Evaluation of miR-526b-3p, miR-1179, miR-3529-3p, miR-5011-5p as potential diagnostic biomarkers in isolated cervical dystonia.

BACKGROUND: Cervical dystonia (CD) also named spasmodic torticollis is the most common type of focal dystonias and characterized by abnormal head, neck, and shoulder movements due to involuntary muscular spasm. Although CD is mostly idiopathic, to date, several genes have been associated with CD. However, to the best of our knowledge, microRNAs (miRNAs) which are interacted with CD-associated genes have been not evaluated yet. miRNAs are regulatory small non-coding RNAs and are suggested as potential biomarkers for many diseases through their stability in clinical samples. Therefore, we aimed to assess the expression levels of miRNAs (miR-526b-3p, miR-1179, miR-3529-3p, miR-5011-5p) which are targeted the CD-associated genes, and evaluate their performance as diagnostic biomarkers. METHODS: Peripheral blood samples were obtained from 30 patients with isolated CD (ICD) and 25 healthy controls. The expression levels of miR-526b-3p, miR-1179, miR-3529-3p, and miR-5011-5p were analyzed via quantitative real-time PCR (qRT-PCR), and receiver operating characteristic (ROC) curves were generated to evaluate the diagnostic values. RESULTS: miR-526b-3p, miR-1179, and miR-3529-3p were significantly up-regulated while miR-5011-5p was significantly down-regulated in ICD patients compared to healthy controls. ROC analysis revealed that all miRNAs, especially miR-1179 and miR-3529-3p were statistically significant with the area under the curve (AUC) of 0.905 and 0.933, respectively. CONCLUSION: Altered expression levels of aforementioned miRNAs may be associated with CD pathogenesis. Our findings suggest using these four miRNAs as remarkable biomarkers in the diagnosis of ICD.

The effect of helicobacter pylori eradication on atrophic gastritis and intestinal metaplasia : a retrospective single center research.

BACKGROUND AND STUDY AIMS: Gastric cancer (GC) is one of the major causes of cancer-related deaths worldwide. Helicobacter pylori (Hp) plays an important role in gastric carcinogenesis by inducing precancerous changes such as atrophic gastritis (AG) and intestinal metaplasia (IM). In our study, we aim to compare the grade of AG and IM before and after Hp eradication in patients who underwent esophagogastroduodenoscopy (EGD) in our center. PATIENTS AND METHODS: The data of 40.060 patients who underwent EGD for various reasons in our Endoscopy Unit between June 2011 and November 2017 were retrospectively evaluated. The grade of AG and IM before and after Hp eradication of patients meeting the study criteria were compared with each other. In addition, these findings were compared using OLGA and OLGIM staging systems. RESULTS: A total of 175 patients, 89 (50.9%) women and 86 (49.1%) men, were included in the study. The mean age was 55±12 years. The mean time between two EGD examinations was 38±14 months. Significant improvement was observed in the grade of AG on corpus and antrum after Hp eradication (P=0.000, P=0.008). In the corpus and antrum, the grade of IM was regressed but this was not significant (P=0.80 and P=0.370 respectively). There was a decrease in OLGA stages after Hp eradication (P=0.000). There was also a reduction in the OLGIM stages, but this was not significant(P=0.341). CONCLUSION: Our study demonstrates that Hp eradication may reduce the risk of developing GC by providing an improvement in AG and IM which are precancerous changes in GC.

EFFECT OF INSULIN RESISTANCE ON THE OCCURRENCE OF PREGNANCY IN WOMEN TREATED EMPIRICALLY FOR UNEXPLAINED INFERTILITY.

