Macronodular adrenocortical hyperplasia in long-standing Cushing's disease

Clinical and biochemical findings in 13 patients (11 women and 2 men) with macronodular adrenocortical hyperplasia (MNH; nodule size, greater than 0.5 to 5.3 cm) were compared with those of 18 patients (15 women and 3 men) with Cushing's disease and diffuse (n = 9) or micronodular (n = 9) hyperplasia (DH). All were bilaterally adrenalectomized for their hypercorticism. The clinical picture was almost identical in both groups, except for greater frequency of hypertension (13 of 13 vs. 10 of 18; P less than 0.05), alopecia (4 of 11 vs. 0 of 15; P less than 0.05), and scintigraphic lateralization (6 of 7 vs. 1 of 7; P less than 0.05) in the MNH group than in the DH group. The sella turcica was enlarged in 30% of the patients in both groups. Patients with MNH were significantly older than DH patients [43.5 +/- 7.8 (mean +/- SD) vs. 31.7 +/- 10.1 yr; P less than 0.005] and had a 3-fold longer duration of disease (7.8 +/- 4.6 vs. 2.0 +/- 1.1 yr; P less than 0.001) than those with DH. The mean plasma ACTH and cortisol levels and urinary 17-hydroxycorticosteroid excretion were elevated in both MNH and DH patients and responded similarly to specific (corticotropin-releasing hormone and metyrapone) and nonspecific (TRH and LHRH) stimuli. However, dexamethasone suppressibility and the stimulatory effect of ACTH on adrenocortical function were less in the MNH than in the DH group or its subgroups, suggesting a greater degree of adrenal autonomy in the former. Adrenal weight in MNH (15.8 +/- 12.1 g each) was almost twice as high as in DH (8.2 +/- 2.0 g) patients and positively correlated with the duration of the disease. The data suggest that MNH may be a result of long-standing Cushing's disease with varying degrees of pituitary dependence and adrenocortical autonomy, which may lead to confusing biochemical and radiological findings. Bilateral adrenalectomy, rather than hypophysectomy, is the treatment of choice in MNH.