Excess Cortisol Due to Adrenal Gland Tumor Tied to Bone Loss in Study

Margarida Maia, PhD avatar

by Margarida Maia, PhD |

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People with an excess of cortisol due to a benign tumor in the adrenal glands, known as an adrenal adenoma, can be more prone to bone loss even if the excess is mild, according to a Japanese study.

Bone loss was more common in women and patients with a low body mass index (BMI), a measure of body fat that takes into account both body weight and height.

Researchers also observed that in women with a mild excess of cortisol, but not in men, the risk of bone loss rose with age.

The study, “Sex difference in the association of osteoporosis and osteopenia prevalence in patients with adrenal adenoma and different degrees of cortisol excess,” was published in the International Journal of Endocrinology.

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Cushing’s syndrome occurs when there is an excess of cortisol in the body. Sometimes, this is caused by excessive levels of adrenocorticotropic hormone (ACTH), a hormone that drives the adrenal glands to produce cortisol. Other times, there is a problem with the adrenal glands themselves.

This is the case for people with a tumor in the adrenal glands, found atop each kidney. As a result, the adrenal glands become too big and overly active, and start producing higher-than-normal levels of cortisol.

One common symptom of Cushing’s syndrome is bone loss leading to osteoporosis, a condition that causes bones to become brittle and prone to fractures, or osteopenia, a less severe form of osteoporosis.

While osteoporosis and osteopenia are more common in women than men, their relationship with cortisol excess in women versus men is unknown.

Researchers drew on data from 10 centers that took part in the Advancing Care and Pathogenesis of Intractable Adrenal Disease in Japan (ACPA-J) study (UMIN000021437) as a way to build a registry of patients with adrenal adenoma.

The study included 237 people diagnosed with adrenal adenoma associated with cortisol excess from January 2006 to December 2015. Patients with ACTH-dependent or iatrogenic (medication-induced) Cushing’s syndrome were not included.

Patients median age was 56, and 182 (76.8%) were women. Osteopenia or osteoporosis was present in 112 (47.2%) of these people, and Cushing’s syndrome symptoms in 96 (40.5%) of them. The other patients had mild autonomous cortisol secretion (MACS), meaning that they had a mild excess of cortisol but no overt Cushing’s symptoms.

Osteopenia or osteoporosis was more common in women than men (54.4% vs. 23.6%), and patients with osteopenia or osteoporosis had a lower BMI (23.0 vs. 24.2 kg/m2) than those without either bone disorder. Those with these disorders also had lower blood levels of ACTH and DHEAS, a hormone produced by the adrenal glands, and higher cortisol levels in the blood and urine.

According to researchers, these findings suggest the level of cortisol excess might be tied to bone loss.

To understand whether this indeed was the case, researchers set a threshold based on the results of a dexamethasone suppression test. Dexamethasone is a corticosteroid that mimics the effects of cortisol, and a dexamethasone suppression test can tell whether the body is making more cortisol than normal. Dexamethasone usually suppresses cortisol production; however, in people with Cushing’s, its administration often fails to do so.

Researchers found that cortisol levels were linked to the development of osteopenia or osteoporosis both in the entire group of patients, and in those with MACS (mildly elevated cortisol levels but no Cushing’s symptoms).

After setting the threshold, they found that patients with a cortisol level greater than 5.0 micrograms per deciliter (mcg/dl) after the suppression test were at least three times more likely to develop osteopenia or osteoporosis than those with lower levels. This relationship did not hold true for patients with MACS.

Next, researchers looked at differences by sex. They found that cortisol level and the presence of Cushing’s symptoms were stronger risk factors for osteopenia or osteoporosis in men than in women. They also found that age was a risk factor for bone loss in women with MACS, but not in men.

“The severity of cortisol excess associated with adrenal adenoma was independently associated with the coexistence of osteoporosis and osteopenia,” the researchers wrote.

However, “cortisol excess in mild autonomous cortisol secretion had different effects on osteoporosis and osteopenia” in women than men.