Combination Medical Treatment for Difficult-to-manage Cushing's Disease: A Single Tertiary Pituitary Center's Experience
NAMIK KEMAL MEDICAL JOURNAL, cilt.14, sa.3, ss.323-332, 2026 (ESCI, TRDizin)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 14 Sayı: 3
- Basım Tarihi: 2026
- Doi Numarası: 10.4274/nkmj.galenos.2026.7903
- Dergi Adı: NAMIK KEMAL MEDICAL JOURNAL
- Derginin Tarandığı İndeksler: Emerging Sources Citation Index (ESCI), TR DİZİN (ULAKBİM)
- Sayfa Sayıları: ss.323-332
- İstanbul Üniversitesi-Cerrahpaşa Adresli: Evet
Özet
Aim: The primary treatment for cushing's disease (CD) is transsphenoidal surgery (TSS). However, in refractory cases where medical monotherapy fails, combination therapy may enhance efficacy through synergistic mechanisms and reduce side effects by using lower drug doses. This study aimed to evaluate the efficacy of mono-and combination therapies in difficult-to-manage patients with CD treated at our center. Materials and Methods: This retrospective, single-center study included 55 patients with persistent CD treated between 2010 and 2025 with monotherapy or combination therapy after TSS. Clinical and biochemical parameters were compared between pretreatment and the last follow-up following mono-or combination therapy, and remission status was also assessed. Results: Following TSS, all 55 patients received medical management [median duration of therapy: 21.0 (12.0-61.0) months]; therapy was initiated postoperatively in 44 patients (80%), while the remaining 11 (20%) continued their preoperatively initiated treatment. At the last follow-up, 77.5% of patients achieved remission. The most common regimens were pasireotide (30.9%), cabergoline + metyrapone (18.2%), and cabergoline + ketoconazole (14.5%). Overall, cabergoline (67.3%) and pasireotide (58.2%) were the most frequently administered agents across all treatment periods. Twenty-three patients (41.8%) required treatment changes, mostly due to lack of remission (23.6%). Medical therapy decreased baseline cortisol, adrenocorticotropic hormone, urinary free cortisol, late-night salivary cortisol, and adenoma size, with a significant reduction in dexamethasone suppression test (p=0.016). Monotherapy and combination therapy showed no significant differences in hormonal control, metabolic outcomes, remission rates, or adverse events. Conclusion: Our findings suggest that medical combination therapy is a feasible, safe, and effective treatment option for the long-term treatment of CD in patients who could not achieve remission after TSS or who have persistent disease activity.