Case Series: Exposure to Glucagon-like Peptide-1 Receptor Agonist in the First Trimester of Pregnancy in Two Siblings.

BACKGROUND: The safety of glucagon-like peptide-1 receptor agonists in pregnancy is under investigation. In this report, we want to share the results of a patient with polycystic ovary syndrome who applied to our outpatient clinic for diabetes and had two unplanned pregnancies following the initiation of exenatide for obesity treatment. CASE PRESENTATION: A 40-year-old woman with diabetes was admitted to the endocrinology outpatient clinic. On physical examination, the body mass index was over 35 kg/m ², therefore, exenatide treatment was started. Four weeks later, she came to suspicion of pregnancy, and obstetric ultrasound revealed a fetus at 17 weeks of gestation. Exenatide was interrupted. At 37 weeks of gestation, she gave birth to a female baby with atrial septal defect. The baby was followed with echocardiography annually until spontaneous closure of ASD when she was three years old. Two years later, the patient consulted us again for weight gain. Exenatide was prescribed again. After 6 months, an abdominal ultrasound revealed a fatty liver and detected a pregnancy compatible with 13 weeks of gestation. Two siblings are healthy now, 7 and 5 years old, respectively. CONCLUSION: This report contributes to our knowledge of fetal exposure to exenatide. Large-scale randomized studies are needed for its safe use in pregnancy.

A Case Presenting with Neck Pain and High Sedimentation Rate: Amyloid Goiter.

INTRODUCTION: Amyloid goiter is a rare disease characterized by amyloid deposits that cause sudden growth in the thyroid gland. CASE PRESENTATION: Here we present a case of a 26-year-old woman with euthyroid amyloid goiter who presented with subacute granulomatous thyroiditis clinic. Amyloid goiter was detected as a result of core biopsy from the thyroid parenchyma of the patient with sudden thyroid enlargement. Surgery was not applied to the patient who had no pressure symptoms or signs. In systemic amyloidosis secondary to Familial Mediterranean fever, involvement was found in the heart, kidney, liver, and intestines, except for the thyroid. CONCLUSION: Amyloid accumulation should be considered in addition to anaplastic thyroid cancer and lymphoma in patients with sudden thyroid enlargement. It should not be overlooked that amyloid goiter may mimic subacute thyroiditis clinic. Systemic amyloidosis should be considered in patients with amyloid goiter, and an examination should be made to assess the presence of amyloid accumulations in other organs.

Effects of empagliflozin against indomethacin induced gastric mucosa.

BACKGROUND: Sodium-glucose cotransporter 2 (SGLT2) inhibitors (SGLT2i) are considered a new class antidiabetic agent, as well as lowering blood sugar, it has many positive effects. This study aimed to investigate the effects of SLGT2i on the gastric mucosa. METHODS: We investigated the effects of empagliflozin on indomethacin-induced gastritis using 48 male Wistar Albino rats. We performed histopathological evaluations of gastric mucosa tissue. And we studied the levels of serum disulfide, native thiol, total thiol, and ischemia modified albumin, disulfide/native thiol ratio (SSSH), native thiol/total thiol percent ratio (SH total SH), and disulfide/total thiol percent ratio (SS total SH). RESULTS: We found that empagliflozin increased mucin production in rat gastric mucosa. Besides, we observed milder inflammation findings and lower gastritis scores in the empagliflozin receiving groups than the placebo groups. Native thiol, total thiol, and disulfide levels were lower in the indomethacin-induced gastritis groups. CONCLUSIONS: This study is the first to investigate the effect of empagliflozin on the gastrointestinal tract in a rat model. We concluded that empagliflozin increased mucin production and revealed positive effects in an indomethacin-induced gastritis model.

Evaluation of management of patients with postoperative permanent hypoparathyroidism. How close are we to the targets?

