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.

Serum fetuin-A is associated with the components of MIAC(malnutrition, inflammation, atherosclerosis, calcification) syndrome in different stages of chronic kidney disease

Background/aim: Fetuin-A, a circulating inhibitor of calcification, is a marker of inflammatory-nutritional state. We evaluated the association between serum fetuin-A levels and vascular calcification, intima-media thickness, and nutritional and inflammatory markers in different stages of chronic kidney disease (CKD). Materials and methods: CKD patients were sampled for calcium-phosphate parameters and nutritional and inflammatory markers [highly sensitive C-reactive protein (hs-CRP)], and serum fetuin-A levels. Intima-media thicknesses of the common carotid arteries (CIMT) were measured. Peripheral artery calcification scores were obtained. Results: A total of 238 patients were included in the study. Fetuin-A levels in patients with end-stage renal disease were significantly lower than those in patients with stage-3 and stage-4 CKD (stage-5 vs. stage-4, P < 0.001; stage-5 vs. stage-3, P < 0.001). Fetuin-A was negatively correlated with creatinine (P < 0.001), Ca × P product (P < 0.001), hs-CRP (P = 0.01), vascular calcification score (P < 0.001), and CIMT (P < 0.001), and positively correlated with BMI (P < 0.001, r = 0.30) and serum albumin (P < 0.001). Conclusion: Lower levels of fetuin-A were associated with higher vascular calcification scores, CIMT, hs-CRP levels, and lower BMI and albumin. Fetuin-A deficiency may be a key element for MIAC syndrome.

RANKL/Osteoprotegerin System and Bone Turnover in Hashimoto Thyroiditis.

Hypothyroidism is associated with changes in bone metabolism. The impact of hypothyroidism and the associated autoimmunity on the mediators of bone turnover in Hashimoto's thyroiditis (HT) is not known. In this study, we assessed the levels of OPG, RANKL, and IL-6 along with markers of bone formation as osteocalcin (OC) 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 HT patients and 20 healthy premenopausal controls. We found that TRAcP 5b (p = 0.006), CTX (p = 0.01), OC (p = 0.017), and IL-6 (p < 0.001) levels were lower in the hypothyroid group compared to euthyroid HT patients and controls. OPG levels were higher (p < 0.001) and RANKL levels were lower (p = 0.021) in hypothyroid and euthyroid HT patients compared to controls. TSH was negatively correlated with IL-6 (rho = -0.434, p < 0.001), OC (rho = -0.313, p = 0.006), TRAcP 5b (rho = -0.335, p = 0.003), and positively correlated with OPG (rho = 0.248, p = 0.029). RANKL/OPG ratio was independently associated with the presence of HT. In conclusion, bone turnover is slowed down by hypothyroidism in premenopausal patients with HT. Thyroid autoimmunity might have a unique impact on OPG/RANKL levels apart from the resultant hypothyroidism.

Lymph node fine-needle aspiration washout thyroglobulin in papillary thyroid cancer: Diagnostic value and the effect of thyroglobulin antibodies.

PURPOSE: Thyroglobulin (Tg) assessment in the needle washout after fine-needle aspiration biopsy (FNAB) of a suspicious neck lymph node (LN) is known to improve the diagnostic accuracy in patients with papillary thyroid cancer (PTC). However, there is still controversy on the best diagnostic cut-off levels for FNAB-Tg and whether thyroglobulin antibody (TgAb) positivity affects FNAB-Tg. The objectives of this study were to determine (i) the diagnostic power of different cut-offs for FNAB-Tg and (ii) if serum TgAb(+) negatively affects the FNAB-Tg evaluation. METHODS: This was a retrospective cohort study analyzing PTC patients with suspicious neck LNs, in a university hospital setting, from October 2009 to October 2013. In total, 103 patients with PTC (226 LNs) undergoing ultrasound-guided FNAB for LNs were included. Cytology and FNAB-Tg levels were compared in reference to LN histopathology and the effect of TgAb(+) on FNAB-Tg levels was evaluated. RESULTS: The diagnostic accuracies of FNAB-Tg cut-off of 1 and 10 ng/mL were 94.1% and 88.2%, respectively. Raising the cut-off from 1 to 10 ng/mL led to decreased sensitivity rates (91.9% vs. 83.9%). The receiver operating characteristic curve analysis demonstrated that the best FNAB-Tg cut-off was 1.2 ng/mL. There were no LNs with an FNAB-Tg ≥ 10 ng/mL that turned out to be cytologically or histopathologically benign. FNAB-Tg levels of the histopathologically malignant LNs were similar between TgAb (+) and TgAb (-) patients (p = 0.546). Serum Tg predicted FNAB-Tg levels above 1 ng/mL (p = 0.002) and FNAB-Tg predicted malignant histopathology (p = 0.004), both independently of the TgAb status of the patient. CONCLUSIONS: FNAB-Tg ≥ 1 ng/mL has a superior diagnostic power, irrespective of TgAb (+), in PTC patients with suspected LN involvement.

The effect of thyroid autoimmunity on T-cell responses in early pregnancy.

