Diagnostic and therapeutic aspects on adrenocortical carcinoma and pheochromocytoma

Abstract

Adrenocortical Carcinoma (ACC) is a rare malignant tumour with poor prognosis. Surgical removal is the only cure. Adjuvant use of mitotane, an adrenolytic drug with toxic effects, is controversial at best. We evaluated our treatment program for patients with ACC including active surgery, adjuvant mitotane treatment monitored by serum levels of the drug, and urinary steroid profiles in the follow-up to detect early recurrences. Monitoring of serum levels of mitotane made long-term treatment possible in advanced disease with moderate side effects. Repeat surgery for recurrence was valuable in patients with long disease-free intervals, and urinary steroid profiles indicated early recurrence in individual patients. The 5-year survival of 30 consecutive patients with ACC (44% low Stage and 56% high Stage tumours) in our series was 64%. Patients with high Stage ACC (Stage III-IV), treated with mitotane after surgery, seemed to have better prognosis than expected. The results of cytotoxic treatment in advanced disease, using single or multiple cytotoxic agents, have so far been disappointing. Better results were obtained when mitotane was combined with the chemotherapy. Multicenter trials are needed in order to find the best combined medical therapy for these patients.In order to find histopathological markers that can predict the prognosis in ACC and pheochromocytoma (PC), 87 adrenal tumours were analysed for the expression of cell adhesions molecules by immunocytochemistry and Western blotting. Both cortical and medullary adrenal tumours expressed NCAD, NCAM and CD44, but all tumours were devoid of ECAD. The expression of CD44 and NCAM did not correlate with the malignant potential of the tumours. During cell transformation and tumour progression NCAD expression seemed to be up-regulated in medullary tumours, but down-regulated in cortical tumours. Loss of NCAD may thus be involved in the development of malignant adrenocortical tumours. Thus, NCAD may function as tumour suppressor and lack of its expression may be of prognostic significance in adrenocortical tumours.PC and paraganglioma (PG) rarely metastasize, but may still be life-threatening due to excessive secretion of catecholamines (CA). The cause of death in untreated PC/PG is hypertensive complications and in rare cases metastatic disease. The overall prognosis after surgical removal of PC has not been studied in detail. In the present study with long-term follow-up (1950-1997), 121 consecutive cases of surgically treated PC/PG were reviewed in order to evaluate outcome, cause of death and histopathological features. There was no intra- or post-operative mortality. Eight patients proved to have malignant PC/PG during the period. The number of deaths in the series was higher than expected in the general population (p <0.001). The main causes of death were cardiovascular and other tumour diseases. High age at primary surgery and high urinary excretion of methoxy-CA were significant risk factors for death. For comparative reasons, all cases with adrenal PC, diagnosed in Sweden 1958-1997, were investigated. Patients in the national cohort had almost 4 times higher risk for death in tumour diseases than the general population, but no elevated death risk for cardiovascular diseases. Life-long follow-up of these patients is important not only to diagnose and treat cardiovascular diseases and recurrent PC at early Stage, but also to diagnose other tumour diseases.