CLINICOPATHOLOGICAL STUDY OF CUSHINGS-DISEASE WITH LARGE PITUITARY-ADENOMA

OBJECTIVE To explore the biological and morphological differences betw een large Gushing's adenomas and small adenomas, we investigated the c linical, endocrinological, neuroradiological, and histological feature s of patients with large Gushing's adenomas and compared them with pat ients with small Cushing's adenomas, PATIENTS Five of 250 patients wit h Gushing's disease undergoing trans-sphenoidal operations from 1989 t o 1995 had large adenomas with maximum diameters greater than 30 mm, T he clinical characteristics of these five patients were compared with the 14 patients with Gushing's disease with small adenomas in our seri es, RESULTS Oedema, myopathy, and mental disturbance were more frequen t and hypertension war; less frequent among patients with large adenom as, The high-dose (8 mg) dexamethasone test did not suppress cortisol production in any of the five patients, Invasion into surrounding tiss ue wa!; demonstrated by magnetic resonance imaging in all five cases, All five large adenomas had scarce or no periodic acid-Schiff-positive granules and were sparsely granulated ultrastructurally, Three tumour s contained cells with honeycomb Golgi apparatus which rarely containe d immature secretory granules, One Crooke's cell adenoma contained tra pped or displaced secretory granules. The other tumour had dilated tra ns-Golgi network-derived vacuoles that contained reticular or circular electron-dense material. These findings were in striking contrast to those of small Gushing's adenomas, which showed strong PAS positivity, densely-packed granulation, and had prominent Golgi complex harbourin g developing secretory granules, CONCLUSIONS We found that the tumour cells in large adenomas produced only small amounts of ACTH, and showe d indications of disturbances in the regulated exocytotic pathways. Th ese factors may account for the different clinical characteristics of Gushing's disease with large pituitary adenomas.