High Cortisol Levels, as Seen in Cushing’s, Can Lead to Greater Risk of Heart Disease, Study Finds

People with high cortisol levels have lower muscle mass and higher visceral fat deposits, putting them at a greater risk for cardiovascular disease, new research shows.

High levels of cortisol can result from a variety of reasons, including Cushing’s disease and adrenal tumors. Most adrenal tumors are found to be non-functioning, meaning they do not produce excess hormones. However, up to 47 percent of patients have mild autonomous cortisol excess (MACE).

The study, “Impact of hypercortisolism on skeletal muscle mass and adipose tissue mass in patients with adrenal adenomas,” was published in the journal Clinical Endocrinology.

Long-term studies have shown that as a group, patients with MACE tend to have increased cardiovascular risk factors, such as hypertension, type 2 diabetes mellitus (DM2), obesity, and high lipid levels, which are associated with higher cardiovascular death rates.

Abdominal adiposity, which refers to fat deposits around the abdomen and stomach, and central sarcopenia, referring to loss of skeletal muscle mass, are both known to be linked to higher cardiovascular risk and increased mortality.

Overt hypercortisolism is known to lead to increased visceral adiposity (body fat stored within the abdominal cavity) and muscle loss. However, little is known about the body composition of patients with adrenal adenomas and MACE.

Therefore, researchers set out to determine whether central sarcopenia and adiposity are present in patients with MACE, and whether they can be markers of disease severity in patients with adrenal adenomas. To determine this, researchers used body composition measurements of 25 patients with Cushing’s disease, 48 patients with MACE, and 32 patients with non-functioning adrenal tumors (NFAT) using abdominal CTs.

Specifically, researchers looked at visceral fat, subcutaneous fat, and total abdominal muscle mass. Visceral fat refers to fat around organs, and it is “deeper” than subcutaneous fat, which is closer to the skin.

Results showed that, compared to patients with non-functional tumors, those with Cushing’s disease had a higher visceral to total (V/T) fat ratio but a lower visceral to subcutaneous (V/S) fat ratio. In MACE patients, however, both ratios were decreased compared to patients with non-functional tumors.

Cushing’s disease patients also had 10 cm2  less total muscle mass, compared to patients with non-functional tumors.

An overnight dexamethasone suppression test was conducted in these patients to determine levels of cortisol in the blood. The next morning, cortisol levels were checked. High levels of cortisol indicate the presence of a disease, such as MACE or Cushing’s disease.

After administering the test, researchers determined that for an increase in cortisol in the morning, there was a correlating increase in the V/T ratio and the V/S fat ratio, and a decrease in the mean total muscle mass.

Therefore, the higher the degree of hypercortisolism, the lower the muscle mass and the higher the visceral adiposity.

These results could prove to be clinically useful as both visceral adiposity and low muscle mass are risk factors of a number of diseases, including cardiovascular disease.

“Body composition measurement may provide an additive value in making a diagnosis of clinically important MACE and aid in individualizing management of patients with ACAs and MACE,” the researchers concluded.

From https://cushingsdiseasenews.com/2017/11/30/cushings-disease-high-cortisol-levels-leads-to-greater-risk-heart-disease/

Lowest cortisol levels found in women with overweight, mild obesity

Women with overweight and class I obesity appear to have the lowest cortisol levels, while more significant obesity appears to be associated with higher cortisol levels, according to recent findings.

In the cross-sectional study, Karen K. Miller, MD, of Massachusetts General Hospital, and colleagues evaluated 60 premenopausal women aged 18 to 45 years: 28 with overweight or obesity, 18 with anorexia nervosa and 21 healthy controls at normal weight. Overweight was defined as BMI 25 to 29.9 kg/m2, and obesity was classified as class I (30-34.9 kg/m2) and class II (35-39 kg/m2).

Anorexia nervosa was classified based on DSM-IV criteria, which includes extreme fear of weight gain, body image dysmorphia, weight that is 85% of ideal body weight and cessation of menstruation for 3 consecutive months. Participants were asked to collect 24-hour urine samples, in addition to 11 p.m. and 7 a.m. salivary samples within 1 week of an inpatient hospital visit. For each sample, researchers assessed creatinine clearance, and urinary free cortisol/creatinine clearance was calculated for each specimen to account for the decreased creatinine and filtered cortisol linked to anorexia nervosa.

During the inpatient visit, participants underwent placement of an IV catheter and fasting blood was sampled every 20 minutes from 8 p.m. to 8 a.m. Fasting cortisol and cortisol binding globulin concentrations were measured at 8 a.m. Participants were asked to take 5 g of oral dexamethasone every 6 hours for 48 hours to decrease endogenous disparities in cortisol levels.

The researchers found that with the exception of dexamethasone-suppression-CRH testing, all cortisol measures exhibited a U-shaped association with BMI, most notably urinary free cortisol/creatinine clearance (P = .0004) and mean overnight serum cortisol (P < .0001).

The lowest cortisol levels were seen in the overweight-class I obesity range, and these were also associated with visceral fat tissue and total fat mass. Participants with anorexia nervosa had higher mean cortisol levels than participants with overweight or obesity. Attenuated inverse relationships were seen between lean mass and some measures of cortisol, and most measures of cortisol were inversely related to posterior-anterior spine and total hip bone mineral density.

According to the researchers, these findings have not determined the precise nature of the relationship between cortisolemia, hypothalamic-pituitary-adrenal activation and adiposity.

“The [hypothalamic-pituitary-adrenal] axis activation associated with obesity and excess adiposity raises the question of whether hypercortisolemia contributes to increased adiposity in the setting of caloric excess, whether increased adiposity drives [hypothalamic-pituitary adrenal] activation, or whether the relationship between hypercortisolemia and adiposity is bidirectional,” the researchers wrote. – by Jennifer Byrne

Disclosure: The researchers report no relevant financial disclosures.

From http://www.healio.com/endocrinology/obesity/news/online/%7B73cac1c4-af30-4f24-89e3-86f50d05aaa2%7D/lowest-cortisol-levels-found-in-women-with-overweight-mild-obesity

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