Biochemical characteristics and calcium and PTH levels of patients with high normal and elevated serum 25(OH)D levels in Turkey: DeVIT-TOX survey.

Vitamin D intake over the recommended dose is usually associated with high serum 25(OH)D levels and generally not associated with symptoms of hypercalcemia. High doses of cholecalciferol need to be avoided to protect against vitamin D toxicity and related complications. Strict adherence to the clinical guidelines for treating vitamin D deficiency can ensure safe and effective treatment. PURPOSE: We observed a tendency to use high doses of cholecalciferol for vitamin D deficiency treatment or vitamin D supplementation. We aimed to determine the biochemical characteristics of patients with high normal and elevated serum 25(OH)D levels. METHODS: An online invitation was sent to all tertiary endocrinology clinics in Turkey to complete an online retrospective survey (DeVIT-TOX Survey) for patients diagnosed with high serum 25(OH)D levels (> 88 ng/mL) between January 2019 and December 2019. The patients were evaluated according to the presence of signs and symptoms of hypercalcemia and doses of vitamin D intake, evaluated into the following three groups according to their 25(OH)D levels: group 1, > 150 ng/mL; group 2, 149-100 ng/mL; and group 3, 99-88 ng/mL. RESULTS: A total of 253 patients were included in the final analysis (female/male: 215/38; mean age, 51.5 ± 15.6 years). The average serum 25(OH)D level was 119.9 ± 33 (range, 88-455) ng/mL, and the average serum calcium level was 9.8 ± 0.7 (range, 8.1-13.1) mg/dL. Most (n = 201; 75.4%) patients were asymptomatic despite having high serum 25(OH)D and calcium levels. The serum 25(OH)D level was significantly higher in the symptomatic groups than in the asymptomatic groups (138.6 ± 64 ng/mL vs. 117.7 ± 31 ng/mL, p < 0.05). The most common cause (73.5%) associated with high serum 25(OH)D levels was the inappropriate prescription of a high dose of oral vitamin D (600.000-1.500.000 IU) for treating vitamin D deficiency/insufficiency in a short time (1-3 months). The cut-off value of 25 (OH) D level in patients with hypercalcemia was found to be 89 ng/mL [median 116.5 (89-216)]. CONCLUSIONS: High dose of vitamin D intake is associated with a high serum 25 OH D level, without symptoms of hypercalcemia. Inappropriate prescription of vitamin D is the primary cause for elevated 25(OH) D levels and related hypercalcemia. Hypercalcemia may not be observed in every patient at very high 25(OH) D levels. Adherence to the recommendation of guidelines is essential to ensure safe and effective treatment of vitamin D deficiency.

Serum levels of fetuin A are increased in women with gestational diabetes mellitus.

PURPOSE: Fetuin A is associated with insulin resistance and type 2 diabetes mellitus (DM). We aimed to investigate circulating fetuin A concentrations in gestational diabetes mellitus (GDM). METHODS: Serum fetuin A levels were studied in 26 pregnant women with GDM and 24 healthy pregnant women between 24th and 28th gestational weeks. Fetuin A levels were also evaluated in 18 of women with GDM at postpartum. RESULTS: Fetuin A concentrations were significantly increased in women with GDM compared to healthy pregnant women (35.0 ± 3.2 vs. 32.0 ± 4.4 ng/ml; p = 0.01). Also, fetuin A levels in women with GDM significantly decreased at postpartum period (35.0 ± 3.2 vs. 31.7 ± 3.9 ng/ml; p = 0.001). In whole pregnant women, there were positive correlations between fetuin A and HbA1c (r = 0.418, p = 0.002), total cholesterol (r = 0.332, p = 0.018) and triglycerides (r = 0.306, p = 0.031). Multivariate regression analysis demonstrated that HbA1c was the important predictor of circulating fetuin A level (beta = 0.375, p = 0.01). CONCLUSION: In conclusion, our results indicate that serum fetuin A concentrations are increased in women with GDM and decreased after delivery. Therefore, fetuin A might have a role in the development of insulin resistance and the metabolic changes in GDM.

Hyperparathyroid crisis presenting with hyperemesis gravidarum.