BACKGROUND: Postoperative hypoparathyroidism (PO-HypoPT) is a complication usually seen after thyroid surgery. PO-HypoPT, which lasts longer than 6 months is defined permanently. The aim of this study was to evaluate how close permanent PO-HypoPT patients can approach target values. METHODS: One hundred seven patients who were followed-up with permanent diagnosis of PO-HypoPT between 2016-2020 were included in the study. The study protocol includes serum albumin corrected total calcium (Alb-sCa), phosphate (P), Ca-P product, and 24 h urine calcium measurements. Laboratory measurements of the patients include the values recorded in 4-year visits and in the last visit. In addition, radiological reports of renal/abdominal ultrasound and cranial tomography examinations performed in our hospital for any reason during this period were also reviewed. RESULTS: When looking at the total measurements in the 4-year period, the Alb-sCa level was below the target in most of the measurements (68.1%). P level was higher than normal in 296 (46.2%) measurements. Twenty-four h urine ca excretion was measured 185 times in total visits, and 81 (43.7%) of these measurements showed hypercalciuric values. The patient's latest visit measurements were evaluated on 4 targets (Alb-sCa, P, Ca-P product and 24 h urine Ca excretion). The number of patients meeting all four targets was only 21 (19.6%). Six (7.5%) patients had kidney stones or nephrocalcinosis. Three (0.09%) patients with imaging had calcification in the basal ganglia. CONCLUSIONS: Our study shows that the management of the patients with PO-HypoPT is suboptimal with active vitamin D and cholecalciferol treatment.

The role of IL-6 and osteoprotegerin in bone metabolism in patients with Graves' disease.

BACKGROUND: Increased bone turnover is a hallmark of hyperthyroidism. The underlying factors of how thyroid hormones affect bone cells are still under the spotlight. Previous studies indicated serum osteoprotegerin (OPG), receptor activator of NF-kB ligand (RANKL), and interleukin-6 (IL-6) as mediators of the effect of thyroid hormones on bone metabolism. Ultimately, the present research aimed to examine the association of IL-6 with OPG and RANKL in patients with hyperthyroidism. METHODS: We carried out this study with 39 newly diagnosed and untreated Graves' patients and 43 healthy controls. In addition to routine tests, we measured serum OPG, RANKL, and IL-6 levels. RESULTS: Mean age and sex distribution were similar in both groups. The hyperthyroid group had significantly higher OPG (p = 0.002) and IL-6 (p < 0.001) levels, but RANKL levels were significantly lower in this group (p < 0.001). We found OPG not to correlate with free T4 and T3, while it had a moderate and negative correlation with thyrotropin (TSH) (r = -0.372, p = 0.001). IL-6 had no correlation with OPG but positively correlated with free T4 (r = 0.445, p < 0.001) and free T3 (r = 0.326, p = 0.035). It also negatively correlated with RANKL (r = -0.247, p = 0.033). DISCUSSION: Maintaining skeletal development and integrity is partially regulated by a normal balance of thyroid hormones. We concluded that increases in serum OPG and IL-6 levels accompanied hyperthyroidism. However, excessive levels of the hormones might cause drops in serum RANKL levels. Our results suggested that OPG, RANKL, and IL-6 might be involved in the cross-talking among immunity, thyroid function, and bone metabolism in the case of hyperthyroidism.

Renoprotective effects of dapagliflozin in an iron overload non-diabetic rat model.

