Introduction: Cushing’s disease (CD) is characterized by multiple complications, particularly due to the condition itself, but also as a result of curative treatment. Nowadays, transsphenoidal surgery is considered the ﬁrst-line therapy. Persistent hypercortisolism requires the initiation of medical therapy in order to limit the consequences of the disease. A common complication of pasireotide treatment is type 2 diabetes mellitus. We present a case of persistent Cushing’s disease after transsphenoidal adenomectomy and pasireotide therapy, evaluated in several medical centers. Case presentation: A 27-year-old female was referred to our clinic for weight gain, hypertension, transient headache and recurrent depression. Clinical examination revealed plethoric moon face, purple striae, hirsutism with a Ferriman-Gallwey score of 14, acanthosis nigricans. The hormonal proﬁ le showed high ACTH (adrenocorticotropic hormone) levels (of 110.6 pg/mL, normal: 7.2-63.3 pg/mL), high urinary free cortisol (UFC) (of 846.5 μg/24h, normal: 50-190 μg/24h) and serum cortisol, accompanied by non-suppression of cortisol after the 1 mg DXM (Dexamethasone) suppression test (of 26.6 μg/dL, normal: 18 μg/dL) and adequate suppression after the overnight 8 mg DXM test. Pituitary MRI (Magnetic Resonance Imaging) revealed a microadenoma measuring 4.3/4.4/6.2 mm. Transsphenoidal adenomectomy was recommended. After surgery, the patient developed multiple pituitary hormone deﬁciency, without signiﬁcant remission of hypercortisolism. Pasireotide therapy was initiated, followed by inadequate control of hypercortisolism and the onset of type 2 diabetes mellitus, requiring oral antidiabetic agents and insulin. Conclusion: In persistent Cushing’s disease, the challenge lies in identifying the optimal therapeutic methods in order to achieve a cure while, at the same time, limiting their side effects. Careful long-term follow-up by a multidisciplinary team is required.