Atypical endocrine manifestations in Gordon syndrome caused by CUL3 mutation: a case report

Gordon syndrome (Pseudohypoaldosteronism type II) is a rare autosomal dominant disorder characterized by hyperkalemia, hypertension, and metabolic acidosis. Among the four causative genes, CUL3 mutations produce the most severe phenotype, yet endocrine manifestations beyond growth delay remain poorly described. We report a 22-year-old male who presented with chronic hyperkalemia, hypertension, insulin resistance with steatohepatitis, and testicular hypoplasia with elevated gonadotropins, consistent with compensated primary testicular dysfunction. Genetic analysis identified a de novo heterozygous CUL3 c.1207-26A>G splice-site mutation resulting in exon 9 skipping. Treatment with hydrochlorothiazide normalized blood pressure and serum potassium while improving metabolic and hormonal abnormalities. Notably, these improvements reversed upon treatment discontinuation. This case suggests that certain endocrine manifestations in CUL3-related Gordon syndrome may be secondary to chronic electrolyte imbalance rather than direct genetic effects, highlighting the importance of comprehensive endocrine evaluation and sustained thiazide therapy in affected patients.