The association between treatment and systemic inflammation in acromegaly,Growth Hormone and IGF Research

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The association between treatment and systemic inflammation in acromegaly
Growth Hormone and IGF Research ( IF 1.6 ) Pub Date : 2021-04-30 , DOI: 10.1016/j.ghir.2021.101391
T L C Wolters ₁ , C D C C van der Heijden ₂ , O Pinzariu ₃ , B T P Hijmans-Kersten ₄ , C Jacobs ₁ , C Kaffa ₅ , A Hoischen ₆ , M G Netea ₇ , J W A Smit ₁ , D H J Thijssen ₈ , C E Georgescu ₉ , N P Riksen ₁ , R T Netea-Maier ₁

Affiliation

Department of Internal Medicine, Radboud University Medical Center, Nijmegen, the Netherlands.
Department of Internal Medicine, Radboud University Medical Center, Nijmegen, the Netherlands; Radboud Institute of Molecular Life Sciences (RIMLS), Radboud University Medical Center, Nijmegen, the Netherlands.
6(th) Department of Medical Sciences, Department of Endocrinology, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania.
Radboud Institute for Health Sciences, Department of Physiology, Radboud University Medical Center, Nijmegen, the Netherlands.
Centre for Molecular and Biomolecular Informatics (CMBI), Radboud Institute for Molecular Life Sciences, Radboud University Medical Centre, Nijmegen, the Netherlands.
Department of Internal Medicine, Radboud University Medical Center, Nijmegen, the Netherlands; Department of Human Genetics, Radboud University Medical Center, Nijmegen, the Netherlands.
Department of Internal Medicine, Radboud University Medical Center, Nijmegen, the Netherlands; Department for Genomics & Immunoregulation, Life and Medical Sciences Institute (LIMES), University of Bonn, Bonn, Germany.
Radboud Institute for Health Sciences, Department of Physiology, Radboud University Medical Center, Nijmegen, the Netherlands; Research Institute for Sport and Exercise Sciences, Liverpool John Moores University, United Kingdom.
6(th) Department of Medical Sciences, Department of Endocrinology, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania; Endocrinology Clinic, Cluj County Emergency Clinical Hospital, Cluj-Napoca, Romania.

Objective

Acromegaly is characterized by an excess of growth hormone (GH) and insulin like growth-factor 1 (IGF1), and it is strongly associated with cardiovascular diseases (CVD). Both acute and long-lasting pro-inflammatory effects have been attributed to IGF1. Previous results suggest the presence of systemic inflammation in treated patients. Here we assessed the association between treatment of acromegaly, systemic inflammation and vascular function.

Design

Ex vivo cytokine production and circulating inflammatory markers were assessed in peripheral blood from treated and untreated acromegaly patients (N = 120), and compared them with healthy controls. A more comprehensive prospective inflammatory and vascular assessment was conducted in a subgroup of six treatment-naive patients with follow-up during treatment.

Results

Circulating concentrations of VCAM1, E-selectin and MMP2 were higher in patients with uncontrolled disease, whereas the concentrations of IL18 were lower. In stimulated whole blood, cytokine production was skewed towards a more pro-inflammatory profile in patients, especially those with untreated disease. Prospective vascular measurements in untreated patients showed improvement of endothelial function during treatment.

Conclusions

Acromegaly patients are characterized by a pro-inflammatory phenotype, most pronounced in those with uncontrolled disease. Treatment only partially reverses this pro-inflammatory bias. These findings suggest that systemic inflammation could contribute to the increased risk of CVD in acromegaly patients.

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