The role of radiologic studies in the evaluation and management of primary hyperaldosteronism.

BACKGROUND: Surgical treatment of primary hyperaldosteronism (PHA) requires demonstration of unilateral adrenal hypersecretion. Optimal methods for interpretation of imaging and invasive testing are still in development. METHODS: A retrospective review from 1996-2007 of 106 patients with PHA was undertaken. Patient demographics, biochemical studies, radiologic imaging, operative reports, and pathology were reviewed and comparisons made. Optimal ratios for adrenal vein sampling were tested with regard to sensitivity and specificity. Preoperative and postoperative medication requirements and blood pressures were compared among different treatment groups. RESULTS: Seventy-eight patients (62 surgically treated) met criteria for inclusion. Median arterial blood pressure at diagnosis was 150/86 mm Hg while taking 3 antihypertensive medications. 69.2% required potassium supplementation. Median aldosterone:renin ratio was 107.0. Forty-two AVS procedures changed the management of 15 patients (35.7%) when compared to CT results. AVS accuracy was 96.6 vs 88.9% for NP-59 scintigraphy. Operative patients remained on fewer antihypertensive medications (1 vs 3), and mean systolic pressure was lower (130 vs 146 mm Hg) compared with medically managed patients. CONCLUSION: When used together, pre-ACTH aldosterone ratios, normalized A/C:A/C ratios, ratios to define contralateral suppression, and post-ACTH stimulated values allowed for capture of episodically secreting tumors and subtle unilateral or bilateral hyperaldosteronism.

Steroid receptor coactivator-1-deficient mice exhibit altered hypothalamic-pituitary-adrenal axis function.

Steroidogenic factor-1 (SF-1), has emerged as a critical nuclear receptor regulating development and differentiation at several levels of the hypothalamic-pituitary-steroidogenic axis. Although many coregulatory factors have been shown to physically and functionally interact with SF-1, the relative importance of these interactions in SF-1 target tissues has not been thoroughly established. In this study we assessed roles of steroid receptor coactivator-1 (SRC-1) in hypothalamic-pituitary-adrenal (HPA) axis function using SRC-1-deficient (SRC-1-/-) mice in the absence or presence of SF-1 haploinsufficiency. Surprisingly, SRC-1 deficiency did not alter baseline HPA axis function or the acute rise in corticosterone after ACTH administration and failed to exacerbate adrenocortical dysfunction in SF-1+/- mice. However, after exposure to paradigms of acute and chronic stress, SRC-1-/- mice exhibited an elevation in serum corticosterone despite normal (nonsuppressed) ACTH, suggesting an increase in adrenal sensitivity as well as a concomitant defect in glucocorticoid-mediated feedback inhibition of the HPA axis. An examination of potential compensatory mechanism(s) revealed an increase in adrenal weight, selective elevation of melanocortin 2 receptor mRNA, and a coincident increase in SRC-2 and SRC-3 expression in SRC-1-/- adrenals. A reduction in blood glucose was observed in SRC-1-/- mice after chronic stress, consistent with a generalized state of glucocorticoid resistance. Dexamethasone suppression tests confirmed a weakened ability of glucocorticoids to 1) elevate serum glucose levels and induce hepatic phosphoenolpyruvate carboxykinase transcription and 2) suppress pituitary proopiomelanocortin transcript levels in SRC-1-/- animals. Collectively, these data are consistent with an indispensable role for SRC-1 in mediating actions of glucocorticoids in pituitary and liver.