PURPOSE: Primary hyperparathyroidism during pregnancy is a rare condition, and the diagnosis may be confounded by pregnancy related conditions. Since the appropriate management reduces the maternal and fetal complications; differential diagnosis becomes quite crucial. METHOD: Clinical course of a patient with hyperparathyroid crisis will be discussed with the review of the literature. A 22-year- old, (gravida 2, para 1) woman was presented with hyperparathyroid crisis at the 11th weeks' gestation. She was hospitalized twice due to hyperemesis gravidarum. When she was admitted to the hospital for the third time due to increased vomiting and weight-loss, serum biochemistry panel was performed and it revealed severe hypercalcemia that serum Ca was 17.59 mg/dl, and she was referred to our hospital as parathyroid crisis. Maternal hypercalcemia was resolved after urgent parathyroidectomy. She was diagnosed as preeclampsia at the 30 weeks' gestation and delivered a male infant weighing 1,090 g at 33 weeks' gestation with APGAR scores 6 at 1 min, and 7 at min 5, without evidence of neonatal hypocalcemia or tetany. RESULTS: Urgent parathyroidectomy is the definite treatment in symptomatic patients with hyperparathyroidism during pregnancy. Resolving maternal hypercalcemia prevents neonatal tetany and hypocalcemia. CONCLUSION: Hyperemesis may lead to hypercalcemic crisis in patients with hyperparathyroidism, so serum Ca level should be checked in patients with hyperemesis gravidarum especially who detoriate rapidly. Although they share some common pathogenetic mechanisms, there is not enough evidence for attributing preeclampsia to primary hyperparathyroidism.

Elevated mean platelet volume is associated with gestational diabetes mellitus.

The mean platelet volume (MPV) is an indicator of the average size and activity of platelets. Elevated MPV values are associated with larger and more active platelets and perceived as a new independent cardiovascular risk factor. The aim of this study was to determine the MPV in women with gestational diabetes mellitus (GDM) and to determine the correlation of MPV with metabolic parameters in GDM. We retrospectively analyzed 30 women with GDM and 38 body mass index-matched women with healthy pregnancies as controls. MPV and platelet counts were recorded in the third trimester and at postpartum 6-12 months for GDM group and in the third trimester for control group. Third-trimester MPV was significantly higher in GDM group compared to control group (8.8 ± 1.0 versus 8.1 ± 0.7 fl, p = 0.002). In women with GDM, there was a significant decrease in MPV in the postpartum period (8.8 ± 1.0 versus 8.1 ± 0.8 fl, p < 0.001). Fasting plasma glucose levels and glucose area under the curve were positively correlated with third trimester MPV (r = 0.346, p = 0.007 and r = 0.346, p = 0.02, respectively). Our results indicate that MPV is increased in GDM. Monitoring MPV, which is widely available in clinical practice, may potentially identify women who will develop gestational diabetes during pregnancy.

Lack of association of hepatic estrogen receptor-alpha expression with histopathological and biochemical findings in chronic hepatitis C.

Estrogens exert a protective effect against hepatic steatosis and fibrosis. Loss of estrogen receptor-alpha (ER-α) in the liver is associated with hepatic steatosis and inflammation in animal models. We conducted a study in order to investigate the presence and extent of ER-α expression in HCV infection, and its relationship with histological and biochemical findings. Ninety biopsy-proven chronic hepatitis C (CHC) patients were enrolled in the study. Liver biopsy specimens were immunohistochemically stained for ER-α expression. Nuclear ER-α expression percentage was calculated. ER-α was positive in 69 of the patients (76%). ER-α positive and negative groups were not significantly different in terms of age, gender, necroinflammatory activity, fibrosis, steatosis, serum levels of AST, ALT, ALP, GGT, and bilirubin. ER-α expression percentage was not correlated with fibrosis, steatosis, necroinflammatory activity and biochemical findings. Although estrogens are known to be protective against fibrosis and steatosis in animal models, we did not find any significant correlation between ER-α expression and histopathological and biochemical findings in CHC patients. These findings should be verified in further large scale studies.

Serum liver fatty acid binding protein shows good correlation with liver histology in NASH.

BACKGROUND/AIMS: Simple, reproducible and non-invasive tests that can be used to determine the severity of non-alcoholic steatohepatitis (NASH) are needed. Liver-type fatty acid binding protein (L-FABP) plays a key role in the fatty acid metabolism of the liver. We aimed to determine whether serum L-FABP levels in patients with NASH were different from those in healthy controls, and if so, whether this was associated with the degree of fibrosis, steatosis and inflammatory activity. METHODOLOGY: Forty-seven patients with histologically confirmed NASH and 41 healthy controls were included in the study. Serum L-FABP levels were measured in all participants. RESULTS: Mean L-FABP levels were significantly higher in patients with NASH compared to the control group (2703.19±1603.47 vs. 1684.58±860.19, p<0.001). Serum L-FABP levels showed a significant positive correlation with NAS score (p=0.03, r=0.312), the degree of fibrosis (p=0.02, r=0.324) and inflammation (p=0.03, r=0.312), BMI (p=0.05, r=0.303), serum ALT (p=0.01, r=0.28), AST (p=0.04, r=0.315), and triglyceride levels (p=0.03, r=0.328). CONCLUSIONS: Serum L-FABP levels are elevated in NASH and this elevation is positively correlated with the degree of fibrosis and inflammation. L-FABP levels may aid as a non-invasive marker in determining the severity of fibrosis and inflammation in patients with NASH.