PURPOSE: Sodium glucose co-transporter (SGLT) 2 inhibitors are oral anti-diabetic drugs with proven kidney protective effects. Renal protective effects in non-diabetic individuals have also been shown in recent studies. The aim of this study was to determine the renal protective effects of dapagliflozin by evaluating the oxidative stress markers in the kidney tissue and demonstrating it in renal histological sections in an iron-overloaded rat model. METHODS: A total of 24 Wistar Albino rats were separated into 3 groups of 8 rats. Iron sucrose (60 â€‹mg/kg/day) was administered intraperitoneally to the first group (Group Fe) (n â€‹= â€‹8), iron sucrose and dapagliflozin (0.1 â€‹mg/kg/day) to the second group (Group Fe â€‹+ â€‹D) (n â€‹= â€‹8) and intraperitoneal saline as placebo to the control group (Group C) (n â€‹= â€‹8) for 4 weeks. The glomerular changes were semi-quantitatively scored with Oxford Classification. Oxidative stress was analyzed from the tissue fluorescent oxidation product (FLOP), malondialdehyde (MDA) and total sulfhydryl (T-SH) levels. RESULTS: Dapagliflozin prevented glomerular and mesangial damage of iron overload in the non-diabetic rat model. MDA levels were significantly higher in Group Fe compared to the Group C, and there was no significant difference between the Fe â€‹+ â€‹D group and Group C. T-SH levels were preserved in the Fe â€‹+ â€‹D group and were significantly higher than in the Fe group. CONCLUSIONS: The results of this study showed that dapagliflozin helped preserve the glomerular and mesangial structure histologically and reduced oxidative stress markers in a non-diabetic iron overload rat model.

Pedabarography May Play a Role in Foot Plantar Scanning in Acromegaly.

Aims: Acromegaly is associated with symptoms in many organs, including the heart, colon, skin, bones, and many joints. Patients with long-term treatment or biochemical control still suffer from acromegaly arthropathy (AA). Primarily, the weight-bearing joints of the lower extremity are affected and at last deformation emerges. The aim of this study is to detect the changes in the feet with pedabarography in patients with acromegaly. Materials and Methods: Nineteen patients with acromegaly (4 males and 15 females) and 13 healthy controls (1 male and 12 females) were included in the study (p=0.31). There was no difference between acromegaly patients and controls in terms of gender, age, and BMI; median age and BMI were (54 (20-67) vs. 52 (30-58), p=0.85) and (32.5 (20.3-42.7) vs. 29.5 (22.4-38.6), p=0.93), respectively. Static plantar pressures of bilateral foot of all participants in the standing position were measured by pedabarography. Results: In pedabarographic analysis, there were only significant difference in rearfoot surface right and rearfoot surface left (p=0.04 and p=0.01), respectively. The mean of the right rearfoot surface (43.5 cm2 vs. 36.6 cm2) and the mean of the left rear foot surface were higher than the controls (47.4 cm2 vs. 40.2 cm2). Forefoot surface, forefoot load, forefoot weight ratio, rearfoot load, total foot surface, total load, total peak pressure, and total average pressure were higher in left foot in both groups, but there was no difference between the two groups. Conclusion: In our study, there was a significant difference between acromegaly patients and healthy controls, only on the right rarefoot surface and the left rarefoot surface, and was higher on the left in both groups. These patients often experience changes in the hindfoot and heel, and foot surface area and pressure distribution may vary. Early diagnosis and proper treatment of the disease can prevent the development of complications and improve the quality of life. Foot scanning using pedabarography in the management of AA is a useful tool that can be used to manufacture customized orthopedic insoles and ergonomic shoe designs to prevent irreversible damage and reduce overload and lower extremity pain.

Dietary Acid Load Associated with Hypertension and Diabetes in the Elderly.

BACKGROUND: Diet can affect the body's acid-base balance due to its content of acid or base precursors. There is conflicting evidence for the role of metabolic acidosis in the development of cardiometabolic disorders, hypertension (HT), and insulin resistance (IR). OBJECTIVE: We hypothesized that dietary acid load (DAL) is associated with adverse metabolic risk factors and aimed to investigate this in the elderly. METHODS: A total of 114 elderly participants were included in the study. The participants were divided into four groups, such as HT, diabetes (DM), both HT and DM, and healthy controls. Anthropometric, biochemical, and clinical findings were recorded. Potential renal acid load (PRAL) and net endogenous acid production (NEAP) results were obtained for three days, 24-hour dietary records via a nutrient database program (BeBiS software program). RESULTS: The groups were matched for age, gender, and BMI. There was a statistically significant difference between the groups regarding NEAP (p =0.01) and no significant difference for PRAL ( p = 0.086). The lowest NEAP and PRAL levels were seen in the control group while the highest in the HT group. Both NEAP and PRAL were correlated with waist circumference (r = 0,325, p = 0.001; r=0,231, p =0,016, respectively). CONCLUSION: Our data confirmed that subjects with HT and DM had diets with greater acid-forming potential. High NEAP may be a risk factor for chronic metabolic diseases, particularly HT. PRAL could not be shown as a significantly different marker in all participants. Dietary content has a significant contribution to the reduction of cardiovascular risk factors, such as HT, DM, and obesity.

