Salt wasting disorder in the newborn
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《美国医学杂志》
1 Kerala Institute of Medical Sciences (KIMS),Trivandrum, Kerala, India
2 SAT Hospital, Medical College, Trivandrum,Kerala, India
Abstract
The clinical presentation of pseudohypoaldosteronism (PHA) mimics congenital adrenal hyperplasia (CAH). Poor response of the dehydration and electrolyte abnormalities to steroid therapy should make one suspect PHA. The treatment is supportive in the form of salt replacement and sodium resonium. We report a case of PHA that presented as salt wasting on the second day of life, initially appearing like CAH. The baby responded well to sodium resonium and salt replacement.
Keywords: Pseudohypoaldosteronism; Sodium resonium
Congenital adrenal hyperplasia (CAH) is the commonest cause of severe dehydration, hyponatremia and hyperkalemia in neonates. Dehydration and electrolyte abnormalities of CAH respond dramatically to steroid replacement therapy, often making a clinical diagnosis even before 17 hydroxyprogesterone reports are available. Poor response to steroids should alert the neonatal unit to a possibility of end organ resistance to aldosterone. Pseudohypoaldosteronism (PHA) may be diagnosed after secondary causes of "resistance to aldosterone" like urinary infection and obstructive uropathy are excluded. In PHA, one must consider use of sodium type of ion binding resin to correct hyponatremia. The initial severe electrolyte abnormalities and dehydration require aggressive treatment but the children seem to do well on follow up.
Case report
A term baby boy (birth weight 3.5 kg) was referred to us on day 8 of life, from the Republic of Maldives, with severe dehydration (17 % weight loss since birth), severe metabolic acidosis (lowest serum bicarbonate 4mEq/L) and serious electrolyte abnormalities, refractory to supportive therapy, detected on the second day of life. The sodium at admission was 110mEq/L and potassium 11mEq/L. With a clinical diagnosis of CAH, the baby was started on hydrocortisone and fludrocortisone. The baby had received no steroids at the referring center. Simultaneously, the baby was also treated with normal saline boluses followed by half normal saline for correction of dehydration and hyponatremia. Glucose insulin infusion, ion binding resin (calcium resonium, K-bind), sodium bicarbonate and calcium gluconate were given in high doses to control hyperkalemia. The response was disappointing. The baby did not show evidence of rehydration (weight gain) in spite of large fluid intake, and the hyponatremia was not corrected. Attempts at tapering glucose insulin infusion, sodium bicarbonate and ion binding resin resulted in recurrence of severe hyperkalemia. Increasing doses of hydrocortisone (20mg tid) and fludrocortisone (0.3 mg) did not correct the electrolyte abnormalities.
End organ resistance to aldosterone was suspected. The baby had no urinary infection and no evidence of obstructive uropathy. Hence, a diagnosis of PHA was made. Serum cortisol level (105.7mcg/dl; normal reference range for the lab in newborns- 1-24 mcg/dl) was high and 17-hydroxy progesterone level (330ng/dl, reference normal range for the lab in newborns-up to 630ng/dl) four weeks after stopping steroids was normal. The serum renin levels (16.5ng/ml/hr, reference normal range for the lab-0.5-1.9 ng/ml/hr) and the aldosterone levels, checked one week and one month after (650pg/ml, 590pg/ml, respectively, reference normal range 8-172pg/ml), were elevated.
Glucose insulin infusion and sodium bicarbonate were tapered and stopped and potassium controlled with high dose ion binding resin. But the hyponatremia and dehydration continued to be severe in spite of large fluid and sodium intake. Based on published experiences with PHA, we changed the ion binding calcium resonium (K-bind) to sodium resonium (kayexalate). The baby's dehydration and hyponatremia were completely corrected. Oral indomethacin was also added, which, by virtue of its antiprostaglandin effect, decreases renal salt wasting.[1]
Ultrasonogram of kidneys at admission showed medullary echogenicity. Cross examination, 1 week after, when the baby developed acute onset oliguria showed calcification of the kidneys and gall bladder. Calcification is a described complication of PHA. There was no evidence of obstructive uropathy on the scan.
Two weeks after admission, the baby was discharged on kayexalate, oral 3% saline and indomethacin, with near normal electrolytes. The baby was born to non-consanguineous parents, with history of unexplained sudden death of the first child in the neonatal period and several unexplained neonatal deaths on the paternal side.
The baby had recurrences of fluid and electrolyte problems precipitated by respiratory infections and vomiting, necessitating repeated hospitalization. All episodes were managed by rehydration and electrolyte correction alone. At 5 months follow-up the baby's serum electrolytes, renal function, and ultrasonogram of kidneys were normal. The growth parameters (length, head circumference and weight) were normal and the baby had a normal Denver Developmental Screening Test. Salt losing persisted (Fractional excretion of sodium of 4). The oral saline intake, kayexalate and indomethacin could not be tapered significantly.
