Associação singular de síndrome de Kallmann e cisto aracnóide da fossa média: relato de caso Singular association of Kallmann's syndrome and arachnoid cyst of middle fossa: case report

O hipogonadismo hipogonadotrófico pode resultar de diferentes anomalias do sistema nervoso central, apresentando sinais clínicos que dependem da idade de aparecimento, bem como do grau de deficiência gonadotrófica e de sua associação com outras deficiências hipofisárias. Relatamos o caso de um rapaz de 18 anos com atraso puberal, retardo de crescimento estatural a partir de 10 anos e história de dificuldade de aprendizado escolar. Ao exame apresentava discreto aspecto eunucóide, 162 cm de altura (z score = -2,17), estadiamento puberal GII, PII, testículos de 4 cm³. A avaliação complementar demonstrou níveis pré-puberais de testosterona, megateste com resposta normal, exceto ao teste de estímulo com GnRH agudo e prolongado. CT de crânio mostrou cisto aracnóide da fossa média esquerda com extensão supra-selar. Foi feito o diagnóstico de hipogonadismo hipogonadotrófico provavelmente secundário à compressão pelo cisto aracnóide e por isso, optou-se por derivação cisto-peritoneal. Após a cirurgia não houve retomada do desenvolvimento puberal, sendo então verificada anosmia bilateral e, portanto, diagnosticada Síndrome de Kallmann, que foi confirmada pelos achados da RNM, embora os resultados hormonais não sejam totalmente compatíveis com a referida síndrome. Não encontramos na literatura descrição da associação entre Síndrome de Kallmnann e cisto aracnóide e acreditamos que neste caso os resultados da avaliação hormonal possam ser devidos a tal associação que provocou adicionalmente uma disfunção hipofisária.<br>Hypogonadotrophic hypogonadism can result from different abnormalities in the central nervous system. The clinical picture depends upon the time of onset the deficiency, the magnitude of the gonadotropins deficiency and whether there are other pituitary hormone deficiencies as well. We report on a 18-year-old boy, who was investigated because of pubertal and growth delay. He also had learning disabilities. On physical examination he exhibited mild eunuchoid aspect, 162 cm height (z score = -2,17), pubertal development on stage G II, P II, and 4 cm5 testis. Laboratory investigation revealed pre-pubertal levels of testosterone and normal results of the combined test of anterior pituitary function, except for in GnRH acute and prolonged test. Brain CT showed an arachnoid cyst on left middle fossa with expansion to suprasellar cisterna. He was diagnosed as having hypogonadotrophic hypogonadism secondary to compression by the cyst, and a cyst-peritoneal derivation was performed. After surgery there was no improvement of the pubertal state and bilateral anosmia was discovered, so Kallmann's syndrome was then diagnosed and was confirmed by MRI, even though the hormonal results are not totally matched with the refered syndrome. We did not find in the literature any description of the association between Kallmann's syndrome and arachnoid cyst and we believe that in this case the results of the hormonal measurement may be due to such association that provoked an additional hypophysis dysfunction

HMGB1 Is Involved in IFN-α Production and TRAIL Expression by HIV-1-Exposed Plasmacytoid Dendritic Cells: Impact of the Crosstalk with NK Cells.

Plasmacytoid dendritic cells (pDCs) are innate sensors of viral infections and important mediators of antiviral innate immunity through their ability to produce large amounts of IFN-α. Moreover, Toll-like receptor 7 (TLR7) and 9 (TLR9) ligands, such as HIV and CpG respectively, turn pDCs into TRAIL-expressing killer pDCs able to lyse HIV-infected CD4+ T cells. NK cells can regulate antiviral immunity by modulating pDC functions, and pDC production of IFN-α as well as cell-cell contact is required to promote NK cell functions. Impaired pDC-NK cell crosstalk was reported in the setting of HIV-1 infection, but the impact of HIV-1 on TRAIL expression and innate antiviral immunity during this crosstalk is unknown. Here, we report that low concentrations of CCR5-tropic HIV-1Ba-L promote the release of pro-inflammatory cytokines such as IFN-α, TNF-α, IFN-γ and IL-12, and CCR5-interacting chemokines (MIP-1α and MIP-1β) in NK-pDCs co-cultures. At high HIV-1BaL concentrations, the addition of NK cells did not promote the release of these mediators, suggesting that once efficiently triggered by the virus, pDCs could not integrate new activating signals delivered by NK cells. However, high HIV-1BaL concentrations were required to trigger IFN-α-mediated TRAIL expression at the surface of both pDCs and NK cells during their crosstalk. Interestingly, we identified the alarmin HMGB1, released at pDC-NK cell synapse, as an essential trigger for the secretion of IFN-α and IFN-related soluble mediators during the interplay of HIV-1 exposed pDCs with NK cells. Moreover, HMGB1 was found crucial for mTRAIL translocation to the plasma membrane of both pDCs and NK cells during their crosstalk following pDC exposure to HIV-1. Data from serum analyses of circulating HMGB1, HMGB1-specific antibodies, sTRAIL and IP-10 in a cohort of 67 HIV-1+ patients argue for the in vivo relevance of these observations. Altogether, these findings identify HMGB1 as a trigger for IFN-α-mediated TRAIL expression at the surface of pDCs and NK cells, and they suggest a novel mechanism of innate control of HIV-1 infection