ACTA ENDOCRINOLOGICA (BUC)

Cushing syndrome (CS) is a severe clinical condition caused by prolonged and inappropriate exposure to cortisol. Excluding exogenous cortisol excess, adrenocorticotropic hormone (ACTH) secretion from a pituitary adenoma, also called Cushing disease (CD), represents by far the most common CS etiology. Since Harvey Cushing first reported the classical clinical syndrome over 100 years ago, much clinical progress has been made, however disease management remains a challenge both in terms of diagnosis and treatment.Treatment is often complex and may require surgery, medical management and radiotherapy. Here we focus on the key findings of recent clinical trials with new therapeutic agents (1-3) and discuss how these new treatments fit in the armamentarium for patients with CD.

Pituitary radiotherapy (RT) has undergone important progress in the last decades due to the development of new stereotactic techniques which provide more precise tumour targeting with less overall radiation received by the adjacent brain structures. Pituitary surgery is usually firstline therapy in most patients with nonfunctioning (NFPA) and functioning adenomas (except for prolactinomas and large growth hormone (GH) secreting adenomas), while RT is used as second or third-line therapy. The benefits of RT (tumour volume control and, in functional tumours, decreased hormonal secretion) are hampered by the long latency of the effect and the potential side effects. This review presents the updates in the efficacy and safety of the new stereotactic radiation techniques in patients with NFPA, GH-, ACTH- or PRL-secreting pituitary adenomas. Methods. A systematic review was performed using PubMed and articles/abstracts and reviews detailing RT in pituitary adenomas from 2000 to 2017 were included. Results. Stereotactic radiosurgery (SRS) and fractionated stereotactic RT (FSRT) provide high rates of tumour control i.e. stable or decrease in tumour size, in all types of pituitary adenomas (median 92 - 98%) at 5 years. Endocrinological remission is however significantly lower: 44-52% in acromegaly, 54-64% in Cushing’s disease and around 30% in prolactinomas at 5 years. The rate of new hypopituitarism varies from 10% to 50% at 5 years in all tumour types and as expected increases with the duration of follow-up (FU). The risk for other radiation-induced complications is usually low (0-5% for new visual deficits, cranial nerves damage or brain radionecrosis and extremely low for secondary brain tumours), however longer FU is needed to determine rates of secondary tumours. Notably, in acromegaly, there may be a higher risk for stroke with FSRT. Conclusion. Stereotactic radiotherapy can be an effective treatment option for patients with persistent or recurrent pituitary adenomas after unsuccessful surgery (especially if residual tumour is enlarging) and/or resistance or unavailability of medical therapy. Comparison with conventional radiation therapy (CRT) is rather difficult, due to the substantial heterogeneity of the studies. In order to evaluate the potential brain-sparing effect of the new stereotactic techniques, suggested by the current data, longterm studies evaluating secondary morbidity and mortality are needed.