Clinicopathological features of primary aldosteronism associated with subclinical Cushing's syndrome.

Primary aldosteronism (PA), an autonomous aldosterone hypersecretion from adrenal adenoma and/or hyperplasia, and subclinical Cushing syndrome (SCS), a mild but autonomous cortisol hypersecretion from adrenal adenoma without signs or symptoms of Cuhing's syndrome, are now well-recognized clinical entities of adrenal incidentaloma. However, the clinicopathological features of PA associated with SCS (PA/SCS) remain unknown. The present study was undertaken to study the prevalence of PA/SCS among PA patients diagnosed at our institute, and characterize their clinicopathlogical features. The prevalence of PA/SCS was 8 of 38 PA patients (21%) studied. These 8 PA/SCS patients were significantly older and had larger tumor, higher serum potassium levels, lower basal plasma levels of aldosterone, ACTH and DHEA-S as well as lower response of aldosterone after ACTH stimulation than those in 12 patients with aldosterone-producing adenoma without hypercortisolism. All 8 PA/SCS patients showed unilateral uptake by adrenal scintigraphy at the ipsilateral side, whereas the laterality of aldosterone hypersecretion as determined by adrenal venous sampling varied from ipsilateral (3), contralateral (2), and bilateral side (2). 6 PA/SCS patinets who underwent adrenalectomy required hydrocortisone replacement postoperatively. Histopathological analysis of the resected adrenal tumors from 5 PA/SCS patients revealed a single adenoma in 3, and double adenomas in 2, with varying degrees of positive immunoreactivities for steroidgenic enzymes (3ß-HSD, P450(C17)) by immunohistochemical study as well as CYP11B2 mRNA expression as measured by real-time RT-PCR. In conclusion, PA/SCS consists of a variety of adrenal pathologies so that therapeutic approach differs depending on the disease subtype.

Clinicopathological features, biochemical and molecular markers in 5 patients with adrenocortical carcinoma.

Adrenocortical carcinoma (ACC) is a very rare malignant tumor with poor prognosis. To gain insight into the pathogenic significance of ACC, we studied clinicopathological features and gene expression profile in ACC. We analyzed five ACC cases (two men and three women) with the median age of 45-year-old who underwent adrenalectomy at our institute. Endocrine studies revealed that two cases had subclinical Cushing's syndrome (SCS) and one with concomitant estrogen-secreting tumor, while the rest of three cases had non-functioning tumors. Analysis of urinary steroids profile by gas chromatography/mass spectrometry showed increased metabolites of corticosteroid precursors, such as 17-OH pregnenolone, 17-OH progesterone, dehydroepiandorosterone (DHEA), and 11-deoxycortisol in all five cases. The pathological diagnosis of ACC was based on Weiss's criteria with its score ≥ 3. The mean size of the resected tumors was 87 mm and Ki67/MIB1 labeling index, a proliferative marker, was 3-27%. Immunohistochemical analysis revealed a disorganized expression of several steroidogenic enzymes, such as 3ß-hydroxysteroid dehydrogenase, 17α-hydroxylase, and DHEA-sulfotransferase. Among several genes determined by RT-PCR, insulin-like growth factor (IGF)-II mRNA was consistently and abundantly expressed in all 5 tumor tissues. Postoperatively, two cases with SCS developed local recurrence and liver metastasis. The present study suggests that the disorganized expression of steroidogenic enzymes and the overexpression of IGF-II by the tumor are hallmarks of ACC, which could be used as biochemical and molecular markers for ACC.

A rare case of ACTH-independent macronodular adrenal hyperplasia associated with aldosterone-producing adenoma.

A 52-year-old man was evaluated for incidentally discovered bilateral adrenal masses. He had drug-resistant hypertension but lacked Cushingoid features. Endocrinological tests revealed autonomous secretion of cortisol and aldosterone with suppressed plasma ACTH and renin activity. A selective adrenal venous sampling demonstrated aldosterone hypersecretion from the left adrenal vein. The clinical diagnosis of subclinical Cushing's syndrome due to ACTH-independent macronodular adrenal hyperplasia (AIMAH) associated with primary aldosteronism was made, and he underwent left adrenalectomy; the resected adrenal lesion was consistent with the pathological diagnosis of AIMAH coexistent with aldosterone-producing adenoma (APA). This is a very rare case of AIMAH with concomitant unilateral APA, whose hypertension improved after surgery.