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

Summary Vitamin D intake over the recommended dose is usually associated with high serum 25(OH)D levels and gener ally 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 defciency can ensure safe and efective treatment. Purpose We observed a tendency to use high doses of cholecalciferol for vitamin D defciency 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 fnal 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 cal cium levels. The serum 25(OH)D level was signifcantly 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 defciency/insufciency in a short time (1–3 months). The cut-of 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 hypercal cemia. 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 efective treatment of vitamin D defciency

Identifying clinical characteristics of hypoparathyroidism in Turkey: HIPOPARATURK‑NET study

Hypoparathyroidism is an orphan disease with ill-defined epidemiology that is subject to geographic variability. We conducted this study to assess the demographics, etiologic distribution, treatment patterns and complication frequency of patients with chronic hypoparathyroidism in Turkey. This is a retrospective, cross-sectional database study, with collaboration of 30 endocrinology centers located in 20 cities across seven geographical regions of Turkey. A total of 830 adults (mean age 49.6 ± 13.5 years; female 81.2%) with hypoparathyroidism (mean duration 9.7 ± 9.0 years) were included in the final analysis. Hypoparathyroidism was predominantly surgery-induced (n = 686, 82.6%). The insulting surgeries was carried out mostly due to benign causes in postsurgical group (SG) (n = 504, 73.5%) while patients in nonsurgical group (NSG) was most frequently classified as idiopathic (n = 103, 71.5%). The treatment was highly dependent on calcium salts (n = 771, 92.9%), calcitriol (n = 786, 94.7%) and to a lower extent cholecalciferol use (n = 635, 76.5%) while the rate of parathyroid hormone (n = 2, 0.2%) use was low. Serum calcium levels were most frequently kept in the normal range (sCa 8.5–10.5 mg/dL, n = 383, 46.1%) which might be higher than desired for this patient group. NSG had a lower mean plasma PTH concentration (6.42 ± 5.53 vs. 9.09 ± 7.08 ng/l, p < 0.0001), higher daily intake of elementary calcium (2038 ± 1214 vs. 1846 ± 1355 mg/day, p = 0.0193) and calcitriol (0.78 ± 0.39 vs. 0.69 ± 0.38 mcg/day, p = 0.0057), a higher rate of chronic renal disease (9.7% vs. 3.6%, p = 0.0017), epilepsy (6.3% vs. 1.6%, p = 0.0009), intracranial calcifications (11.8% vs. 7.3%, p < 0.0001) and cataracts (22.2% vs. 13.7%, p = 0.0096) compared to SG. In conclusion, postsurgical hypoparathyroidism is the dominant etiology of hypoparathyroidism in Turkey while the nonsurgical patients have a higher disease burden with greater need for medications and increased risk of complications than the postsurgical patients

The effect of thyroid hormone levels on osteoprotegerin/rankl system and bone turnover in hashimoto thyroiditis

