Cushing’s syndrome linked to liver fat buildup: Study
High cortisol levels directly tied to metabolic abnormalities
High levels of cortisol in the bloodstream of people with Cushing’s syndrome were directly linked to significant metabolic abnormalities leading to the buildup of fat deposits in the liver, according to a new study from researchers in China.
The researchers noted that liver fat accumulation increases a person’s risk of metabolic conditions, cardiovascular problems, and even death “independently of classic risk factors.”
Thus, “addressing the metabolic effects of elevated cortisol through targeted interventions could improve patient outcomes and reduce the burden of [fatty liver disease] and other metabolic complications,” the team wrote.
Their study, “Impact of cortisol on liver fat and metabolic health in adrenal incidentalomas and Cushing’s syndrome,” was published in the journal Endocrine.
Investigating what factors contribute to liver fat
Cushing’s syndrome is marked by hypercortisolism, or elevated levels of cortisol, a hormone produced by the adrenal glands. Cortisol regulates various body functions, including glucose (blood sugar) metabolism, fat distribution, and stress response.
Both Cushing’s and hypercortisolism can be triggered by several causes, including tumors in the brain’s pituitary gland. This specific form of Cushing’s syndrome, known as Cushing’s disease, is one of the most common. Less frequently, tumors in the adrenal glands or other locations in the body can cause cortisol levels to become excessively high.
Understanding the factors contributing to liver fat is crucial for preventing and managing [liver] conditions.
Elevated cortisol can disrupt metabolic processes and increase fatty deposits in the liver, a condition known as steatosis. It’s formally called metabolic dysfunction-associated steatotic liver disease, or MASLD, which was formerly known as nonalcoholic fatty liver disease, or NAFLD.
“Understanding the factors contributing to liver fat is crucial for preventing and managing these conditions,” the researchers wrote.
To that end, a team of scientists from Fudan University in Shanghai used blood tests and CT scans to assess relationships between cortisol levels, metabolic markers, and fatty liver deposits. Their retrospective study examined data from 59 people with Cushing’s syndrome. CT data were used to calculate the liver-to-spleen ratio (L/S), a marker for liver fat buildup. L/S values lower than 1 indicate the presence of fatty liver.
For comparison, 100 people with mild autonomous cortisol secretion (MACS), a condition marked by subtle elevations in cortisol levels that don’t cause overt symptoms, were assessed. The control group comprised 103 individuals with nonfunctioning adrenal incidentalomas (NFAI), a common condition in which tumors in the adrenal glands do not produce and release cortisol.
Blood cortisol levels significantly elevated in Cushing’s syndrome patients
The incidence of MASLD was highest among patients with Cushing’s syndrome (66.1%), followed by those with MACS (57%), and NFAI (26.2%).
Blood cortisol levels, measured in the morning and midnight, were markedly elevated in both Cushing’s and MACS patients. Sugar metabolic indicators, such as fasting glucose and HbA1c levels, and fat metabolism markers, including triglyceride and low-density lipoprotein (LDL) cholesterol levels, were significantly higher in those with Cushing’s and MACS compared with the NFAI group.
Liver enzymes, markers of liver injury and inflammation, were significantly higher in the Cushing’s group, “indicating potential liver dysfunction,” according to researchers. The L/S ratio was significantly lower in patients with Cushing’s and MACS compared with controls, “suggesting higher liver fat content in these groups.”
High levels of cortisol in the morning and midnight were significantly associated with a lower L/S ratio, “indicating that higher cortisol levels are associated with increased liver fat content,” the researchers wrote. In line with these results, both Cushing’s and MACS were found to be associated with the presence of MASLD.
Additionally, high cortisol affected waist circumference, fasting glucose, LDL and high-density lipoprotein (HDL) cholesterol, HbA1c, and most liver enzymes. Such high levels also had an effect on the triglyceride-glucose index, which is a marker for insulin resistance associated with type 2 diabetes.
These results demonstrate the broad influence of cortisol on fat and glucose metabolism, according to the researchers.
Further, the L/S ratio was found to be significantly influenced by several factors, including body mass index (used as a measure of body fat content), markers of glucose and fat metabolism, insulin resistance, and liver enzymes.
In a causal analysis, Cushing’s had a direct effect on liver fat, another sign that it substantially increases liver fat content. Fasting glucose and triglycerides significantly, but indirectly, affected liver fat, reinforcing the notion that Cushing’s influences liver fat content through metabolic pathways involving glucose and lipids, or fatty molecules.
The team acknowledged that lifestyle factors such as diet, physical activity, and alcohol consumption were not assessed in this study, which could also impact metabolic health and liver fat content.
“This study highlights the significant association between elevated cortisol levels and increased liver fat content in patients with MACS and CS, accompanied by notable metabolic disturbances,” the researchers wrote. “Further research is needed to confirm these findings, explore underlying mechanisms, and develop effective treatment strategies.”
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