Adrenal Cushing’s patients in Japan showing fewer syndrome features
Study finds patients diagnosed in 2000s less likely to have specific symptoms
People with adrenal Cushing’s syndrome who were diagnosed in the 2000s often had the condition identified incidentally — but also experience fewer symptoms specific to Cushing’s compared with individuals receiving a diagnosis in previous decades, a study in Japan has found.
However, the prevalence of Cushing’s-related complications, including cardiovascular events and severe infections, remains elevated, data show.
“Adrenal [Cushing’s syndrome] became less florid in the 2000s, showed no improvement in the following years, and remained associated with a high complication rate,” the researchers wrote.
Per the team, these findings on the changes in the clinical symptoms of adrenal Cushing’s syndrome may “provide clinical insights that may aid in earlier disease diagnosis.” The scientists added, however, that “further research is needed to establish an early detection model.”
Their study, “Changes in clinical features of adrenal Cushing syndrome: a national registry study,” was published in the journal Endocrine Connections.
Moon face remains the most common symptom
Cushing’s syndrome comprises several conditions driven by hypercortisolism, or elevated levels of the hormone cortisol. Cushing’s disease, one of its most common forms, is caused by a tumor in the brain’s pituitary gland. Such tumors cause the gland to produce and release excessive amounts of adrenocorticotropic hormone (ACTH), which acts on the adrenal glands to promote cortisol production.
Less frequently, Cushing’s is caused by tumors in the adrenal glands themselves — particularly benign adenomas. In Japan, these cases account for more than half of all Cushing’s cases, a proportion that is higher than that seen in other countries.
However, the researchers wrote, “there is limited evidence regarding diagnostic clues, clinical presentation, … and disease progression in a large cohort of patients with adrenal [Cushing’s] caused by adenomas in this century.”
To learn more about the condition’s characteristics and how they may have changed over time, the team of researchers retrospectively analyzed data from 101 Japanese individuals who had been diagnosed with adrenal Cushing’s due to an adenoma between 2005 and 2016. The participants had a mean age of 46.9, and 90% were women.
In about one-third, the disease was found unexpectedly during an imaging test performed for other reasons. In about 30% of the patients, the symptom leading to diagnosis was high blood pressure. Specific symptoms of Cushing’s, such as moon face and muscle weakness, led to the diagnosis of approximately 15% of the patients.
In almost all of them (90%), adenomas were larger than 2 cm (about 0.8 inches); nearly 20% of patients had tumors in both adrenal glands. Most exhibited few specific disease symptoms (mean of 2.5). The most common were moon face, seen in 84%, central obesity, affecting 59%, easy bruising or thin skin, experienced by 45%, and facial redness, seen in 25%.
Among nonspecific features, menstrual irregularity was the most common (25%), while acne, psychiatric disorders, or the appearance of masculine features in women were each seen in fewer than 15% of cases.
Serious illnesses seen for 16% of adrenal Cushing’s syndrome patients
There were no differences in disease characteristics when patients were divided into two groups by date of diagnosis, the researchers noted. Those in the earlier group were diagnosed between August 2005 and November 2011, while individuals in the later group received their diagnosis between December 2011 and November 2016.
In all patients, midnight blood cortisol levels were elevated and blood cortisol levels did not drop after low- and high-dose dexamethasone tests. Blood ACTH levels were also low in all patients, consistent with adrenal Cushing’s syndrome.
Our study found that one-sixth of patients with adrenal Cushing syndrome continued to develop severe complications in this century despite their specific cushingoid features being less pronounced than in the past.
Regarding coexistent conditions, patients most commonly had high blood pressure (79%), followed by dyslipidemia, or high levels of fats in the blood (62%). Obesity was found for 41% of patients and 33% had glucose intolerance. Bone fractures or osteoporosis, a condition characterized by fragile bones that are prone to break, were more commonly seen in patients in the later group than in those in the earlier group (60% vs. 35.3%).
Overall, 16 patients (16%) experienced serious illnesses, including major adverse cardiac and cerebrovascular events and severe infections. Among the cardiovascular events were cerebral infarction, which occurs when the blood flow to a part of the brain is interrupted, as well as heart attacks and chest pain.
When comparing data from patients enrolled in this study with data from a nationwide survey in Japan and previously published data, the team found that the frequency of specific Cushing’s symptoms (except moon face), diabetes, menstrual irregularities, obesity, and dysregulated fat levels in the blood were lower in this study.
“Our study found that one-sixth of patients with adrenal Cushing syndrome continued to develop severe complications in this century despite their specific cushingoid features being less pronounced than in the past,” the researchers wrote.
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