Primary Hyperaldosteronism with Syndrome of Inappropriate Antidiuretic Hormone (SIADH) and Nephrocalcinosis

Introduction: Primary hyperaldosteronism (PA), traditionally characterized by hypertension, sodium retention, and hypokalemic metabolic alkalosis, is often managed effectively with mineralocorticoid receptor antagonists. We present a case of PA management complicated by concurrent SIADH, hypercalciuria, and nephrocalcinosis. Case Description: Our 39 year-old woman presented in 2019 with hypertension due to primary hyperaldosteronism, without hypokalemia or metabolic alkalosis. Serum aldosterone ranged from 16-70 ng/dL, plasma renin activity 0.1-0.5 ng/mL/hr, with elevated aldosterone:renin ratios of 140-350. Oral salt load did not suppress aldosterone excretion. On CT, adrenals were normal, and adrenal vein sampling showed bilateral disease. Genetic testing was negative for glucocorticoid-remediable aldosteronism. Spironolactone was initiated then discontinued due to a worsening of chronic hyponatremia to 123 mEq/L. Serum sodium on eplerenone ranged from 127-131 mEq/L; hyponatremia did not resolve off MRAs. Hyponatremia workup was consistent with SIADH without identifiable cause. Her hyponatremia responded well to oral urea, however dosing has been limited by worsening hypercalciuria and noted medullary nephrocalcinosis on CT. Discussion: PA is typically effectively managed with MRAs, however this strategy can be limited with concurrent SIADH. Hypercalciuria and nephrocalcinosis further complicates management. For example, increasing solute therapy or adding loop diuretics is contraindicated. There are few other case reports of PA associated with nephrocalcinosis. PA has been observed with increased urinary calcium excretion and oxalate crystal formation, though proposed mechanisms including prolonged hypokalemia, hypocitraturia, and urine acidification are not present in our patient. Thus far no unifying etiology has been identified, including tubulopathies (no proteinuria, hematuria) or rheumatic disease, to link these conditions. The next management step for this patient will be repeat eplerenone trial with oral urea for hyponatremia. Amiloride could also be considered.Workup summary