Tp-e interval, Tp-e/QT, and Tp-e/QTc ratios in patients with primary hyperparathyroidism and their relationship with cardiac arrhythmic events.

BACKGROUND: Primary hyperparathyroidism (PHPT) is an endocrine disorder characterized by hypercalcemia caused by excessive parathyroid hormone (PTH) secretion from the parathyroid gland. PHPT was previously shown to increase cardiac arrhythmias. Besides, new indices, such as the Tpeak-Tend (Tp-e) interval, Tp-e interval/QT interval (Tp-e/QT) ratio, and Tp-e interval/corrected QT interval (Tp-e/QTc) ratio may be associated with ventricular arrhythmias and sudden cardiac death. Therefore, we aimed to investigate the relationship between PHPT and the changes to Tp-e interval, Tp-e/QT ratio, and Tp-e/QTc ratio. METHODS: We carried out the study with 41 patients with PHPT and 40 control subjects. We calculated the Tp-e interval, Tp-e/QT ratio, and Tp-e/QTc ratio of the participants from the V5 derivations on their ECG papers. While we defined Tp-e interval as the distance between the peak and the end of the T wave, Tp-e/QT and Tp-e/QTc ratios were calculated by dividing Tp-e by QT and Tp-e by QTc, respectively. RESULTS: Total calcium, albumin-corrected calcium, phosphorus, and PTH levels were significantly higher in patients with PHPT. We also found positive correlations between albumin-corrected calcium and PTH levels and Tp-e interval, Tp-e/QT ratio, and Tp-e/QTc ratio (p < 0.001). DISCUSSION: : Our results suggest that Tp-e may enhance the current knowledge on arrhythmic risk in PHPT patients better than basal ECG. In addition, both high PTH and high calcium levels appear to have the potential to cause arrhythmogenic effects.

Atrial electromechanical delay is impaired in patients with primary hyperparathyroidism.

INTRODUCTION: Primary hyperparathyroidism (PHPT) is an endocrine disease that poses a risk for cardiac arrhythmias. Atrial electromechanical delay (EMD) has been known as an early marker of atrial fibrillation (AF). This study aimed to evaluate the atrial EMD in PHPT. MATERIAL AND METHODS: Fifty PHPT patients (45 females, 5 males) aged 30-75 years and 38 controls (35 females, 3 males) aged 31-73 years were included in the study. Atrial EMD parameters were measured by using tissue Doppler imaging (TDI). Inter-atrial EMD was calculated as the difference between PA lateral and PA tricuspid; intra-atrial EMD was calculated as the difference between PA septum and PA tricuspid, and left-atrial EMD was calculated as the difference between PA lateral and PA septum. RESULTS: Atrial EMD parameters (PA lateral, PA septum, PA tricuspid) significantly increased in the PHPT group compared to the control group (p < 0.001, for all). Also, inter-atrial and intra-atrial EMD were higher in the PHPT group than in the control group (p < 0.001, for all). In correlation analysis, calcium was closely associated with PA lateral (r = 0.749, p < 0.001), PA septum (r = 0.735, p < 0.001), inter-atrial EMD (r = 0.807, p < 0.001), and intra-atrial EMD (r = 0.838, p < 0.001). The same correlation relationship was seen between PTH levels with PA lateral (r = 671, p < 0.001), PA septum (r = 0.660, p < 0,001), inter-atrial EMD (r = 0.674, p < 0.001), and intra-atrial EMD (r = 0.732, p < 0.001). CONCLUSIONS: Atrial EMD parameters were prolonged in PHPT. The measurement of atrial EMD parameters might be used in determining the risk of AF development in PHPT.

The significance of estrogen receptors in acromegaly: Are they useful as predictors of prognosis and therapy regimen?