Effects of sitagliptin on nonalcoholic fatty liver disease in diet-induced obese rats.

BACKGROUND: Studies investigating the effects of dipeptidyl peptidase-4 inhibitors on hepatic steatosis are lacking. We aimed to determine the effects of sitagliptin on nonalcoholic fatty liver disease (NAFLD) in rats with diet-induced obesity. METHODS: A total of 24 adult female Sprague-Dawley rats, which were 24 weeks old and weighed 199-240 grams, were used. The rats were randomly separated into two groups. The control group (n=6) was fed with standard rat diet; the remaining rats (n=18) were fed with a high-fat diet (HFD) to induce NAFLD. After 12 weeks, rats that were fed with a HFD were randomly separated into two groups: (1) HFD-only group (n=8) was fed with a HFD for an additional 4 weeks, (2) HFD-sitagliptin group (n=10) received sitagliptin (3 mg/kg) for 4 weeks in addition to HFD. At the end of the study (16(th) week), blood samples were drawn from all rats to determine serum glucose, triglyceride, cholesterol, alanine aminotransferase (ALT), and plasma insulin levels. Insulin resistance was determined using the homeostasis model assessment of insulin resistance (HOMA-IR) index. Histopathologic evaluation of liver samples was undertaken. RESULTS: The HFD-sitagliptin group had significantly lower serum glucose (140.8±18.8 vs. 224.7±20.6 mg/dL, P<0.001), plasma insulin (15.8±4.4 vs. 28.0±5.9 µIU/L, P<0.001), HOMA-IR index (4.9±1.8 vs. 15.9±2.3, P<0.001), serum triglycerides (199.0±108.7 vs. 468.0±370.7 mg/dL, P<0.001), and cholesterol (82.0±26.7 vs. 90.5±7.0, P<0.001) values compared to the HFD-only group. Hepatic steatosis was significantly less (mean score, 1 vs. 2; P<0.001) in the HFD-sitagliptin group compared to the HFD-only group, whereas there was no difference in hepatic inflammation (P=0.057), liver weight (P=0.068), and ALT levels (P=0.232). CONCLUSION: Sitagliptin may improve hepatic steatosis by increasing insulin sensitivity and improving lipid profiles in rats.

Dialysis type may predict carotid intima media thickness and plaque presence in end-stage renal disease patients.

INTRODUCTION: Carotid intima media thickness (CIMT) and carotid plaques (CP) were shown to be independent predictors of mortality in end-stage renal disease (ESRD) patients. In this study, the authors aimed to compare the two dialysis modalities for CIMT and CP presence (CPP). METHODS: ESRD patients who had been on the same renal replacement therapy for at least 24 months were selected. CIMT, CPP, known risk factors, and laboratory parameters for atherosclerosis were determined for each patient. RESULTS: A total of 77 hemodialysis (HD) patients (68% male, 47.6±17.0 years), 61 continuous ambulatory peritoneal dialysis (CAPD) patients (51% male, 45.3±13.9 years), and 36 age- and sex-matched controls (61% male, 43.3±10.6 years) were included. The mean CIMT (m-CIMT) were 0.99±0.24, 0.86±0.22, and 0.60±0.13 mm in the HD, CAPD, and control groups, respectively (HD vs. CAPD, P=0.001; HD vs. control, P<0.001; and CAPD vs. control, P<0.001). The CPP occurred more frequently in the HD group compared to the CAPD group (64% vs. 39%, respectively, P=0.004). The backward linear and logistic regression analysis of potential confounders revealed that both m-CIMT and CPP was independently associated with dialysis type (beta=0.249, P=0.008; and odds ratio [OR]=4.11, 95% CI, 1.72 to 6.73, P=0.015, respectively). CONCLUSION: The authors have shown that dialysis type may be an independent predictor of m-CIMT and CPP in long-term ESRD patients.