Cushing's disease across the lifespan: a case-based clinical review

Cushing'sdisease (CD), caused by an adrenocorticotropin-secreting pituitary adenoma, is a rare but severe endocrine disorder associated with high cardiometabolic morbidity and mortality. Diagnosis is challenging as many symptoms are nonspecific, and biochemical or imaging results may be inconclusive, contributing to substantial diagnostic delay. Although the core features of CD are consistent across the lifespan, certain clinical manifestations of chronic hypercortisolism vary from childhood through older age, reflecting differences in growth, puberty, metabolism, and comorbidity burden. In children, impaired growth coupled with weight gain is most prominent, whereas adolescents often present with pubertal disturbances and psychological or academic difficulties. Adults typically exhibit the classic Cushingoid features such as round face, plethora, and central obesity, along with metabolic and reproductive complications. Older individuals typically present with frailty, sarcopenia, fractures, and cognitive decline. Age also influences the interpretation of endocrine tests, the accuracy of pituitary magnetic resonance imaging, the role of inferior petrosal sinus sampling, perioperative risks, and the long-term impact of remission or persistent disease. Given this context, this narrative review used five representative clinical vignettes (pediatric, adolescent, adult female, adult male, and elderly) to illustrate how the presentation, diagnostic evaluation, and management of CD vary across the lifespan. Each case was paired with a structured synthesis of current evidence, highlighting both shared principles and age-specific nuances essential for timely diagnosis, appropriate treatment selection, and effective long-term multidisciplinary care. Understanding age-related differences is crucial to improving outcomes and reducing the substantial morbidity and mortality associated with CD throughout the lifespan.