Transient Pseudohypoaldosteronism Caused by Intestinal Abnormalities

To the Editors,

I read with great interest the article in the Journal entitled “Congenital jejunal membrane causing transient pseudohypoaldosteronism and hypoprothrombinemia in a 7-week-old infant” [Nissen M, et al. Klin Padiatr 2017, Epub ahead of print]. The authors presented a 50-day-old infant with a congenital jejunal membrane who developed secondary and transient pseudohypoaldosteronism (PHA), and stated that “the pathogenesis of the resulting tubular mineralocorticoid resistance remains unclear” in this patient.

Secondary PHA results from different pathologies related to dysfunction of the kidneys, other organs, or the use of medications [Watanabe T. Austin Pediatr 2017; 4: 1050]; however, urinary tract infections and/or urinary tract abnormalities in young infants have been most frequently described, and only 2 patients with secondary PHA due to intestinal pathology other than the case described by Nissen have previously been reported.

Sugawara et al. reported an 82-year-old man with colon cancer who developed secondary PHA after a subtotal colectomy and ileal resection [Sugawara M, et al. Nephron 1989; 51: 567–568]. Because the urinary sodium concentration was low in this patient, Sugawara et al. reasoned that the primary abnormality was resection of the ileum and colon, the principal site of sodium and water movement. Excessive loss of sodium and water from the intestine causes hyponatremia and hypovolemia, which leads to hyperaldosteronism. Sodium delivery to the distal renal tubules is markedly reduced because of increased sodium absorption in the proximal renal tubules. Potassium secretion in exchange for sodium is suppressed in the distal renal tubules, which leads to hyperkalemia despite hyperaldosteronism, a mechanism similar to secondary PHA due to sweat gland dysfunction [Anand SK, et al. Pediatr Res 1976; 10: 677–682].

Vantyghem et al. described a 54-year-old woman with colon cancer who developed secondary PHA following a subtotal colectomy and ileal resection [Vantyghem MC, et al. J Endocrinol 1999; 22: 122–127]. Because their patient had high fecal sodium and low potassium concentrations, and normal urinary sodium and potassium levels, Vantyghem et al. suggested that hyperkalemia reflected aldosterone resistance related to resection of the colon. Colon is the major site of mineralocorticoid receptor (MR) expression in the intestine, and sodium absorption and potassium excretion in the colon is mediated by epithelial sodium channels (ENaCs), which are regulated by aldosterone via MR in the colon [Lienhard D, et al. PLoS One 2012; 7: 1453–1464]. Recently, Malsure et al. reported that mice lacking colon-specific ENaCs exhibited PHA [Malsure S, et al. J Am Soc Nephrol 2014; 25: 1453–1464], which supports the hypothesis of Vantyghem et al.

In either case, PHA is caused by sodium and water loss from the intestine, not from renal tubular resistance to aldosterone. Because of a low urinary sodium level, PHA in the patient reported by Nissen likely resulted from hyponatremia and hypovolemia caused by a deficient supply of sodium and water to the colon due to the jejunal membrane, which led to a marked reduction of sodium delivery to the distal renal tubules and hyperkalemia, which was similar to the mechanism described in the patient by Sugawara et al.