Electrolyte disturbance in an infant with failure to thrive

Presentation

A six-week-old girl was born to a healthy mother via uncomplicated vaginal delivery at full term and subsequently had a normal newborn screen. She had a birthweight of 4.48 kg (LGA, 97% percentile). At her 1-month well-child visit, she weighed 3.7 kg. Although offered 2–3 ounces of pumped breastmilk each feed, she was taking approximately 1 ounce every 2 hours without cyanosis, tachypnea, or sweating. She had no trouble latching onto the bottle, a normal suck and swallow, and no choking with feeds. After feeding, she had frequent non-bloody/non-bilious vomiting episodes that most often occurred soon after a feed, but occasionally a few hours later. Her primary care provider (PCP) recommended fortifying the breastmilk with formula to 22 kcal/ounce, but it was not well-tolerated due to vomiting. On a repeat weight check 2 weeks prior to admission, she demonstrated continued poor weight gain and was started on a histamine 2-blocker for possible gastrointestinal reflux. Two days prior to admission, this was switched to a proton-pump inhibitor with no improvement in symptoms. The PCP obtains bloodwork, urine studies, and an abdominal ultrasound as part of an evaluation for failure to thrive. The bloodwork shows: sodium 115 mmol/L, potassium 8.7 mmol/L, chloride 71 mmol/L, carbon dioxide 15 mmol/L, urea nitrogen 53 mg/dL, creatinine 0.8 mg/dL, glucose 50 mg/dL. The mother is asked to bring the baby to the emergency department (ED). In the ED, the parents state she has not had fever, congestion, rhinorrhea, cough, or rash. She continues to have yellow pasty stools daily and wet diapers every 4 to 6 hours. The family history is unremarkable. On physical exam in the ED, she has normal vital signs (temperature 36.5°C, heart rate 132, respiratory rate 48, blood pressure 93/60, oxygen saturation 100%) and is alert and interactive, but appears small-for-age (3.8 kg, 5^th percentile for weight) with a mildly sunken anterior fontanelle. The exam is otherwise normal including moist mucous membranes and normal capillary refill time

Discussion

Differential Diagnosis

The differential diagnosis for failure to thrive is broad and can include decreased delivery of nutrition as a primary cause (i.e. failure to provide adequate nutrition due to inadequate resources or neglect), but this seemed less likely given the history and this infant’s attentive family. Secondary causes of decreased intake include anatomic abnormalities of the gastrointestinal tract (such as esophageal strictures/fistulas, pyloric stenosis, abnormal gastrointestinal motility, and atresia of the post-pyloric gastrointestinal tract such as duodenal atresia). Some of these causes were less likely given the non-bilious nature of the emesis. Other secondary causes of failure to thrive include neurologic causes such as poor oromotor function/coordination, endocrine causes leading to electrolyte abnormalities, genetic causes such as inborn errors of metabolism, infectious causes such as gastroenteritis or other infections that would make an infant more prone to vomiting, and kidney failure. Another cause of failure to thrive is secondary to increased metabolic demand (caloric need) due to cardiac or respiratory disease, often associated with tachypnea, cyanosis and/or sweating with feeding.

Patient Course

In the ED, bloodwork reveals a normal complete blood cell count including a white count of 8,100/μL (8.1×10⁹/L) with 40% neutrophils and 0.9% bands. Her electrolyte panel was abnormal: sodium 122 mmol/L, potassium 6.2 mmol/L, chloride 85 mmol/L, carbon dioxide 13 mmol/L, urea nitrogen 46 mg/dL, creatinine 0.6 mg/dL, glucose 80 mg/dL, calcium 11.9 mg/dL, total protein 8.3 g/dL, and albumin 4.8 g/dL. Urinalysis showed 15 to 20 WBC/HPF, 5 to 10 RBC/HPF, many bacteria, moderate leukocyte esterase, and 1+ protein. Urine culture was sent and returned negative. The endocrinology service was consulted given the hyponatremia and hyperkalemia with metabolic acidosis, and a serum cortisol and aldosterone level were obtained. The cortisol was normal at 15.3 mg/dl and aldosterone returned elevated at 2,119 ng/dL (normal range, 2–70 ng/dL). Urine sodium and osmolality were <20 mmol/L and 212 mosm/kg respectively. Abdominal ultrasound with Doppler showed no pyloric stenosis, but showed an avascular, hypoechoic structure at the superior pole of the left kidney with echogenic debris that appeared to communicate with the renal collecting system compatible with duplicated renal collecting system and superior pole hydronephrosis. The right kidney was normal (Fig. 1).

