Cushing syndrome in older women: age-related differences in disease origin and clinical manifestations

A. Akirov*^a (Prof), I. Shimon^b (Prof), Y. Manisterski^c (Dr), N. Aviran-Barak^c (Dr), V. Nadler^d (Dr), S. Alboim^d (Dr), G. Tsvetov^c (Dr), D. Hirsch^c (Prof)

^a Rabin Medical Center, Petach Tikva, ISRAEL ; ^b Rabin Medical Center, Tel-Aviv, ISRAEL ; ^c Maccabi Health Care Services, Tel Aviv, ISRAEL ; ^d Maccabi Health Care Services-Central Laboratory, Rehovot, ISRAEL

* amit.akirov@gmail.com

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%) patients with pituitary CS and 61 patients (43.0%) with adrenal CS: 68 young, 55 middle-aged, and 19 elderly women.

Pituitary source was more common among young women (48 patients, 70.6%), compared with middle-aged (27 patients, 49.1%) or elderly women (6 patients, 31.6%) (P<0.05). Weight gain was evident in 57.4% of young (60.0% pituitary, 56.3% adrenal) compared with 15.8% of elderly women (50% pituitary, 0% adrenal) (P=0.011).

Cushingoid features were more common among young vs. elderly patients, but the difference was not significant (40.0% vs. 22.1%, respectively; P=0.15). Among patients with adrenal CS, diagnosis of hypercortisolism was established following an incidental finding of an adrenal mass in 3 of 20 (15.0%) young women vs. 7 of 13 (53.8%) 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), while no difference was recorded for serum cortisol levels following low-dose dexamethasone. Adrenal or pituitary tumor size was not different between groups. While in young patients with CS, urinary free cortisol levels were higher for those with adrenal vs. pituitary CS (6.61±3.2xULN vs. 4.36±3.6xULN), in middle aged (3.42±3.4xULN vs. 6.24±7.7xULN) and elderly (2.62±1.9xULN vs. 5.33±2.9xULN) patients, levels were higher for those with pituitary CS.

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.

The author has declared no conflict of interest.