CONTEXT: The detrimental effects of hyperinsulinemia on human ovaries during follicular development process have been shown in various studies, particularly in women with polycystic ovary syndrome. To our knowledge there is no study regarding the effect of insulin resistance (IR) on the intrauterine insemination (IUI) success in women with unexplained infertility (UEI). OBJECTIVE: To evaluate the effects of IR on the occurrence of pregnancy among infertile women undergoing ovulation induction (OI) with IUI for UEI. DESIGN: Prospective cohort study. SUBJECTS AND METHODS: 173 patients who met the criteria for UEI and under the age of 35 were included in this study. All women underwent OI with IUI and, subsequently, they were divided into two groups based on the presence of pregnancy. Data reviewed for analysis were demographic, clinical, and laboratory features. RESULTS: There were 37 (21.4%) cycles with pregnancy and 136 (78.6%) cycles without pregnancy. Median infertility duration was significantly lower in the pregnant group when compared with non-pregnants (p=0.018). The mean number of previous cycles per patient was also lower in this group (p=0.028). No significant differences were found between the groups in terms of other variables. Levels of insulin, fasting glucose and HOMA-IR were also similar between the two groups. CONCLUSIONS: IR calculated by using HOMA-IR index has no positive or negative effect on the occurrence of pregnancy in women undergoing OI therapy with IUI for UEI.

The impact of the multifocality and subtypes of papillary thyroid carcinoma on central compartment lymph node metastasis.

OBJECTIVE: Papillary thyroid carcinoma (PTC) may often appear as multifocal disease. Few studies demonstrated a higher rate of central compartment lymph node metastasis (CCLNM) in multifocal PTC patients. Therefore, the effect of different histological subtypes of multifocal PTC on CCLNM is another subject for further examination. The aim of the present study is to evaluate the rate of central lymph node positivity in multifocal PTC as compared to unifocal disease, and to identify the role of different histologic subtypes of PTC on central neck lymph node positivity. PATIENTS AND METHODS: Patients with PTC who underwent total thyroidectomy (TT) + central cervical lymph node dissection (CCLND) at authors' institution between January 2012 and June 2016 were included (n=274). Independent Samples t-test, Mann-Whitney U test and Chi-square tests were used to determine univariate associations, and multivariate analysis was conducted by logistic regression. RESULTS: The rate of CCLND positivity in multifocal PTC is higher than unifocal tumors and the difference is significant (p < 0.05). The univariate analysis demonstrated significant relation with male sex, lymphovascular invasion and size of dominant nodule > 10 mm regarding of CCLND positivity in multifocal PTC patients. The comparison between solitary and mixed histologic subtype of multifocal PTC is also significant (p < 0.05). CONCLUSIONS: Multifocality is an important risk factor for CCLNM. Male sex, dominant tumor size >10 mm and mixed histological subtype in multifocal PTC may play an important role in CCLND positivity.

The risk of hypoparathyroidism after central compartment lymph node dissection in the surgical treatment of pT1, N0 thyroid papillary carcinoma.

OBJECTIVE: The role of central compartment lymph node dissection (CCLND) in the treatment of papillary thyroid carcinoma (PTC) is still controversial. The benefits of CCLND should be weighed against its potential risks. We aim to evaluate the positivity of central lymph nodes in pT1, N0 PTC and to establish the complication rates of total thyroidectomy (TT)+CCLND. PATIENTS AND METHODS: This is a retrospective study on prospectively collected data over a 45-month period. A total of 329 patients were included. Total thyroidectomy was performed in 130 (39.5%) of these patients due to benign thyroid pathologies, and 199 (60.5%) pT1, N0 PTC patients had TT+CCLND. Our TT technique was applied in the same way in both groups. Central lymph node positivity, the number of lymph nodes removed during CCLND and the operative complications were evaluated. T-test and chi-square analysis were conducted in independent groups for statistical evaluation. RESULTS: The rate of central lymph node positivity in TT+CCLND group was 38%. The average number of lymph nodes removed by CCLND is 10.2 (1-36). Complication rates between TT and TT+CCLND groups were statistically significant (3.8% vs. 11.1%, respectively) (p<0.05). The difference was found to be particularly more pronounced for transient hypocalcemia. Although there was no significant relation between the number of lymph nodes removed during CCLND and the number of parathyroid glands detected in the pathology specimens (p>0.05), the relation between the development of symptomatic hypocalcemia and the number of the parathyroid glands removed during surgery was significant (p <0.05). CONCLUSIONS: Central compartment lymph node metastasis in PTC is common. CCLND may increase the rate of transient hypocalcemia.