Figure 1.

Renal ultrasound showing hypoechoic structure at the superior pole of the left kidney with echogenic debris and normal kidney on the right.

A Narrowed Differential Diagnosis

Aldosterone is an important hormone activated in the setting of hypovolemia and hyperkalemia. Aldosterone facilitates kidney distal tubular reabsorption of sodium and secretion of potassium/hydrogen. The patient had elevated aldosterone levels making an adrenal production problem (primary hypoaldosteronism) unlikely. Given elevated aldosterone levels, the following clinical scenarios were considered. First, this could be appropriate aldosterone elevation in the setting of dehydration and/or hyperkalemia. However, the patient’s physical exam was consistent with minimal dehydration and her electrolyte derangement was out of proportion to her degree of dehydration assuming she had a normal response to aldosterone. Second, the patient could have lack of response to aldosterone due to a rare inactivating mutation in the epithelial sodium channel of the kidney tubule cells (autosomal recessive) or the mineralocorticoid receptor (autosomal dominant) known as pseudohypoaldosteronism type 1. (1) Third, she could have a transient acquired resistance or diminished response to aldosterone in the setting of pyelonephritis. There are a few reported cases in which infants presented similarly with failure to thrive. (2) Physiologically, infants may have immaturity of tubular responsiveness to aldosterone even in the absence of infection. This is likely exacerbated in the presence of inflammation that accompanies infection of the kidney parenchyma. Accordingly, this phenomenon is most often seen in those less than 7 months of age. (3) Finally, the infant could also have acquired aldosterone resistance in the setting of acute or chronic kidney injury; this infant was noted to have an elevated creatinine.

Patient Course Continued

The infant was admitted to the pediatric intensive care unit for management of her electrolyte derangement which had a pattern most consistent with resistance to aldosterone (hyponatremia, hyperkalemia, metabolic acidosis). Initially, there was concern for congenital adrenal hyperplasia (CAH) and she was started on intravenous hydrocortisone and fludrocortisone, but as her genital exam was normal and cortisol and aldosterone levels were not low, suspicion for CAH decreased. The infant’s serum sodium was corrected with intravenous fluid over 48 hours, and the intravenous fluid, hydrocortisone as well as fludrocortisone were subsequently discontinued. She was treated with ceftriaxone for empiric coverage of presumed pyelonephritis despite lack of fever in the setting of pyuria and the structural urologic/kidney abnormality seen on ultrasound. After stabilization of electrolyte status, she was resumed oral feeding of breast milk and by the time of discharge, she was gaining an appropriate amount of weight daily, the vomiting had resolved, and her creatinine trended down to 0.3 mg/dL. Transient acquired aldosterone resistance due to presumed pyelonephritis and acute kidney injury was the most likely diagnosis given that she was able to be off all medications and sodium supplementation with resolution of her electrolyte disturbance and poor feeding pattern.

Follow-up

She continues to gain weight and have normal electrolytes. She had a MAG3 renogram which showed decreased uptake of radiotracer in the superior moiety of the left kidney suggesting poor function of that portion of the kidney (Fig. 2). A voiding cystourethrogram showed no vesicoureteral reflux. A non-refluxing duplicated collecting system of the left kidney with possible upper pole obstruction, predisposing this infant to urinary tract infection, is considered the most likely diagnosis. She is on prophylactic antibiotics to prevent urinary tract infections. If she continues to have repeat urinary tract infections, partial nephrectomy of her left upper pole may be considered. She continues to be followed by urology and nephrology.

Figure 2.

MAG3 Renogram showing decreased uptake of tracer in the superior moiety of the left kidney.

Lessons for the Clinician.

• Pyelonephritis can present in a subacute fashion without fever.

• Pyelonephritis can cause transient aldosterone resistance, leading to electrolyte disturbance, particularly in infants.

• Electrolyte disturbances can be the cause for failure to thrive.