Progressive height increase in an adult patient: Aromatase Deficiency

Abstract

Abstract Introduction Aromatase deficiency (AD) is a rare autosomal recessive disease in that androgens are not converted into estrogens due to the CYP19A1 gene mutation. As estrogen deficiency is predominant, it is easier to diagnose females presented with ambigus genitalia, virilization and lack of secondary sexual characteristics during puberty. Diagnosis of aromatase deficiency is challenging in male patients. Male subjects usually present with bone and metabolic abnormalities. Here, we present a 31-year-old patient with a late diagnosis of aromatase deficiency. Clinical Case A 31-year-old male, medical doctor, was admitted to the Marmara University endocrinology outpatient clinic with a 5 cm progressive increase in height within 6 years, also complain of bone pain and cramps. Family history reveals born with ambiguous genitalia, etiology was not detected and she is followed up with oral contraceptive pills. In physical examination, his height was 193 cm and weight was 103 kg. He had eunuchoid body habitus. Secondary sexual characteristics were normal. Laboratory tests revealed that FSH:25.3 IU/l (1.5–12.4), LH:11.7 IU/l (1.7–8.6), total testesterone:957 ng/dl (249–836), E2<5 ng/l (11.3–43.2), DHEA-S:793 µg/dl (160–449), 17-OH progesterone:2.82 µg/l (0.5–2.1), Prl:7 µg/l (4.04–15.2), osteocalcin:44.1 ng/ml (9–42), Ca:9.7 mg/dl (8.8–10.5), P:3.3 mg/dl (2.5–4.5), ALP:208 U/l (33–98), PTH:12.7 µg/l (15–65), 25-OH vitamin D:29.3 µg/l, AST:47 U/l (10–37), ALT:40 U/l (10–37). Bone survey demonstrated that bilateral humerus, radius, ulna, femur, tibia and fibula epiphyses were still unfused, bilateral genu varum, bilateral hallux valgus, scaphocephaly, scoliosis (Fig 1). Bone densitometry results were in osteoporotic range BMD at the femoral neck was 0.684 g/cm2, Z score was -2.6 and at the lumbar spine was 0.895 g/cm2, Z score was -2. An incidentaloma (12×6 mm) detected in the right adrenal gland and testicular dimensions in scrotal ultrasound were normal. 1 mg DST was 0.24 µg/l, 24-hour urine metabolites were in the normal range, so it was evaluated as non-functional adenoma. In the genetic analysis, homozygous exon 6 deletion was detected in the CYP19A1 gene. Genetic counseling was recommended for CYP19A1 gene mutation. Since liver function tests were elevated mildy, 12.5 μg transdermal estradiol was started. Androgens follow-up and bone survey 1 year later were planned. Conclusion AD should be kept in mind progressive height increase in adults other than gigantism. Since estrogen is essential for epiphysis fusion, bone health, fat and carbohydrate metabolism, estrogen treatment should be initiated as early as possible before bone and metabolic abnormalities develop.