Conn’s syndrome caused by aldosterone-producing adrenocortical carcinoma: report of two divergent cases and a meta-analysis of all reported cases since 1955

Abstract

Aldosterone-producing adrenocortical carcinoma (APAC) is a rare disorder: hence, as a result of the paucity of information on its biological behaviour, the diagnosis is often delayed. To date, no data on survival rates and diagnostic markers signs of malignancy is available. To report on two cases that featured an unusual course and to delineate the clinical characteristics and natural history of APAC based on a meta-analysis of all reported cases from the literature since 1955. A database was created with all available information on demography, imaging results, hormonal data, gross features, histology, and clinical course. We used Kaplan Meier and Cox regression analysis to calculate survival curves and recurrence-free survival, and to identify the impact of several covariates on survival. We identified in the literature 62 cases of APAC, including the present two, all presenting the classical signs of Conn's syndrome. Plasma aldosterone levels exhibited on average a 14-fold increase; plasma renin activity was suppressed in 55% of cases. The tumour showed no gender or side preference and extremely variable size and weight. At the time of initial diagnosis metastases were present in 10% of all cases; they were detected at follow-up in 48% additional cases. Median survival was 546 days (95% c.i.: 240–851); median time to either recurrence or death was 212 days (95% c.i.: 29–395). Neither clinical signs nor histological features of malignancy did predict survival. The clinical features of APAC are variable, but an ominous clinical course with a very poor survival rate is common. No clinical signs were found to accurately predict malignant clinical course. Hence, molecular studies to identify diagnostic markers and predictors of survival are mandatory.