MON-457 One in Five Patients Develop Multiple Hormone Deficiencies Following Radiotherapy for Acromegaly or Cushing's Disease

Abstract

Aim: To characterise the use of radiotherapy (RTx) for corticotropinomas and somatotropinomas and the long-term clinical outcome for these patients. Methods: All patients with corticotropinomas (CD) and somatotropinomas (AC) who were treated at the Royal Melbourne and the Royal Adelaide Hospitals between 1980 and 2017 were included. Long-term clinical outcome data were obtained via a clinical database (Biogrid) and medical records from the respective hospitals. There were no standard guidelines for recommending RTx during this period at either institution, however, it was considered in the presence of non-operable persistent or relapsed disease. Statistical analyses applied included binary logistic regression, propensity score matching and Fisher’s exact test. Results In total, 171 patients were assessed and 30 patients were excluded due to insufficient data. Of the 141 patients included, 32 patients (23%) received RTx (20 - AC, 12 - CD). The non-RTx group (n=109) consisted of 78 CD and 31 AC patients. Patients with macroadenomas were significantly more likely to receive RTx (OR 5.93, p < 0.05, CI 1.9-18.3). Details regarding the modality of RTx were recorded in 18 of 32 patients: 9 fractionated stereotactic, 7 single dose radiosurgery, 2 deep-radiotherapy. Twenty-nine (21%) patients in this study had evidence of persistent ACTH or GH hyper-secretion post initial surgery and 14 received RTx. Amongst 9 AC patients who required medical therapy for disease control, 6 patients (67%) were able to stop their medication post RTx. The median time for medication cessation was 78 months (IQR 31, 106). None of the patients (n=12, 2 had CD, 10 had AC) in non-RTx group were able to cease medication (p < 0.05). After adjustment for tumour size, number of surgeries and surgery performed within the past 10 years, RTx was independently associated with increasing risk of hypopituitarism (adjusted OR 3.04, CI 1.01-9.17, p = 0.048). Overall, 11 out of 32 patients (34%) in the RTx group developed hypopituitarism. The median time to onset of first hormone deficiency post RTx was 36 months (IQR 7-60). Hypogonadotrophic hypogonadism was the most common deficiency detected (n=7), followed by ACTH (n=5) and TSH deficiency (n=4). Seven patients (22%) developed more than one hormone axis deficiency and 2 patients (6%) developed panhypopituitarism. Conclusion In this study, approximately 1 in 5 (22%) corticotropinoma and somatotropinoma patients developed multiple hormone deficiency post RTx. The median time to develop first hormone deficit was 36 months, confirming that long-term follow-up is required for these patients. Further studies are needed to compare mortality and cost-effectiveness of RTx versus medical therapy for persistent or recurrent corticotropinomas and somatotropinomas.