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PURPOSE Primary hypophysitis is a rare disease, with an autoimmune aetiology. As few papers have investigated genetic of hypophysitis, our aim was to evaluate HLA status in a single-centre series of patients. PATIENTS AND METHOD A retrospective, longitudinal and cross-sectional study was conducted. In consecutive Caucasian patients, clinically or histologically diagnosed for primary autoimmune hypophysitis (PAH), the HLA genotype having been determined. This cohort was compared with a control group. Anti-pituitary and anti-hypothalamus auto-antibodies evaluation was included. RESULTS 16 patients were enrolled. Fourteen patients were female (87.5%). According to HLA-DR status, we found the following: 9 of 16 patients (56.3%) haplotypes that were associated with coeliac disease (CD). Among these, 5 carried the DR7-DQ2 heterozygote haplotype (55.5%) while the remaining ones only the following haplotypes: DR3-DQ2 homozygote (25%), DR4-DQ2 heterozygote (25%), DR4-DQ8 heterozygote (50%) and DR4-DQ8 homozygote (25%), respectively. A total of 12 CD-associated haplotypes were identified. In PAH, we found a significantly higher frequency of patients carrying CD-associated HLA haplotypes as compared to the control group (respectively, 75% vs 48% P = .03; OR: 3.25 95%IC:1.1-10.3), particularly, for DQ2 and DQ8 haplotypes. DQ2 haplotype was detected in 50% of PAH and 38.4% of the control group (P = .3), while DQ8 haplotype in 25% of PAH and 7.2% of the control group (P = .01 OR:4.3 95%IC:1.3-14.7). CONCLUSION Our data suggest that PAH and CD share some HLA haplotypes, reinforcing the knowledge of their association. HLA haplotypes, particularly DQ8, may play a role in PAH management and diagnosis, also suggesting the predisposition to other autoimmune diseases.

SummaryIntroduction Growth hormone deficiency is considered the most important factor determining skeletal fragility in hypopituitary patients. Osteoblasts and chondrocytes express growth hormone (GH) receptor. Two GH receptor isoforms (GHRi) have been identified: they differ for the presence/absence of a protein fragment encoded by exon 3 of GHR gene. Consequently, three genotypes were identified: carriers of both the full-length proteins (flfl-GHR), carriers of one full-length protein and one deleted protein (fld3-GHR) and carriers of both deleted proteins (d3d3-GHR). This polymorphism confers a higher sensitivity to endogenous GH and to recombinant human GH (rhGH); its effect on bone metabolism and skeletal fragility is unknown. The aim of this article was to investigate the role of GHRi in predicting skeletal fragility in adult-onset GHD (AO-GHD) patients. Subjects and methods A cross-sectional study was conducted to investigate the association between the d3-GHR isoform and the prevalence of morphometric vertebral fractures (VFs) in AO-GHD. Ninety-three AO-GHD were enrolled. Forty-nine patients carried flfl-GHRi (52·7%), and 44 patients (47·3%) carried at least one allele of the d3-GHR isoform. Thirty-two VFs were documented. Fifty-seven patients underwent rhGH replacement therapy. Results Median age was significantly higher in fractured patients as compared to nonfractured ones; d3-carrier patients showed a lower VF risk as compared to flfl-GHRi (OR: 0·37, 95% IC: 0·24–0·55, P < 0·0001). This finding was also confirmed in AO-GHD undergoing rhGH replacement therapy. Conclusion This study suggests that d3-GHR may protect AO-GHD particularly when treated with rhGH from the risk of VFs.