Volatile compound profiling of Turkish Divle Cave cheese during production and ripening.

The formation of volatile compounds in Turkish Divle Cave cheese produced in 3 different dairy farms was determined during production and ripening, revealing 110 compounds including acids, alcohols, ketones, esters, and terpenes. The presence and concentration of these volatile compounds varied between specific phases of the production and the 120-d ripening process. Smaller differences were also detected between cheeses produced at different farms. Carboxylic acids were established as a major class at the end of ripening. The relative amounts of acids and ketones increased until d 90 of ripening, whereas alcohols increased for the first 30d and tailed off during the remaining part of the ripening process. The level of esters increased gradually until the end of ripening. Butanoic, acetic, and valeric acids, 2-butanol, 2-butanone, 2-heptanone, ethyl butanoate, α-pinene, and toluene were the most abundant compounds, likely contributing to the characteristic aroma of this traditional cheese.

Role of milk protein-based products in some quality attributes of goat milk yogurt.

Goat milk yogurts were manufactured with the fortification of 2% (wt/vol) skim goat milk powder (SGMP), sodium caseinate (NaCn), whey protein concentrate (WPC), whey protein isolate (WPI), or yogurt texture improver (YTI). Yogurts were characterized based on compositional, microbiological, and textural properties; volatile flavor components (with gas chromatography); and sensory analyses during storage (21d at 5 °C). Compared with goat milk yogurt made by using SGMP, the other goat milk yogurt variants had higher protein content and lower acidity values. Goat milk yogurts with NaCn and WPC, in particular, had better physical characteristics. Using WPI caused the hardest structure in yogurt, leading to higher syneresis values. Acetaldehyde and ethanol formation increased with the incorporation of WPI, WPC, or YTI to yogurt milk. The tyrosine value especially was higher in the samples with NaCn and YTI than in the samples with WPC and WPI. Counts of Streptococcus thermophilus were higher than the counts of Lactobacillus delbrueckii ssp. bulgaricus, possibly due to a stimulatory effect of milk protein-based ingredients other than SGMP on the growth of S. thermophilus. Yogurt with NaCn was the best accepted among the yogurts. For the parameters used, milk protein-based products such as NaCn or WPC have promising features as suitable ingredients for goat milk yogurt manufacture.

Conservative surgical management of multiple myometrial abscesses; an unusual case with review of the literature.

Myometrial abscess, especially with multiple foci, is quite rare and previous literature prevalently discusses unique locus of intramyometrial abscesses, usually treated with hysterectomy accompanied with or without bilateral salpingo-oophorectomy. The presented case, to the authors' knowledge, is the first multiple myometrial abscess case treated with conservative surgical approach.

Melatonin in aging women.

Melatonin is a neurohormone secreted mainly by the pineal gland that controls circadian rhythm, which is primarily regulated by light. Although melatonin levels are known to be altered in individuals with sleep disorders, melatonin also has modulatory effects on other body systems, including the skeletal and immune systems. In addition, melatonin has been shown to interfere with carbohydrate and lipid metabolism and to have significant antioxidant effects, both directly and via its metabolites. Melatonin levels vary throughout human life and are known to decrease with age but the effects of declining melatonin levels are poorly understood. In women, this age-related decrease in melatonin levels coincides with the menopause. This review aims to summarize the impact of altered melatonin levels in aging women and the outcomes of exogenous replacement therapies.

Knowledge, attitudes and behaviors of physicians towards thyroid disorders and iodine requirements in pregnancy.

