Evaluation of the Relationship Between Vitamin D Deficiency and Subclinical Cardiac Dysfunction Using 2D/3D Strain Echocardiography in Healthy People.

AIM: Vitamin D deficiency has a high prevalence in the population and is highly associated with cardiovascular diseases. The aim of this study was to evaluate subclinical left ventricular (LV) function using strain analysis in healthy individuals with vitamin D deficiency. MATERIAL AND METHODS: 113 healthy volunteers were enrolled in the study (age, 44.1±7 yrs, 34 male). All volunteers underwent two-dimensional (2D) and three-dimensional (3D) speckle tracking echocardiography after conventional echocardiographic evaluation. The subjects were divided into two groups according to their vitamin D concentrations. 61 subjects with vitamin D less than 20 ng / ml were included in the vitamin D deficiency group. The baseline clinical characteristics, laboratory measurements, echocardiographic data, including 2D and 3D global longitudinal strain (GLS) values, were compared between the groups. RESULTS: The 2D GLS values of the subjects with vitamin D deficiency were lower (mathematically less negative) than subjects with normal vitamin D (-16.1±3.4 vs -19.3±4.2, p<0.001). Similarly, the 3D GLS results were lower in subjects with vitamin D deficiency (-18.3±5.2 vs -24.1±6.9, p<0.001). A significant correlation was detected between the vitamin D concentrations and the 2D and 3D GLS measurements. (r=0.765 and r=0.628, respectively, p<0.001). Vitamin D was found to be an independent predictor of impaired 2D and 3D LV GLS (p=0.031, p=0.023, respectively). CONCLUSION: Subclinical LV dysfunction in healthy individuals with vitamin D deficiency was demonstrated by 3D and 2D strain analysis. Due to potential negative effects of vitamin D deficiency on cardiac function, more attention should be paid to healthy individuals with vitamin D deficiency.

Sonographic Features of Atypical and Initially Missed Parathyroid Adenomas: Lessons Learned From a Single-Center Cohort.

CONTEXT: Awareness of typical and atypical ultrasonographic (US) features of parathyroid adenomas (PAs) is crucial since US is the most widely used first-line imaging modality. OBJECTIVE: The purpose of this study was to describe the atypical features of PAs on US and other possible factors leading to a false negative examination in a large single-center cohort. MATERIALS AND METHODS: The US records of 457 PAs in 445 patients with biochemically proven primary hyperparathyroidism (PHPT) were evaluated in a prospectively maintained database. Atypical size, composition, shape, echogenicity, location, and vascular pattern on US were noted. For patients who previously had at least one negative US examination in referring centers, the main possible reason was defined accordingly. RESULTS: The study group included 359 female and 86 male patients with PHPT. Typical sonographic features were observed in 231 PAs (51%), whereas 226 (49%) had at least one atypical US feature. The most common atypical features were atypical size (29%), followed by atypical echogenicity (19%), shape (8%), location (7%), and composition (7%), respectively. There were 122 initially missed PAs in all groups. The most frequent main atypical US features leading to false negative examinations were atypical size (22.1%) and atypical location (18.8%). Inexperience was third most common reason (16.3%) for false negative US examinations. CONCLUSIONS: Almost half of PAs have at least one atypical feature on US. Awareness of the high prevalence of atypical US features could increase the accuracy of US examination and potentially decrease demand for more expensive second-line imaging modalities.

The impact of vitamin D deficiency on clinical, biochemical and metabolic parameters in primary hyperparathyroidism.

