ACTA ENDOCRINOLOGICA (BUC)

Context. Persistent inflammation and impaired neovascularization are important contributors to the development of diabetic retinopathy (DR). Gene polymorphisms of adiponectin (APN) were demonstrated to have an important role on the plasma level and activity of adiponectin. APN has anti-inflammatory, anti-diabetic and anti-atherogenic properties. Toll-Like Receptor 4 (TLR4) is a critical mediator of innate immunity. Polymorphisms in TLR-4 gene were shown to be associated with impaired inflammatory response in diabetes. Objective. The aim of the study was to analyze the association of +276G>T variant of APN gene and Asp299Gly and Thr399Ile of TLR-4 gene variants in relationship with T2DM and DR in an Eastern European population group. Design. The distribution of the mutant alleles in 198 T2DM patients with DR and 200 non-T2DM controls was examined. Genomic DNA from T2DM patients and healthy controls genotyped through the use of PCR-RFPL assay. Results. Genotype and allele frequencies of the Asp299Gly and Thr399Ile polymorphisms differed between T2DM patients and non diabetic subjects (P<0.001). Moreover, the presence of the minor alleles of these polymorphisms were significantly identified as protective factors against T2DM, under a dominant model of Fisher’s exact test (χ2=4.988, phi=0.745, OR=0.767, 95% CI=0.602-0.867, P<0.001; respectively χ2=5.254, phi=0.820, OR=0.487, 95% CI=0.211- 0.648, P<0.001). Genotype analysis for the adiponectin 276G>T gene polymorphism yielded no significant association with T2DM, but revealed a borderline significance for the association with DR (χ2=5.632, phi=0.423, OR =1.101, 95% CI=0.887-1.203, P=0.009). Conclusions. We found an association between the TLR4 Asp299Gly and Thr399Ile polymorphisms and protection for DR. The APN genetic polymorphism is not associated with T2DM.

Turner syndrome is one of the genetic disorders studied on their association with celiac disease. We present a 27 year old female with an association of Turner syndrome and celiac disease. Gluten intolerance presenting with atypical extraintestinal symptoms (recurrent aphthous stomatitis, iron-deficient anemia, short-stature) was confirmed by intestinal biopsy showing flat small bowel mucosa (Marsh IIIc lesion) and a peripheral lymphocyte karyotype analysis revealed a Turner syndrome determined by isochromosome 46,X,i (Xq) structural abnormality. Our patient fits perfect into this variant of Turner&#8217;s Syndrome presenting at least one autoimmune disorder (celiac disease) and hearing loss. Her clinical, biological and immunological disturbances caused by two irreversible disorders have a poor outcome in the absence of gluten-free diet associated with adequate endocrinologic treatment and need sustained long-term follow - up for a good quality of life.

We present the case-report of a 56 years-old woman with hypothyroidism due to autoimmune thyroiditis. The family history was positive for biopsy proven celiac disease (CD) in her daughter. The patient declared gluten-containing diet and was completely asymptomatic regarding gastrointestinal tract. The serological screening for CD reflected an activity of the disease by the presence of antiendomysial antibodies (EMA). Consequently, an upper gastrointestinal endoscopy was performed and biopsy specimens were obtained. The standard histopathological examination was unremarkable for a defined CD. However, the results of immunohistological techniques showed intestinal IgA deposits compatible with early developing CD. In patients with family history of CD, even without any suggestive symptoms, high index of suspicion regarding CD should be kept even more in those associating other autoimmune disease.

