Cushing’s syndrome patients who have adrenal insufficiency have increased risk of death due to disease-related complications, rather than adrenal crisis or adverse occurrences, an observational study suggests.
The study, “Mortality data from the European Adrenal Insufficiency Registry—Patient characterization and associations,” was published in the journal Clinical Endocrinology.
Adrenal insufficiency is a condition that occurs when the adrenal glands do not produce enough of the hormone cortisol and, in some cases, the hormone aldosterone.
Patients often experience weight loss, muscle weakness, fatigue, low blood pressure, and sometimes darkening of the skin in both exposed and non-exposed parts of the body.
Adrenal insufficiency may lead to premature death, even if patients receive glucocorticoid replacement therapy. But what causes these patients to die early remains undetermined.
The European Adrenal Insufficiency Registry (NCT01661387) is an observational study monitoring the safety of glucocorticoid replacement therapies in patients with adrenal insufficiency.
Researchers examined clinical data from patients who died during the trial, in an attempt to recognize risk factors that contribute to the poorer outcomes of patients with adrenal insufficiency.
The study included 2,034 patients at endocrinology centers in Germany, the Netherlands, Sweden, and the United Kingdom. Among them, 26 patients died, including 1% of those with primary adrenal insufficiency and 1.5% of patients with secondary adrenal insufficiency.
Primary adrenal insufficiency occurs when at least 90% of the adrenal cortex has been destroyed. This might happen due to an infection, autoimmune disease, or the surgical removal of both adrenal glands, as occurs in some Cushing’s syndrome patients and in those with kidney tumors.
Secondary adrenal insufficiency is traced to a lack of adenocorticotropic hormone (ACTH), which causes a drop in the adrenal glands’ production of cortisol. Patients with Cushing’s disease who have their pituitary gland removed may experience a form of secondary adrenal insufficiency.
The main causes of death in the study were cardiovascular disease (35%), infection (15%) and suicide (8%). In 19% of cases, the cause of death was unclear due to lack of information.
Among the 26 patients who died, eight had primary adrenal insufficiency, including three who had undergone bilateral removal of the adrenal glands for uncontrolled Cushing’s disease, three with metastatic kidney cancer, and two with an autoimmune disorder.
Secondary adrenal insufficiency, in most cases, was caused by surgery to the pituitary gland.
In general, patients with adrenal insufficiency who died were older and more likely to have high blood pressure and diabetes mellitus. No differences were seen in body mass index, cholesterol levels, blood potassium or sodium levels between patients who died and those who remained alive.
A detailed analysis of the primary adrenal insufficiency cases revealed that patients who died had higher levels of HbA1c (hemoglobin A1c), a common biomarker of diabetes. However, this trend was not significant in patients with secondary adrenal insufficiency.
Also, fatal cases of secondary adrenal insufficiency were predominantly males and patients who had been treated with higher doses of hydrocortisone, probably in an attempt to control an adrenal insufficiency crisis.
“The low number of adverse events and adrenal crisis in [the primary adrenal insufficiency] group supports the greater influence of their comorbidities,” the researchers wrote. In addition, “male, older individuals [with secondary adrenal insufficiency] who had a higher prevalence of hypertension and diabetes mellitus, is a high-risk group which deserves further attention and care,” they said.
Despite the relevant information of the study, researchers note that the trial only included patients from specialized centers, which may not fully represent the entire European population with adrenal insufficiency.