BACKGROUND: It has been suggested that vitamin D deficiency is associated with worse clinical outcomes in primary hyperparathyroidism (PHPT). We aimed to evaluate the relationship between vitamin D deficiency and clinical, biochemical and metabolic parameters in PHPT patients. METHODS: A total of 128 patients with biochemically confirmed PHPT were included. Patients were categorized as vitamin D deficient if 25-OH vitamin D was <50nmol/L, or normal if vitamin D was ≥50nmol/L. Biochemical parameters, bone mineral densitometry (BMD), and urinary tract and neck ultrasonography were assessed. RESULTS: In the study group, 66 (51.6%) patients had vitamin D deficiency and 60 (48.4%) had normal vitamin D levels. Nephrolithiasis and osteoporosis were found in 26.6% and 30.5% of subjects, respectively. The prevalence of metabolic syndrome (MetS), obesity (BMI≥30kg/m2) and hypertension (HTN) were higher in the vitamin D deficient group when compared to the normal group (p=0.04, p=0.01 and p=0.03, respectively). There was no difference regarding the presence of nephrolithiasis and osteoporosis between the groups. The mean adenoma size was similar in both groups. CONCLUSIONS: Vitamin D deficiency was not associated with osteoporosis, nephrolithiasis, adenoma size or biochemical parameters in PHPT. However, vitamin D deficiency may be a risk factor for developing HTN and MetS in PHPT.

Type 1 diabetes mellitus following SARS-CoV-2 mRNA vaccination.

PURPOSE: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) vaccines have been reported to trigger immune side effects. Type 1 diabetes as a manifestation of autoimmune/inflammatory syndrome induced by adjuvants has been reported in a limited number of cases after vaccinations. A few type 1 diabetes cases after SARS-CoV-2 vaccination have been reported. This study aims to report type 1 diabetes cases associated with the mRNA-based SARS-CoV-2 vaccination. METHODS: We report four cases of type 1 diabetes mellitus after mRNA-based SARS-CoV-2 vaccine, BNT162b2 (Pfizer-BioNTech). In the medical history, one subject had autoimmune thyroid disease. All patients had autoantibodies against glutamate decarboxylase. RESULTS: In the presented case series, type 1 diabetes developed a few weeks after BNT162b2 vaccination. After developing type 1 diabetes, the insulin dose requirements of all patients decreased rapidly, and the need for insulin therapy in three patients disappeared during follow-up. Acute deterioration of glucose regulation in a patient followed by BNT162b2 administration may be due to vaccine-induced autoimmune diabetes. CONCLUSION: Vaccination with BNT162b2 may trigger type 1 diabetes.

Intensifying Iodine Deficiency Throughout Trimesters of Pregnancy in a Borderline Iodine-Sufficient Urban Area, Ankara, Turkey.

Iodine has long been recognized as an essential micronutrient for maternal thyroid function, as well as fetal growth and development during pregnancy. The current study aimed to evaluate thyroid hormone status, urinary iodine concentration (UIC), thyroid volume, and nodularity in pregnant women, throughout trimesters, in a borderline iodine sufficient, urban area with mandatory table salt iodization. Two-hundred-sixty-five pregnant women ranging from 17 to 45 years participated in this prospective longitudinal study. Thyroid function tests, thyroid volume, nodule growth, and UIC were recorded throughout the first, second, and third trimesters with no intervention. Median UIC was 96, 78, and 60 µg/L in the first, second, and third trimester of pregnancy, respectively (p < 0.001). Mean TSH values increased significantly (i.e. 0.65 mIU/ml, 1.1 mIU/ml, and 1.3 mIU/ml in the first, second, and third trimesters, respectively) (p < 0.001). Mean ± s.d. thyroid volume was significantly higher in the third trimester (14.72 ± 6.8 ml) compared with the first trimester (13.69 ± 5.31 ml) (p < 0.001). An intensifying iodine deficiency (ID) was reported throughout trimesters in this cohort of pregnant women from Ankara. A significant percentage of pregnant women from a borderline iodine sufficient, urban area in Turkey were iodine deficient during all trimesters, and the deficiency increased throughout the pregnancy. Pregnant women should receive iodine supplementation, besides consuming iodized salt in borderline iodine sufficient areas.

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 Association of Histologically Proven Chronic Lymphocytic Thyroiditis with Clinicopathological Features, Lymph Node Metastasis, and Recurrence Rates of Differentiated Thyroid Cancer.