OBJECTIVE: In this study, we considered to assess the presence of estrogen receptors (ER) and the expression of estrogen receptor genes (ESR) in the surgical tissue samples of acromegaly patients and the control group patients with nonfunctioning adenoma and their association with disease activity. We also aimed to determine the significance of ER positivity in acromegaly patients and to find out whether it carries a potential to be used as a predictor of prognosis and therapy regimen in the future. DESIGN: This study was conducted on a total of 67 patients over 18 years of age. The study group consisted of 34 patients with acromegaly and 33 patients with nonfunctioning pituitary adenoma. The pre- and post-operative basal pituitary hormone levels and magnetic resonance images (MRI) of all patients, as well as their remission status of all acromegaly patients were evaluated. Immunohistochemical (IHC) staining procedures for ER-α were performed on surgical tissue samples. Real-time quantitative polymerase chain reaction (RT-qPCR) method was used to determine the levels of ESR1 and ESR2 gene expressions. RESULTS: We found that IHC staining for ER-α was positive in 31.3% and 45.5% of the patients with acromegaly and nonfunctioning adenoma respectively. There was no statistically significant difference of ER-α positivity, ER-α immunoreactivity score and ESR1/ESR2 gene expression levels among the study groups (p > .05). Nevertheless, the expression of ESR1 gene was found to be 0.26 times more, and the ESR2 gene to be 0.11 times less in the acromegaly group compared to those of the nonfunctioning adenoma group. Additionally, we detected the positivity of ER-α only in acromegaly patients who were in remission. An inverse association was found between the pre-operative insulin-like growth factor-1 (IGF-1) levels and the expressions of ESR1/ESR2 gene in acromegaly patients. So these results indicated that the high ESR1 and ESR2 gene expressions in acromegaly patients are associated to the decrease of pre-operative IGF-1 values. Also an inverse association was found between the pre-operative adenoma volume and ESR1 Ct values, means that increase in ESR1 gene expression is associated to the decrease of adenoma volume. CONCLUSIONS: The current results may suggest the use of these parameters as useful prognostic markers because all ER-positive acromegaly patients were in remission and the high ESR1 and ESR2 gene expressions in acromegaly patients is associated to the decrease of pre-operative IGF-1 values. Our results need to be supported by further studies.

Assessment of vestibular-evoked myogenic potentials and video head impulse test in type 2 diabetes mellitus patients with or without polyneuropathy.

This study aimed to compare cervical vestibular-evoked myogenic potentials (cVEMP), ocular vestibular-evoked myogenic potentials (oVEMP) and video head impulse test (vHIT) results between patients with type 2 diabetes mellitus (DM) or diabetic polyneuropathy (DPN) and healthy controls to determine vestibular end-organ pathologies. The participants in the present study consisted of three groups: the type 2 DM group (n = 33 patients), the DPN group (n = 33 patients), and the age- and sex-matched control group (n = 35). Cervical VEMP, oVEMP and vHIT were performed for each participant in the study and test results were compared between the groups. Peak-to-peak amplitudes of cVEMP (p13-n21) and oVEMP (n10-p15) were significantly lower in the DM and DPN groups than the control group. The values of vHIT were not statistically different between the groups. To our knowledge, the present study is the first report investigating oVEMP and cVEMP responses combined with vHIT findings in patients with DM and DPN. Vestibular end-organ pathologies can be determined via clinical vestibular diagnostic tools in spite of prominent vestibular symptoms in patients with type 2 DM as well as patients with DPN.

Effects of Vitamin D treatment on thyroid autoimmunity.

BACKGROUND: Vitamin D was shown to be related to autoimmune thyroid diseases (AITDs) in the previous studies. We aimed to investigate the relationship between Vitamin D and thyroid autoimmunity. MATERIALS AND METHODS: Eighty-two patients, diagnosed with AITD by the endocrinology outpatient clinic, were included in this prospective study. All of the patients had both AITD and Vitamin D deficiency, defined as serum values <20 ng/mL. They were randomly assigned into two groups. The first group included 46 patients and the second one included 36 patients. The first group was treated with Vitamin D for 1 month at 1000 IU/day. The second group served as the control group and was not treated with Vitamin D replacement. Serum thyroid-stimulating hormone, free T4 (fT4), thyroid peroxidase antibody (TPO-Ab), thyroglobulin antibody (TgAb), and Vitamin D levels were measured at the initiation of the study and again at 1 month in all patients. RESULTS: Two groups were similar with regard to age, sex, and type of thyroid disease. Whereas TPO-Ab (before; 278.3 ± 218.4 IU/ml and after; 267.9 ± 200.7 IU/ml) and TgAb (before; 331.9 ± 268.1 IU/ml and after; 275.4 ± 187.3 IU/ml) levels were significantly decreased by the Vitamin D replacement therapy in group 1 (P = 0.02, P = 0.03, respectively), the evaluated parameters in the control group did not significantly change (P = 0.869, P = 0.530, respectively). In addition, thyroid function tests did not significantly change with Vitamin D replacement in two groups. CONCLUSION: Vitamin D deficiency may contribute to the pathogenesis of AITDs. Since supplementation of the Vitamin D decreased thyroid antibody titers in this study in Vitamin D deficient subjects, in the future Vitamin D may become a part of AITDs' treatment, especially in those with Vitamin D insufficiency. Further clinical and experimental studies are required to understand the effect of Vitamin D on AITD.

