Case Report: Paradoxical responses to pasireotide in a patient with a silent corticotroph adenoma that transformed into an ACTH-secreting adenoma

Introduction: There are only a few reported cases of paradoxical response to pasireotide treatment of adrenocorticotropic hormone (ACTH)-secreting tumors, mostly aggressive macroadenomas, which led to therapy discontinuation. We present a case of a patient with Cushing's disease and paradoxical responses to pasireotide Long-Acting Release (LAR) in whom, despite the initial increase in hypercortisolemia, the treatment was successful in terms of tumor shrinkage. The rarity of paradoxical responses to pasireotide LAR makes this case a valuable insight into a potentially dangerous and poorly understood clinical situation. Case description: The patient was diagnosed in 2008 with a non-secreting pituitary macroadenoma, causing only neurological symptoms. Initial therapy included two transsphenoidal surgeries and stereotactic radiotherapy. The pathological report indicated ACTH expression, although it was clinically silent. After 7 years, the patient underwent reoperation due to sudden deterioration of the neurological condition and regrowth of the tumor. In 2019, hypercortisolemia appeared, and treatment with pasireotide LAR was initiated. Pharmacotherapy continued for 4 years; four of eight pasireotide LAR injections were followed by paradoxical responses, which were managed with steroidogenesis inhibitors. During this therapy, the tumor size was significantly reduced. Conclusions: Pasireotide LAR successfully reduced the tumor mass despite paradoxical responses. A transient increase in hypercortisolemia after pasireotide LAR was difficult to predict but was managed with steroidogenesis inhibitors.