Discussion
PHA can be differentiated from CAH by an earlier onset and absence of dramatic response to steroid therapy. In the present case, the electrolyte abnormalities were noted on the second day of life and were refractory to high doses of steroids. It is important to exclude secondary causes of aldosterone end organ resistance like obstructive uropathy, urinary tract infections and certain drugs like NSAID.
PHA is a heterogeneous group of serious disorders of electrolyte metabolism essentially due to renal tubular unresponsiveness to aldosterone. The present case is probably a case of classical or type I PHA.[2] Here the underlying abnormality is a maturation disorder of number or function of aldosterone receptors. Inheritance may be autosomal dominant or sporadic, and the clinical expression is highly variable even in the members of the family with the same gene defect.
The renal variant of type I (index case) may present with severe electrolyte abnormalities in the newborn period and through the first 2 weeks of life and may be totally asymptomatic later on, in the clinically milder cases. Renal PHA type I usually improves with increasing age of the child and represents the most common form of PHA. Severe salt wasting and polyuria, dehydration and failure to thrive characterize this variant of PHA. The antenatal period may show polyhydramnios. PHA is treated in the acute phase with liberal administration of fluids, sodium and anti-hyperkalemia measures. The sodium type of potassium binding resin is the resin of choice, as its use will result in the simultaneous correction of both hyponatremia and hyperkalemia.[3] In the long term, liberal doses of sodium, ion binding resins and indomethacin will control the electrolyte abnormality. Food and drugs that precipitate hyperkalemia should be avoided. Symptoms usually resolve completely by the age of 2, and this rare cause of salt losing crisis in the newborn period is associated with a good long-term outcome.
References
1. Rampini S, Furrer J, Keller HP, Bucher H, Zachmann M; Congenital pseudohypoaldosteronism: case report and review. Effect of indomethacin during sodium chloride depletion. Helv Paediatr Acta 1978; 33(2): 153-167.
2. Jose F Pascaul-y-Baralt. Pseudohypoaldosteronism (on the internet); last updated on April 11,2003;available from; http://www.emedicine.com/ped/topic1931.htm.
3. Porter J, Kershaw M, Kirk J, Trevelyan N, Shaw NJ. The Use of Sodium resonium in pseudohypoaldosteronism (letter). Arch Dis Child 2003; 88(12): 1138-1139.(Ranjith G, Uthup Susan, S)
2 SAT Hospital, Medical College, Trivandrum,Kerala, India
Abstract
The clinical presentation of pseudohypoaldosteronism (PHA) mimics congenital adrenal hyperplasia (CAH). Poor response of the dehydration and electrolyte abnormalities to steroid therapy should make one suspect PHA. The treatment is supportive in the form of salt replacement and sodium resonium. We report a case of PHA that presented as salt wasting on the second day of life, initially appearing like CAH. The baby responded well to sodium resonium and salt replacement.
Keywords: Pseudohypoaldosteronism; Sodium resonium
Congenital adrenal hyperplasia (CAH) is the commonest cause of severe dehydration, hyponatremia and hyperkalemia in neonates. Dehydration and electrolyte abnormalities of CAH respond dramatically to steroid replacement therapy, often making a clinical diagnosis even before 17 hydroxyprogesterone reports are available. Poor response to steroids should alert the neonatal unit to a possibility of end organ resistance to aldosterone. Pseudohypoaldosteronism (PHA) may be diagnosed after secondary causes of "resistance to aldosterone" like urinary infection and obstructive uropathy are excluded. In PHA, one must consider use of sodium type of ion binding resin to correct hyponatremia. The initial severe electrolyte abnormalities and dehydration require aggressive treatment but the children seem to do well on follow up.
Case report
A term baby boy (birth weight 3.5 kg) was referred to us on day 8 of life, from the Republic of Maldives, with severe dehydration (17 % weight loss since birth), severe metabolic acidosis (lowest serum bicarbonate 4mEq/L) and serious electrolyte abnormalities, refractory to supportive therapy, detected on the second day of life. The sodium at admission was 110mEq/L and potassium 11mEq/L. With a clinical diagnosis of CAH, the baby was started on hydrocortisone and fludrocortisone. The baby had received no steroids at the referring center. Simultaneously, the baby was also treated with normal saline boluses followed by half normal saline for correction of dehydration and hyponatremia. Glucose insulin infusion, ion binding resin (calcium resonium, K-bind), sodium bicarbonate and calcium gluconate were given in high doses to control hyperkalemia. The response was disappointing. The baby did not show evidence of rehydration (weight gain) in spite of large fluid intake, and the hyponatremia was not corrected. Attempts at tapering glucose insulin infusion, sodium bicarbonate and ion binding resin resulted in recurrence of severe hyperkalemia. Increasing doses of hydrocortisone (20mg tid) and fludrocortisone (0.3 mg) did not correct the electrolyte abnormalities.