The influence of chronic lymphocytic thyroiditis (CLT) on clinicopathological features and behavior of differentiated thyroid carcinoma (DTC) is still debated. In the present study, we aimed to evaluate the prognosis of DTC on the presence of CLT. A total of 649 total thyroidectomized patients (379 female, 270 male) with DTC, who had follow-up data for at least 36 months were included. Clinical, histopathological data, preoperative thyroid peroxidase antibody (TPO-ab), thyroglobulin antibody (Tg-ab), thyroid-stimulating hormone (TSH) levels, and presence of recurrent/persistent disease (R/PD) were evaluated retrospectively. Presence of CLT was defined by histopathology. Frequency of CLT was 32% (n = 208) among DTC patients. Mean tumor size (maximal diameter) was smaller in CLT group when compared to non-CLTs (p = 0.006). Capsular invasion, vascular invasion, tumor stage, risk groups, and R/PD were negatively associated with CLT (p < 0.01, p = 0.04, p = 0.03, p = 0.02, p < 0.01, respectively). Extrathyroidal extension was more frequent in non-CLT group when compared CLT (p = 0.052). Preoperative TSH level was positively associated with lymph node metastasis (LNM) and higher in patients with lateral LNM when compared to central LNM (p < 0.01). Central LNM, lateral LNM, stage 4 tumor, and intermediate- and high-risk tumor groups increased the risk of R/PH, 2.5-, 2.9-, 12.7-, 2.3-, and 4.2-fold, respectively. Presence of CLT was independently related with favorable outcomes, as the risk of R/PD was decreased by 0.49-fold. In conclusion, coexistence of CLT was negatively associated with tumor size, capsular invasion, vascular invasion, and tumor stage in DTC. Risk of R/PD was decreased by approximately half in patients with CLT.

Primary hyperparathyroidism as first manifestation in multiple endocrine neoplasia type 2A: an international multicenter study.

OBJECTIVE: Multiple endocrine neoplasia type 2A (MEN 2A) is a rare syndrome caused by RET germline mutations and has been associated with primary hyperparathyroidism (PHPT) in up to 30% of cases. Recommendations on RET screening in patients with apparently sporadic PHPT are unclear. We aimed to estimate the prevalence of cases presenting with PHPT as first manifestation among MEN 2A index cases and to characterize the former cases. DESIGN AND METHODS: An international retrospective multicenter study of 1085 MEN 2A index cases. Experts from MEN 2 centers all over the world were invited to participate. A total of 19 centers in 17 different countries provided registry data of index cases followed from 1974 to 2017. RESULTS: Ten cases presented with PHPT as their first manifestation of MEN 2A, yielding a prevalence of 0.9% (95% CI: 0.4-1.6). 9/10 cases were diagnosed with medullary thyroid carcinoma (MTC) in relation to parathyroid surgery and 1/10 was diagnosed 15 years after parathyroid surgery. 7/9 cases with full TNM data were node-positive at MTC diagnosis. CONCLUSIONS: Our data suggest that the prevalence of MEN 2A index cases that present with PHPT as their first manifestation is very low. The majority of index cases presenting with PHPT as first manifestation have synchronous MTC and are often node-positive. Thus, our observations suggest that not performing RET mutation analysis in patients with apparently sporadic PHPT would result in an extremely low false-negative rate, if no other MEN 2A component, specifically MTC, are found during work-up or resection of PHPT.

Frequency of thyroid nodules and thyroid cancer in thyroidectomized patients with Graves' disease.

INTRODUCTION: Incidental thyroid cancers are frequently detected in patients operated on for Graves' disease (GD). There are no clear data about the incidence and risk factors of incidental thyroid cancer in operated GD patients. The aim of this study is to evaluate the risk of thyroid carcinoma in surgically treated GD patients. MATERIAL AND METHODS: The data of 121 GD patients who underwent total thyroidectomy in a single center between 2005 and 2015 were retrospectively evaluated. The diagnosis of thyroid cancer was based on pathological examination. RESULTS: Thyroid cancer was demonstrated in postoperative pathology specimens of 34 patients who were surgically treated for GD (28.1%). Preoperative thyroid ultrasonography (USG) revealed a nodular goiter in 62 (51.2%) patients. Nodules were not detected in the other 59 (48.8%) patients with GD. The frequency of thyroid cancer was significantly higher in patients with nodules (38% vs. 16%; p = 0.009). Thirty-two of the 34 cancer cases had papillary thyroid cancer (PTC), and the remaining 2 had follicular thyroid cancer (FTC). Of the 32 PTC patients, 28 were classical type, 2 patients had the follicular variant, 1 was the oncocytic variant, and 1 was a tall cell variant. CONCLUSIONS: The incidence of thyroid cancer was higher in patients who underwent surgery for GD. In addition to a careful physical examination in the follow-up of the patients with GD, ultrasonographic evaluation should be performed. Surgical treatment should not be delayed in patients with GD when indicated.

