High Cortisol Levels in Urine May Be Linked to Changes in Blood Sugar Metabolism

High Cortisol Levels in Urine May Be Linked to Changes in Blood Sugar Metabolism
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Abnormally high levels of cortisol in the urine — one of the hallmarks of Cushing’s syndrome — seem to be associated with alterations in blood sugar metabolism in obese patients, a study found.

The study, “Hypercortisolism and altered glucose homeostasis in obese patients in the pre-bariatric surgery assessment,” was published in the journal Diabetes/Metabolism Research and Reviews.

Cushing’s syndrome is a disorder characterized by excessive levels of the glucocorticoid hormone cortisol circulating in the bloodstream and urine, a condition normally known as hypercortisolism.

A series of metabolic alterations are associated with Cushing’s, including central or abdominal obesity, changes in blood sugar metabolism, type 2 diabetes, high blood pressure, and dyslipidemia, which is excessive levels of fatty molecules circulating in the bloodstream.

When clustered together, these features also make up a condition known as metabolic syndrome. Individuals with metabolic syndrome have a higher risk of developing heart disease and having a stroke.

The similarities between Cushing’s and metabolic syndrome led a team of Italian scientists to question whether screening for Cushing syndrome in patients with obesity should be performed “with the specific aim to exclude the presence of underlying hypercortisolism.”

Moreover, in patients with obesity or metabolic syndrome, excessive activity of the hormonal signaling cascade — leading to the production of cortisol — could be linked to changes in blood sugar metabolism, such as insulin resistance. Of note, insulin resistance is a condition in which cells become insensitive to the hormone insulin, which may lead to prediabetes or type 2 diabetes.

To investigate if hypercortisolism could be associated with alterations in blood sugar metabolism and other features of metabolic syndrome in obese patients, the team reviewed the medical records of a group of 884 obese patients who had been referred for weight-loss surgery.

All of the patients included in the analyses were being followed at the Policlinico di Monza, a tertiary care center for obesity, in Italy, between January 2013 and January 2020.

Among the obese patients included in the analyses, 129 (14.6%) had excessive levels of cortisol in their urine, while the remaining 755 (85.4%) were within the normal range.

For those whose levels of cortisol in the urine were found to be excessively high, a second test, called the overnight dexamethasone suppression test (ODST), was performed. This test measures the levels of cortisol found in the blood in the morning after patients take a tablet of dexamethasone, a corticosteroid that normally blocks the production of cortisol. It is used to confirm the presence of hypercortisolism.

In nine patients, dexamethasone failed to lower the levels of cortisol in the blood to a normal range. That confirmed the presence of hypercortisolism in 7% of the patients who had high levels of cortisol in the urine, and in 1% of those included in the analyses.

Statistical analyses showed that the individuals who had prediabetes or type 2 diabetes were approximately 2-times more likely to have abnormally high levels of cortisol in their urine.

This risk association continued to be found, even after researchers normalized their data to take into account patients’ age, sex, and body mass index.

In contrast, the researchers failed to identify a link between other features of metabolic syndrome, such as high blood pressure and dyslipidemia, and excessively high levels of cortisol in the urine.

Importantly, they also found that individuals who did not have either prediabetes or type 2 diabetes, but who already had early signs of insulin resistance, were 2.84-times more likely to have high levels of cortisol in the urine.

“In obese patients, hypercortisolism was more frequent across the entire spectrum of altered glucose homeostasis [blood sugar metabolism] including the very early stages,” the researchers wrote, adding that “this relation could not be detected for the other criteria of the MS [metabolic syndrome].”
According to researchers, these findings suggest that the excessive activity of signaling pathways leading to the production of cortisol is reflected by alterations in blood sugar metabolism, which can range from minor alterations to type 2 diabetes.
Joana holds a BSc in Biology, a MSc in Evolutionary and Developmental Biology and a PhD in Biomedical Sciences from Universidade de Lisboa, Portugal. Her work has been focused on the impact of non-canonical Wnt signaling in the collective behavior of endothelial cells — cells that made up the lining of blood vessels — found in the umbilical cord of newborns.
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Ana holds a PhD in Immunology from the University of Lisbon and worked as a postdoctoral researcher at Instituto de Medicina Molecular (iMM) in Lisbon, Portugal. She graduated with a BSc in Genetics from the University of Newcastle and received a Masters in Biomolecular Archaeology from the University of Manchester, England. After leaving the lab to pursue a career in Science Communication, she served as the Director of Science Communication at iMM.

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Joana holds a BSc in Biology, a MSc in Evolutionary and Developmental Biology and a PhD in Biomedical Sciences from Universidade de Lisboa, Portugal. Her work has been focused on the impact of non-canonical Wnt signaling in the collective behavior of endothelial cells — cells that made up the lining of blood vessels — found in the umbilical cord of newborns.
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