Biochemical and Clinical Features of Insulinoma in a Patient with Turner Syndrome.

Turner syndrome (TS), i.e., mosaic or nonmosaic states with only one normal X chromosome in females, is characterized by a wide spectrum of somatic, hormonal, and metabolic features. Here we report an unusual case of recurrent hypoglycemia in a 53-year-old woman with TS. Biochemical work-up following a 72h fast revealed detectable, inappropriate for low glucose insulin levels and elevated proinsulin and beta-hydroxybutyrate (BOHB) levels. MR and multiphase CT showed a solid 2.5 cm pancreatic tail mass with absent uptake in the 111In-pentetreotide (Octreoscan) scan. Subsequent hepatic vein blood sampling after intra-arterial calcium stimulation showed sharp increase in insulin and modest increase in proinsulin levels. The patient underwent excision of the mass with resolution of symptoms. Histopathologic examination confirmed the neuroendocrine etiology of the tumor. This is, to our knowledge, the third report of TS and concomitant insulinoma. Impaired counterregulatory response to hypoglycemia in patients with TS may result in symptomatic hypoglycemia with only mild insulin elevation and elevated proinsulin in setting of hypoglycemia may be the only indication of insulinoma in these patients. BOHB levels should not be used for ruling out EHH in patients with TS.

From the simple detection of microchimerism in patients with autoimmune diseases to its implication in pathogenesis.

Long-term persistence of fetal cells in parous women (fetal microchimerism, FM) as well as maternal cells in their offspring (maternal microchimerism, MM) have been reported. Systemic sclerosis (SSc), primary biliary cirrhosis (PBC), and Sjögren's syndrome (SS) share similar epidemiology with a predilection for females following childbearing years, with clinical similarities to chronic graft-versus-host disease, a known condition of chimerism. This led to the hypothesis that FM could be involved in the pathogenesis of autoimmune diseases. Initial investigations were conducted in SSc, where the hypothesis was supported by the more frequent occurrence and, quantitatively, a greater degree of FM in women with SSc compared to matched healthy women. Long-term persistence, however, of fetal cells in healthy women indicates that FM per se is not sufficient for causing SSc, but may be important in the context of other risk factors, such as genetic susceptibility and HLA relationship among host and nonhost cells. Contradictory results have recently been published for both PBC and SS and cause difficulty in drawing any conclusions about the role of FM in their pathogenesis. On the other hand, MM has been investigated as a risk factor in patients with systemic lupus (SLE) and juvenile dermatomyositis (JDM). A potential role of MM has been suggested in the pathogenesis of SLE. Recent publications also support the hypothesis that MM might lead to increased risks for JDM. In conclusion, contradictory results have been observed. This reflects a need for standardization of protocols and the selection of control populations. Detection of microchimerism has to be quantitatively studied in the context of genetic factors in order to study its relationship to the pathogenesis of autoimmune diseases.

HLA-DQA1*0501 is associated with diffuse systemic sclerosis in Caucasian men.

OBJECTIVE: Systemic sclerosis (SSc) is uncommon in men, and relatively little is known about factors contributing to its pathogenesis in this population. In the current study, we investigated HLA class II alleles in men with SSc. We also investigated the hypothesis that HLA compatibility of the mother could be a risk factor for SSc in men. METHODS: Sequence-specific oligonucleotide probe typing was used to determine DQA1, DQB1, and DRB1 alleles of SSc patients (50 men and 36 parous women), healthy controls (59 men and 80 parous women), 26 mothers of men with SSc, and 44 mothers of healthy men. All study subjects were Caucasian, and allele frequencies were compared with those of Caucasian controls from the Eleventh International Histocompatibility Workshop as well as those of local controls. RESULTS: The DQA1*0501 allele was significantly increased among men with SSc compared with healthy men (odds ratio [OR] 2.3, P = 0.006, Pcorr = 0.04). DQA1*0501 was associated with diffuse SSc in men (OR 3.0, P = 0.004, Pcorr = 0.03), but not with limited SSc in men. Maternal HLA compatibility was not a risk factor for SSc in men. CONCLUSION: Previous studies have shown associations of DRB1 alleles with SSc, but have rarely determined DQA1 allele frequencies. Our findings indicate that a specific DQA1 allele is associated with SSc, and that DRB1 associations may be due to linkage disequilibrium with DQA1. Moreover, by analyzing genetic susceptibility according to sex, we found that the contribution of HLA genes to the risk of SSc was substantially greater in men than in parous women.