Clinical characterization of Japanese children with Cushing’s disease

Abstract

Cushing’s disease (CD) is very rare in children. Nineteen children (≤18 years) with CD (median age at diagnosis: 13 [6–17] years; 12 females) were retrospectively analyzed using medical records (1994–2025) from Toranomon Hospital, Tokyo, Japan. Facial changes (88.9%), weight gain with decreased growth rate (88.9%), central obesity (88.9%) and hirsutism (94.4%) were frequently observed at diagnosis. Median time to diagnosis was 2.7 (0.25–5.8) years. Screening for endogenous hypercortisolism was assessed by 24-hour urinary free cortisol levels, serum cortisol levels at 23:00, and serum cortisol levels at 8:00 after a low-dose dexamethasone suppression test (DST), each with 100% sensitivity. Etiological diagnosis was evaluated by serum cortisol levels at 8:00 after a high-dose DST, plasma adrenocorticotropic hormone (ACTH) levels after a corticotropin-releasing hormone test, and plasma ACTH levels at 8:00, with sensitivities of 85.7%, 93.8%, and 83.3%, respectively. The actual tumor detection rate on magnetic resonance imaging (MRI) was 72.2%. Micro-pituitary neuroendocrine tumors were identified in 77.8% of patients. The total remission rate was 94.4% (median follow-up: 3.8 [0–10.4] years). The mean standard deviation scores (SDS) (SD) of height and body mass index (BMI) at onset and diagnosis were –0.45 (0.63) and –2.0 (1.1), and 0.61 (0.95) and 1.6 (0.75), respectively. Height and BMI SDS (SD) improved to –1.0 (0.80) and 0.091 (1.2) at the last visit (age: 11.4–17.5 years; follow-up: 1–8.6 years), respectively. This study revealed clinical characteristics of Japanese children with CD, including distinctive BMI SDS and a high tumor detection rate by MRI.