ACTA ENDOCRINOLOGICA (BUC)

Context. Hereditary hypophosphatemic rickets with hypercalciuria (HHRH) is a rare autosomal recessive disorder, which is characterized by renal phosphate wasting, hypercalciuria, increased 1,25-dihydroxyvitamin D, and decreased parathormone (PTH) levels. Objective. Here we report different clinical features of two siblings with HHRH, confirmed with molecular diagnosis. Subjects and methods. 16.4 years old boy (P1), and 8.7 years old girl (P2) were referred to our outpatient clinic due to clinical suspicion of metabolic bone diseases. Results. P1 had severe hypophosphatemia. Additionally, PTH concentration was near to the lower limit, 1,25-dihydroxyvitamin-D concentration was near to the upper limit. P2 had relatively milder clinical and laboratory findings. Bilateral renal calculi were detected on ultrasound in both of them. HHRH was suspected due to their described biochemistry and the presence of bilateral renal calculi. Molecular analysis of SLC34A3 gene revealed a homozygous variant c.756G>A (p.Gln252=) and a splice donor variant c.1335+2T>A. After oral phosphate treatment, clinical and biochemical improvements were observed. However treatment nonadherence of patients was a barrier to reach treatment goal Conclusion. The clinical phenotype due to the same mutation in the SLC34A3 gene may vary even among the members of the same family. An accurate diagnosis is important for the appropriate treatment.

Context. Alimentary supplements may have beneficial effects on retinal microvasculature in diabetic patients. Objective and Design. State-of-the-art imaging techniques were used to assess retinal microcirculation in diabetic patients in an observational study before and after 3 months treatment with a multinutrient complex including resveratrol, vitamins D3, C, E, essential fatty acids, trace elements (zinc and copper) and macular pigments (lutein and zeaxanthin)-Resvega. Subjects and Methods. Fifteen subjects were included in this study. Adaptive optics ophthalmoscopy was used to measure the parameters of temporal retinal arterioles. Optical coherence tomography angiography was employed to assess foveal avascular zone and vessel densities of the superficial capillary plexus, deep capillary plexus and choricapillary plexus. Results. After 3 months of treatment, there was a statistically significant median decrease in wall-to-lumen ratio (p=0.0001). The same tendencies were noticed for wall thickness values (p=0.008) and wall cross sectional area values (p=0.001). On the other side, no significant changes were noticed concerning the OCTA parameters. Conclusions. Resvega seems to have a beneficial effect on the retinal arterioles in diabetic patients.

Context. GnRHa treatment has been a standard of care in progressive early puberty (EP). Choice of the GnRHa formulation is dependent on the preference of the clinician. Objective. To compare the effects of triptorelin acetate (TA) and leuprolide acetate (LA) on anthropometry in girls with EP. Design. A descriptive observational study. Subjects and Methods. Girls diagnosed with central EP and treated with GnRHa at least for one year were included; treated with TA (n=46) and LA (n=35). First year anthropometric response and final height were evaluated. Results. The mean age at the initiation of GnRHa treatment of girls was 8.5±0.5 years. The ratio of obesity and of overweight was 7.4 and 25.9%, respectively. In both TA and LA groups, anthropometric data of the patients at initiation and at the first year of treatment were similar. Although growth velocity was similar in each group, in LA group height SDS at the first year of the treatment showed a significant decrease (p=0.045), but not in TA group (p=0.317). No significant ΔBMI was observed with treatment. The differences between FH – PAH at initiation (height gain) in TA and LA groups were 2.9±4.7 and 4.0±5.8 cm, respectively (p=.316). Height gain per treatment year was 1.7±3.0 cm. Conclusions. There was a significant decrease in height SDS at the first year of leuprolid treatment, but not in triptorelin. Although these two analogs show similar effects on treatment, a not significant but slightly better benefit in leuprolide was observed.