Ameliorating effects of N-acetyl cysteine against early liver damage of radioiodine in rats.

OBJECTIVE: The present study was aimed to explore the potential ameliorating effects of N-acetyl cysteine (NAC) against radioiodine (RAI)-induced early liver damage. METHODS: Thirty Wistar Albino male rats were arbitrarily allocated into three groups each containing 10 rats: the control group (group 1); the RAI group (group 2), oral 111 MBq/kg radioiodine was administered to rats; the RAI + NAC group (group 3), 150 mg/kg/day intraperitoneal NAC treatment was initiated 3 days prior to the RAI administration and continued for 10 days. Liver samples were obtained 24 h after the last dose of NAC therapy for biochemical and histopathologic evaluation. RESULTS: In the RAI + NAC group, the histopathologic damage was found significantly less than in the RAI group for whole parameters except inflammatory cell infiltration (P < 0.05). Unlike the RAI group which had marked histopathologic damage, the RAI + NAC group had only mild histologic activity index scores with no granuloma formation observed. Oxidative stress parameters were demonstrated that the NAC treatment significantly decreased the tissue malondialdehyde (MDA) and catalase levels and increased the total sulfhydryl (total sulfhydryl) levels when compared to the RAI group (P < 0.01). CONCLUSION: The outcomes of the study exhibited that the NAC treatment improved RAI-induced early liver damage. This improving effect considered to be caused by its antioxidant, anti-inflammatory, and likely vasodilator properties of NAC. Having advantages such as inexpensive, easy access, and tolerability, the NAC can be used as a radioprotective agent, especially in patients with liver diseases and requiring RAI treatment.

Assessment of inner retina layers thickness values in eyes with pituitary tumours before visual field defects occur.

BACKGROUND: The purpose of this study was to evaluate macula, retinal nerve layer (RNFL), ganglion cell layer (GCL), inner plexiform layer (IPL) and macular nerve fibre layer (mNFL) thickness in patients with pituitary tumours who has normal visual field (VF). METHODS: Thirty-five eyes of 35 patients with pituitary tumours with normal VF and 41 eyes of 41-healthy subjects were underwent a complete ophthalmic examination. The spectral domain- optical coherence tomography (OCT) was used to measure macular and optic disc parameters. Layer-by-layer segmentation was done automatically by using the new software. Data analyses were performed by using SPSS for Windows, version 22.0. RESULTS: Average of total macula thickness inner temporal (p: 0.006), outer temporal (p < 0.001), inner nasal (p: 0.03), outer nasal (<0.001) were significantly lower in pituitary tumour group than normal group. Average of RNFL (p:0.009), temporal (p: 0.001), superiotemporal (p:0.004) and inferiotemporal (p: 0.01) were significantly lower in pituitary tumour group than normal group. Average of central GCL (p: 0.01) and central NFL (p: 0.03) were significantly lower in pituitary tumour group than normal group. There was no statistically significant difference between the two groups in IPL averages. CONCLUSIONS: Pituitary tumour patients with normal VF had reduced nasal and temporal section of the total macula, temporal RNFL, central mGCL and mNFL thicknesses, reflecting the corresponding to the anatomical substrate of the underlying pathology of chiasmal compression. This indicates that the presence of retinal thinning may be a sign of early detection of anterior visual pathway injury before VF loss becomes apparent.

