SAT-205 - Beyond Aldosterone Resistance: Endocrine Manifestations in Pediatric Pseudohypoaldosteronism

Background:
Pseudohypoaldosteronism (PHA) type 1 is a rare genetic disorder characterized by resistance to aldosterone, leading to sodium wasting, hypovolemia, hyperkalemia, and failure to thrive, with markedly elevated plasma aldosterone and renin levels. The autosomal dominant form (PHA1A) is limited to the kidneys and often improves with age, whereas the autosomal recessive form (PHA1B) involves multiple organ systems and is permanent. In contrast, PHA type 2 (PHA2) is characterized by suppressed renin and is commonly associated with short stature and hypercalciuria. Transient hypercalcemia has been reported in PHA1A, and isolated cases of hyperthyroidism have been described in PHA2.

Objective:
To evaluate the presence of additional endocrinopathies in pediatric patients with PHA.

Methods:
We conducted a retrospective chart review of all patients diagnosed with PHA at our institution between 2010 and 2025.

Results:
Fifteen patients were identified (8 males, 7 females, age range 11 months to 25 years), including 8 with PHA1A, 3 with PHA1B, and 2 with PHA2. One patient had microdeletions on chromosomes 4 and 11 resulting in a complex phenotype including PHA, Bartter syndrome, Jacobsen syndrome, and Paris-Trousseau syndrome. One patient had negative genetic testing, with PHA likely secondary to obstructive uropathy.

Short stature was observed in three patients: one patient with PHA2 and one patient with chromosomal microdeletions, both of whom were diagnosed with growth hormone deficiency (peak growth hormone levels 5.9 ng/mL and 4.8 ng/mL, respectively) and responded well to growth hormone therapy. One male patient with PHA1B had a final adult height of 5 feet 1 inch. Growth hormone stimulation testing was not performed, and growth impairment may have been influenced by prolonged systemic steroid exposure for chronic lung disease.

Intermittent hypercalcemia was observed across PHA subtypes, including 7 of 8 patients with PHA1A (peak calcium 10.8–13.6 mg/dL), 2 of 3 with PHA1B (peak 11.2–11.9 mg/dL), 1 of 2 with PHA2 (peak 11.4 mg/dL), and the patient with secondary PHA due to obstructive uropathy (peak 11.5 mg/dL). One patient with PHA1A had an SLC34A1 mutation consistent with idiopathic infantile hypercalcemia, with normocalciuria but persistent nephrocalcinosis.

Thyroid function tests were normal in all 15 patients.

Conclusions:
Endocrine abnormalities beyond aldosterone resistance, including intermittent hypercalcemia and growth hormone deficiency, were observed in pediatric patients with PHA across multiple subtypes. These findings support the need for broader endocrine surveillance in this population.

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