End organ resistance to aldosterone was suspected. The baby had no urinary infection and no evidence of obstructive uropathy. Hence, a diagnosis of PHA was made. Serum cortisol level (105.7mcg/dl; normal reference range for the lab in newborns- 1-24 mcg/dl) was high and 17-hydroxy progesterone level (330ng/dl, reference normal range for the lab in newborns-up to 630ng/dl) four weeks after stopping steroids was normal. The serum renin levels (16.5ng/ml/hr, reference normal range for the lab-0.5-1.9 ng/ml/hr) and the aldosterone levels, checked one week and one month after (650pg/ml, 590pg/ml, respectively, reference normal range 8-172pg/ml), were elevated.
Glucose insulin infusion and sodium bicarbonate were tapered and stopped and potassium controlled with high dose ion binding resin. But the hyponatremia and dehydration continued to be severe in spite of large fluid and sodium intake. Based on published experiences with PHA, we changed the ion binding calcium resonium (K-bind) to sodium resonium (kayexalate). The baby's dehydration and hyponatremia were completely corrected. Oral indomethacin was also added, which, by virtue of its antiprostaglandin effect, decreases renal salt wasting.[1]
Ultrasonogram of kidneys at admission showed medullary echogenicity. Cross examination, 1 week after, when the baby developed acute onset oliguria showed calcification of the kidneys and gall bladder. Calcification is a described complication of PHA. There was no evidence of obstructive uropathy on the scan.
Two weeks after admission, the baby was discharged on kayexalate, oral 3% saline and indomethacin, with near normal electrolytes. The baby was born to non-consanguineous parents, with history of unexplained sudden death of the first child in the neonatal period and several unexplained neonatal deaths on the paternal side.
The baby had recurrences of fluid and electrolyte problems precipitated by respiratory infections and vomiting, necessitating repeated hospitalization. All episodes were managed by rehydration and electrolyte correction alone. At 5 months follow-up the baby's serum electrolytes, renal function, and ultrasonogram of kidneys were normal. The growth parameters (length, head circumference and weight) were normal and the baby had a normal Denver Developmental Screening Test. Salt losing persisted (Fractional excretion of sodium of 4). The oral saline intake, kayexalate and indomethacin could not be tapered significantly.
Discussion
PHA can be differentiated from CAH by an earlier onset and absence of dramatic response to steroid therapy. In the present case, the electrolyte abnormalities were noted on the second day of life and were refractory to high doses of steroids. It is important to exclude secondary causes of aldosterone end organ resistance like obstructive uropathy, urinary tract infections and certain drugs like NSAID.
PHA is a heterogeneous group of serious disorders of electrolyte metabolism essentially due to renal tubular unresponsiveness to aldosterone. The present case is probably a case of classical or type I PHA.[2] Here the underlying abnormality is a maturation disorder of number or function of aldosterone receptors. Inheritance may be autosomal dominant or sporadic, and the clinical expression is highly variable even in the members of the family with the same gene defect.
The renal variant of type I (index case) may present with severe electrolyte abnormalities in the newborn period and through the first 2 weeks of life and may be totally asymptomatic later on, in the clinically milder cases. Renal PHA type I usually improves with increasing age of the child and represents the most common form of PHA. Severe salt wasting and polyuria, dehydration and failure to thrive characterize this variant of PHA. The antenatal period may show polyhydramnios. PHA is treated in the acute phase with liberal administration of fluids, sodium and anti-hyperkalemia measures. The sodium type of potassium binding resin is the resin of choice, as its use will result in the simultaneous correction of both hyponatremia and hyperkalemia.[3] In the long term, liberal doses of sodium, ion binding resins and indomethacin will control the electrolyte abnormality. Food and drugs that precipitate hyperkalemia should be avoided. Symptoms usually resolve completely by the age of 2, and this rare cause of salt losing crisis in the newborn period is associated with a good long-term outcome.
References
1. Rampini S, Furrer J, Keller HP, Bucher H, Zachmann M; Congenital pseudohypoaldosteronism: case report and review. Effect of indomethacin during sodium chloride depletion. Helv Paediatr Acta 1978; 33(2): 153-167.
2. Jose F Pascaul-y-Baralt. Pseudohypoaldosteronism (on the internet); last updated on April 11,2003;available from; http://www.emedicine.com/ped/topic1931.htm.
3. Porter J, Kershaw M, Kirk J, Trevelyan N, Shaw NJ. The Use of Sodium resonium in pseudohypoaldosteronism (letter). Arch Dis Child 2003; 88(12): 1138-1139.(Ranjith G, Uthup Susan, S)