Excess mortality was found in this nationwide cohort of patients with acromegaly, mainly related to circulatory and malignant diseases. Although still high, mortality significantly declined over time. This could be explained by the more frequent use of pituitary surgery, decreased prevalence of hypopituitarism and the availability of new medical treatment options.

In neutrophils, coupling of chemoattractants to their cell surface receptor at low temperature (<15°C) leads to receptor deactivation/desensitization without any triggering of the superoxide anion-generating NADPHoxidase. We show that the deactivated formyl peptide receptors (FPRs) can be reactivated/resensitized by the cytoskeleton-disrupting drug cytochalasin B. Such cytoskeleton-dependent receptor reactivation occurs also with the closely related receptors FPR-like-1 and C5aR but not with the receptors for interleukin-8 and plateletactivating factor. The reactivation state was further characterized with FPR as a model. The signals generated by receptor reactivation induced superoxide production that was terminated in 5-8 min, after which the neutrophils entered a new state of homologous deactivation. FPR antagonists were potent inhibitors of the superoxide production induced by the reactivated receptors, suggesting that the occupied receptors turn into an actively signaling state when the cytoskeleton is disrupted. The signals generated by the reactivated receptor were pertussis toxin-sensitive, indicating involvement of a G-protein. However, no transient elevation of intracellular Ca 2؉ accompanies the NADPH-oxidase activation. This was not due to a general down-regulation of phospholipase C/Ca 2؉ signaling, and despite the fact that no intracellular Ca 2؉ transient was generated, protein kinase C still appeared to be involved in the response. Further, phosphatidylinositol 3-kinase, mitogen-activated protein kinase, and MEK all participated in the generation of second messengers from the reactivated receptors.

The prevalence of comorbidity is high in patients with acromegaly. The most common first-line treatment in acromegalic patients was surgery followed by somatostatin analogues. The annual per-patient cost of acromegaly and its comorbidities was €12 000.

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They state that after publishing the paper, the collaboration between the research parties was continued to further understand the excess mortality that was found among patients with acromegaly in Sweden between 1987 and 2013. During this process, the authors discovered that all standardized mortality ratios (SMRs) in the article were systematically overestimated. The correct SMRs are summarised in Table 6 below. The authors have suggested the following changes to the various sections in their article.