May the neutrophil/lymphocyte ratio be a predictor in the differentiation of different thyroid disorders?

BACKGROUND: The neutrophil/lymphocyte ratio (NLR) is a simple index of systemic inflammatory response, and has been shown to be a prognostic indicator in some types of cancer. Inflammation has been implicated in the initiation and progression of thyroid cancer. The aim of this study was to examine the relationship of NLR with papillary thyroid cancer (PTC) and different benign thyroid pathologies like multinodular goiter (MNG) and lymphocytic thyroiditis (LT). MATERIALS AND METHODS: We retrospectively evaluated the neutrophil, lymphocyte counts and NLR calculated from these parameters of 232 patients with histologically confirmed as multinodular goiter (group MNG) (n=70), lymphocytic thyroiditis (group LT) (n=97), LT with PTC (group LT- PTC) (n=25) and PTC (group PTC) (n=40). The optimal cut-off value for NLR was determined. RESULTS: NLR level was significantly higher in groups LT-PTC and PTC as compared to groups MNG and LT (p<0.05). NLR of LT subgroups according to TSH levels were not different (p>0.05). When we grouped the patients as benign and malignant according to PTC presence, the optimum NLR cut-off point obtained from ROC analysis was 1.91 (sensitivity 89.0% and specificity 54.5%). CONCLUSIONS: Since NLR was significantly elevated in group LT-PTC and group PTC, NLR value may give an opinion as a potential marker in differentiation of benign and malign thyroid disorders. For this purpose a cut-off value of 1.91 for NLR may be accepted.

The effect of radioactive iodine treatment on 14C urea breath test results in patients with hyperthyroidism.

PURPOSE: Radioactive Iodine therapy (RAIT) plays a major role in the treatment of hyperthyroidism. In addition to the thyroid gland, significant amounts of radioactive iodine are maintained in the stomach. The aim of this study was to determine if RAIT has any effect on Helicobacter pylori infection, based on the C urea breath test (UBT). MATERIALS AND METHODS: The study included 85 patients with hyperthyroidism scheduled to undergo RAIT and 69 hyperthyroid subjects in whom methimazole treatment was planned. All subjects had pretreatment-positive UBT results, and the test was repeated on the first and third months after RAIT and methimazole treatment. RESULTS: After a mean RAIT dose of 15 mCi (range, 10-20 mCi), UBT became negative in 13 (15.3%) of 85 patients on the first month and 18 (21.2%) of 85 patients on the third month. All subjects treated with methimazole remained UBT positive on the first and third months of methimazole treatment (100%). Reduction in the number of UBT-positive patients on both the first and the third months after RAIT was statistically significant (P < 0.001). Distribution of hyperthyroidism etiologies and thyroid autoantibody levels in subjects with UBT that became negative and in subjects with UBT that remained positive were similar in the RAIT group (P > 0.05). Urea breath test negativity rates did not differ according to the radioiodine dose. CONCLUSIONS: Our findings indirectly showed that RAIT might have an antimicrobial effect on H. pylori. Clinical applications of this beneficial effect of RAIT on H. pylori should be further evaluated.

Visceral fat measurement by ultrasound as a non-invasive method - can it be useful in evaluating subclinical atherosclerosis in male patients with hypopituitarism and growth hormone deficiency?

INTRODUCTION: Growth hormone (GH) deficiency, either isolated or combined with other pituitary hormone deficiencies, is associated with increased mortality and abnormal body composition, particularly visceral adiposity. We aimed to investigate the effects of GH deficiency with or without sex steroid deficiencies on ultrasonographic visceral fat (VF) and cardiovascular risk markers in patients with hypopituitarism on conventional hormone replacement therapy. MATERIAL AND METHODS: Forty hypopituitarism patients (24 women, 16 men; mean age 48 ± 16.1 years) with GH deficiency and 15 age- and sex-matched healthy controls were included in this cross-sectional study. The patients were stable on conventional hormone replacement but they were not on GH therapy. Patients who had sex steroid replacement were classified as Group 1 (n = 19), and patients who did not use sex steroids were classified as Group 2 (n = 21). Anthropometric measurements were performed. VF in three regions, subcutaneous fat, and carotid intima-media thickness (CIMT) were measured. VF volume was calculated by using a formula. RESULTS: Visceral fat volume and mean CIMT were significantly higher in patients than healthy controls (p = 0.001 and 0.019 respectively). Homocysteine and hs-CRP were higher in patients (p < 0.05). In males, VF volume and VF thickness measured between abdominal muscle and splenic vein were significantly correlated with CIMT (r = 0.54, p = 0.047 and r = 0.66, p = 0.010 respectively). Furthermore, there was a strong positive correlation between VF thickness in pararenal region and homocysteine (r = 0.74, p = 0.001) in males. CONCLUSIONS: VF volume evaluated by ultrasound can be accepted as a cause of subclinical atherosclerosis in GH deficient hypopituitary patients, particularly males.

