Steroid metabolite cross-reactivity leading to diagnostic dilemma in a male infant with salt-wasting crisis: A case report

Salt-wasting crisis in neonates may arise from aldosterone deficiency, as seen in congenital adrenal hyperplasia (CAH), or aldosterone resistance, as in pseudohypoaldosteronism (PHA). Differentiating between these two conditions is essential for appropriate management to optimize outcomes. We report a 2-month-old male infant presenting with failure to thrive, vomiting, dehydration, and severe electrolyte abnormalities. Initial investigations revealed severe hyponatremia, hyperkalemia, metabolic acidosis, elevated cortisol, aldosterone, renin, and moderately increased 17-hydroxyprogesterone (17OHP), raising suspicion for both CAH and PHA. The presence of bilateral hydronephrosis and pyuria further complicated the diagnosis. Despite initial consideration of PHA secondary to urospesis, an adrenocorticotropic hormone (ACTH) stimulation test showed markedly elevated 17OHP levels, confirming the diagnosis of salt-wasting CAH. Targeted genetic analysis revealed both homozygous and compound heterozygous pathogenic variants in the CYP21A2 gene. The infant improved with glucocorticoid and mineralocorticoid replacement and remained well on follow-up. The index case suggests that the chemiluminescence assays may yield false-positive results for elevated cortisol and aldosterone levels due to cross-reactivity with steroid precursors. ACTH-stimulated 17OHP testing and genetic analysis are essential for accurate diagnosis and management.