Sertoli cell hyperfunction with low FSH in a pubertal boy with bilateral macroorchidism

GRINSPON R; SCAGLIA P; BRASLAVSKY D; CAMPO S; BERGADÁ, IGNACIO; DOMENÉ H; GRYNGARTEN MIRTA; REY RA

Leipzig

Congreso; . 51th Annual Meeting of the European Society for Paediatric Endocrinology; 2012

European Society for Paediatric Endocrinology

Background: Bilateral macroorchidism has been described with no testicular hyperfunction in Fragile X syndrome, adrenal rest tumors or infiltrative disorders, and with testicular hyperfunction, due to increased gonadotropin signaling activity, in gonadotropin-secreting adenomas, McCune-Albright syndrome, aromatase deficiency and severe hypothyroidism. Testis size is mainly dependent on Sertoli cell number, whose proliferation is regulated primarily by FSH. Clinical case: A 10-yr-old boy presented with a remarkable discordance between enlarged testes (20 ml) and penis and pubic hair corresponding only to incipient Tanner stage 3. He had bilateral mild gynecomastia. No signs of Fragile X, McCune-Albright, infiltrative disorders, CAH, aromatase deficiency or hypothyroidism were present. Inhibin B was abnormally high at 464 pg/ml (Tanner 3 range: 126-257), and basal FSH was low at 0.76 IU/L (1.43-7.44) with no response to GnRH (0.97 IU/L). Discordantly, T was 263 ng/dl (12-368) and basal LH 2.23 IU/L (0.67-4.65) with a normal response to GnRH (15.8 IU/L). E2 was 14 pg/mL (10-35). During 2-yr follow-up, testicular size increased to >25 ml and penis and pubic hair progressed to Tanner stage 5. Gynecomastia regressed. Inhibin B persisted high at 628 pg/ml (118-340) with FSH low at 0.82 (1.14-6.99) and normal T and LH. With suspicion of FSH-R constitutive activation, we sequenced FSHR gene (exons 1-10 and flanking intronic regions) and found 3 SNPs in heterozygosis in noncoding regions and 2 in homozygosis in coding regions, but no allegedly activating mutation. Conclusion: Macroorchidism may be a normal variant, or a sign of gonadal hyperfunction. Increased testicular activity may involve both tubular and interstitial compartments or be dissociated. A dissociated primary testicular hyperfunction restricted to Sertoli cells is likely the underlying cause of macroorchidism in this patient. An activating mutation of the FSH-R could not be evidenced.