Aromatase enzyme deficiency in an adult male patient and the effects of estrogen replacement therapy: a rare cause of tall stature.

A 31-year-old male with aromatase enzyme deficiency presented with continued height increase and skeletal abnormalities into adulthood.

• Height was 193 cm and weight was 103 kg, with a eunuchoid body habitus.
• Height had increased by 5 cm over the preceding 6 years.
• Patient's height was above/at +2 SD from target height.
• Symptoms included leg cramps and bone pain.
• Diagnosis was delayed until adulthood, consistent with the pattern described for male AED.

Laboratory findings demonstrated undetectable estrogen levels alongside elevated gonadotropins and testosterone.

• Estrogen levels were undetectable.
• FSH, LH, and testosterone levels were all elevated.
• Serum osteocalcin and alkaline phosphatase were elevated, indicating increased bone turnover.
• These findings are consistent with the inability to convert androgens to estrogens due to aromatase deficiency.

Bone densitometry revealed significantly reduced bone mineral density at both the lumbar spine and femoral neck.

• Z score at the lumbar spine was -2.
• Z score at the femoral neck was -2.6.
• X-rays showed incomplete epiphyseal fusion at age 31.
• These findings indicate osteoporosis and ongoing skeletal maturation deficits attributable to lifelong estrogen deficiency.

Genetic testing confirmed a homozygous exon 6 deletion in the CYP19A1 gene as the causative mutation.

• The mutation was identified as a homozygous exon 6 deletion in CYP19A1.
• CYP19A1 encodes the aromatase enzyme responsible for converting androgens into estrogens.
• AED is described as a rare autosomal recessive disorder.
• AED is typically diagnosed in female infants, but diagnosis in men is often delayed until adulthood due to late-onset skeletal and metabolic issues.

Transdermal estradiol replacement therapy normalized hormone levels and resulted in epiphyseal fusion within 6 months.

• Treatment consisted of transdermal estradiol 25 µg administered twice weekly.
• Estradiol, testosterone, and gonadotropin levels normalized following treatment.
• Epiphyseal fusion occurred within 6 months of initiating estrogen therapy.
• The authors conclude that timely diagnosis is crucial to initiating estrogen treatment early after puberty to prevent skeletal problems.