Adrenal Cushing’s Syndrome More Common in Southeast Asia, Study Finds

Adrenal Cushing’s Syndrome More Common in Southeast Asia, Study Finds
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The proportion of Cushing’s syndrome patients whose disease is caused by a tumor in the adrenal glands is higher in Asia than in other continents. Now, researchers in Thailand suggest that countries in Southeast Asia also may have a higher incidence of this subtype of cases.

The research, “Clinical Characteristics and Treatment Outcomes in Endogenous Cushing’s Syndrome: A 15-Year Experience from Thailand,” was published in Case Reports in Endocrinology.

Endogenous Cushing’s syndrome is a rare condition in which the body makes too much of the cortisol hormone. The condition is most commonly caused by a benign tumor in the pituitary gland that secretes too much adrenocorticotropic hormone (ACTH), which acts on the adrenal glands and instructs them to produce cortisol. In that case, it is called Cushing’s disease.

But in about 15% of cases, the culprit is a tumor on the adrenal glands that makes excess cortisol by itself, and an additional 15% of patients have Cushing’s syndrome due to a tumor elsewhere in the body that also produces high levels of ACTH. In those cases, the disease is called ectopic Cushing’s syndrome.

Studies have suggested that the proportion of these disease subtypes may differ considerably in Asia compared to other continents. Since each subtype is managed differently and has a distinct outcome, this may have an impact in the mortality rate of Cushing’s syndrome patients in Asia.

Researchers in Thailand set out to confirm if the distribution of Cushing’s syndrome also may be different in Southeast Asia. For that, they examined a group of 82 patients diagnosed at the King Chulalongkorn Memorial Hospital from 2001 to 2015.

The group included 45 patients (55%) with Cushing’s disease, 26 patients (37%) with adrenal Cushing’s syndrome, and 11 individuals (13%) with ectopic disease – with tumors mostly found in the thorax.

The findings were in line with other Asian studies, though the proportion of patients with adrenal disease was “not as high as [in] studies from Japan and Taiwan,” the researchers wrote.

Participants were assessed for their symptoms, treatment, and outcomes.

The most common initial manifestation of the disease was weight gain, though about one-third of patients still had a normal body mass index (BMI, a measure of body fat), according to Asian standards. Most patients also had a round face, high blood pressure, and elevated levels of lipids.

However, common features of Cushing’s, like facial redness, purple stretch marks, easy bruising, and muscle weakness were rare, happening in about one-quarter of patients.

Factors like age, ACTH levels, and amount of free cortisol in urine were significantly different among disease subtypes, with patients who had ectopic disease having the highest values for all three factors.

After their diagnosis, all Cushing’s disease patients underwent surgery to remove their pituitary tumor. Overall, 62% achieved remission, but this rate was better for those with smaller tumors (68%) than for patients with larger pituitary tumors (45%). About 13% of patients who initially achieved remission experienced a later relapse, after a median of 23 months.

“Compared to studies from Japan and Korea, our remission rate was lower, but had higher proportion of macroadenomas [larger tumors],” the researchers wrote.

Post-surgery complications were experienced by 67% of patients, and included mainly low levels of pituitary hormones (which is common, since part of the pituitary was removed during surgery), diabetes, and leakage of cerebrospinal fluid (the liquid surrounding the brain and spinal cord).

Regarding patients with adrenal Cushing’s syndrome, most experienced disease remission after undergoing surgical removal of the affected adrenal gland, with only three patients needing a second surgery to remove the other gland.

Most also experienced adrenal insufficiency — when the adrenal gland does not produce enough levels of its hormone. The median time to recovery of adrenal function was 18 months.

Almost half (five patients, 45%) with ectopic disease achieved disease remission, mostly after undergoing surgery to remove both adrenal glands. Only one patient was cured after the removal of an ACTH-producing tumor in the bronchi. During a median follow-up of five months, four patients died and five were lost to follow-up still without a remission.

“Mortality rates were highest among this subtype of CS [Cushing’s syndrome]. It might have been higher since a number of patients were lost to follow-up before cured,” the team noted.

Overall, the findings show that the distribution of Cushing’s syndrome subtypes “was the same as previous studies in Asia, with more proportions of patients with ACTH-independent CS,” they concluded.

Researchers added that studies examining the outcomes of patients across multiple centers are now needed to better understand the natural history of Cushing’s syndrome in Thailand and countries of Southeast Asia.

Inês holds a PhD in Biomedical Sciences from the University of Lisbon, Portugal, where she specialized in blood vessel biology, blood stem cells, and cancer. Before that, she studied Cell and Molecular Biology at Universidade Nova de Lisboa and worked as a research fellow at Faculdade de Ciências e Tecnologias and Instituto Gulbenkian de Ciência. Inês currently works as a Managing Science Editor, striving to deliver the latest scientific advances to patient communities in a clear and accurate manner.
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Ana holds a PhD in Immunology from the University of Lisbon and worked as a postdoctoral researcher at Instituto de Medicina Molecular (iMM) in Lisbon, Portugal. She graduated with a BSc in Genetics from the University of Newcastle and received a Masters in Biomolecular Archaeology from the University of Manchester, England. After leaving the lab to pursue a career in Science Communication, she served as the Director of Science Communication at iMM.

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Inês holds a PhD in Biomedical Sciences from the University of Lisbon, Portugal, where she specialized in blood vessel biology, blood stem cells, and cancer. Before that, she studied Cell and Molecular Biology at Universidade Nova de Lisboa and worked as a research fellow at Faculdade de Ciências e Tecnologias and Instituto Gulbenkian de Ciência. Inês currently works as a Managing Science Editor, striving to deliver the latest scientific advances to patient communities in a clear and accurate manner.
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