Quality of Life in Acromegalic Patients during Long-Term Somatostatin Analog Treatment with and without Pegvisomant

Context: Control of disease activity in acromegaly is critical, but the biochemical definitions remain controversial. Objective: To compare traditional and novel biomarkers and health status in patients with acromegaly treated with either surgery alone or somatostatin analog (SA). Design and methods: Sixty-three patients in long-term remission based on normalized total IGF1 levels after surgery alone (nZ36) or SA (nZ27) were studied in a cross-sectional manner. The groups were comparable at diagnosis regarding demographic and biochemical variables. Each subject underwent 3 h of serum sampling including a 2-h oral glucose tolerance test (OGTT). Health status was measured by two questionnaires: EuroQoL and Acrostudy (Patient-assessed-Acromegaly symptom questionnaire (PASQ)). Results: Total and bioactive IGF1 (mg/l) levels were similar (total: 185G10 (SA) versus 171G8 (surgery) (PZ0.28); bioactive: 1.9G0.2 vs 1.9G0.1 (PZ0.70)). Suppression of total and free GH (mg/l) during OGTT was blunted in the SA group (total GH nadir : 0.59G0.08 (SA) versus 0.34G0.06 (surgery) (PZ0.01); free GH nadir : 0.43G0.06 vs 0.19G0.04 (P!0.01)). The insulin response to OGTT was delayed, and the 2-h glucose level was elevated during SA treatment (PZ0.02). Disease-specific health status was better in patients after surgery (PZ0.02). Conclusions: i) Despite similar and normalized IGF1 levels, SA treatment compared with surgery alone was associated with less suppressed GH levels and less symptom relief; ii) this discordance may be due to specific suppression of hepatic IGF1 production by SA; iii) we suggest that biochemical assessment during SA treatment should include both GH and IGF1.

Section: Discussionsupporting

confidence: 91%

Conventional and novel biomarkers of treatment outcome in patients with acromegaly: discordant results after somatostatin analog treatment compared with surgery

Rubeck

Madsen²,

Andreasen³

et al. 2010

“…Indeed, there is evidence to suggest that combination therapy is superior to monotherapy with LA-SMSA in terms of glucose homeostasis (52) and disease-specific QoL (53). The latter observation also suggests that assessment of QoL could be considered as routine practice during medial therapy.…”

Section: Discussionmentioning

confidence: 99%

“…Thus, low-dose PEGV treatment improved the signs and symptoms of 'extra-hepatic acromegaly' without impacting hepatic IGF1 production consistent with our hypothesis of extrahepatic acromegaly. It is noteworthy that the largest improvement in QoL was observed in patients who also responded to PEGV with alleviation of fluid retention (53). It remains to be studied whether the same favourable effects could be obtained by an increase in the dose of LA-SMSA.…”

Section: What About Combining Smsa and Pegvmentioning

confidence: 97%

“…To date, the focus in these reports has been on patients with an insufficient response to LA-SMSA (51, 52), but we believe that combination treatment may offer benefit to other patients. The strongest evidence for this is presented by Neggers et al (53). They hypothesized that weekly administration of 40 mg PEGV could improve QoL and metabolic parameters in acromegalic patients with normal age-adjusted IGF1 concentrations during LA-SMSA treatment.…”

Section: What About Combining Smsa and Pegvmentioning

confidence: 99%

See 1 more Smart Citation

Hypothesis: Extra-hepatic acromegaly: a new paradigm?

Neggers

Kopchick

Jørgensen

et al. 2011

Medical treatment of acromegaly with long-acting somatostatin analogs (LA-SMSA) and the GH receptor antagonist, pegvisomant (PEGV), has made it possible to achieve normal serum IGF1 concentrations in a majority of patients with acromegaly. These two compounds, however, impact the GH-IGF1 axis differently, which challenges the traditional biochemical assessment of the therapeutic response. We postulate that LA-SMSA in certain patients normalizes serum IGF1 levels in the presence of elevated GH actions in extra-hepatic tissues. This may result in persistent disease activity for which we propose the term extra-hepatic acromegaly. PEGV, on the other hand, blocks systemic GH actions, which are not necessarily reliably reflected by serum IGF1 levels, and this treatment causes a further elevation of serum GH levels. Medical treatment is therefore difficult to monitor with the traditional biomarkers. Moreover, the different modes of actions of LA-SMSA and PEGV make it attractive to use the two drugs in combination. We believe that it is time to challenge the existing concepts of treatment and monitoring of patients with acromegaly.

“…This was interpreted as indicative that 'normal' circulating GH and IGF-I may not reflect 'control' or 'cure' in all body tissues. In fact, despite no change in circulating IGF-I levels, patients perceived improvement in QoL scores and subjective well-being, which was correlated with the physical domain of AcroQoL and loss of body water and weight, suggesting that their muscles were less exposed to excessive GH/IGF after adding pegvisomant (37).…”

Section: Acromegalymentioning

confidence: 96%

MANAGEMENT OF ENDOCRINE DISEASE: Quality of life tools for the management of pituitary disease

Webb

Crespo

Santos

et al. 2017

Background: In the last few years, quality of life (QoL) has become an outcome measure in patients with pituitary diseases. Objective: To describe the available data on QoL impairment evaluated with questionnaires in patients with pituitary diseases. Design: Critical review of the pertinent literature and pragmatic discussion of available information. Methods: Selection of relevant literature from PubMed and WOK, especially from the last 5 years and comprehensive analysis. Results: QoL is impaired in all pituitary diseases, mostly in acromegaly and Cushing's disease (similar to other causes of Cushing's syndrome), but also in non-functioning pituitary adenomas and prolactinomas, especially in the active phase of the disease. Nevertheless, even after endocrine 'cure', scores tend to be below normative values, indicative of residual morbidity after hormonal control. The presence of hypopituitarism worsens subjective QoL perception, which can improve after optimal substitution therapy, including recombinant human growth hormone, when indicated. Conclusions: To improve the long-term outcome of pituitary patients, helping them to attain the best possible health, it appears desirable to include subjective aspects captured when evaluating QoL, so that the affected dimensions are identified and if relevant treated. Additionally, being aware that treatment outcome may not always mean complete normalisation of physical and mental issues related to QoL can be a first step to adaptation and conforming to this new status.