The Pathogenetic Role of Cortisol in the Metabolic Syndrome: A Hypothesis

Abstract

MetS shares many characteristics of CS, and cortisol might play a role in the development of MetS at both a central and a peripheral level.

Effect of Age, Season, Body Condition, and Endocrine Status on Serum Free Cortisol Fraction and Insulin Concentration in Horses

“…Body condition significantly impacted free cortisol as anticipated and as described in people and rodents,16, 17, 34 with significantly increased free cortisol concentration in healthy overweight/obese control horses. The data herein also provide support for our second hypothesis that FCF is increased in horses with endocrine disease and associated with hyperinsulinemia, with a significant, almost 2‐fold increase in FCF, but not total cortisol observed in animals with PPID as compared to healthy age‐matched horses.…”

“…The data herein also provide support for our second hypothesis that FCF is increased in horses with endocrine disease and associated with hyperinsulinemia, with a significant, almost 2‐fold increase in FCF, but not total cortisol observed in animals with PPID as compared to healthy age‐matched horses. Free cortisol fraction was also similarly and significantly increased in horses and ponies with endocrine disease (PPID or EMS) and concurrent ID characterized by hyperinsulinemia, and FCF and insulin were significantly and positively correlated in these hyperinsulinemic animals as anticipated and as described in people 16, 17, 20, 34, 35…”

“…Tissue cortisol metabolism also appears to be altered in obesity. Many tissues, including adipose tissue, can convert the inactive cortisol metabolite cortisone back to biologically active cortisol via the enzyme 11‐β‐hydroxysteroid dehydrogenase type 1 (11‐β‐HSD1), resulting in increased tissue and intracellular levels of cortisol 34, 42. Rodent models and human studies both demonstrate 11‐β‐HSD1 overexpression in adipose tissue and associations between increases in local and systemic cortisol and development of insulin dysregulation and diabetes in the Metabolic Syndrome in people 43, 44, 45, 46, 47…”

“…For instance, increased total plasma cortisol is a typical finding in people with Cushing's Disease68, 69 but is not commonly observed in horses and ponies with PPID 2. Further, atherosclerosis and related cardiovascular disease (ie, stroke, myocardial infarction) are a key aspect of Metabolic Syndrome in people and are associated with increases in total and free cortisol,34, 70 but these clinical abnormalities are not appreciated in EMS 1, 31. In EMS, cardiovascular pathology resulting from vascular endothelial dysfunction might manifest as laminitis,71 but other mechanisms, such as insulin‐mediated overstimulation of the insulin‐like growth factor 1 receptor leading to lamellar hypertrophy and weakening, might also contribute to the development of laminitis in EMS 72.…”

Glucocorticoid treatment and endocrine pancreas function: implications for glucose homeostasis, insulin resistance and diabetes

“…Given GCs' strong capacity to counteract the action exerted by insulin and raise blood sugar levels, it is not surprising that IR and glucose intolerance is a concern in patients with Cushing's syndrome and disease (endogenous GC overproduction) and in patients prescribed GC-based therapy for immunomodulatory purposes (Raú l Ariza-Andraca et al 1998). In addition, hypercortisolaemic conditions share many characteristics with metabolic syndrome, a cluster of abnormalities including hyperglycaemia, abdominal obesity, dyslipidaemia and hypertension (Anagnostis et al 2009). Low-dose GC therapy is considered when the daily dose is !7.5 mg prednisolone or equivalent (van der Goes et al 2010).…”