A certain degree of insulin resistance in patients with Gaucher disease type 1 (GD) under enzyme replacement therapy (ERT) was reported. Data on insulin sensitivity in treatment naïve patients are inconsistent. Objective. To analyse prospectively changes in parameters of insulin resistance under ERT and to estimate when they occur. Design. prospective, controlled study; three years follow-up. Patients and methods. 12 treatment naïve patients with GD type 1 (M/W 8/4), 29.5±12.9 years, without overweight, diagnosed enzymatically and by genotyping, without previous diabetes mellitus. Patients were evaluated before and every 6 months up to 3 years under ERT and compared at baseline and after 3 years with matched healthy controls. Fasting-glucose (FG), - insulin (FI), C-peptide, HOMA-IR, IRI, HOMA-B, blood count, hepatic and splenic volume, chitotriosidase, severity score index di Rocco (SSI) were assessed. Results. Baseline glycemic parameters did not differ from controls. FG increased from baseline after two years of ERT (+16.4%,p<0.010), FI (+40.3%,p=0.030), HOMA-IR (+61.2%,p=0.007) and IRI (+9.1%,p=0.010) after 18 months, HOMA-B after 2.5 years (+51%, p=0.015. After 3 years of ERT patients were more insulin resistant compared to controls (p<0.001): FG (96.0±6.2 vs. 73.2±6.4 mg/dL), FI (11.2±2.4 vs. 5.6±1.3 μU/L), HOMA-IR (2.7±0.6 vs. 1.0+0.3), IRI (3.02±0.10 vs. 2.62±0.13). FG, FI, HOMAIR, IRI, HOMA-B correlated with disease severity markers. Conclusions. This is the first controlled study which evaluates prospectively insulin resistance in GD patients, finding significant differences compared to baseline starting with 18 months ERT.

We present the case of severe hypocalcaemia in a 5 weeks old baby, secondary to pre and postnatal vitamin D deficiency. The symptomatic hypocalcaemia led to several life threatening episodes of seizures. Following initial calcium gluconate infusion, multiple phospho-calcic deposits in the soft tissue and cerebral tissue were observed. A multifactorial etiology of calcinosis cutis was suggested by the association between infusion of high and repeated doses of calcium gluconate in a severely hypocalcaemic baby, with a low 25- hydroxyvitamin D3 level, associated to a renal and bone relative resistance to the high level of PTH. The aim of this report is to raise pediatric health care professionals awareness on the relatively rare entity known as calcinosis cutis.

Introduction. Autoimmunity derives from a complex interplay of genetic and environmental factors. Major histocompatibility complex (MHC) alleles and non-MHC loci have been identified as susceptibility markers. Few studies evidenced an association between autoimmune thyroid disease (ATD) and CT60 or 49 A/G polymorphisms in the CTLA-4 gene. Objectives. The aim of our research was to investigate in a pilot case-control study whether other two CTLA-4 gene polymorphisms, i.e. the CTLA-4 1661 A/G and the CTLA-4 658 C/T single nucleotide polymorphisms (SNP), are involved in genetic predisposition to ATD. Material and methods. Between January and April 2009, 42 subjects entered the study. Of these, ATD (i.e. chronic autoimmune thyroiditis, Graves’ disease) was diagnosed in 21 patients, whereas in 21 subjects no signs of autoimmunity were identified. CTLA-4 gene polymorphisms were genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Results. No association was observed between the CTLA-4 1661A/G gene polymorphism in patients with ATD and controls (p = 0.094, by chi-square test). Likewise, no statistically significant difference was noticed between groups with regard to the CTLA-4 658 C/T gene polymorphism (p = 0.649). Conclusions. At the time being, this is the first case-control study that examined and demonstrated lack of association between CTLA-4 -1661 A\G and -658 C\T SNP and ATD; however, larger numbers of subjects are needed to clarify the role of CTLA-4 gene polymorphisms in endocrine autoimmunity.

Context. Genetic factors are responsible for up to 80% of height variation in humans. SHOX gene mutation could be an important etiologic factor in short stature, being observed in up to 15% of patients. Aim. Our aim was to evaluate the genetic causes of short stature, using classical and molecular cytogenetic techniques by analyzing a group of Romanian patients diagnosed with short stature. Material and methods. Seventy nine patients were analyzed and the main criteria for inclusion in the study was the presence of a height below -2DS. For each of these patients a karyotype was performed. In those with normal karyotype it was indicated FISH technique using probes for SHOX and centromeric regions. Results and discussion. The karyotype revealed the presence of abnormalities in 13 patients (16%), 62% (8 patients) of these being represented by heterosomal abnormalities. SHOX deletion was seen in one patient (2.3%) with short stature and normal karyotype. The initial analysis of the cases with short stature directly by FISH technique can be proposed, using probes for X chromosome centromere and SHOX gene, because it allows, approximately at the same costs with the karyotype, but faster and at a higher rate of mosaicism detection, the explanation of short stature by sex chromosomes abnormalities.