Relationship between gut microbiome and bone deficits in primary hyperparathyroidism: A proof-of-concept pilot study.

Parathyroid hormone (PTH) interacts with components of the gut microbiota to exert its bone-regulating effects. This study aimed to investigate the gut microbial composition in patients with primary hyperparathyroidism (PHPT). Nine patients with PHPT and nine age-sex and body mass index-matched healthy controls were included. Gut microbial composition was assessed using 16S rRNA gene amplicon sequencing in both groups at baseline and 1 month after parathyroidectomy in the PHPT group. Data were imported into QIIME-2 and both QIIME-2 and R packages were used for microbiome analysis. Alpha and beta diversities were similar between the groups and remained unchanged after parathyroidectomy. The relative abundance of Subdoligranulum was significantly higher, whereas Ruminococcus, Alloprevotella, Phascolarctobacterium, and Clostridium sensu stricto_1 were significantly lower in PHPT than in controls (p < 0.001). After parathyroidectomy, the relative abundance of Subdoligranulum decreased, and Ruminococcus and Alloprevotella increased (p < 0.001). The PHPT group had lower total femoral and lumbar bone mineral density (BMD) than the controls (p < 0.05). At baseline, Alloprevotella abundance was positively correlated with serum phosphorus and Subdoligranulum was positively correlated with total lumbar BMD. Clostridium sensu stricto_1 was negatively correlated with serum calcium and positively correlated with femoral neck BMD. Postoperatively, Alloprevotella was positively correlated with baseline serum phosphorus and Phascolarctobacterium was positively correlated with distal radius BMD. This study demonstrated that the diversity of the gut microbiome was altered, possibly in response to electrolyte changes in PHPT, both before and after parathyroidectomy.

Evaluation of common carotid artery in type 1 diabetes mellitus patients through speckle tracking carotid strain ultrasonography.

PURPOSE: We aimed to evaluate the effectiveness of speckle tracking carotid strain (STCS) technique, which enables measurement of arterial stiffness and strain parameters, in the detection of early atherosclerotic findings in type 1 diabetes mellitus (T1DM). METHODS: We prospectively enrolled 30 T1DM patients and 30 age- and sex-matched control participants with no history of cardiovascular disease. All study population underwent carotid ultrasonography. Radial and circumferential movement of the common carotid artery (CCA) in the transverse plane as the well as the radial movement of the CCA in the longitudinal plane were calculated automatically by using the STCS method. In addition, the strain (%), strain rate (per second), and peak circumferential and radial displacements (mm) were calculated. Arterial stiffness parameters, such as elastic modulus, distensibility, arterial compliance, and ß-stiffness index, were calculated using the radial measurements. The mean value of the carotid intima media thickness (CIMT) was calculated semi-automatically for each CCA, in the longitudinal plane. We also analyzed the patients' overall body composition. RESULTS: T1DM and control groups were compared in terms of strain and stiffness parameters and no statistically significant difference was found (p > 0.05). CIMT was higher in diabetic patients than in the control group (p = 0.039). In both groups, age was correlated with all arterial stiffness and strain parameters (p < 0.05). The duration of diabetes was also correlated with ß-stiffness index, distensibility, and elastic modulus in the longitudinal plane (p < 0.05). In the diabetic group, abdominal fat ratio, whole body fat ratio, and fat mass were correlated with radial and circumferential displacement and strain parameters in transverse plane, and radial displacement in longitudinal plane (p < 0.05, for each). Diabetic patients were divided into subgroups according to the presence of nephropathy and dyslipidemia. Although no significant difference was found between the groups in terms of CIMT, patients with nephropathy had higher values for transverse and longitudinal elastic modulus, pulse-wave velocity, and longitudinal ß-stiffness index, as well as lower values for longitudinal arterial compliance and distensibility, compared with patients without nephropathy (p < 0.05). Also, patients with dyslipidemia had higher longitudinal ß-stiffness and elastic modulus values compared with patients without dyslipidemia (p < 0.05). CONCLUSION: STCS ultrasonography is an effective, easy, and noninvasive method for evaluating the arterial elasticity. It may provide an early assessment of atherosclerosis in patients with T1DM, especially in the presence of nephropathy and dyslipidemia; thus, together with CIMT measurement, it may be used more frequently to detect subclinical damage and stratify atherosclerosis.

The evaluation of the tendon and muscle changes of lower extremity in patients with acromegaly.

