Cushing’s syndrome (CS) can be tricky to recognize in older adults. Classic signs (purple striae, skin thinning, central obesity, hirsutism) are often muted or absent, and common age-related problems—hypertension, diabetes, osteoporosis, cognitive decline—can mask hypercortisolism. Etiology also shifts with age: adrenal causes are more common in the elderly, while pituitary disease dominates in younger patients. Diagnosis and treatment require age-aware strategies, with careful attention to comorbidities and postoperative risks.
How Cause and Presentation Shift with Age
- Etiology: Adrenal adenoma/mild autonomous cortisol secretion becomes more frequent ≥65; pituitary-dependent CS (Cushing’s disease) is relatively less common.
- Phenotype: Older patients often lack striking skin/androgenic signs and may have lower BMI despite visceral adiposity. They present more with frailty, muscle weakness, fractures, hypertension, diabetes, thromboembolism, and cognitive complaints.
- Sex differences: The usual female preponderance narrows with age (postmenopausal hormonal milieu may play a role).
Diagnostic Nuances in the Elderly
- Screen thoughtfully: Broad screening of all patients with metabolic syndrome/obesity isn’t advised; target those with unexplained osteoporosis, muscle wasting, dorsocervical fat pad, difficult-to-control hypertension or diabetes, recurrent fractures, or hypokalemia.
- Testing pitfalls: Cortisol production and responses can vary with age and comorbidities (renal function, medications), complicating interpretation of UFC, late-night salivary cortisol, and suppression tests.
- Ectopic ACTH: Tends to present abruptly with severe catabolic features and hypokalemia; distinguish from CD with ACTH levels, imaging, and targeted workup.
Treatment Considerations
- Surgery (first-line for CD): Transsphenoidal surgery can be safe and effective in selected older adults at experienced centers; monitor closely for hyponatremia and fluid/sodium balance.
- Medical therapy: Ketoconazole, metyrapone, mitotane, osilodrostat, and (in severe cases) etomidate can control cortisol; data in ≥70s are more limited for newer agents.
- Radiotherapy: Useful when surgery isn’t feasible, but weigh risks (cerebrovascular disease, hypopituitarism) against benefits.
- Aftercare: Expect slower recovery of muscle function and bone quality; prioritize fall prevention, vitamin D, resistance exercise, diabetes/BP/lipid control, and VTE prophylaxis around procedures.
Outcomes & Quality of Life
- Mortality risk rises with age (largely cardiovascular). Early diagnosis and timely cortisol control are critical.
- QoL often improves post-treatment but remains impacted by comorbidities and residual myopathy—set expectations and support rehabilitation.
- Cognition and mood: Cognitive deficits may only partly reverse; screen and treat depression, which may present atypically in late life.
Takeaway
In older adults, CS often hides behind “normal aging.” A targeted index of suspicion, careful interpretation of tests, and individualized therapy—delivered in specialized centers—are key to improving survival, function, and quality of life.