PURPOSE: Thyroid disorders including iodine deficiency during pregnancy are important health problems worldwide. However, considering real life, assessment of knowledge, attitudes, and practice of physicians is lacking. We aim to evaluate knowledge, attitudes and behaviors of physicians towards thyroid disorders and requirements of iodine during pregnancy on a nationwide basis. METHODS: Clinicians from different medical disciplines most likely to encounter pregnant women in daily practice (i.e., obstetricians, endocrinologists, and family physicians) were included. Family physicians were selected from primary care centers; endocrinologists and gynecologists were selected from state hospitals. Randomly selected 322 physicians from seven geographical regions of Turkey were included. Subjects filled a questionnaire which consisted of three sections about knowledge, attitudes and behaviors towards thyroid disorders and iodine requirements during pregnancy. RESULTS: Physicians had insufficient and/or erroneous knowledge about thyroid disorders during pregnancy. 73.1 % of endocrinologists, 32.7 % of family physicians, and 17.8 % of obstetricians knew the correct level of TSH during pregnancy (p < 0.001). 67.1 % of physicians thought it is unnecessary to offer iodine supplementation to pregnant women. Endocrinologists achieved the highest scores in each section, and also had the highest total scores (p < 0.001). Family physicians achieved higher scores than obstetricians. CONCLUSIONS: Physicians who encounter pregnant women in Turkey do not have sufficient information about management of thyroid disorders and providing iodine support during pregnancy and lactation.

The prevalence of benign breast diseases in patients with nodular goiter and Hashimoto's thyroiditis.

PURPOSE: The evidence regarding association between thyroid disorders and benign and malignant breast diseases is increasing. The studies exploring the relationship between thyroid and breast diseases usually have focused on thyroid autoimmunity and functions in patients with breast pathologies. In this study, we aimed to reveal the frequency of benign breast conditions in patients with nodular thyroid disease (NTD) and Hashimoto's thyroiditis (HT). METHODS: Seventy-one women with NTD, ninety-five women with HT and seventy-two healthy people as a control group were included in the study. Serum thyroid-stimulating hormone, free triiodothyronine, free thyroxine, and thyroid peroxidase autoantibody levels were measured, and thyroid and breast ultrasonography were performed by a single operator in order to determine thyroid and breast pathology. RESULTS: Benign breast diseases were detected in 54.9% of patients with NTD, in 47.4% of those with HT, and 29.2% of control group in the study (p < 0.01 for nodular and Hashimoto groups versus control group). Simple cyst was found to be the most frequent pathology among benign breast diseases; fibrocystic changes, mixed lesions, benign solid mass, ductal ectasia, and complex cyst followed it. No significant relation was found regarding thyroid function and autoimmunity in patients diagnosed with benign breast disease (p > 0.05). CONCLUSIONS: The results of our study support the association between benign breast diseases and thyroid diseases. An important implication of this finding may be demonstration of the necessity of scanning for potential breast pathology in women with nodular or autoimmune thyroid disease in clinical practice.

Maternal and fetal blood levels of S100 and ischaemia modified albumin in term intrauterine growth restricted fetuses with abnormal umbilical artery Doppler values.

The purpose of this study was to investigate whether levels of fetal hypoxia markers, S100 and ischaemia modified albumin (IMA) change in cases of intrauterine growth restriction (IUGR). This case-control study included 15 intrauterine growth restricted fetuses and 20 age-matched controls. During delivery of the fetuses, cord blood and maternal blood S100 and IMA levels were studied. The fetal weight and umbilical cord pH values of IUGR fetuses were significantly lower than the control group. The mean maternal and umbilical cord blood values of S100 and IMA were similar in the two groups. IMA levels in cord blood of the IUGR group were significantly higher than maternal levels, whereas umbilical and maternal levels of IMA did not differ among control cases. In cases without brain sparing effect in Doppler ultrasonography, umbilical cord S100 and IMA levels do not change significantly in IUGR when compared with appropriate-for-gestational-age (AGA) fetuses.

Iodine intake is still inadequate among pregnant women eight years after mandatory iodination of salt in Turkey.