Is autoimmune thyroiditis a risk factor for early atherosclerosis in premenopausal women even if in euthyroid status?

Autoimmune thyroiditis (AIT) is a systemic disease. It is well-known that overt thyroid dysfunction is a cardiovascular risk factor. However, the influence of euthyroid status is unclear. The aim of this study was to evaluate the metabolic parameters and carotid intima-media thickness (CIMT) in euthyroid premenopausal women with AIT. Fourty-eight premenopausal women and 18 age-matched healthy controls attending the Endocrinology and Metabolism Clinic from 2008 to 2009 were enrolled to this cross-sectional study. Patients were divided into 2 groups according to TSH levels; patients in group 1 (n = 23) had TSH levels ≤ 2.5 µIU/mL and patients in group 2 had TSH levels > 2.5 µIU/mL (n = 25). All participants were evaluated by ultrasound for CIMT (mean of three segments in both carotid arteries) by the same experienced investigator. Fasting venous blood samples were collected to evaluate insulin resistance (HOMA-IR), TSH, FT4, plasma lipids, high-sensitive CRP (Hs-CRP), homocysteine, and fibrinogen. Carotid intima-media thickness was found to be significantly higher in patients than the controls (p < 0.001). However, there was no significant difference in average CIMT between group 1 and 2 (0.66 ± 0.08 vs 0.63 ± 0.09 mm). Anti-Tg levels were independently associated with CIMT in the patient group (p = 0.014). There were no significant correlations between serum TSH levels and BMI; waist circumference, serum lipids, and glucose levels. However, there was a positive significant correlation between TSH levels and blood pressure in the patients (for systolic blood pressure r = 0.466, p = 0.001, for diastolic blood pressure r = 0.372, p = 0.009). In the present study, it was shown that CIMT is increased in euthyroid premenopausal women with autoimmune thyroiditis compared to age-matched healthy controls.

Association between C-reactive protein, carotid intima-media thickness and P-wave dispersion in obese premenopausal women: an observational study.

OBJECTIVE: The aim of the present study was to evaluate P-wave dispersion (PWD) in obese women, and to investigate the relationship between P-wave measurements, high sensitive C-reactive protein (hsCRP), carotid intima-media thickness (CIMT) and echocardiographic findings. METHODS: Forty-four patients with obese premenopausal women and 30 females with normal weight were enrolled this cross sectional, observational study. Results of anthropometric measurements, laboratory assays, electrocardiographic and echocardiographic findings were recorded for each participant. Student t, Mann-Whitney U and Pearson Chi-square tests, and Spearman correlation analysis were used for statistical analysis. Multiple regression analysis was used to identify independent factors associated with PWD development. RESULTS: The obese group had significantly higher values for PWD (41.8 ± 11.8 ms vs. 28.5 ± 9.3ms; p<0.001) as well as for P max (105.2 ± 14.3 ms vs. 89.0 ± 13.3 ms; p<0.001). Correlation analyses revealed the presence of a positive correlation between PWD and each of insulin, systolic blood pressure, diastolic blood pressure, hsCRP, CIMT, left atrial diameter (LAD), waist circumference, waist to hip ratio and body mass index in obese participants. The only significant association that was observed on multiple linear regression analysis, after adjustments for confounding risk factors, was between LAD and PWD (ß=4.290, 95% CI:1.870-9.720, p=0.032). CONCLUSION: We found that increased PWD values in obese patients are correlated positively with hsCRP, CIMT and abdominal obesity. However, independent and significant association was found only between LAD and PWD.

Clinical and radiological findings in macroprolactinemia.

