Too Many Inflammatory Molecules Increase Risk of Heart Disease in Subclinical Cushing’s, Study Shows

High levels of inflammatory cytokines — molecules that mediate the body’s immune response — may increase the risk of metabolic and heart disease in subclinical Cushing’s syndrome patients, a retrospective study shows.

The study, “Adipokine and cytokine levels in patients with adrenocortical cancer, subclinical Cushing’s syndrome and healthy controls,” was published in Steroids.

Cushing’s syndrome is a medical condition caused by the excessive production of the hormone cortisol by the adrenal glands, which sit atop the kidneys.  The disease can be caused by external factors, including some medications, or by tumors that cause an excessive production of cortisol.

When the levels of cortisol rise to unhealthy levels — a condition known as hypercortisolism — patients start gaining weight and experience fat accumulation around the torso (central obesity), which increases  patients’ risks of heart disease and other medical complications.

Previous studies demonstrated that fat accumulation is linked with the production of inflammatory molecules, including interleukin 6 (IL6), tissue necrosis factor alpha (TNFα), resistin, and monocyte chemoattractant protein 1 (MCP-1). It also raises the levels of adipokines, which are cytokines produced the fat tissue, such as leptin and adiponectin.

However, the role of inflammatory cytokines and adipokines in patients with subclinical Cushing’s syndrome (SCS) and adrenocortical cancer (ACC)  a rare type of tumor in the adrenal glands that causes hypercortisolism in nearly half of the patients — never had been addressed properly.

Subclinical Cushing’s syndrome happens when a patient has hypercortisolism, but lacks other Cushing’s symptoms.

In this study, researchers aimed to evaluate the levels of inflammatory cytokines and adipokines in SCS and ACC patients. The retrospective study included 20 SCS and seven ACC patients, together with 18 age-, gender-, and weight-matched healthy individuals used as controls.

Researchers then evaluated cortisol activity and the levels of cytokines (IL6, TNFα, resistin and MCP1) and adipokines (leptin and adiponectin) present in the patients’ serum.

Overall, SCS patients had higher levels of inflammatory cytokines and adipokines — although statistically significant differences were observed only for IL6 and TNFα — in comparison with healthy control subjects. Conversely, the levels of adiponectin were significantly lower in SCS patients compared to healthy controls.

Importantly, serum concentrations of cytokines and adipokines in SCS patients seemed to be independent of the patients’ body mass index (BMI) and were not associated with other medical conditions such as diabetes mellitus and hypertension.

“In SCS even mild but chronic excessive levels of glucocorticoids lead to central adipose tissue accumulation. This, in turn, is connected with an adverse adipokine and cytokine profile that comprises an additional factor for metabolic complications in SCS patients,” researchers proposed.

Finally, in ACC patients the levels of IL6, TNFα, and MCP1 were significantly higher in comparison with controls.

“Higher concentrations of TNFα and IL6 may result in the reduction of adiponectin in this group of patients and indirectly affect tumor proliferation,” the authors said.

Altogether, these findings indicate that the excessive production of cytokines and adipokines by fat tissue have a direct impact in metabolism and may contribute to increase SCS patients’ susceptibility to develop metabolic and heart disease.