Neutrophil-to-lymphocyte ratio, monocyte-to-lymphocyte ratio, and platelet-tolymphocyte ratio in different etiological causes of thyrotoxicosis

Background/aim: The most common causes of thyrotoxicosis include Graves' disease (GD), toxic multinodular goiter (TMNG), toxic adenoma (TA), and subacute granulomatous thyroiditis (SAT). In our study, we aimed to see whether neutrophil­to­lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet­to­lymphocyte ratio (PLR), and mean platelet volume (MPV) may be helpful in the differential diagnosis of these diseases. Materials and methods: We retrospectively analyzed the hospital records of the Endocrinology Clinic of our hospital between 2016 and 2019. We included data from 66 GD, 37 TA, and 35 SAT patients. We compared the data with those of 35 healthy subjects as controls. Results: NLR, MLR, and PLR were found to be higher in the SAT group when compared to other groups. The post hoc analysis of comparison of NLR, MLR, and PLR in each group showed that NLR and PLR were significantly different in the SAT group when compared to the GD, TA, and controls groups (P < 0.001, P = 0.003, and P < 0.001 for NLR respectively and P < 0.001 for PLR in all groups). MPV levels were different between groups (P = 0.007). However, the intergroup analysis (Tukey's test) failed to show a statistically significant difference for any of the groups. In patients with SAT, PLR and NLR were significantly higher than in the GD, TA, and control groups. MLR was also higher in SAT when compared to other groups, but the difference was not statistically significant. Conclusion: High PLR and NLR may be helpful to differentiate SAT from GD and TA, the other common causes of thyrotoxicosis.

Evaluation of Platelet Functions in Patients with Hashimoto's Thyroiditis Versus Healthy Controls: a Cross-Sectional Analysis.

BACKGROUND: To evaluate platelet functions in patients with Hashimoto's thyroiditis (HT) versus healthy controls. METHODS: Seventy-five patients with HT and 29 healthy controls were included in this study. Age, serum levels of thyroid stimulating hormone (TSH), free triiodothyronine (FT3), free thyroxine (FT4), anti-thyroglobulin (anti-Tg) antibody and anti-thyroid peroxidase (anti-TPO) antibody, platelet count, in vitro platelet aggregation and ATP release reaction tests were recorded and compared between HT and control groups. RESULTS: Median (IQR) serum levels for TSH (p = 0.001), anti-TPO (p = 0.001), and anti-Tg (p = 0.001) antibodies were significantly higher, while FT4 levels (p = 0.005) were significantly lower in patients with HT than in controls. Patients had lower levels of ADP-induced platelet aggregation (p = 0.05) and lower ristocetin-induced ATP release activity (p = 0.05) compared to controls. Platelet count was positively correlated with serum FT4 levels (r = 0.27, p < 0.05). Conclusions: We found decreased ADP-induced platelet aggregation and ristocetin-induced platelet release activity as well as a positive correlation of platelet count with FT4 levels in patients with HT. Our findings support the role of thyroid hormone status and autoimmunity in the association between HT and platelet aggregation and secretion functions.

Serum nesfatin-1 levels are decreased in pregnant women newly diagnosed with gestational diabetes.

OBJECTIVE: To investigate serum nesfatin-1 levels at 24-28 weeks of pregnancy in women newly diagnosed with gestational diabetes and determine the association of nesfatin-1 with several metabolic parameters. SUBJECTS AND METHODS: Forty women newly diagnosed with gestational diabetes at 24-28 weeks of pregnancy and 30 healthy pregnant women matched in age and gestational week were included in this cross-sectional study. Serum nesfatin-1 levels were analyzed using ELISA, and the relationship between nesfatin-1 and several metabolic parameters were assessed. RESULTS: Serum nesfatin-1 levels were found to be lower in women with gestational diabetes compared to the pregnant women in the control sample (p = 0.020). Multiple linear regression analysis revealed that nesfatin-1 was lower in participants with gestational diabetes independently from gestational age, BMI, HOMA-IR, fasting plasma glucose, and age. In correlation analysis, the only variable that was found to have a statistically significant correlation with nesfatin-1 was gestational age (p = 0.015, r = 0.30). CONCLUSION: Lower nesfatin-1 levels in women with gestational diabetes compared to the control group at 24-28 weeks of gestation draws attention to nesfatin-1 levels in gestational diabetes and motivates further research in this area.