Thyroid autoimmunity (TAI) is common in women of reproductive age. There is a relationship between TAI and recurrent pregnancy loss and infertility. In pregnant patients with thyroid autoimmunity, the T helper-1 (Th1)/T helper-2 (Th2) ratio may shift to a Th1-type response and these activated T lymphocytes may lead to implantation failure. The aims of this study were to investigate the serum levels of Th1-, Th2-, and T-helper-17-(Th17)-associated cytokines in pregnant patients with TAI, and to evaluate how these cytokines change with l-thyroxin treatment during pregnancy. Twenty pregnant women with TAI diagnosed in the first trimester of pregnancy who were not on l-thyroxine treatment, 14 pregnant women with known TAI before pregnancy already been on l-thyroxine treatment, and 19 pregnant patients without TAI were included in this study. Thyroid function tests, thyroid autoantibodies, and cytokine levels were measured at the first and the second trimesters. In pregnant patients who were diagnosed with TAI in the first trimester, both serum IL-2 levels and IL-17 levels were significantly higher than those of the control group. There were no significant differences between groups for serum IL-4, IL-6, IL-23, IL-10, and IFNγ levels. In the second trimester, no significant differences were found between groups for all the cytokines measured. There are significant differences in Th1- and Th17-associated cytokine levels between patients with TAI and the control group in the first trimester. In the second trimester cytokine levels were similar among all groups. This pattern may be associated with the clinical benefits of l-thyroxine treatment.

A Rare Presentation of Extramedullary Hematopoiesis in Post-polycythemic Myelofibrosis.

Polycythemia vera is a clonal proliferative disorder of the bone marrow that could possibly evolve into myelofibrosis in its natural course. Progression to myelofibrosis is usually a late stage complication and presents clinically with refractory cytopenias and extramedullary hematopoiesis (EMH). EMH can occur in any tissue during the course of post-polycythemic myelofibrosis. However, skin and cardiac involvements seems to be very rare. We present a 56-year-old woman with post-polycythemic myelofibrosis refractory to treatment, developing EMH after splenectomy in various organs, exceptionally the skin and the heart. Along with the case, the clinical presentations, treatment options, prognostic significance of EMH and the role of cytogenetics is discussed in the light of the literature.

The relationship between advanced oxidation protein products (AOPP) and biochemical and histopathological findings in patients with nonalcoholic steatohepatitis.

OBJECTIVE: To investigate the correlation between advanced oxidation protein products (AOPP) levels and biochemical and histopathological findings in patients with nonalcoholic steatohepatitis (NASH). METHODS: Sixty biopsy-proven NASH patients and 60 individuals with ultrasonographically healthy liver (the control group) were included in the study. AOPP levels were determined in all the participants and liver histopathological examination based on liver biopsy was performed in NASH patients. The NASH activity score (NAS), hepatosteatosis, liver inflammation and fibrosis were evaluated. RESULTS: Serum AOPP level was significantly higher in the NASH group than that in the control group (461.8 ± 201.9 µmol/L vs 191.7 ± 152.5 µmol/L, P < 0.001). The receiver operating characteristic (ROC) curve revealed a sensitivity of 73.3% and a specificity of 88.3% for the diagnosis of NASH with an AOPP cut-off value of 332 µmol/L (the area under ROC curve 0.88, 95% confidence interval 0.82-0.94, P < 0.01). AOPP levels were positively correlated with NAS (r = 0.27, P = 0.035), fibrosis (r = 0.27, P = 0.037) and inflammation (r = 0.34, P = 0.008), but not the grade of steatosis (r = 0.02, P = 0.83) or ballooning (r = 0.02, P = 0.55). CONCLUSIONS: AOPP levels are significantly higher in patients with NASH than in those with ultrasonographically healthy liver. AOPP levels are positively correlated with biochemical and histopathological findings (NAS, liver inflammation and fibrosis), indicating that AOPP may play a role in the development of liver fibrosis and inflammation and may predict liver histopathology in NASH.

Presence and extent of estrogen receptor-alpha expression in patients with simple steatosis and NASH.

Loss of estrogen receptor-alpha (ER-α) in the liver is associated with hepatic steatosis and inflammation. We conducted a study in order to investigate the presence and extent of ER-α expression in NASH, and its relationship with histological findings. Fifty-four patients with histologically confirmed NASH, 12 patients with simple steatosis (SS), and 6 patients with normal liver tissue (NLT) were included. NASH activity score and fibrosis score were calculated according to biopsy findings. Liver biopsy specimens were immunohistochemically stained for ER-α expression. Nuclear ER-α expression percentage (staining index) 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 was significantly higher in women than in men (19.4±22.2 vs. 7.9±15.3, respectively, p=0.003). Staining index 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-α expression percentage (staining index) is lower in patients with NASH when compared to SS and NLT groups. Staining index is negatively correlated with serum ALT levels, plasma glucose, and fibrosis score. Further studies are required to clarify the significance of ER-α expression in NASH.

Diffuse amyloid deposition in thyroid gland: a cause for concern in familial Mediterranean fever.

Thyroid gland is among the many organs that could be infiltrated in systemic amyloidosis. However, diffuse infiltration of the thyroid gland secondary to systemic amyloidosis associated with Familial Mediterranean fever (FMF) is rare. Here, we present a 49-year-old woman diagnosed with FMF and systemic amyloidosis, who had a large goiter and multiple nodules that developed slowly through the years and was complicated by tracheal compression symptoms and a mild thyroid dysfunction. Multiple fine needle aspiration biopsies of the nodules and the thyroid parenchyma revealed amyloid deposits. We would like to point out that amyloidosis may have a significant impact on the thyroid gland and fine needle aspiration biopsy is a valuable tool for diagnosis.