BACKGROUND: A recent study showed first sign of reduction in goiter prevalence and elimination of iodine deficiency state among school-age children in Turkey after a decade of mandatory iodination of table salt. However, iodine status among pregnant women is a still debated issue in our country. AIM: To investigate iodine status, iodized salt consumption rate, and goiter prevalence in 1st trimester pregnant women 8 yr after the mandatory iodination. MATERIAL/ SUBJECTS AND METHODS: One hundred and forty-one 1sttrimester pregnant women who had been followed-up between January and October 2006 in the obstetric outpatient clinics in Turkey were included. Besides a physical examination, subjects underwent laboratory investigations for free T(3), free T(4), and urinary iodine concentration (UIC). All subjects completed a questionnaire regarding sociodemographic parameters, use of iodized salt, and pregnancy history. Goiter status was revealed by a palpation method according to World Health Organization (WHO) guidelines. RESULTS: In this study, we found that the median UIC of pregnant women was 149.7 microg/l (range 20.9-275.1 microg/l). Almost half of the subjects were below the WHO, United Nations Children's Fund, and International Council for the Control of Iodine Deficiency Disorders lower median reference limits of 150 microg/l. Total goiter prevalence was 24.8%, of which 9.2% were visible goiters. Among the study patients, 2.1% had subclinical hypothyroidism, and 0.7% had overt hypothyroidism. The rate for iodized salt use among the pregnant women was 95%. CONCLUSION: Our study revealed that iodine deficiency still remains a serious problem for pregnant women. Based on our results, antenatal follow-up protocols in the primary care setting in Turkey must include iodine supplementation.

Systolic pulmonary artery pressure and echocardiographic measurements in patients with euthyroid Hashimoto's thyroiditis.

BACKGROUND: The aim of this study was to investigate systolic pulmonary artery pressure (SPAP) and echocardiographic findings in patients with euthyroid Hashimoto's thyroiditis (HT). METHODS: Thirty (8 male, 22 female, mean age 47.4+/-10.5 yr) consecutive patients with euthyroid HT and 30 (9 male, 21 female, mean age 46.4+/-10.7 yr) healthy controls were included in the study. Transthoracic echocardiography was performed for all patients and levels of thyroid hormones, thyroid autoantibodies, glucose, insulin, urea, and creatinine were compared. RESULTS: There were no significant differences in sex, age, body mass index, serum free T4, serum TSH, lipid profiles between patients and controls. Mean SPAP in patients with euthyroid HT were significantly higher than in controls (31.6+/-5.0 vs 25.6+/-4.5 mmHg, p=0.005). Late diastolic transmitral velocity and isovolumic relaxation time were also significantly higher in patients in comparison to controls. In addition, euthyroid HT patients with tricuspid or mitral regurgitation had a higher grade. Correlation between SPAP and antithyroid antibodies and TSH, however, was not significant in this population. CONCLUSIONS: Pulmonary arterial pressure is higher in patients with euthyroid HT. There may be a relationship between elevated pulmonary arterial pressure and autoimmune thyroid disease independent from thyroid function status. However, further investigations are needed to determine the exact mechanism of association between autoimmune thyroid diseases and pulmonary hypertension.

Cytotoxic T lymphocyte-associated molecule-4 polymorphism in Turkish patients with Hashimoto thyroiditis.

We previously shown that in a Turkish population, the A/G polymorphism in exon 1 of the cytotoxic T cell lymphocyte-associated molecule-4 (CTLA-4) gene is associated with Graves' disease, and that the G allele may contribute to susceptibility for developing Graves' disease. This polymorphism was identified in 197 patients with Hashimoto thyroiditis (HT) (126 women, 71 men; aged, 42.92 +/- 13.4 years) and 98 healthy individuals (56 women, 21 men; aged, 42.27 +/- 13.43 years) in Turkish population. Polymorphisms were analysed using a polymerase chain reaction-restriction fragment length polymorphism method. Frequency of the A/G genotypes was not significantly different in patients with HT when compared with controls in both sexes (P > 0.05). There was no statistical difference in age, sex, cigarette smoking, initial serum thyroid hormone levels, initial goiter size and thyroid autoantibodies among the patients with the three different genotypes (G/G, A/G and A/A). We concluded that A/G polymorphism of CTLA molecule is linked to occurrence of Graves' disease bu not to HT in the Turkish population.

