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

Abstract

Aromatase enzyme deficiency (AED) is a rare autosomal recessive disorder caused by mutations in the CYP19A1 gene. This disorder causes an inability to convert androgens into estrogens, resulting in excess androgens and estrogen deficiency. AED is typically diagnosed in female infants, but diagnosis in men is often delayed until adulthood due to late-onset skeletal and metabolic issues. We report the case of a 31-year-old male referred for increased height and bone discomfort. Over the past 6 years, his height had increased by 5 cm, accompanied by leg cramps and bone pain. He had a height of 193 cm, weighed 103 kg, and presented with a eunuchoid body habitus. The patient's height was above/at + 2 SD from target height. Laboratory findings revealed elevated FSH, LH, and testosterone, with undetectable estrogen levels. Serum osteocalcin and alkaline phosphatase were elevated. X-rays showed incomplete epiphyseal fusion. Bone densitometry revealed Z scores of -2 (lumbar spine) and - 2.6 (femoral neck). Genetic testing confirmed a homozygous exon 6 deletion in CYP19A1. The patient was treated with transdermal estradiol (25 µg twice weekly), which normalized estradiol, testosterone, and gonadotropin levels. Epiphyseal fusion occurred within 6 months. Aromatase deficiency in men frequently goes undiagnosed until adulthood. Timely diagnosis is crucial to initiating estrogen treatment early after puberty to prevent skeletal problems linked to this disorder.

Keywords: Aromatase deficiency; Autosomal recessive; Estrogen; Hight increase.