Tiroid hormonları, kemik üzerine direkt etkisi olan ajanlardır. Hipotiroidide kemik döngüsünde yavaşlama ve artmış kırık riski söz konusudur. Son yıllarda, otoimmün hastalıkların da kemik döngüsü üzerine etkisi olduğuna dair çalışmalar bildirilmektedir. Kemik döngüsünde anahtar rol oynadığı düşünülen sistem ise Osteoprotegerin (OPG) / Reseptör aktivatör nükleer kappa B ligand (RANKL) yolağıdır. Osteoklastojenik bir sitokin olan interlökin-6 (IL-6)?nın da etkisini indirekt olarak OPG/RANKL dengesini bozarak gösterdiği düşünülmektedir. Hashimoto hastalığı gibi otoimmün olduğu bilinen bir hastalıkta, otoimmünitenin ve hastalığın sonucunda ortaya çıkan hipotiroidinin kemik döngüsünü nasıl etkilediğini araştırdığımız çalışmamıza, premenopozal 30 hipotiroid ve 30 ötiroid Hashimoto hastası ve 20 premenopozal sağlıklı kontrol dahil edildi. Tüm grupta OPG, RANKL ve IL-6 düzeyleri, kemik yapım göstergeleri olan osteokalsin (OC), prokolajen tip I N propeptide (PINP), alkalen fosfataz (ALP) ve kemik yıkım göstergeleri olan tip 1 kollajen C telopeptid (CTX) ve tartrat rezistan asit fosfataz izoform 5b (TRAcP 5b) düzeyleri ölçüldü. Çalışmamızda, TRAcP 5b, CTX ve OC düzeylerinin hipotiroid Hashimoto vakalarında diğer iki gruba göre düşük, ALP düzeylerinin benzer, PINP?nin ise yüksek olduğunu bulduk. Hem hipotiroid hem de ötiroid Hashimoto hastalarında OPG düzeylerinin birbirine benzer şekilde sağlıklı kontrol grubuna oranla yüksek, RANKL düzeylerinin ise düşük olduğunu, OPG düzeylerinin TSH ile pozitif korelasyon gösterdiğini tespit ettik. IL-6 düzeylerinin hipotiroid Hashimoto grubunda ötiroid Hashimoto grubuna ve sağlıklı kontrollere göre düşük olduğunu gördük. Hashimoto hastalığı varlığının RANKL/OPG oranı, bu oranın da kemik döngüsü üzerine bağımsız bir etken olduğunu saptadık. Çalışmamızın, literatürde tiroid disfonksiyonu ile kemik döngüsü ilişkisini araştıran diğer çalışmalara kıyasla güçlü yönü, mekanizmada rolü olabilecek birçok farklı parametrenin bir arada değerlendirilmiş olmasıdır. Çalışmanın bir diğer özelliği ise tiroid disfonksiyonunun yanında tiroid otoimmünitesinin etkisinin de araştırılmış olmasıdır. Bu bulgu çalışmamızın orijinal özelliğini teşkil etmektedir. Literatürde, hipotiroidinin etkisinden bağımsız olarak sadece tiroid otoimmünitesinin kemik döngüsü göstergeleri üzerine etkisini araştıran bir çalışmaya rastlamadık. Sonuç olarak, premenopozal hipotiroid Hashimoto hastalarında kemik döngüsünün olumsuz etkilendiğini ve bu etkinin muhtemelen OPG/RANKL sistemi üzerinden olduğunu düşünmekteyiz.Thyroid hormones are necessary for normal skeletal growth and bone remodelling. Hypothyroidism causes slowing of bone turnover and an increase in the fracture risk by adversely affecting bone quality. A new body of evidence suggests that autoimmune disorders, as well, are associated with a disturbed bone turnover. Hashimoto?s thyroiditis is an autoimmune disorder in origin and the impact of autoimmunity and the resultant hypothyroidism on bone turnover in Hashimoto?s thyroiditis is not known. Osteoprotegerin(OPG)/Receptor activator nuclear kappa B ligand (RANKL) pathway is known to play a major role in bone remodelling and interleukin-6 (IL-6), which is an osteoclastogenic cytokine, may exert its inhibitory effect on bone formation indirectly by influencing the balance between OPG/RANKL. In this study, we assessed the levels of OPG, RANKL and IL-6 along with markers of bone formation as osteocalcin (OC), procollagen type I N propeptide (PINP), alkaline phosphatase (ALP) and markers of bone resorption as type 1 collagen C telopeptide (CTX) and tartrate resistant acid phosphatase isoform 5b (TRAcP 5b) in 30 hypothyroid and 30 euthyroid premenopausal Hashimoto?s thyroiditis patients and 20 healthy premenopausal controls. We found that TRAcP 5b, CTX and OC levels were lower and PINP was higher in the hypothyroid group compared to euthyroid Hashimoto patients and controls while serum ALP levels were similar among groups. OPG levels were higher and RANKL levels were lower in hypothyroid and euthyroid Hashimoto patients compared to controls. OPG was positively correlated with serum TSH. Hypothyroid Hashimoto patients had lower IL-6 levels compared to euthyroid Hashimoto and control groups. RANKL/OPG ratio was independently associated with the presence of Hashimoto thyroiditis and markers of bone turnover. In conclusion, bone turnover is adversely affected by hypothyroidism, potentially through OPG/RANKL pathway, in premenopausal patients with Hashimoto thyroiditis

Tip 2 Diabetes Mellitus’ lu hastalarda serum ve ı?drar galektin-3 düzeyi ile mikroalbuminüri arasındaki ı?lişkinin deg?erlendirilmesi

Amaç: Bu çalıs?manın amacı Tip 2 diyabetes mellitusu olan hastalarda mikroalbuminürigelis?imi ile serum ve idrar galektin-3 düzeyleri arasındaki ilis?kiyi deg?erlendirmektir.Yöntem: Tip 2 diyabet tanısı olan mikroalbüminüri gelis?mis? 30 hasta ve tip 2 diyabettanısı olan normoalbüminürik 30 hasta çalıs?maya dahil edildi. Tüm hastalarda açlık kans?ekeri, hemoglobin A1c, kan üre nitrojeni, kreatinin, düs?ük dansiteli lipoproteinkolesterol, total kolesterol, tam idrar tetkiki, spot idrarda albümin, spot idrarda kreatinin,serum galektin-3 ve idrar galektin-3 çalıs?ıldı. Serum galektin-3, idrar galektin-3,hemoglobin A1c, düs?ük dansiteli lipoprotein kolesterol, total kolesterolmikroalbüminürik ve normoalbüminürik gruplar arasında kars?ılas?tırıldı. Bulgular:Çalıs?mamızda mikroalbüminürik grupta, normoalbüminürik gruba göre hem serumgalektin-3 düzeyi (20.1±14.9 ng/ml ve 4.8±5.6 ng/ml, p <0.001) hem de idrar galektin-3düzeyi (19.6±18.7 ng/ml ve 10.5±10.2 ng/ml, p = 0.027) yüksek tespit edildi.Mikroalbüminüri düzeyi ile serum ve idrar galektin-3 düzeyi arasında pozitif korelasyontespit edildi (r=0.614, p<0.01 ve r=0.268, p<0.05, sırasıyla). Serum galektin-3 düzeyinin,mikroalbüminüriyi öngörmede bag?ımsız bir etken oldug?u görüldü (Odds oranı:1.26,güven aralığı:1.07-1.46, p=0.004). Sonuç: Tip 2 diyabetes mellitusu olan hastalardamikroalbüminürisi olan hastalarda normoalbüminürisi olanlara göre hem serum hem deidrar galektin-3 düzeylerinde artıs? saptandı. Çalıs?mamızın bulguları diyabetiknefropatide galektin-3’ün bir biyobelirteç olarak kullanılabileceg?i görüs?ünüdesteklemis?tir