Prevalence and clinical significance of antineutrophil cytoplasmic antibody in Graves' patients treated with propylthiouracil.

Development of antineutrophil cytoplasmic antibody (ANCA) during therapy with propylthiouracil (PTU) is not uncommon and PTU-induced ANCA-positive vasculitis is also reported. The aim of this study was to assess the presence and clinical significance of ANCA positivity in Graves' patients treated with PTU. Newly diagnosed Graves' disease patients (prospective group, n = 58) were evaluated before and during therapy with PTU to investigate the development of ANCA positivity. ANCA positivity is also investigated in previously diagnosed Graves' patients who had already been receiving PTU treatment (cross-sectional group, n = 51). Comparisons with Hashimoto thyroiditis (n = 55) and toxic nodular goitre (n = 20) patients, and healthy control subjects (n = 20) were carried out to define the possible influence of hyperthyroidism and/or thyroid autoimmunity on ANCA positivity. At baseline evaluation, ANCA was negative in all newly diagnosed Graves' patients. Only 28 of the 58 patients in prospective group completed 2 years of follow-up which occurred at 3-month intervals. ANCA positivity was detected 32.1% (n = 9) in a mean period of 11.7 +/- 6.1 months in prospective group. Only two (3.9%) patients in a cross-sectional group had ANCA positivity in a mean treatment period of 7.6 +/- 4.6 months. None of the patients with ANCA positivity developed symptoms and signs related to vasculitis. None of the patients with Hashimoto thyroiditis and toxic nodular goitre, and healthy control subjects had ANCA positivity. PTU therapy is associated with asymptomatic production of ANCA in a time-dependent manner, which mostly disappears after discontinuation of therapy. Hyperthyroidism or autoimmunity per se does not appear to have effect on development of ANCA positivity.

Unresectable huge sternal and mediastinal metastasis of follicular thyroid carcinoma; radiotherapy as first-line and palliative therapy.

Distant metastases as initial manifestation of follicular thyroid carcinoma is rare. We report a case of an unusual initial presentation of follicular thyroid carcinoma on follow-up. A 52- year-old woman presented with a 12-month history of progressively enlarging mass in the anterior chest wall. The mass was fixed to the chest wall, measuring 12 x 10 cm in diameter. Computed tomography demonstrated a lobulated soft-tissue mass (17 x 11 x 6 cm) destructing sternum and extending into the anterior mediastinum. There was no lung metastasis. Invasion of tumor to the ascending aorta, superior vena cava, and right atrium could not be excluded. Multiple lymph nodes were observed in the supraclavicular regions. Ultrasonography of the thyroid gland showed 46 x 37 mm nodule in the left lobe with milimetric gross calcifications and cystic-necrotic areas. Hyperthyroidism was detected. Biopsy from this nodule and the sternal mass revealed typical histology of follicular carcinoma. She was considered inoperable. Since there was huge tumor burden and iodinated contrast exposure for several times during evaluation, we decided to treat the patient with external beam radiotherapy (EBRT) rather than radioiodine as first-line therapy. After a course of conventional radiation with 50 Gy in 25 fractions over 4 weeks, encompassing the thyroid bed and the gross disease, tumor regressed remarkably in 6 months. In conclusion, when surgical resection is not possible, EBRT may be used for palliative purpose to obtain local control for extensive disease as first-line therapy. The indications of EBRT for differentiated thyroid cancer still remain poorly defined.

Towards drugs targeting multiple proteins in a systems biology approach.

