The association between treatment and systemic inflammation in acromegaly

Growth Horm IGF Res. 2021 Apr-Jun:57-58:101391. doi: 10.1016/j.ghir.2021.101391. Epub 2021 Apr 30.

Abstract

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.

Keywords: Acromegaly; Cardiovascular disease; Endothelial dysfunction; IGF1; Inflammation.

MeSH terms

  • Acromegaly / metabolism
  • Acromegaly / physiopathology
  • Acromegaly / therapy*
  • Adenoma / metabolism
  • Adenoma / physiopathology
  • Adenoma / therapy*
  • Adult
  • Aged
  • Antineoplastic Agents, Hormonal / therapeutic use*
  • Carotid Intima-Media Thickness
  • Cytokines / metabolism
  • Dopamine Agonists / therapeutic use
  • E-Selectin / metabolism
  • Endothelium, Vascular / physiopathology*
  • Female
  • Growth Hormone-Secreting Pituitary Adenoma / metabolism
  • Growth Hormone-Secreting Pituitary Adenoma / physiopathology
  • Growth Hormone-Secreting Pituitary Adenoma / therapy*
  • Human Growth Hormone / analogs & derivatives
  • Human Growth Hormone / therapeutic use
  • Humans
  • Inflammation / metabolism*
  • Inflammation / physiopathology
  • Interleukin-18 / metabolism
  • Male
  • Matrix Metalloproteinase 2 / metabolism
  • Middle Aged
  • Neurosurgical Procedures*
  • Pulse Wave Analysis
  • Radiotherapy*
  • Somatostatin / analogs & derivatives
  • Treatment Outcome
  • Vascular Cell Adhesion Molecule-1 / metabolism

Substances

  • Antineoplastic Agents, Hormonal
  • Cytokines
  • Dopamine Agonists
  • E-Selectin
  • IL18 protein, human
  • Interleukin-18
  • SELE protein, human
  • Vascular Cell Adhesion Molecule-1
  • Human Growth Hormone
  • Somatostatin
  • MMP2 protein, human
  • Matrix Metalloproteinase 2
  • pegvisomant