Context. State of art imaging techniques might be a useful tool to early detect the retinal vessels lesions in diabetes. Objective and design. This analytical observational study investigates the retinal microcirculation changes in type I and II diabetic patients without retinopathy using adaptive optics ophthalmoscopy (AOO) and optical coherence ophthalmoscopy angiography (OCTA). Subjects and methods. Fifty-five subjects were included in this study and were divided in three groups: type I diabetic group (n=16), type II diabetic group (n=19) and control group (n=20). An adaptive optics retinal camera was used to assess the parameters of the temporal superior retinal arterioles. Moreover, vessel density of the superficial capillary plexus across the parafoveal area was measured with OCT-A. All cases were investigated once, in a cross-sectional design. Results. Diabetic patients from both groups had a higher wall-to-lumen-ratio compared to the controls (p=0.01 and 0.01, respectively). Interestingly, no significant differences were found between the two diabetic groups (p=0.69). Moreover, the vessel density was smaller in the type I diabetic group than in the control group (p=0.001) Conclusion. AOO might be a useful tool to detect early retinal vascular changes in diabetes before any clinical signs and together with OCTA it might bring important information on the prognostic and pathophysiology of the disease.

Context. Obesity is a complex and heterogeneous disorder with multiple phenotypes described. Although metabolomic biomarkers of obesity have been extensively studied, biomarkers of obesity phenotypes and differences between these phenotypes and normal-weight (NW) persons have been less investigated. Objective. The objective of this cross-sectional analysis was to investigate serum amino acids (AA) as markers of metabolic alterations in obesity phenotypes and NW. Design. Cross-sectional Subjects and Methods. By targeted metabolomics we analyzed serum samples of 70 women using ultrahighperformance liquid chromatography/mass spectrometry. Participants were divided into 3 groups: NW, metabolically healthy obesity (MHO) and metabolically unhealthy obesity (MUHO). Results. Five AAs were significantly different between study groups: cysteine, methionine, asparagine, glutamine, and lysine (p-value <0.05 and variable importance in the projection >1). Cysteine increased linearly with metabolic unwellness from NW to MUHO. Lysine and glutamine were significantly higher, and asparagine was significantly lower in NW and MHO than in MUHO. Conclusions. By trend and group analysis we identified specific changes in serum AAs along with the progression of metabolically unwellness.

Background. Although cardiovascular risk is increased in patients with subclinical hypothyroidism (SCH), replacement therapy is not recommended in those with TSH levels\r\nbetween 5 and 10 mU/L.\r\nObjective. We aimed to evaluate the effects of levothyroxine (LT4) treatment on cardiovascular risk factors and carotid artery intima media thickness (CIMT) in patients with SCH who had TSH levels between 5 and 10 mU/L.\r\nSubjects and Methods. Sixty SCH patients with TSH levels between 5 and 10 mU/L were included in the study. Patients\r\nwere randomized into two groups as treatment (n=30) and control (n=30) groups. BMI, blood pressure, lipid profile, fibrinogen, homocysteine, hs-CRP and CIMT were measured in all patients at baseline and after six months. LT4 treatment was initiated and the dose was tapered according to TSH levels in treatment.\r\nResults. There was no significant difference between baseline and six month measurements in the control group. However, TSH, LDL-C, fibrinogen and mean CIMT measurements were decreased and HDL-C level was increased in the treatment group.\r\nConclusions. We suggest that LT4 therapy is necessary for the prevention of modifiable cardiovascular risk factors in\r\npatients with TSH levels between 5 and 10 mU/L.

Nodular thyroid disease (NTD) is represented by palpable thyroid nodules (solitary, multiple) and thyroid incidentalomas (identified by means of thyroid ultrasonography). The discussed entities carry the same risk of malignancy (about 5 %). The main objective in evaluating NTD is represented by the exclusion of malignancy by means of corroborated investigations, focused on the value of a panel of IHC markers.\r\nMaterial and methods. We included in the study 27 cases of NTD, evaluated by means of: clinical investigation, ultrasonography of the thyroid, cytological examination, morphological analysis and IHC. The used panel of IHC markers comprised: Ki-67, PCNA, CK 19 and c-erbB2 (DAKO LSAB method)\r\nResults. From the total of cases, 8 presented positivity with Ki-67 and 17 with PCNA. Regarding CK 19, the majority of PTC cases stained ++ and diffusely, but not papillary hyperplasia (focal positivity).c-erbB2 diffuse and intense positivity (+++) was noticed in PTC.The case with a follicular tumor of uncertain malignant potential stained weakly only with c-erbB2.\r\nConclusions. From the used panel of IHC markers, CK 19 presented the best value, being able to differentiate FVPTC from FTC and PTC from papillary hyperplasia.

