Abstract 23

Gonadotropin-independent precocious puberty (GIPP) is a form of isosexual precocious puberty in boys in which testosterone levels are elevated independent of changes in the luteinizing hormone (LH) levels. The pattern of inheritance is autosomal dominant, although sporadic cases occur. Several activating point mutations have been mainly described within transmembrane (TM) helices V and VI, and the third cytoplasmic loop of the LH receptor (LHR) and only one in the second TM helix in families affected by GIPP. In the present study, we evaluated a boy who was first seen at 2 yr and 6 months of age because of penile enlargement, frequent erections, fast growth, deepening of the voice and aggressive behavior. He had 113.3 cm (+6.2 SD) and 24.3 kg. Penile length was 10.3 × 3.0 cm, testicular size was 2.0 × 1.4 cm bilaterally, pubic hair Tanner stage IV. His bone age was 6 yr. Basal serum testosterone ranged from 392 to 623 ng/dl (RIA). Basal and GnRH-stimulated serum LH and FSH were both undetectable (LH <0.6 U/L and FSH <1.0 U/L, IFMA). Selective venous catheterization revealed very high levels of testoterone in both testicular veins when compared with peripheral veins. He was treated with ketoconazole and cyproterone acetate. Molecular analysis of exon 11 of the LHR gene revealed a heterozygote substitution of T for G at nucleotide 1370, that converts Leu 457 (CTC) to Arg (CGC) in the fourth TM domain of the LHR. In contrast, his both parents showed a normal sequence. DNA analysis of the patient and the parents, using repeat markers, was compatible with biological paternity and maternity. Further studies of the mutant receptor will provide the functional role of this new sporadic Leu457Arg mutation in the LHR.

Supported by FAPESP 96/2020-1