Higher Risk of Ocular Hypertension in Cushing’s Disease Patients: Study

Importance of considering increased intraocular pressure, Cushing's noted

Teresa Carvalho, MS avatar

by Teresa Carvalho, MS |

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People with pituitary gland tumors that cause Cushing’s disease are at higher risk of developing ocular hypertension — increased blood pressure inside the eyes — than those with other types of pituitary tumors, according to a study in China.

Its authors highlighted the importance of these results in ensuring ophthalmologists and neuroendocrinologists consider Cushing’s in patients with high pressure inside the eyes and glaucoma — a group of eye disorders characterized by optic nerve damage.

Findings were reported in the study, “Increased risk of ocular hypertension in patients with Cushing’s disease,” published in the Journal of Glaucoma.

Cushing’s disease is usually caused by the presence of benign tumors in the brain’s pituitary gland, called corticotroph pituitary adenomas. These tumors lead to the excessive production of adrenocorticotropic hormone, or ACTH, which stimulates the production of cortisol by the adrenal glands sitting atop the kidneys.

Most corticotroph pituitary adenomas are smaller than 1 centimeter in diameter and are called microadenomas. More rarely, patients may develop larger tumors, called macroadenomas.

Patients usually undergo surgery to remove the pituitary tumor causing the condition. After that, they typically need to take cortisol replacement medications, such as steroids, to provide the body with the correct amount of cortisol.

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An association between the use of steroids and the risk of increased intraocular pressure (IOP) has been reported. IOP is the fluid pressure inside the eyes that, once increased, leads to ocular hypertension. This is the most important risk factor for glaucoma, a condition estimated to affect 2.6% of the Chinese population.

Several studies also have explored the potential relationship between ocular hypertension and high cortisol levels (endogenous hypercortisolemia) in Cushing’s disease patients. However, the incidence of ocular hypertension in patients with endogenous hypercortisolemia, as well as the increase in IOP following tumor removal, is still unclear.

Increased risk of ocular hypertension hypothesized

Based on these observations, a team of researchers in China hypothesized that patients with Cushing’s disease are at an increased risk of developing ocular hypertension. To test this theory, they assessed and compared eye symptoms between 52 Cushing’s disease patients and two control groups.

One control group comprised 43 patients with acromegaly, a condition in which pituitary tumors lead to the overproduction of growth hormone, causing body tissues to grow excessively. The other group had 44 patients with clinically nonfunctioning pituitary adenomas (NFPAs), or pituitary adenomas that are not hormonally active, and therefore do not cause clinical syndromes like Cushing’s disease. These comparisons were made to differentiate hormonal from tumor-related effects.

Study participants were referred to hormonal assessment after having undergone pituitary surgery from January to July 2019.

All patients were submitted to eye examinations. Those with an IOP higher than 21 millimeters of mercury (mmHg) were diagnosed with ocular hypertension. The presence of glaucoma was also evaluated. Follow-up assessments were made at one and three months after tumor removal.

Imaging tests were performed to assess tumor size and invasion to surrounding brain tissues, namely to the cavernous sinuses — hollow spaces located under the brain, behind each eye socket.

In Cushing’s patients, several clinical parameters were recorded before and after surgery, namely morning ACTH and 24-hour urinary free cortisol levels. Thyroid hormone levels also were evaluated. Cushing’s disease remission was confirmed when early morning blood cortisol levels were lower than 1.8 micrograms per deciliter (mcg/dL).

Imaging scans revealed the presence of microadenomas in 92.3% of the patients with Cushing’s. All of these patients also had elevated 24-hour urinary free cortisol levels, with normal or elevated ACTH levels.

Compared with the control groups, patients with Cushing’s were younger, mostly female, more prone to having high blood pressure or diabetes, and less likely to have macroadenomas.

The study also found that IOP was higher in patients with Cushing’s than in those with acromegaly or with NFPAs.

Ocular hypertension was diagnosed in 21 eyes (20.2%) in Cushing’s patients, while it was found in four eyes (4.7%) of those with acromegaly, and in four eyes (4.5%) of those with NFPAs.

Results also showed Cushing’s disease patients were 5.1-times more likely to develop ocular hypertension than those with acromegaly. When compared with patients in the NFPA group, this risk was 6.6-times higher.

While glaucoma was not observed in any of the patients in the control groups who had ocular hypertension, the condition was found in 6.7% of the eyes of Cushing’s patients.

Assessing risk factors

Researchers further assessed the risk factors for developing ocular hypertension in patients with Cushing’s, such as age, sex, body mass index (a measure of body fat), the presence of other conditions, tumor features, and 24-hour urinary free cortisol levels.

From all of these, only 24-hour urinary free cortisol levels were found to be linked to the development of ocular hypertension. According to findings, patients whose 24-hour urinary free cortisol levels were higher than three times the normal upper normal limit were nearly 20-times more likely to develop ocular hypertension.

After surgery, nearly all Cushing’s patients (94.3%) were in remission. Additionally, IOP decreased in both eyes of Cushing’s patients at one and three months after tumor removal. In patients in the acromegaly group, this change was not significant. Of all the eyes that had glaucoma, only one did not show improvements during follow-up.

Overall, these results “can inform ophthalmologists and neuroendocrinologists that in patients with ocular hypertension and glaucoma, endogenous hypercortisolemia should be considered,” the researchers wrote.