Context. Changes in the secretion of signaling molecules that originates from adipose tissue and inflammation draw attention in the pathogenesis of type 2 DM. Chemerin, one of the signaling molecules of adipose origin, and irisin, defined as the Renaissance of the metabolism, are among these molecules. Objectives. This cross-sectional study was planned in order to compare the values of serum irisin and chemerin levels in patients newly diagnosed with T2DM and in healthy subjects. Subjects and Methods. The study included 41 patients newly diagnosed with T2DM and 49 healthy individuals. The chemistry parameters were analyzed with a biochemistry autoanalyzer, and hormonal parameters were analyzed with an immunoassay analyzer. Plasma irisin and chemerin levels were measured using the enzyme-linked immunosorbent assay method. Results. There was a significant difference between the groups in terms of glucose, HbA1C, Insulin, HOMA-IR and lipid panel results. Irisin levels in the group of patients newly diagnosed with T2DM were lower than in the control group. Chemerin levels in the group of patients newly diagnosed with T2DM were higher than in the control group. Conclusion. Consequently, diabetes-dependent changes in chemerin and irisin concentrations suggest that these two hormones have a role in the pathophysiology of DM. Further studies are required to understand the complex structure of the signaling pathways of chemerin and irisin molecules as well as the physiological importance of these molecules as metabolism regulators especially in humans.

Introduction. Pulmonary hypertension (PHT) is a quite frequent echocardiographic finding in hyperthyroid patients and it regresses slowly under therapy with thiamazol.\r\nAim. The aim of the study was to follow the evolution of PHT over a period of a year, in two groups of hyperthyroid patients.\r\nMaterial and Methods. We followed up two groups of patients: one consisted of patients with chronic Graves Basedow\r\ndisease, some of them with good response to antithyroidian treatment and some other patients with repeated episodes of\r\ndecompensation despite medical therapy. The second group contained new diagnosed cases, a supgroup of patients with overt hyperthyroidism and one with subclinical forms. All 4 subgroups were followed over a period of 12 months. These subjects underwent thyroid hormone determinations and echocardiographic examination at 0, 1, 3, 6 and 12 months.\r\nResults. Our study group consisted of 92 patients with hyperthyroidism of different etiologies. None of the subjects had pulmonary or cardiovascular diseases severe\r\nenough to cause PHT by itself. We determined the presence and severity of pulmonary hypertension at the initial visit and followed its evolution at each scheduled visit in all four subgroups. All patients got antithyroidian therapy with thiamazol, but some chronic cases, with episodes of exacerbation, needed adjustments of their initial treatment. We noticed that PHT appeared in a higher percent and was more severe in the patients with severe hyperthyroidism or in the chronic cases with poor therapeutic response. We observed after some months a tendency to regression in\r\nthe well controlled patients or in those with subclinical disease.\r\nConclusion. The duration and severity of hyperthyroidism had a strong influence on the evolution of pulmonary hypertension in our patients.

Introduction. The definition of severity and activity of Graves' ophthalmopathy (GO)comprises different parameters.\r\nThe aim of this study is to select the most appropriate severity and activity criteria, respectively scores and to investigate a possible correlation among them.\r\nSubjects and methods. The study included 51 patients with GO (43 females, 8 males), mean age 46.8?11.2 years. The patients were evaluated by: clinical exam, laboratory\r\nparameters (TSH, FT4, FT3, thyroid autoantibodies) and imagistic means, performed in selected cases (CT or MRI).\r\nResults. The GO activity was assessed by the clinical activity score (CAS). We quantified the EUGOGO severity criteria, by allotting points for each selected parameter.\r\nAccording to the recommended criteria, the cases were divided into active (n=26) and inactive forms (n=25). There were no significant statistical differences regarding CAS\r\nbetween euthyroid cases (n=14) and dysthyroid cases (n=37). Serum thyroid receptor antibodies (TRAb) levels did not correlate with CAS or severity scores. Severity scores\r\ncorrelated significantly with CAS (Pearson correlation index 0.546, r2=0.290, p=0.0001).\r\nConclusion. Active forms of GO showed higher severity scores than the inactive ones. The severity scores correlated significantly with CAS scores. Neither CAS, nor severity scores correlated significantly with the severity of thyrotoxicosis.