The boy was born at 35 weeks without complications. He has not received his two-month vaccinations because “he was sick that day”. She explains that he always seems fussy, and never eats enough. During a family party last night, she was upset that he wasn’t “awake enough” for relatives to visit him. There has been no fever, vomiting, or diarrhea. She has not noticed a rash. There are no dominant illnesses in the family that she can recall.
On examination, the child does not track with his eyes and is lethargic. He has decreased tone, but holds his head up appropriately when mother sits him up in her lap after his formula feeds.
His vitals show T 36.9 HR 152 BP 78/50 RR 36 SpO2 99% RA. He appears volume depleted, with slightly sunken eyes and capillary refill of 2-3 seconds. His pulses are not bounding; his breathing is slightly tachypneic, but appears effortless. His abdomen is soft, non-tender, without organomegaly; the boy’s scrotum appears slightly darker than his general skin tone. You do not appreciate a rash; there is no evidence of trauma.
At this point, what are your management priorities?
What ancillary studies would be helpful?
What is your differential diagnosis based on what you know now?
You recognize that this infant is in compensated shock, with an elevated heart rate and ill appearance, and begin volume resuscitation with 20 mL/kg 0.9% sodium chloride. A point-of-care blood analyzer reports: pH 7.34 Na+ 97 K+ 7.5 Ca2+ 10 Glucose 66.
Does this help to hone your differential diagnosis?
You decide that this child is at risk for sepsis (among other things), and perform a full workup including chest radiograph, urinalysis with culture, blood cultures, blood work, and a lumbar puncture. Luckily, you have the presence of mind to send an additional set of blood vials to the laboratory to freeze and send out for specialized analysis.
Based on the information you have at this point, you treat for sepsis while you consider other etiologies.
What metabolic pattern can you recognize from the bedside blood analysis?
A sick infant with hyponatremia and hyperkalemia suggests congenital adrenal hyperplasia or pseudohypoaldosteronism.
Classic congenital adrenal hyperplasia (CAH) involves a salt-wasting syndrome, most commonly due to 21-hydroxylase deficiency. Since 21 hydroxylase is not available to convert 17-hydroxyprogesterone to 11-deoxycortisol, there is a decreased synthesis of cortisol and therefore an increased secretion of corticotropin (ACTH). Decreased cortisol results in salt wasting while increased ACTH results in increased androgen synthesis. Both baby boys and girls experience salt wasting, but baby girls present virilized or with ambiguous genitalia. This is often diagnosed in the newborn nursery. Baby boys, however, appear normal, and may present in the first few weeks of life (typically) on the spectrum from vague symptoms of failure to thrive to an adrenal crisis.
Bottom line: a young sick infant who may fit this pattern should receive a stress dose of steroid: give 25 mg hydrocortisone IV (same dose during the first year of life).
What other etiologies are possible here?
Failure to thrive may be due to a long list of illnesses that are rarely clarified in the ED. (Formula mishaps, non-accidental trauma, poisoning, and other etiologies should be considered in the differential diagnosis in the ED.)
Renal tubular acidosis, type IV presents with hyperkalemia and often no salt wasting in adults; children may present with a metabolic acidosis, hyperkalemia, and hyponatremia – similarly to CAH.
Pseudohypoaldosteronism (type 1, transient) is an acquired form, most commonly in pediatrics from a urinary tract infection. Other causes in other populations include nephritis, amyloidosis, ACE inhibitors, and beta-blockers. Presumably, parenchymal inflammation leads to tubular resistance to aldosterone. The treatment is to address the underlying cause and offer supportive care. In the case where there is uncertainty between CAH and pseudohypoaldosteronism, always investigate and treat for sepsis, and give hydrocortisone. It can be discontinued if/when an alternative diagnosis (such as pseudohypoaldosteronism) is made.
What happened in this case?
The boy was treated for possible sepsis and presumed CAH with antibiotics, IV fluids, and hydrocortisone. Samples taken when blood was first drawn were sent for cortisol, 17OHP, aldosterone, and renin (and other genetic testing) which ruled out CAH. The urine culture grew E. coli, and the child was investigated for urethral valves with a voiding cystourethrogram (VCUG), renal anomalies with renal ultrasound, and parenchymal disease with a DMSA scan. His posterior urethral valves were ablated with cystoscopy, and his vesicoureteral reflux has begun to resolve. This was a case of transient pseudohypoaldosteronism, secondary to urinary tract infection (secondary to posterior urethral valves and vesiculoureteral reflux).
Take home messages
- Newborn screening is generally an effective public health measure, but relies on prompt processing of samples in hospital (institutions have been known to send samples in batches) and good contact information for the family. Any break in the chain can lead to a delay in diagnosis and treatment, with subsequent decompensation. A recent study in Colorado found that their screening missed up to 30% of cases of CAH. Vigilance is essential.
- An ill appearing child is septic until proven otherwise, regardless of the atypical presentation. In this case, had he presented with CAH, an infection may have tipped the balance, precipitating this crisis in the context of sepsis.
- Be careful not to hypercorrect serum sodium. In general, in matters of volume versus osmoles, volume typically wins. That is, resuscitate those in shock to euvolemia (remember that normal saline is already “hypertonic” in relation to most hyponatremia). Do not directly treat the hyponatremia unless the child is profoundly altered acutely or seizing (i.e. treat acute, severely symptomatic hyponatremia). At that point, an easy remedy to remember is: 3 mL/kg of 3% saline over 30 minutes. Stop giving the 3% as soon as the seizure stops.
- In this case, our child may have had a smoldering urinary tract infection or recurrent mild infections that led to parenchymal insult and pseudohypoaldosteronism that resolved after resolution of his urinary tract infection/pyelonephritis.
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Speiser PW, Azziz R, Baskin LS, et al. Congenital adrenal hyperplasia due to steroid 21-hydroxylase deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2010; 95:4133.