Researchers Find Corticol Deficiency Rare in PWS, Advise Against Routine Hydrocortisone Use

Central adrenal insufficiency, a deficiency in cortisol levels due to problems in the pituitary or hypothalamus, is rare in people with Prader-Willi syndrome (PWS), affecting 1.2% of patients, a study shows.

Researchers, therefore, do not recommend routinely prescribing medications for central adrenal insufficiency to PWS patients — as is common practice — since it is more likely to cause harm than to help.

The study, “Central adrenal insufficiency is rare in adults with Prader-Willi syndrome,” was published in the Journal of Clinical Endocrinology and Metabolism.

While the most notable clinical feature of PWS is an insatiable appetite, hormonal deficiencies are common and may increase the risk of sudden death in these patients.

In PWS patients, cortisol levels may be lowered due to a deficiency in the adrenocorticotropic hormone (ACTH) — which is produced by the pituitary glands and acts on the adrenal glands to make them release cortisol — or in the cortocotropin-releasing hormone, secreted by the hypothalamus to make the pituitary produce ACTH.

This is called central adrenal insufficiency, as opposed to primary adrenal insufficiency caused by problems in the adrenal glands.

Cortisol is a hormone that helps to keep blood sugar at a normal level and helps the body deal with physical stress, such as fevers or injuries. When cortisol drops to critical levels, patients may experience a life-threatening condition called adrenal crisis.

Medications that replace cortisol (a synthetic cortisol called hydrocortisone) are recommended to patients with adrenal insufficiency, but signs of this condition are often masked by the clinical features of PWS.

As a result, most PWS patients end up receiving hydrocortisone replacement treatment on a regular basis, even though the actual prevalence of central adrenal insufficiency in this population is unknown.

“Ideally, hydrocortisone should only be prescribed when it is absolutely necessary,” researchers wrote, adding that this medication increases the likelihood of weight gain, osteoporosis, diabetes, and high blood pressure, which are all associated with a higher risk of death.

Aiming to prevent both under- and overuse of hydrocortisone in PWS patients, a team of PWS experts across seven countries collaborated to determine the prevalence of central adrenal insufficiency in these patients.

The analysis included 82 adults, who were assessed for central adrenal insufficiency with one of the two most robust tests for such effect: the insulin tolerance test (ITT) and multiple-dose metyrapone test (MTP).

The group included 56 patients from the Netherlands, 10 from France, 10 from the U.K, and six from Sweden. Most (46) were men, and their median age was 25 years (range 18 to 55).

Results showed that one patient had central adrenal insufficiency (CAI), for a prevalence of 1.2%. “This low prevalence of CAI is in line with the majority of studies investigating CAI in people with PWS,” the researchers wrote.

To confirm the findings, the team examined a group of 645 PWS patients who had visited centers participating in the INfoRMEd-PWS network — which aims to advance research and understanding of PWS — to examine use of hydrocortisone and prevalence of central adrenal insufficiency.

They found that eight patients from INfoRMEd-PWS centers used hydrocortisone daily due to a diagnosis of adrenal insufficiency. Thirty Dutch patients also received hydrocortisone due to guidelines recommending its use during stressful situations, but none of the patients tested had central adrenal insufficiency.

“This finding is in line with the results of the MTP and ITT demonstrating that CAI is virtually absent in adults with PWS,” the researchers wrote, adding that hydrocortisone should not be routinely used in adults with PWS undergoing psychological stress or surgery.

The team will implement the findings in new guidelines for the clinical management of people with PWS.