Japanese children face years-long delays in Cushing’s disease diagnosis
Surgery achieved remission in 17 of 18, with height and BMI measures improving
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Japanese children with Cushing’s disease often went years before receiving a diagnosis, but surgery led to remission in most of those with outcome data. Measures of growth and body mass index also improved during follow-up, a study suggests.
Researchers noted that although the children’s overall characteristics were mostly similar to those reported in other countries, their degree of obesity at diagnosis was lower than generally reported in previous studies. They suggested this might partly reflect the generally lower BMI reported in Japanese people compared with Western populations. The researchers also noted a relatively high tumor-detection rate on MRI in this study.
The study, “Clinical characterization of Japanese children with Cushing’s disease,” was published in Endocrine Journal.
How Cushing’s disease develops
Cushing’s disease is the most common form of endogenous Cushing’s syndrome, a group of conditions caused by excessive levels of cortisol, or hypercortisolism. Cushing’s disease is caused by tumors in the pituitary gland, which is located at the base of the brain. Endogenous means the disease arises from a problem within a person’s body.
These pituitary tumors produce too much adrenocorticotropic hormone (ACTH). ACTH then signals the adrenal glands, which sit above the kidneys, to produce excessive amounts of cortisol.
Although Cushing’s disease is rare in children, previous pediatric cases and case series have been reported. However, “there has been no clinical investigation that includes a substantial number of Japanese children with [Cushing’s disease],” the researchers wrote.
Researchers in Japan reviewed past medical records to characterize Cushing’s disease in children and adolescents. The analysis included all 19 children diagnosed by age 18 and treated at Toranomon Hospital in Tokyo from 1994 through 2025. The group included 12 girls and seven boys.
Among the 18 children with available onset data, the median age when symptoms began was 9.3 years. Across the full group, the median age at diagnosis was 13. The median time from symptom onset to diagnosis was 2.7 years. This delay suggests that “diagnosis of pediatric [Cushing’s disease] remains challenging regardless of the health check-up system or health insurance coverage,” the researchers wrote.
At diagnosis, among children with available symptom data, 94.4% had excessive body hair, or hirsutism. A rounded “moon face,” weight gain with slowed growth, and central obesity — excess fat around the abdomen — each affected 88.9%.
Growth analysis showed that all children with available data were growing more slowly than expected for their age and sex. The slowdown was less pronounced among those who had reached the final stage of puberty. Their average BMI, adjusted for age and sex, was elevated at diagnosis but lower than generally reported in previous studies.
Laboratory tests confirmed excessive cortisol production in every child tested. The low-dose dexamethasone suppression test was positive in all 17 children who underwent it, giving it 100% sensitivity as part of diagnosing Cushing’s disease.
Additional tests helped correctly diagnose Cushing’s disease in 83.3% to 93.8% of the children who underwent them. These included the high-dose dexamethasone suppression test, morning blood ACTH levels, and ACTH levels after the corticotropin-releasing hormone test. MRI scans showed findings suggestive of a pituitary tumor in 16 of the 18 children with available scans.
In eight patients who underwent petrosal sinus sampling — an invasive test that measures ACTH in the veins draining the pituitary gland — the test confirmed the pituitary gland as the source of excess ACTH in seven, or 87.5%. It also correctly identified which side of the gland was producing ACTH in four of the eight patients, or 50%.
Surgery leads to remission in most children
Surgery led to remission in 17 of the 18 children with surgical outcome data, or 94.4%, including two who required a second procedure. Most identified tumors were small, and when surgeons could not locate a tumor, they removed part of the pituitary gland. Overall, based on clinical and surgical findings, MRI scans correctly identified the tumor in 13 of 18 children, or 72.2%.
According to the researchers, identifying the source of excess ACTH can be challenging because pituitary tumors causing Cushing’s disease in children are often very small, meaning MRI may fail to detect some tumors.
Following surgery, children were monitored for hormone deficiencies caused by reduced pituitary function. Among 14 children with available data, hydrocortisone replacement for adrenal insufficiency lasted a median of 18.5 months. One third of the children received growth hormone replacement. In addition, 27.8% received hormone treatment related to puberty.
After treatment, significant improvements were seen in height and BMI measures adjusted for age and sex.
According to the researchers, this study shows that the characteristics of Japanese children with Cushing’s disease are generally similar to those seen in other countries. However, “several distinctive features were identified … particularly regarding the extent of obesity at diagnosis, and the high tumor detection rate by MRI.”
Study limitations identified by the researchers included the small number of participants from a single center and the retrospective design, which left them unable to analyze symptoms such as fatigue, emotional instability and depression.
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