PURPOSE: Although it is well known that acromegaly causes enlargement in the extremities, studies investigating the effects of acromegaly on tendons, muscles and soft tissue are limited. The aims of our study were to investigate tendons, the presence of enthesitis, soft tissue, muscle groups in terms of thickness and pennation angle (PA) which is an indicator of microstructure and strength of the muscle, of the lower extremities. METHODS: Thirty-nine patients with acromegaly and thirty-nine healthy control subjects similar for age, sex and body mass index were enrolled. Lower extremity tendons, skin, muscle groups were evaluated by ultrasound. RESULTS: The thicknesses of heel skin, heel pad, plantar fascia and Achilles tendon were higher in acromegaly than the control group (p < 0.05). The incidence of Achilles enthesitis were increased in the acromegaly group (p < 0.05). The thicknesses of the gastrocnemius medial head, vastus medialis, lateralis muscles for both sides and the left rectus femoris muscle were found to be lower in the acromegaly patients than controls (p < 0.05). However, thicknesses of vastus intermedius, gastrocnemius lateral head and soleus were similar between the acromegaly and control groups (p > 0.05). PA values of the right and left vastus medialis and the right vastus lateralis were found to be decreased in the acromegaly group (p < 0.05). Myostatin levels were lower in acromegaly group (p < 0.05). CONCLUSIONS: Acromegaly may cause to an increase in tendon and soft tissue thickness, enthesitis formation, decrease in the thickness of some muscles, and deterioration in microstructures in lower extremity.

Serum activities of dipeptidyl peptidase-4 and adenosine deaminase in polycystic ovary syndrome: association with obesity.

Dipeptidyl peptidase-4 (DPP-4) plays a role in metabolic and inflammatory diseases. Increased adenosine deaminase (ADA) has been suggested to induce insulin resistance and inflammation. We measured serum DPP-4 and ADA activities. Serum ADA activity was significantly higher in PCOS group (p = .006), whereas there was no difference in serum DPP-4 activity between the groups (p > .05). When the study subjects were divided into four groups in terms of obesity; an increasing trend in serum ADA activity between the groups was observed and ADA activity was significantly higher in overweight and obese patients with PCOS than nonobese controls (p = .016), there were no significant differences between the other groups (p > .05). A positive correlation was found between ADA and BMI in the whole group (p = .022). Multivariate regression analyses revealed that significant determinants were diastolic blood pressure, ADA, and the presence of PCOS for DPP-4 (R2 = 0.344, F = 9.079, p < .001); the presence of PCOS and DPP-4 for ADA (R2 = 0.123, F = 6.302, p = .003). We demonstrated increased serum ADA activity as well as its association with obesity in PCOS, while there was no change in serum DPP-4 activity in women with PCOS.

Is thyroid autoimmunity itself associated with psychological well-being in euthyroid Hashimoto's thyroiditis?

Recent studies imply that euthyroid Hashimoto's thyroiditis (HT) might be related with impaired HRQoL, depression and anxiety. Ninety three patients with euthyroid HT and 31 age- and gender-matched euthyroid control subjects were enrolled into this study. SF-36 questionnaire, Beck Depression Inventory and Beck Anxiety Inventory tests were used for evaluating HRQoL, depression and anxiety. Beck Depression Inventory scores were higher in patients with HT compared to control subjects (7.5 (4.0-14.75) vs. 5.0 (2.25-9.0), p=0.008). Beck Anxiety Questionnaire scores were also higher in patients with HT than controls (9.50 (5.0-17.0) vs. 5.0 (2.0-11.75), p=0.021). In SF-36 questionnaire; physical functioning (26.0 (20.0-28.0) vs. 29.0 (26.0-30.0), p=0.038), general health (16.4 (13.4-20.4) vs. 19.4 (16.3-21.2), p=0.026) and mental health (20.5 (16.0-23.0) vs. 23.0 (21.0-25.0), p=0.001) scores were lower in patients with HT than control subjects. There were no significant differences between patients with HT under levothyroxine replacement therapy compared to those without therapy in terms of depression and anxiety scores and components of SF-36 questionnaire. Beck Depression Inventory scores were positively correlated with TSH (r=0.250, p=0.01). In SF-36, role physical (r=0.192, p<0.05) and vitality (r=0.181, p<0.05) were positively correlated with fT4. Role emotional was negatively correlated with TSH (r=-0.185, p<0.05) and anti-TPO (r=-0.234, p<0.05). Mental health was negatively correlated with anti-TPO (r=-0.287, p<0.01). HRQoL is impaired and depression and anxiety scores are high in patients with euthyroid HT independent of levothyroxine replacement. Therefore, our results indicate that thyroid autoimmunity itself may have an impact on psychological well-being in euthyroid patients with HT.