Presence and severity of estrogen receptor-alpha expression in patients with simple steatosis and nash

Loss of estrogen receptor-alpha (ER-?) in the liver is associated with hepatic steatosis and inflammation.We conducted a study in order to investigate the presence and extent of ER-? expression in NASH, andits relationship with histological findings. Fifty-four patients with histologically confirmed NASH, 12patients with simple steatosis (SS), and 6 patients with normal liver tissue (NLT) were included. NASHactivity score and fibrosis score were calculated according to biopsy findings. Liver biopsy specimenswere immunohistochemically stained for ER-? expression. Nuclear ER-? expression percentage (stainingindex) was calculated. Mean staining index was significantly different across the NASH, SS, and NLT groups(6.3±9.9 vs. 22.1±26.4 vs. 44.2±24.8, respectively, p < 0.001 for all comparisons). Staining index wassignificantly higher in women than in men (19.4±22.2 vs. 7.9±15.3, respectively, p = 0.003). Stainingindex negatively correlated with serum ALT (r =-0.240; p = 0.04), fasting plasma glucose (r =-0.261;p = 0.027), and fibrosis score (r =-0.312; p = 0.011). As a conclusion, hepatic nuclear ER-? expressionpercentage (staining index) is lower in patients with NASH when compared to SS and NLT groups. Stainingindex is negatively correlated with serum ALT levels, plasma glucose, and fibrosis score. Further studiesare required to clarify the significance of ER-? expression in NASH

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- ) in the liver is associated with hepatic steatosis and inflammation in animal models. We conducteda study in order to investigate the presence and extent of ER- 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 stainedfor ER- expression. Nuclear ER- expression percentage was calculated. ER- was positive in 69 of thepatients (76%). ER- 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- expression percentage was not correlated with fibrosis, steatosis, necroinflammatory activity and biochemicalfindings. Although estrogens are known to be protective against fibrosis and steatosis in animalmodels, we did not find any significant correlation between ER- expression and histopathological andbiochemical findings in CHC patients. These findings should be verified in further large scale studies

Association between vascular calcification, atherosclerosis and inflammatory markers in end-stage renal disease patient and simple method for detecting vascular calcification (direct radiography)

Purpose: In our study, we planned to investigate the relationship of malnutrition with inflammation, atherosclerosis and calcification in dialysis patients. Materials and methods: 140 Chronic kidney disease (CKD) patients and 44 healthy controls were included in the study. Carotid artery intima-media thickness (CIMT) was measured by doppler ultrasonography. Valvular calcification was assessed by echocardiography and vascular calcification scores (VCS) were done based on the radiograms. Biochemical parameters were assessed using routine laboratory methods. Subjective global assessment (SGA) was used to evaluate malnutrition. Results: In the study, VCS showed no differences between hemodialysis (HD) and peritoneal dialysis (PD) patients (1.84±2.35 for HD, 1.77±1.64 for PD; p=0.83). CIMT, Osteopontin (OPN), interleukin-6 (IL-6) and homocysteine were significantly different in both dialysis groups compared to healthy controls. The Mean carotid intima-media thickness (m-CIMT) was higher in HD patients compared to PD group. CIMT, vascular calcification and SGA scores showed positive correlation with age, dialysis duration and valvular calcification grades, and negative correlation with albumin levels. A positive correlation between SGA scores and high-sensitive C-reactive protein (hs-CRP) levels was also noted. On multiple regression analysis, m-CIMT was independently associated with age, VCS and albumin levels. VCS was found to be independently associated with only albumin levels. Conclusion: Vascular and valvular calcification, an indicator of cardiovascular mortality and morbidity in dialysis patients, was found to be significantly associated with malnutrition. We found higher rates of valvular calcification in patients with vascular calcification. Malnutrition was more prominent in these patients