Serum nesfatin-1 levels are decreased in pregnant women newly diagnosed with gestational diabetes

ABSTRACT Objective To investigate serum nesfatin-1 levels at 24-28 weeks of pregnancy in women newly diagnosed with gestational diabetes and determine the association of nesfatin-1 with several metabolic parameters. Subjects and methods Forty women newly diagnosed with gestational diabetes at 24-28 weeks of pregnancy and 30 healthy pregnant women matched in age and gestational week were included in this cross-sectional study. Serum nesfatin-1 levels were analyzed using ELISA, and the relationship between nesfatin-1 and several metabolic parameters were assessed. Results Serum nesfatin-1 levels were found to be lower in women with gestational diabetes compared to the pregnant women in the control sample (p = 0.020). Multiple linear regression analysis revealed that nesfatin-1 was lower in participants with gestational diabetes independently from gestational age, BMI, HOMA-IR, fasting plasma glucose, and age. In correlation analysis, the only variable that was found to have a statistically significant correlation with nesfatin-1 was gestational age (p = 0.015, r = 0.30). Conclusion Lower nesfatin-1 levels in women with gestational diabetes compared to the control group at 24-28 weeks of gestation draws attention to nesfatin-1 levels in gestational diabetes and motivates further research in this area.

Is There a Tendency for Thrombosis in Gestational Diabetes Mellitus?

CONTEXT: Impact of gestational diabetes mellitus (GDM) on the coagulation system, dynamics involved at a pathophysiological level and the exact mechanism remain unclear. AIMS: To evaluate the association between diabetes-related parameters and hemostatic factors to search for a tendency of thrombosis in GDM. SETTINGS AND DESIGN: Nineteen pregnant women who had GDM, 16 healthy pregnant and 13 healthy nonpregnant controls admitted to the Endocrinology outpatient clinics were enrolled in the study. SUBJECTS AND METHODS: Fasting and postprandial glucose, hemoglobin A1c and insulin levels, and insulin resistance; fructosamine, thrombin activatable fibrinolysis inhibitor (TAFI), tissue factor pathway inhibitor (TFPI), plasminogen activator inhibitor Type-1 (PAI-1), tissue-type plasminogen activator (t-PA), fibrinogen, plasminogen and hemoglobin levels, platelet counts, prothrombin time (PT), and activated partial thromboplastin time (aPTT) were studied. STATISTICAL ANALYSIS USED: One-way analysis of variance, Kruskal-Wallis, and post hoc Tukey honestly significant difference or Conover's nonparametric multiple comparison tests for comparison of the study groups. RESULTS: PT and aPTT were significantly lower in GDM patients compared to controls (P < 0.05), whereas fibrinogen and plasminogen levels were significantly higher in this group compared to both nonpregnant and healthy pregnant controls (P < 0.05 for each). TAFI, TFPI, PAI-1, and tissue t-PA levels were not significantly different among groups. CONCLUSIONS: Our findings indicate tendency to develop thrombosis in GDM similar to diabetes mellitus; but more comprehensive studies with larger sample size are needed to determine the relationship between GDM and hemostasis.

The role of ultrasound elastography in preoperative localization of parathyroid lesions: a new assisting method to preoperative parathyroid ultrasonography.