Evaluation of ambulatory arterial stiffness index in hyperthyroidism

Background/aim: Hyperthyroidism causes hemodynamic changes that are associated with adverse cardiovascular outcomes. Twenty-four-hour ambulatory blood pressure monitoring recordings provide us with some essential data: BP variability and ambulatory arterial stiffness index (AASI). In this study, we aimed to investigate AASI and short-term BP variability in both overt and subclinical hyperthyroidism and their relationship with thyroid hormones. Materials and methods: We enrolled 36 patients with subclinical hyperthyroidism, 23 patients with overt hyperthyroidism, and 25 healthy euthyroid controls. ABPM recording was performed for 24 h for all patients. Results: There were no statistically significant differences among the overt hyperthyroidism, subclinical hyperthyroidism, and control groups in terms of AASI (0.43 ± 0.15, 0.38 ± 0.12, 0.42 ± 0.13, respectively; P = 0.315). Variability of diastolic BP was significantly higher in patients with overt hyperthyroidism than in patients with subclinical hyperthyroidism (14.8 ± 2.6 vs. 12.8 ± 2.5%, P = 0.023). There were significant positive correlations between AASI and fT3 (r = 0.246, P = 0.02) and fT4 (r = 0.219, P = 0.04) while TSH was not correlated with AASI (r = 0.023, P = 0.838). After adjusting for confounders, age, 24-h systolic and diastolic BP, variability of systolic and diastolic BP, and fT4 were independent predictors of AASI (r2 = 0.460, P < 0.001). Conclusion: Although AASI did not differ between overt and subclinical hyperthyroidism, there was a positive relationship between AASI and free thyroid hormone levels. Furthermore, short-term BP variability was higher in overt hyperthyroidism than in subclinical hyperthyroidism.

Circulating Th17 cytokine levels are altered in Hashimoto's thyroiditis.

The disrupted autoimmune response in Hashimoto's thyroiditis (HT) has long been considered to be dominantly T helper type 1 (Th1) mediated. Recent advances in the field of immunology have introduced a new class of effector T cells, named 'Th17', which plays important roles in autoimmune disorders once thought to be merely Th1 mediated. We aimed to examine the levels of major Th17 cytokines in patients with HT in this study. We studied serum interleukin 17 (IL-17) and interleukin 23 (IL-23) levels in 46 newly diagnosed, untreated patients with HT (40 women and 6 men, aged 40.0 ± 11.8 years) divided into euthyroid (n=22) and hypothyroid (n=24) groups and compared them with age and sex matched 26 healthy euthyroid controls without HT (21 women and 5 men; aged 36.0 ± 12.9 years). Serum IL-17 and IL-23 levels were significantly different among euthyroid and hypothyroid HT patients and controls, with highest levels obtained in the euthyroid HT group (p=0.041 for IL-17 and p<0.001 for IL-23). TSH was negatively and FT4 was positively correlated with IL-17 (p=0.016 for TSH and p=0.004 for FT4) and IL-23 (p<0.001 for TSH and p=0.003 for FT4) levels. There were no correlations between thyroid volumes calculated on thyroid ultrasonography and IL-17 (p=0.630) or IL-23 (p=0.321) levels. In conclusion, the levels of IL-17, one of the major effector cytokines of the Th17 system, and IL-23, which had been implicated in the generation, survival and expansion of Th17 cells, are altered in HT. How thyroid hormone status and the course of disease affect Th17 system in chronic autoimmune thyroiditis needs to be determined with further studies.

Fibroblast growth factor 21 and its relationship with insulin sensitivity in first-degree relatives of patients with type 2 diabetes mellitus.

