Cardiometabolic Risk in Acromegaly: A Review With a Focus on Pasireotide

Abstract

Acromegaly is a disease due to chronic GH excess and a consequent rise in IGF-1 levels. This rare endocrine condition is associated with metabolic alterations such as hyperglycaemia, dyslipidaemia, and systemic arterial hypertension, which, in addition to GH excess-related cardiovascular changes, play critical roles in increasing cardiovascular risk and mortality rates. Biochemical control of acromegaly, achieved by means of surgical, and/or medical treatment, positively impacts on cardiovascular risk factors and metabolic alterations, reducing overall patient mortality. However, treatment modalities of acromegaly and disease control differently impact on glucose homeostasis and lipid changes, and consequently on cardiometabolic risk. In this regard, pasireotide was shown to significantly influence glucose metabolism. This review summarizes the cardiometabolic consequences of acromegaly and its treatment, focusing on available data around the effects of medical therapy with pasireotide on factors that influence cardiometabolic risk.

Pasireotide—a novel somatostatin receptor ligand after 20 years of use

“…Glucagon-producing alpha cells predominantly express SSTR2, whereas insulinproducing beta cells mainly express SSTR2 and SSTR5. By its high-affinity binding to SSTR5, PAS potently suppresses insulin secretion, whereas the drug's inhibitory effect on glucagon secretion is only modest, PAS does not influence insulin resistance [29,31,32]. Before starting PAS therapy, patients should undergo an assessment of glucose metabolism and, in diabetic patients, anti-diabetic treatment should be initiated or optimized [14,28].…”

Cardiovascular Diseases in Acromegaly: Not Diagnosed What is Not Suspected

“…In this pathophysiological process, immune cells invade the arterial wall and induce expression of adhesion molecules, with subsequent leukocyte adhesion, which creates a pro-inflammatory and pro-atherogenic environment [9]; which together, with hypertensive glomerulopathy, secondary to systemic arterial hypertension, accelerates the glomerular lesion, while at the peripheral level, the destabilization of an atherosclerotic plaque together with inflammatory adhesion cells, precipitates the formation of a thrombus/embolus. Acromegaly has been described as a rare disease, the result of chronic excessive secretion of growth hormone (GH), with subsequent elevation of Insulin-like Growth Factor I (IGF-1) levels [1]. This condition is associated with an increase in morbidity and mortality compared to the general population, without taking into account that this endocrine disorder per se, increases cardiovascular risk by causing metabolic disorders such as hyperglycemia, dyslipidemia and systemic hypertension [2].…”