SONOGRAPHIC FOLLOW-UP OF PATIENTS WITH DIFFERENTIATED THYROID CARCINOMA: A COMPARISON OF THE ULTRASOUND ELASTOGRAPHY, POWER DOPPLER ULTRASOUND, AND B-MODE ULTRASOUND FEATURES IN DETECTING MALIGNANT LYMPH NODES.

Objective: The aim of this study was to assess and compare the diagnostic power of B-mode ultrasonography (US), power Doppler US (PD), and ultrasound elastography (USE) in detecting malignant lymph nodes (LNs) during follow-up of patients who were operated on for differentiated thyroid cancer (DTC). Methods: In this prospective study, a total of 103 cervical LNs having suspicious malignant features from 72 patients with DTC were examined using US, PD, and USE. USE scores were classified from 1 to 3 according to the presence of elasticity (1, soft; 2, intermediate; 3, hard). The strain ratios (SRs) of all LNs were calculated according to adjacent muscle tissue. Results: The most-sensitive ultrasonographic features were hilum loss and hypoechogenicity, with 94.4% and 80.6% sensitivity and 93.5% and 84.4% negative predictive value, respectively. The most-specific feature was the presence of cystic component, with 98.5% specificity and 85.7% positive predictive value. Presence of diffuse/chaotic or irregular vascularity in PD had 47.2% sensitivity and 83.6% specificity in predicting metastasis. In USE, the sensitivity and specificity of score 3 were 56.7% and 74.2%, respectively. The median SR of metastatic LNs was higher than that of benign LNs (median SR [min-max], 3.0 [0.16 and 29] vs. 1.89 [0.26 and 37.9]), but the difference was not significant (P = .07). Multivariate logistic regression analyses revealed 4.9-, 6.6-, and 10-fold increases in metastasis risk for short/long axis ratio ≥0.5, nodal vascularity, and score 3 USE, respectively (P<.05). Conclusion: While USE had higher sensitivity, PD had higher specificity in detecting malignant LNs, but none of these techniques was as sensitive and specific as gray-scale US features. Abbreviations: CI = confidence interval; DTC = differentiated thyroid cancer; LN = lymph node; LN-Tg = lymph node-thyroglobulin; NPV = negative predictive value; PD = power Doppler; PPV = positive predictive value; ROI = region of interest; SR = strain ratio; US = ultrasonography; USE = ultrasound elastography.

Could a nonfunctional adrenal incidentaloma be a risk factor for increased carotid intima-media thickness and metabolic syndrome.