INTRODUCTION: Fibroblast growth factor 21 (FGF 21) has been suggested as a predictor for the development of type 2 diabetes mellitus (T2DM). MATERIAL AND METHODS: We aimed to determine FGF 21 levels in normoglycaemic (Group 1) and prediabetic (Group 2) first-degree relatives (FDR) of patients with T2DM in comparison with normoglycaemic subjects without a history of T2DM in their FDR (Group 3). RESULTS: There was a significant difference between Group 1, 2, and 3 with respect to plasma FGF 21 concentrations (143.3 ± 93.8, 221.9 ± ± 171.7 and 121.2 ± 119.8 pg/mL, respectively, p = 0.01). FGF 21 levels were significantly increased in prediabetic FDR of patients with T2DM compared to normoglycaemic subjects without a history of T2DM in their FDR (p = 0.02). FGF 21 levels did not differ between normoglycaemic FDR of patients with T2DM and normoglycaemic subjects without a history of T2DM in their FDR (p > 0.05). In the whole group, FGF 21 correlated positively with age (r = 0.31, p = 0.003), BMI (r = 0.38, p < 0.001), systolic blood pressure (r = 0.38, p = 0.001), diastolic blood pressure (r = 0.26, p = 0.02), fasting blood glucose (r = 0.24, p = 0.02), HOMA-IR (r = 0.23, p = 0.03), AUC glucose (r = 0.35, p = 0.001), and AUC insulin (r = 0.32, p = 0.003) and negatively with HDL cholesterol (r = -0.24, p = 0.02) and Matsuda ISI (r = -0.33, p = 0.002). In the regression analysis, BMI was the most predictive factor for FGF 21 levels (beta = 0.41, r2 = 0.17, p < 0.001). CONCLUSIONS: We showed that FGF 21 concentrations are increased in prediabetic FDR of patients with T2DM and that there is a significant association between FGF 21 and obesity and insulin sensitivity. (Endokrynol Pol 2016; 67 (3): 260-264).

Proprotein convertase subtilisin/kexin type 9 (PCSK9), soluble lectin-like oxidized LDL receptor 1 (sLOX-1) and ankle brachial index in patients with differentiated thyroid cancer.

The cardiovascular effects of short-term overt hypothyroidism are not well known. We investigated proprotein convertase subtilisin/kexin type 9 (PCSK9), soluble lectin-like oxidized LDL receptor 1 (sLOX-1) and the ankle brachial index (ABI) in thyroid cancer patients with short-term overt hypothyroidism due to thyroid hormone withdrawal (THW). Twenty-one patients requiring radioactive iodine (RAI) ablation or scanning and 36 healthy control subjects were enrolled. Patients were evaluated in the subclinical thyrotoxic phase when they were on suppressive levothyroxine therapy and in the overt hypothyroid phase due to THW for four weeks. PCSK9, sLOX-1, lipids and ABI were measured in the patient and control groups. Total cholesterol, LDL cholesterol, triglycerides and Apo B levels were increased in short overt hypothyroidism compared with the control group (p<0.001). PCSK9 levels increased before THW and after THW in the patients compared to control group (p<0.001, p=0.004, respectively). sLOX-1 levels were not different between patients with short term overt hypothyroidism and control group (p=0.27). ABI was found to be significantly decreased in patients with thyroid cancer before and after THW compared to control group (p=0.04, p=0.002 respectively). PCSK9 levels were correlated negatively with ABI (r=-0.38, p=0.004). In conclusion; our study demonstrated that patients with differentiated thyroid cancer both before and after THW which is a short term overt hypothyroid phase, had increased PCSK9 levels and decreased ABI. Short term overt hypothyroidism also leads to increased HDL, LDL, total cholesterol, Apo A and Apo B levels.

Craniofacial and pharyngeal airway morphology in patients with acromegaly.

OBJECTIVE: The aim of this study was to assess differences in craniofacial characteristics, upper spine and pharyngeal airway morphology in patients with acromegaly compared with healthy individuals. MATERIALS AND METHODS: Twenty-one patients with acromegaly were compared with 22 controls by linear and angular measurements on cephalograms. The differences between the mean values of cephalometric parameters were analyzed with Mann-Whitney U-test. RESULTS: With respect to controls, anterior (p<0.05), middle (p<0.01) and posterior (p<0.05) cranial base lengths were increased, sella turcica was enlarged (p<0.001) and upper spine morphology demonstrated differences in the height of atlas (p<0.01) and axis (p<0.05) in patients with acromegaly. Craniofacial changes were predominantly found in the frontal bone (p<0.01) and the mandible (p<0.05). As for the airway, patients with acromegaly exhibited diminished dimensions at nasal (p<0.001), uvular (p<0.01), mandibular (p<0.01) pharyngeal levels and at the narrowest point of the pharyngeal airway space (p<0.001) compared to healthy controls. Soft palate width was significantly higher (p<0.001) and the hyoid bone was more vertically positioned (p<0.01) in patients with acromegaly. CONCLUSIONS: Current results point to the importance of the reduced airway dimensions and that dentists and/or orthodontists should be aware of the cranial or dental abnormalities in patients with acromegaly.