ESPE Abstracts

Introduction: Heritable conditions causing aldosterone deficiency (hypoaldosteronism) or target-organ resistance (pseudohypoaldosteronism, PHA) can lead to life-threatening salt-wasting crises in early life. Prompt evaluation and correct interpretation of aldosterone and renin are crucial to guide differential diagnosis and further testing. Here we report on the similarities and differences of two neonates presenting with salt-wasting: Patient (P1) due to PHA type 1A and, Patient 2 (P2) due to aldosterone-synthase deficiency type 2 (ASD).

Case reports: Both patients were admitted in their first month of life for failure to thrive, dehydration, with features of severe hyponatremia and hyperkalemia. They had normal external genitalia and no hyperpigmentation. Whilst 17-OH-progesterone and ACTH-test were normal, renin was markedly elevated. P1 (female) had substantially elevated serum aldosterone concentrations, while P2 (male) had low-normal aldosterone. Both patients were initially treated with intravenous NaCl, salbutamol-inhalations, glucose/insulin infusions and fludrocortisone. P1 also received oral and rectal resonium, but was unresponsive to fludrocortisone. Thus, PHA type 1A was suspected in P1 and later on confirmed by genetic testing (heterozygous NR3C2 mutation: c.2306T>C). Further management for P1 consisted of oral resonium (0.3 g/kg/d) and NaCl (5.7 mmolNa/kg/d) with decreasing requirements incrementally. P2 had a history of neonatal sepsis and developed E. coli sepsis on readmission. He was initially presumed to have acquired hypoaldosteronism secondary to a critical illness. He was discharged on oral NaCl (9 mmolNa/kg/d) and followed-up at a peripheral hospital, where he was weaned off NaCl. He was readmitted at one year of age with severe hyponatremia and hyperkalemia and persistent failure to thrive. Reevaluation revealed a plasma aldosterone/renin ratio < 1pmol/mU (normal reference range 1-72 pmol/mU) and elevated urinary aldosterone-precursors suggestive of ASD. Fludrocortisone and oral sodium were restarted leading to prompt stabilization. Genetic testing confirmed ASD type 2 (homozygous CYP11B2 mutation: c.554C>T).

Conclusion: Salt loss in neonates is an endocrine emergency, requiring tertiary endocrine care. While renin and aldosterone are markedly elevated in patients with PHA, as in our case, aldosterone may remain inappropriately normal in ASD2. Thus, a decreased aldosterone/renin ratio should prompt further investigation to avoid delay in diagnosis and life-saving treatments.