BACKGROUND: This study was designed to detect the potential association of a nonfunctional adrenal incidentaloma (NFAI) with insulin resistance and associated metabolic disturbances, with a subsequent increase in cardiovascular risk factors. METHODS: Eighty-three NFAI patients and 56 volunteers (controls) without any adrenal abnormalities on computed tomography (CT) were included. Fasting blood glucose (FBG), fasting insulin, lipid profiles, uric acid, homocysteine, fibrinogen, high sensitivity C-reactive protein (hs-CRP), and adiponectin levels were measured in both groups. Blood pressure (BP), waist circumference, body mass index (BMI), and carotid intima media thickness (CIMT) were evaluated in both the patients and volunteers. RESULTS: There were no significant difference between the NFAI and control groups with respect to age, sex, BMI, waist circumference, systolic and diastolic BP, smoking, concomitant disease, and medications. Fasting insulin and glucose levels and homeostasis model of assessment-insulin resistance (HOMA-IR) scores were significantly higher in the NFAI group as compared with those in the control group (p<0.01). The frequency of metabolic syndrome in the NFAI group was higher than that in the control group (p<0.01). All the lipid fractions, except triglyceride (TG), (p<0.05), homocysteine (p=0.01), and fibrinogen levels (p<0.001), were significantly higher in the NFAI group as compared with the levels in the control group. There were no significant differences between the NFAI and control groups in terms of uric acid, hs-CRP, and adiponectin levels. The CIMT values in the NFAI group were significantly higher than those in the control group (0.74±0.14 vs. 0.53±0.09, p<0.001). The mean CIMT value showed a statistically positive correlation with age (r=0.245, p=0.004); the HOMA-IR score (r=0.490, p<0.001); and FBG (r=0.521, p<0.001), fasting insulin (r=0.432, p<0.001), total cholesterol (TC) (r=0.267, p=0.002), and fibrinogen (r=0.398, p<0.001) levels in the NFAI group. CONCLUSIONS: The results indicated that the NFAI patients had an elevated risk of insulin resistance, with metabolic syndrome and increased CIMT values. Long-term follow-up studies should be designed to evaluate postsurgical alterations in metabolic parameters and cardiovascular risk factors in NFAI patients.

The influence of thyroid nodule size on the diagnostic efficacy and accuracy of ultrasound guided fine-needle aspiration cytology.

BACKGROUND: Diagnostic accuracy of fine-needle aspiration cytology (FNAC) in large and subcentimeter nodules is still debated. We aimed to evaluate the impact of nodule size on efficacy of the ultrasound-guided FNAC. METHODS: B-mode grayscale ultrasound (US), US-guided FNAC according to Bethesda system and histopathological data of 514 nodules from 371 patients, who underwent thyroidectomy were examined retrospectively. Nodules were grouped by maximal diameter; group A nodules were smaller than 10 mm (n = 59), group B nodules were between 10 and 29 mm (n = 218), and group C nodules were 30 mm or greater (n = 130). RESULTS: Sensitivity, specificity, and accuracy of FNAC was 92.0%, 100%, and 95.1% in group A, 80.7%, 99.1%, and %92.9 in group B, 70.0%, 98.9%, and 95.8% in group C nodules, respectively. The prevalence of papillary thyroid cancer (PTC) and incidental PTC were 44.2% (n = 164) and 6.4% (n = 24), respectively. Malignancy rate was more frequent in group A when compared to groups B and C (P < 0.01). Nodule size was positively associated with follicular cancer risk (P = 0.009). The thyroid stimulating hormone level was positively associated with malignancy (P = 0.02) and optimal cut-off value was 0.96 mIU/L. False-negative rate was 8.0%, 19.3%, and 30.0% in groups A, B, and C nodules, respectively. CONCLUSIONS: Although the malignancy rate was low in nodules ≥30 mm, diagnostic surgery for large nodules should be considered because of decreased reliability of FNAC, ineffectiveness of clinical and sonographic criteria. False-negative rate was relatively low and malignancy rate was high in subcentimeter nodules, supporting the accuracy of FNAC.

The Prognostic Roles of the Ki-67 Proliferation Index, P53 Expression, Mitotic Index, and Radiological Tumor Invasion in Pituitary Adenomas.

