A congenital renal anomaly can cause pseudohypoaldosteronism (PHA) due to a lack of response to aldosterone in the distal tubule in infants less than three months of age in the presence of obstructive uropathy, vesicoureteral reflux (VUR) and/or urinary tract infection (UTI)¹ and this can be confused with congenital adrenal hyperplasia. 

An inherited disorder in terminal steps in aldosterone biosynthesis leads to deficient synthesis of aldosterone and overproduction of metabolic products proximal to the enzymatic block.² Aldosterone levels are low or inappropriately normal, plasma renin activity (PRA) and aldosterone precursors (18-hydroxycorticosterone) are elevated.² There have been several reports of secondary PHA in infancy associated with urinary tract abnormalities, and less commonly, with urinary tract infections (UTI).^3,4,5 We present this case to emphasise that the diagnosis of transient pseudohypoaldosteronism should be seriously considered in the dehydrated, febrile or failing to thrive infant with hyponatraemia.

Case report

We report on a three-month-old girl referred from her general practitioner with fever and vomiting for three days. Baseline investigations: urine dipstick showed both leukocyte esterase and nitrite positive; serum sodium 114mmol/L and potassium 6.7mmol/L; and normal urea and creatinine. She was started management with normal saline and intravenous antibiotics after blood and urinary cultures. Further investigations showed high serum aldosterone 30200pmol/L and her urine grew Escherichia Coli on culture. Her deranged electrolytes were normalised in three days and she responded clinically to intravenous antibiotics. 

Renal ultrasonography revealed hydronephrosis and hydroureter on left side. She was discharged in good stable health with follow up in outpatient department and showed normal serum electrolytes and negative urine culture. Further follow up radiological investigations showed normal MCUG and MAG-3 scan confirmed mild left vesicoureter junction obstruction. During further follow up she showed normal growth parameters and had no further episodes of urine infection.

Discussion

Our patient has demonstrated the transient nature of the aldosterone resistance, distinguishing this condition from other important differentials such as congenital adrenal hyperplasia (CAH), congenital adrenal hypoplasia, genetic causes of pseudohypoaldosteronism and  isolated aldosterone deficiency, all having the same clinical presentations. 

In a paediatric setting, the combination of hyponatraemia and hyperkalaemia, with the key finding of an elevated serum aldosterone, strongly suggests the diagnosis of PHA. It has been shown that urinary tract infection and obstructive and non-obstructive renal lesions are associated with biochemical and hormonal disturbances, indicating renal tubular aldosterone resistance and secondary PHA.⁶ Renal tubular resistance to aldosterone has been previously described in patients with a variety of urinary tract malformations.^7,8 In our case aldosterone resistance was obvious in the setting of a urinary tract infection. However, with the treatment of infection the state of hyperaldosteronism was settled. There remains controversy in the literature regarding the role of microbial infection versus anatomic anomaly in the urinary tract as the underlying pathology leading to mineralcorticoid resistance.

There is a possibility that the association with urinary tract malformations is due to their high incidence in infants diagnosed with severe urinary tract infections. There are many reports in literature^1,5,9 supporting that a severe urinary tract infection itself, rather than combination with an underlying malformation, may cause aldosterone resistance. The mechanism of aldosterone resistance is not fully understood, but it becomes exaggerated in the presence of a UTI.¹⁰

However, the condition may be difficult to diagnose promptly, in part because the aldosterone assay is generally sent to a reference laboratory, and results are not available for several days. Thus, the measurement of a urinary sodium level, if possible done prior to sodium replacement and antibiotic therapy, may reveal excessive urinary sodium excretion, suggesting aldosterone deficiency or resistance. The implications of our case are that the diagnosis of transient pseudohypoaldosteronism needs to be a strong consideration in any infant presenting with hyponatraemia and hyperkalaemia during the first few months of life, by which time most cases of congenital adrenal hyperplasia have been diagnosed. 

It is also worth considering that our patient did not present with the typical findings associated with acute urinary tract infection. So this condition should be considered even in the afebrile infant with hyponatraemia.¹¹ Urinary sodium, serum aldosterone and urine cultures need to be ordered without delay and a renal ultrasound should be obtained if there is pyuria or a positive urine culture. Furthermore, in any particularly ill infant who has evidence of an upper urinary tract infection, serum electrolytes should be checked so that hyponatraemia can be detected and treated promptly with intravenous saline.

Conclusion

During early infancy, presentation of hyponatraemia with hyperkalaemia always raises the possibility of aldosterone deficiency due to congenital adrenal hyperplasia. The condition of transient pseudohypoaldosteronism (PHA) could also develop in children with urinary tract infection along with vesicoureteral anomaly.

This case highlights the importance of collecting serum aldosterone, urinary sodium and urine culture in infants with hyponatraemia and hyperkalaemia.

References

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