Cushing Syndrome in Older Women: Age-Related Differences in Disease Origin and Clinical Manifestations

Objective:

Determine age-related clinical presentation, biochemical profile, and cause of non-malignant Cushing syndrome (CS) in women.

Methods:

Retrospective charts review of women with pituitary or adrenal CS, treated at Rabin Medical Center between 2000 and 2017, or at Maccabi Healthcare Services in Israel between 2005 and 2017. Patients were classified into 3 groups, according to age at diagnosis: ≤45 (young), 46-64 (middle-age), or ≥65 (elderly) years.

Results:

The cohort included 142 women (mean age, 46.0 ± 15.1 years), including 81 (57.0%) with adrenocorticotropic hormone-producing pituitary adenoma, and 61 patients (43.0%) with adrenal CS: 68 young, 55 middle-aged, and 19 elderly women.

Pituitary CS was more common among young patients (48 patients, 70.6%), compared with middle-aged (27 patients, 49.1%) or elderly women (6 patients, 31.6%) (P <0.05).
Among patients with adrenal CS, hypercortisolism was diagnosed following an adrenal incidentaloma detection in 15.0% of young and 53.8% of elderly women (P <0.001).
Mean urinary free cortisol levels were highest for young women (5.03±3.6xULN), followed by middle-aged (4.80±6.0xULN) and elderly (3.5±2.6xULN) women (P <0.001), without serum cortisol differences following low-dose dexamethasone.

Weight gain was evident in 57.4% of young women (60.0% pituitary, 56.3% adrenal), compared with 15.8% of elderly women (50% pituitary, 0% adrenal) (P = 0.011).

Conclusion:

Older patients with CS have distinct disease cause and presentation, as pituitary source is less common than adrenal CS, the latter is associated with milder hypercortisoluria and is frequently diagnosed incidentally. Weight gain was prevalent in young women, and uncommon in older women.