The fourth edition of the World Health Organization (WHO) classification of pituitary tumors recommended evaluation of tumor proliferation and invasion to identify aggressiveness. We aimed to assess the prognostic roles of the Ki-67 proliferation index, mitotic index, P53 expression, and cavernous sinus invasion in pituitary adenomas (PAs). Among the 601 patients who underwent transnasal/transsphenoidal adenomectomy from 2001 to 2016, 101 patients (16.8%) who had tumors with a high (≥ 3%) Ki-67 index (group A) and a control group consisting of 43 patients with a low (< 3%) Ki 67 index who were matched for age, gender, and tumor type were included. Mitotic index and P53 expressions were evaluated. Patient characteristics, histopathology reports, pre/postoperative magnetic resonance imaging (MRI), and follow-up data were assessed retrospectively. The frequency of macroadenomas and mean tumor size were greater in group A when compared to group B (67.4 vs. 94.1%, p< 0.01 and 25 ± 10.6 vs. 18 ± 11 mm, p< 0.01, respectively). Invasion to cavernous sinus was found in 53 (36.8%) patients and was more frequent in group A (p<0.01). The mean number of surgery was higher in group A than group B (p< 0.05). The mean follow-up period was 46.6 ± 34 months. The postoperative MRIs and follow-up data for at least 24 months were available in 117 patients. Recurrence risk was higher in group A than group B (p = 0.03). Tumors with high Ki-67 proliferation index were grouped as 3-5, 6-10, 11-15, and > 15%. The risk of recurrence was not different between groups of high Ki-67 index. The optimal cutoff point of the Ki-67 proliferation index that predicted recurrence was 2.5% with 84.6% sensitivity and 47.4% specificity. The cavernous sinus invasion on MRI was associated with recurrence (p = 0.03). Tumor size and recurrence risk were not associated with P53 expression. High P53 expression was related with cavernous sinus invasion (p = 0.03). The mitotic index was not associated with recurrence risk and tumor invasion. Recurrence risk was higher in tumors with ≥ 2 histopathological atypia criteria (p = 0.01). High Ki-67 index with a 2.5% cutoff point and cavernous sinus invasion on MRI are reliable markers for predicting recurrence in PAs. Recurrence risk is also higher in tumors with two histopathological aggressiveness criteria. Strict follow-up and more aggressive treatment approaches may be necessary for invasive-proliferative PAs.

Are thyroid nodules with spongiform morphology always benign?

OBJECTIVE: Fine needle aspiration (FNA) biopsy for evaluation of spongiform nodules ≥20 mm or observation without FNA was recommended by American Thyroid Association. However, this was a weak recommendation supported by moderate quality evidence. We aimed to assess malignancy risk in spongiform nodules. METHODS: From January 2015 to June 2016, an experienced endocrinologist performed B-mode greyscale ultrasonography and observed 96 spongiform nodules among 3748 ultrasound procedures. Power Doppler ultrasonography and ultrasound-guided FNA were performed to 96 spongiform nodules. Both colour elastography and strain ratio measurements of dominantly solid areas were performed. RESULTS: All spongiform nodules had benign cytology. Fifty-two (54.2%) nodules were ≥20 mm and 44 (45.8%) were smaller than 20 mm in maximum diameter. Presence of ultrasonography features related to malignancy was rare; 2% (n = 2) microcalcification, 9.4% (n = 9) taller than wide shape and 2% (n = 2) marked central blood flow were noted. None of the nodules had two or more suspicious features. Ultrasound elastography findings revealed that dominantly solid components of nodules were usually soft as 66.7% had an elasticity score 1 according to colour scale and mean strain ratio was 1.39 ± 0.99. CONCLUSIONS: Follow-up with ultrasonography seems to be an efficacious method even for spongiform nodules larger than 2 cm. Determination of soft appearance according to colour map on ultrasound elastography and low strain ratio values of dominantly solid areas may be useful to avoid unnecessary biopsies.

Clinical Impact of p27Kip1 and CaSR Expression on Primary Hyperparathyroidism.

We aimed to investigate the expressions of p27 kinase inhibitory protein 1 (p27Kip1) and calcium sensing receptor (CaSR) in adenomas and normal parathyroid tissue and to evaluate the relationship of these molecules with clinical and biochemical parameters in primary hyperparathyroidism (PHPT). Fifty-one patients with histopathologically confirmed parathyroid adenomas and 20 patients with normal parathyroid glands (which were removed incidentally during thyroid resection) were included. Immunohistochemical stainings of CaSR and p27Kip1 were performed in surgical specimens. Clinical features, biochemical parameters, and BMD measurements of patients with PHPT were evaluated retrospectively. Expressions of p27Kip1 and CaSR were decreased in parathyroid adenomas, compared to normal glands (p < 0.05). High intensity of CaSR staining (3+) was more frequent in normal parathyroid tissue (75%) than adenomas (12%) (p < 0.01). Hypertension was not observed in patients with high staining intensity of CaSR (p = 0.032). There was a negative association between CaSR expression and body mass index (BMI) (p = 0.027, r = - 0.313). There was no significant relationship between p27Kip1 and CaSR expressions, serum calcium, plasma parathormone, 25-hydroxy vitamin D levels, and bone density (p > 0.05). The expressions of p27Kip1 and CaSR were decreased in PHPT patients. This reduction may play an important role in the pathogenesis of PHPT. However, neither p27Kip1 nor CaSR expression was found to be useful in predicting prognosis or severity of disease.