BACKGROUND: After the definition of minimally invasive procedures, preoperative localization of parathyroid lesions is now crucial. False-positive results up to 30% were reported by B-mode grayscale ultrasonography (US) in localization of parathyroid lesions. Parathyroid adenomas are relatively stiff lesions. Ultrasound elastography (USE) can accurately evaluate tissue stiffness and might detect the stiff parathyroid lesions. OBJECTIVE: The aim of this study is to demonstrate whether USE can detect the level of the stiffness and help the preoperative localization of parathyroid lesions during parathyroid ultrasonography examination. PATIENTS: The patients who were candidates for parathyroidectomy were prospectively enrolled to this study and were evaluated by USE. RESULTS: Seventy-two patients with 93 parathyroid lesions underwent parathyroidectomy. Sixty-three patients including three multiple endocrine neoplasia type-1 patients had primary hyperparathyroidism, three patients with chronic renal disease (CRD) had tertiary hyperparathyroidism, three patients with CRD and two renal transplanted patients had persistent secondary hyperparathyroidism. One patient was excluded. While all parathyroid adenomas exhibited high levels of stiffness (score 3 and 4), 17 (63%) out of 27 parathyroid hyperplasia lesions were shown to have significantly higher elasticity. The evaluation of median strain ratios of parathyroid lesions revealed that parathyroid adenomas demonstrated significantly higher levels of stiffness than hyperplasias (P ≤ 0·001). CONCLUSIONS: This is the first study that evaluates the ultrasound elastographic features of parathyroid lesions. Parathyroid adenomas were shown to appear as stiff lesions, and half of the hyperplasias showed high elasticity. Parathyroid elastography is a novel technique to evaluate parathyroid lesions and might be a guide for surgeons to determine the type of operation to apply.

First missense mutation in the SOST gene causing sclerosteosis by loss of sclerostin function.

Sclerosteosis is a rare bone dysplasia characterized by greatly increased bone mass, especially of the long bones and the skull. Patients are tall, show facial asymmetry and often have syndactyly. Clinical complications are due to entrapment of cranial nerves. The disease is thought to be due to loss-of-function mutations in the SOST gene. The SOST gene product, sclerostin, is secreted by osteocytes and transported to the bone surface where it inhibits osteoblastic bone formation by antagonizing Wnt signaling. In a small Turkish family with sclerosteosis, we identified a missense mutation (c.499T>C; p.Cys167Arg) in exon 2 of the SOST gene. This type of mutation has not been previously reported and using different functional approaches, we show that it has a devastating effect on the biological function of sclerostin. The affected cysteine is the last cysteine residue of the cystine-knot motif and loss of this residue leads to retention of the mutant protein in the ER, possibly as a consequence of impaired folding. Together with a significant reduced ability to bind to LRP5 and inhibit Wnt signaling, the p.Cys167Arg mutation leads to a complete loss of function of sclerostin and thus to the characteristic sclerosteosis phenotype.

Serum fibroblast growth factor 21 levels in polycystic ovary syndrome.

AIM: This study was designed to measure serum fibroblast growth factor 21 (FGF21) levels in patients with polycystic ovary syndrome (PCOS) and healthy subjects. METHODS: A total of 37 women were evaluated. Serum levels FGF21, glucose, lipid profile, hormones (follicle-stimulating hormone, luteinising hormone, oestradiol, testosterone, thyroid stimulating hormone, prolactin and insulin) were determined in 24 PCOS (15 subjects of PCOS BMI < 25 kg/m2, 9 subjects of PCOS BMI ≥ kg/m2) and 13 control group (BMI < 25 kg/m2). RESULTS: Serum FGF21 levels were higher in the PCOS group [99.5 (173.7) pg/ml] than in the control group [52.0 (88.0) pg/ml]. LH and T are significantly higher in PCOS cases (respectively; p < 0.05, p < 0.01). A positive correlation was found between FGF21 and luteinising hormone and testosterone (respectively; r = 0.43 p = 0.007, r = 0.38, p = 0.02). Multivariate discriminant analysis showed that BMI, triglyceride, HOMA-IR, fasting glucose with rise of FGF21 were found significant in PCOS. CONCLUSION: Our study indicates that FGF21 in cases with PCOS exhibit an increase along with the increase of BMI and also has a positive correlation with LH and T. Further studies are required to clarify the aetiology and effects of FGF21 in women with PCOS.