ESPE Abstracts

Background: Pubertal gynecomastia is a common condition appearing in up to 65% of adolescent boys. However, if male breast development is over B3–B4 and lasts more than 2–3 years, persistent pubertal gynecomastia (PPG) may be the sign of serious endocrine disease and the source of considerable psychological discomfort.

Objective and hypotheses: We investigated a cohort of 24 adolescents with PPG followed at the Pediatric Endocrinogy Unit over a 3-year period to determine whether PPG is associated with genetic disorders.

Method: Clinical, endocrine and radiological investigations were performed in all patients. Genetic analyses were done in six patients with suspected genetic disorder.

Results: The patients’ mean age was 14.5±0.8 years and the pubertal Tanner stage was >2 without genital abnormalities. Laboratory evaluation revealed no hormonal disturbance for 18 boys (75%), whereas two patients presented Klinefelter syndrome and three, partial androgen insensitivity syndrome (PAIS) due to AR gene mutation (p.Ala646Asp for twins and c.134C>G for the third). Although external genitalia were normal in these three adolescents, it is likely that PAIS manifested only as PPG. Another patient showed 17α-hydroxylase/17,20-lyase deficiency confirmed by CYP17A1 gene analysis, which revealed compound heterozygosity consisting of c.275C>A/WT in exon 1 (plus three known heterozygous SNPs) and c.887C>T/WT in exon 4, respectively leading to p.Pro35Thr(P35T) and p.Arg239Stop(R239X). To assess the functional consequence of this mutation, COS1 cells were transfected with the expression vector pcDNA3 containing either WT or mutant CYP17A1cDNA. The mutant protein bearing the premature stop codon R239X showed a complete loss of 17α-hydroxylase and 17,20-lyase activity. Compared with the WT protein, the mutant P35T seemed to retain 15–20% of 17α-hydroxylase and about 8–10% of 17,20-lyase activity at two different substrate concentrations.

Conclusion: This work suggests that screening for genetic disorders (besides Klinefelter syndrome, PAIS, and CAH) should be systematic, as they may be the cause of up to 25% of PPG.