Endocrine Abstracts

The great majority of phaeochromocytomas are benign, but some 10–15% are found to be malignant, the proportion being higher when they are extra-adrenal, paragangliomas. Malignant behaviour is hard to predict, and there are few histopathological features that are consistently of use. There are novel biochemical and molecular markers, but none has proven to be as yet especially reliable although elevated urinary methoxytyramine seems to be useful. At present, size is probably as useful as any marker in predicting malignancy. I use ¹²³I-MIBG radionuclide scanning in all patients diagnosed with a phaeochromocytomas in order to identify any possible metastases pre-operatively, and as a marker of possible therapy for recurrent tumours. Where tumours are indeed malignant, it has been found that up to half show germline mutations of the SDH-B gene, and then family counselling and assessment is important. The standard chemotherapy for such tumours is with the combination of cyclophosphamide, vincristine and doxorubicin (CVD), but a long-term effect on survival has been difficult to demonstrate. Recent data have suggested that temozolomide may be useful a second-line chemotherapy, but responses are rarely maintained long-term. Where the tumour shows radiolabelled MIBG uptake then treatment with ¹³¹I-mIBG is effective in controlling symptoms and abnormal biochemistry in many patients, and stabilization of tumour progression is often seen. Very high doses of ¹³¹I-mIBG may cause tumour regression, but at the expense of considerable marrow toxicity. Our recent data also suggest an increase in myeloproliferative disorders in long-terms survivors from this treatment. Knowledge of the molecular pathogenesis of these tumours had indicated that tyrosine kinase inhibitors such as sunitinib, and mTOR inhibitors such as everolimus, may be beneficial: sunitinib may have some temporary inhibiting effect on tumour progression, but everolimus does not appear to show much therapeutic benefit. Recent in vitro and in vivo data suggest that combination therapy with broad-action mTOR and ERK inhibitors may be highly effective, but we await proper clinical trials. At present, these tumours are invariably eventually lethal, although survival can be prolonged for a considerable time by the judicial use of sequential or combination therapies.