Temozolomide therapy for aggressive pituitary Crooke's cell corticotropinoma causing Cushing's Disease - a case report with literature review

Introduction: Aggressive pituitary tumours causing Cushing's Disease are very rare, difficult to treat, and usually resistant to conventional therapy. There is growing evidence for the use of temozolomide (TZM), an alkylating chemotherapeutic agent, as first-line chemotherapy in such tumours. Objective: To present the response to TMZ in an aggressive pituitary tumour and Cushing's Disease and to review the literature referring to similar cases. Case report: A sixty-one-year-old male patient was diagnosed with Cushing's Disease and invasive macroadenoma in 2011. Four transsphenoidal non-radical neurosurgeries (2012, 2013) with rapid tumour progression, repeated non-radical bilateral adrenalectomy (2012, 2013) and stereotactic radiotherapy, and gamma knife surgery (2013, 2015) were performed. Histopathological examination revealed macroadenoma with high cell polymorphism and the presence of Crooke's cells, Ki- < 2%. Since 2015 the patient has been treated with six cycles of TMZ with clinical and biochemical improvement and stabilised tumour size and no side effects. TMZ was continued for up to nine cycles; however, symptoms like headaches, visual field impairment, and hearing loss were progressing. After the ninth cycle of TMZ, there was a sudden increase in the size of the tumour with deterioration of the clinical status. The patient died in February 2016. Conclusions: The case of our patient suggests that the response to the TMZ treatment monotherapy in an aggressive pituitary tumour causing Cushing's Disease could be partial, followed by rapid progression of the tumour mass. Further research should be carried out to investigate predictors of responsiveness and to extend duration of TMZ treatment.