Hyperprolactinemia is the most common abnormality of the hypothalamic-pituitary axis. The aim of this study was to investigate the clinical and radiological features of patients with macroprolactinemia. The study population consisted of patients with elevated serum prolactin (PRL) concentrations who presented to our Endocrinology outpatient clinic. Detection of macroprolactin (macroPRL) was performed using the polyethylene glycol precipitation method. Patients in which macroPRL made up more than 60% of total PRL levels were stratified into the macroPRL group, while the remaining patients were placed in the monomeric prolactin (monoPRL) group. A total of 337 patients were enrolled with a mean age of 33.8 ± 10.8 (16-66) years and a male/female ratio of 29/308. Eighty-eight of the patients (26.1%) had an elevated macroPRL level. The mean age in the monoPRL group was higher than in the macroPRL group (35.0 ± 10.1 vs. 30.7 ± 9.8, P = 0.016). The mean PRL levels (ng/ml) in the macroPRL and monoPRL groups were similar (168.0 ± 347.0 vs. 238.8 ± 584.9, P = 0.239). Frequency of amenorrhea, infertility, irregular menses, gynecomastia, and erectile dysfunction were also similar in both groups. More patients in the macroPRL group were asymptomatic compared to the monoPRL group (30.2 vs. 12.0%, P = 0.006). Compared to the macroPRL group, the monoPRL group had a higher frequency of galactorrhea (39.2 vs. 57.1%, P = 0.04) and abnormal magnetic resonance imaging findings (65.3 vs. 81.1%, P = 0.02). Elevated macroPRL levels should be considered a pathological biochemical variant of hyperprolactinemia that may present with any of the conventional symptoms and radiological findings generally associated with elevated PRL levels.

Gestational diabetes and subclinical inflammation: evaluation of first year postpartum outcomes.

AIM: The aim of this study was to evaluate the relationship between sublinical inflammation and glycemic status in patients with gestational diabetes mellitus (GDM). METHODS: Sixty-one patients with GDM and 40 healthy pregnant women were included in the study. Fasting blood glucose (FBG), insulin, high sensitivity C-reactive protein (hsCRP), lipid parameters and carotid artery intima-media thickness (CIMT) were measured. Fifty-five of the patients with GDM returned for a follow-up visit scheduled at 1-year post-partum. These patients were subjected to 75 g oral glucose tolerance test (OGTT) followed by an evaluation of metabolic and subclinical inflammatory parameters were evaluated. RESULTS: The mean FBG, insulin, homeostasis model assessment insulin resistance (HOMA-IR), triglyceride (TG), hsCRP levels and CIMT in the women with GDM were significantly higher than those in the control group. C-reactive protein and CIMT were positively correlated with insulin, HOMA-IR, glucose value at the time of the OGTT 50, prepregnancy body mass index, TG and FBG. Multivariate logistic regression analysis on patients with sustained hyperglycemia one-year postpartum revealed elevated hsCRP levels to be independent risk factors for the development of dysglycemia. CONCLUSIONS: Elevated hsCRP levels could be predictors of progression to T2DM later in life in patients with GDM.

Comparison of the prevalence and sonographic features of thyroid nodules accompanying autoimmune thyroid diseases.

INTRODUCTION: The coexistence of thyroid nodules and autoimmune thyroid disease (ATD) has been widely reported. The aim of our study was to retrospectively evaluate the prevalence and sonographic features of malignancy of thyroid nodules in ATD patients. MATERIAL AND METHODS: We retrospectively analysed data from 500 patients with ATD in our hospital. We recorded ultrasonographic, histopathological and laboratory features of these patients. Thyroid ultrasonography was performed on all the patients, as well as fine needle aspiration biopsy (FNAB) of the thyroid nodule, when required. Patients underwent operations depending on the result of the FNAB. RESULTS: Of the 500 with ATD (400 female and 100 male; mean age = 42.4 years), 300 (60%) had Hashimoto's thyroiditis (HT) and 200 (40%) presented with Graves' disease (GD). The frequency of thyroid nodules was statistically significantly higher in those with GD (37.8%) than in those with HT (24.3%) (p 〈 0.001). One hundred and forty-nine nodules underwent FNAB (37.8%, 76 out of 200 had GD and 24.3%; 73 out of 300 had HT). The results of the cytological examination were: non-diagnostic cytology, benign, malignant and indeterminate in 19.4%, 73.8%, 2% and 4.5% of the nodules, respectively. When 55 GD and 32 HT patients, on whom total thyroidectomy had been carried out, were evaluated, the incidence of thyroid carcinoma was similar between patients with GD (n = 3, 5.5%) and HT (n = 2, 6.3%) (p 〉 0.05). CONCLUSIONS: We observed that the prevalence of thyroid nodules in patients with GD was higher than patients with HT. However, in general, the characteristics of the nodules and FNAB results were similar in both ATDs.