DOUBLE ADENOMAS WITH DIFFERENT PATHOLOGICAL AND HORMONAL FEATURES IN THE LEFT ADRENAL GLAND OF A PATIENT WITH CUSHING'S SYNDROME

We report a 52‐year‐old woman with Cushing's syndrome who presented with two adenomas in the left adrenal gland. One tumour appeared dark brown and the other appeared yellow on the cut surface. The non‐neoplastic adrenal demonstrated marked cortical atrophy. Upon histological examination, the brown tumour was found to be composed of both compact and clear cells. In contrast, the yellow tumour was composed of clear cells associated with pseudoglandular formation and marked degeneration.  Immunohistochemical studies demonstrated positive immunostaining of cytochrome P‐450 specific for 17α‐hydroxylation (P‐450c17) in the brown but not the yellow tumour. Other steroidogenic enzymes except for dehydroepiandrosterone sulphotransferase were detected in both tumours. The biochemical activities of 21‐hydroxylase, 17‐hydroxylase and 11β‐hydroxylase in the brown tumour (6.10 nmol/mg protein/4 minutes, 1.87 nmol/mg protein/2 minutes and 5.71 μmol 11‐OHCS formed/g protein/10 minutes, respectively) were much greater than those in the yellow tumour. Gel‐supported three‐dimensional native‐state primary culture of the tumours demonstrated a much higher concentration of cortisol in the culture medium for the brown tumour (5750 nmol/l on 4th day). Vimentin expression was detected in both tumours but cytokeratin expression was detected only in the yellow tumour. The Ki67 labelling index in the brown tumour was greater than that in the yellow tumour. These results indicated that these two adenomas had different biological characteristics and the brown tumour was primarily involved in overproduction of cortisol in this patient. When analysing unilateral multiple adrenocortical lesions, approaches using immunohistochemical studies for steroidogenic enzymes, enzyme activity assays and cell culture can help to define the steroidogenesis of individual adrenocortical lesions.