Is primary hyperparathyroidism a cause of endothelial dysfunction?

OBJECTIVE: Symptomatic primary hyperparathyroidism (PHPT) is thought to be related to increased cardiovascular morbidity and mortality. In our study, we aimed to investigate endothelial dysfunction and markers of subclinical atherosclerosis in patients with PHPT. Also we aimed to demonstrate the effect of vitamin D supplementation on these parameters. MATERIALS AND METHODS: Twenty-nine patients followed by medical treatment (A), 25 preoperative (B) and 23 postoperative patients with PHPT (C), and 26 normocalcaemic subjects (D) were included. Groups were assessed by measurements of flow-mediated dilation (FMD), carotid intima-media thickness (CIMT), serum levels of sCD40L, high-sensitivity CRP (hs-CRP) and interleukin-8 (IL-8). Thirteen patients with low levels of 25-hydroxy-vitamin D (25OHD) in the medical treatment group were assessed before and 3 months after vitamin D replacement. RESULTS: The median FMD was 5% in group A, 5.1% in group B, 7.6% in group C and 7.7% in group D. The FMD measurement in group A was significantly lower than groups C and D (P=.02) and was similar to the FMD measurement in group B. FMD measurements of group B were not significantly lower than groups C and D. In 13 patients with low 25OHD in group A, the median FMD increased to 7.07% from 4.71% after vitamin D replacement (P=.02). CONCLUSION: Flow-mediated dilation was impaired in patients with PHPT, particularly in the medically observed group. Vitamin D supplementation seems to provide improvements in FMD in medically observed PHPT patients with low 25OHD levels, and this was the novel observation of our study.

Course of Aggressive Somatotroph, Corticotroph and Mammotroph Tumors under Temozolomide; Report of Three Cases and Review of the Literature.

Treatment of aggressive pituitary tumors may be challenging. Temozolomide (TMZ) is a promising agent when conventional treatment methods fail. We present three patients with aggressive pituitary tumors with atypical morphology, who were resistant to conventional treatments and treated with TMZ. First case had a somatotroph adenoma, second a corticotroph adenoma, and the third a macroprolactinoma. We also reviewed the literature reporting TMZ efficacy in somatotroph, corticotroph and mammotroph tumors of pituitary. TMZ, 150-200 mg/m2 for 5 days in 28 days schedule was given to all patients. Among our patients, even though only the case of macroprolactinoma had a favorable response to TMZ treatment, both radiological and hormonal recurrences occurred 30 months after cessation of TMZ treatment. Then TMZ treatment was applied again. Cases of somatotroph and corticotroph adenomas had progressed under TMZ treatment and patients were lost due to mass effect of the tumor. Review of the literature demonstrated 67.3%, 60% and 26.7% overall response rates to the TMZ treatment in prolactinoma, corticotropinoma and somatostatinoma cases, respectively. There is still need to define response criteria uniformly to TMZ treatment in aggressive pituitary tumors and duration of response should be reported for reliable evaluation of results.

Comparison of Early Total Thyroidectomy with Antithyroid Treatment in Patients with Moderate-Severe Graves' Orbitopathy: A Randomized Prospective Trial.

