Objective:

To report a case of a 22-year-old male with Gordon syndrome due to a CUL3 mutation, highlighting endocrine manifestations including insulin resistance and primary testicular dysfunction.

Approach:

• Case Presentation: A 22-year-old male presented with chronic hyperkalemia, hypertension, insulin resistance, and testicular hypoplasia. Genetic analysis revealed a de novo CUL3 mutation.
• Treatment: The patient was treated with hydrochlorothiazide, which normalized blood pressure and serum potassium, improving metabolic and hormonal abnormalities.

Key Findings:

• The patient exhibited chronic hyperkalemia, hypertension, insulin resistance with steatohepatitis, and primary testicular dysfunction.
• Genetic analysis identified a de novo heterozygous CUL3 c.1207-26A>G splice-site mutation resulting in exon 9 skipping.
• Endocrine abnormalities improved with thiazide therapy but relapsed upon discontinuation.

Interpretation:

The case suggests that endocrine manifestations in CUL3-related Gordon syndrome may be secondary to chronic electrolyte imbalance rather than direct genetic effects.

Limitations:

• The study is based on a single case report, limiting generalizability.
• Long-term effects of thiazide therapy on endocrine abnormalities remain unclear.

Conclusion:

This case expands the clinical understanding of CUL3-related Gordon syndrome, indicating the need for comprehensive endocrine evaluation in affected patients.