Protein-protein interactions are increasingly becoming drug targets. This is understandable, since they are crucial at all levels of cellular expression and growth. In practice, targeting specific disease-related interactions has proven difficult, with success varying with specific complexes. Here, we take a Systems Biology approach to targeting protein-protein interactions. Below, we first briefly review drug discovery targeted at protein-protein interactions; we classify protein-protein complexes with respect to their types of interactions and their roles in cellular function and as being targets in drug design; we describe the properties of the interfaces as related to drug design, focusing on hot spots and surface cavities; and finally, in particular, we cast the interactions into the cellular network system, highlighting the challenge of partially targeting multiple interactions in the networks as compared to hitting a specific protein-protein interaction target. The challenge we now face is how to pick the targets and how to improve the efficiency of designed partially-specific multi-target drugs that would block parallel pathways in the network.

Significance of the RET proto-oncogene polymorphisms in Turkish sporadic medullary thyroid carcinoma patients.

Several single nucleotide polymorphisms (SNP) of the RET gene have been identified in medullary thyroid carcinoma (MTC) patients as well as in the general population. However, the relevance of SNP for MTC patients is still controversial, whether these allelic variants play other interacting, predisposing or modifying roles in clinical behavior of MTC. The aim of this work is to elaborate allelic frequencies of the RET proto-oncogene polymorphisms in Turkish sporadic MTC patients and to demonstrate if there is an association between SNP and the clinical disease features, specifically the age at onset of MTC and lymph node involvement at diagnosis. We analyzed the allelic frequencies of SNP of the exon 11, 13, 14 and 15 of the RET proto-oncogene in blood samples from 50 sporadic MTC patients, using the polymerase chain reaction methodology followed by DNA sequencing. The observed allelic frequencies were 24% for G691S polymorphism in exon 11, 29% for L769L polymorphism in exon 13, 5% for S836S polymorphism in exon 14, and 26% for S904S polymorphism in exon 15. These frequencies are similar to those reported in other countries. We did not observe any significant association of all four SNP with the age at onset of MTC. Our results indicate a possible association between the presence of lymph node involvement at the time of diagnosis (extent of disease) and L769L or S836S polymorphism. However, it is not possible to draw definitive conclusions that these two polymorphisms play a significant role in clinical behavior of MTC. Further studies are needed to evaluate the role of this polymorphism in the clinical behavior of MTC.

Long-term effects of elevated gastrin levels on calcitonin secretion.

Gastrin and pentagastrin stimulate thyroid C cells and elevate serum calcitonin levels. Gastrin levels may be elevated when histamine-2 receptor blockers (H2RB) and/or proton pump inhibitors (PPI) are used, or in patients with pernicious anemia (PA). This study was designed to investigate the long-term effects of elevated gastrin levels on serum calcitonin levels. We conducted a pentagastrin stimulation test to evaluate C cell reserves in patients who had been using PPI and/or H2RB for an extended period, as well as in patients with PA. We compared the results with a healthy control group of similar age and sex. A total of 40 controls (26 women, 24 men) and 25 patients (15 women, 10 men) using H2RB and/or PPI, and 37 patients (24 women, 13 men) with PA were enrolled. The groups were similar in terms of mean age and sex distribution. Mean fasting gastrin levels, and mean baseline and pentagastrin-stimulated calcitonin levels were significantly higher in the H2RB+PPI and PA groups than in controls. No significant differences were observed between the H2RB+PPI and PA groups. There was no correlation between gastrin and calcitonin levels. However, mean calcitonin levels were significantly higher in subjects with high baseline gastrin levels than in controls. The prevalence of autoimmune thyroid disease was 32% in the PA group. Patients with PA and thyroiditis had significantly higher baseline gastrin levels than patients with PA only (p<0.01). PA with autoimmune thyroid disease had also significantly higher baseline and pentagastrin-stimulated calcitonin levels than did PA patients without autoimmune thyroid disease. In conclusion, chronic elevated gastrin levels led to elevated calcitonin levels. Further histopathological studies showing C cell hyperplasia are needed to confirm the mechanism of this relationship.