. The adjustment made according to hypogonadism low sex hormone levels (which includes both pathologic hypogonadal status and menopause) did not change our results and the significant difference among sexes. This suggests that the association of female sex with worse depression and anxiety scores is not due to post-menopausal changes. In fact, the interactions between the somatotropic and the gonadal axes are complex, with both a central stimulatory effect and a peripheral liver resistance to GH mediated by estradiol, leading to different hormonal profiles in male and female subjects [23]; also, a different social and psychological impact of the acromegaly-related facial changes could justify this sex gap in anxiety and depression scores.
According to the existing literature, previous treatments represent another factor associated with depression. RT [6, 8] is known to correlate with worse depression scores, probably due to a more severe disease status in patients undergoing this treatment, rather than indicating a direct relationship. Sievers and colleagues also reported that ongoing medical therapy is associated with major depression [6, 8]; however, since there was no adjustment for disease duration, an increased time lapsed from diagnosis in patients still assuming medical therapies could explain this correlation. In our study, we found RT to be significantly correlated only with worse anxiety scores and this association was lost in the multivariate model. This could be explained with a lesser damage to the remaining pituitary using stereotactic technologies and with the minimal number of patients who underwent fractionated RT in our cohort (n = 8).
The evaluation of the impact of depression and arthropathy on QoL in patients with acromegaly showed a strong correlation of both these variables with a worse well-being. The presence of an association between depression and QoL confirms findings of other smaller studies [24]. The strong association of psychologic and articular complications can be due to a bidirectional cause-effect: it is known that chronic pain has a negative effect on mood disorders and, the other way around, depressed patients are more inclined to score higher to pain scales, having a decreased tolerance to pain. More, our data show that, analyzing these variables together, their association with impaired QoL remains significant, probably because each condition has an independent disrupting potential on patients’ well-being. (Fig. 2). The implications of these findings are twofold. Firstly, it is important to assess and monitor the psychological status of patients affected with acromegaly, since they are at risk of incurring in psychopathological symptoms, which have a negative effect on their QoL. Secondly, these findings suggest that psychological factors should be treated during rehabilitation programs. Preliminary studies have evaluated the feasibility and the effects of psychological treatments specifically tailored for patients with acromegaly, but this field of study is still in its infancy [25, 26].
Concluding, we report a high prevalence of depression among patients with acromegaly, which is associated with female sex and especially arthropathy, with which independently impairs patients’ quality of life. Also, considering the finding of suicides among acromegalic subjects with a high AIMS depression score, it is always necessary to investigate the mood and anxiety of patients. Further studies could confirm the usefulness of depression scales in the screening of depression in acromegaly.