BACKGROUND: The optimal therapeutic choice for Graves' hyperthyroidism in the presence of moderate-severe Graves' orbitopathy (GO) remains controversial. OBJECTIVES: We aimed to compare GO course in patients with moderate-severe GO treated with early total thyroidectomy (TTx) versus antithyroid drug (ATD) regimens, in a prospective, randomized manner. METHODS: Forty-two patients with moderate-severe GO were enrolled. A total of 4.5 g of pulse corticosteroids were given intravenously to all patients before randomization. Patients in the first group were given TTx, whereas patients in the second group were treated with ATDs. TSH was kept between 0.4 and 1 mIU/l. The clinical course of GO was evaluated with proptosis, lid aperture, clinical activity score (CAS), and diplopia. RESULTS: Eighteen and 24 patients were randomized to the TTx and ATD groups, respectively. Thyroid autoantibodies decreased significantly, and there were significant improvements in proptosis, lid aperture, and CAS in the TTx group. While in the ATD group the decrement in thyroid autoantibodies was not significant, there were significant improvements in proptosis and CAS. When the TTx group was compared with the ATD group, anti-TPO, anti-Tg, and TSH-receptor antibodies were significantly decreased in the TTx group (p < 0.01), but there was no significant difference with respect to proptosis, lid aperture, CAS, and diplopia between the two groups during a median (min.-max.) follow-up period of 60 months (36-72). CONCLUSION: Although no definitive conclusions could be drawn from the study, mainly due to limited power, early TTx and the ATD treatment regimens, followed by intravenous pulse corticosteroid therapy, seemed to be equally effective on the course of GO in this relatively small group of patients with moderate-severe GO during a median (min.-max.) follow-up period of 60 months (36-72).

Cervical Paraganglioma Mimicking Thyroid Nodule: A Rare Clinical Case.

Objective. Paraganglioma is a rare neuroendocrine tumor. When it is located in the neck, it is commonly misdiagnosed as other thyroid neoplasms. Case Report. We report a case of cervical paraganglioma in a 55-year-old female. Patient was admitted to our clinic with goiter and neck pain. Thyroid ultrasonography revealed a 20 mm solitary, heterogeneous nodule located in the upper pole of left thyroid lobe. Fine needle aspiration cytology was nondiagnostic. She underwent left lobectomy and histopathology showed paraganglioma. Discussion. Cervical paragangliomas should be considered in the differential diagnosis of thyroid nodules.

Distribution of RET Mutations and Evaluation of Treatment Approaches in Hereditary Medullary Thyroid Carcinoma in Turkey.

OBJECTIVE: This retrospective multicenter study, centrally conducted and supported by the Society of Endocrinology and Metabolism of Turkey, aimed to evaluate the impact of free RET proto-oncogene testing in medullary thyroid carcinoma (MTC) patients. Surgical timing, adequacy of the treatment, and frequency of prophylactic thyroidectomy (PTx) in mutation carriers were also assessed. METHODS: Genetic testing for MTC and pheochromocytoma was conducted between July 2008 and January 2012 in 512 patients. Application forms and RET mutation analyses of these patients whose blood samples were sent from various centers around Turkey were assessed retrospectively. An evaluation form was sent to the physicians of the eligible 319 patients who had confirmed sporadic MTC, familial MTC (FMTC), multiple endocrine neoplasia type 2 (MEN2), or who were mutation carriers. Physicians were asked to give information about the surgical history, latest calcitonin levels, morbidity, mortality, genetic screening, and PTx among family members. Twenty-five centers responded by filling in the forms of 192 patients. RESULTS: Among the 319 patients, RET mutation was detected in 71 (22.3%). Cys634Arg mutation was the most prevalent mutation (43.7%), followed by Val804Met in 18 patients (25.4%), and Cys634Tyr in 6 patients (8.5%). Among 192 MTC patients, the diagnosis was sporadic MTC in 146 (76.4%), FMTC in 14 (7.3%), MEN2A in 15 patients (7.9%), and MEN2B in one patient. The number of mutation carriers among 154 apparently sporadic MTC patients was 8 (5.2%). Ten patients were submitted to PTx out of twenty-four mutation carriers at a mean age of 35±19 years. CONCLUSION: Turkish people have a similar RET proto-oncogene mutation distribution when compared to other Mediterranean countries. Despite free RET gene testing, the number of the PTx in Turkey is limited and relatively late in the life span of the carriers. This is mainly due to patient and family incompliance and incomplete family counselling.