Anterior pituitary hormone dysfunction among individuals with complete heart block requiring pacemaker.

Background & objectives Neuronal hypoxia associated with conditions like traumatic brain injury and cardiac tachyarrhythmia has been implicated in causing hypopituitarism. Individuals with complete heart block (CHB) may be predisposed to develop anterior pituitary hormone dysfunction in the long term. The objective of this study was to investigate anterior pituitary hormone functions in individuals after CHB. Methods This prospective cohort study included 30 individuals (21 men and 9 women) with CHB requiring pacemaker implantation, who were evaluated at admission and then at a mean follow up of 12.4 ± 2.2 months to look for development of any degree of hypopituitarism. In addition to the measurement of hormones like follicle-stimulating hormone (FSH), luteinising hormone (LH), thyroid stimulating hormone (TSH), total tetra iodothyronines (TT4), free tetraiodothyronines (FT4), cortisol, insulin-like growth factor-1 (IGF-1), testosterone and estradiol, a fixed-dose glucagon stimulation test (GST) was performed to assess growth hormone (GH) and adrenocorticotrophic hormone (ACTH) axis. Results The mean age of the participants was 64.9 ± 11.3 yr. At follow up evaluation, 17 (56.7%) had low serum IGF-1, and among them, seven (23%) had growth hormone deficiency (GHD) (peak GH <1.0 ng/ml after GST). Six participants (20%) had ACTH deficiency (peak cortisol <9 ug/dl after GST) and one had TSH deficiency. None had prolactin (PRL) or gonadotropin deficiency. Overall, hormone deficiencies were observed in nine patients (30%). Interpretation & conclusions This pilot study detected loss of anterior pituitary hormones in a significant number of individuals of CHB at 12 months follow up. Unrecognised hypopituitarism may have resulted in significant morbidity and mortality in these individuals.

High prevalence of coronary artery calcification and increased risk for coronary artery disease in patients with Sheehan syndrome-A case-control study.

OBJECTIVE: Patients with Sheehan syndrome (SS) are predisposed to coronary artery disease (CAD) due to risk factors like abdominal obesity, dyslipidemia and chronic inflammation. In addition to estimate CAD risk enhancers like high sensitive C reactive protein (hsCRP), apolipoprotein B (ApoB) and lipoprotein A [Lp(a)], this study applies Framingham risk score (FRS) and coronary artery calcium (CAC) score to compute a 10-year probability of cardiovascular (CV) events in SS patients. DESIGN: Case-control study Sixty-three SS patients, on a stable hormonal replacement treatment except for growth hormone and 65 age, body mass index and parity-matched controls. MEASUREMENTS: Measurement of serum hsCRP, ApoB and Lp(a) and estimation of CAC with 16-row multislice computed tomography scanner. RESULTS: The concentrations of hsCRP, ApoB and Lp(a) were significantly higher in SS patients than in controls (p < .01). After calculating FRS, 95.2% of SS patients were classified as low risk, 4.8% as intermediate risk and all controls were classified as low risk for probable CV events. CAC was detected in 50.7% SS patients and 7.6% controls (p = .006). According to the CAC score, 26.9% SS patients were classified as at risk (CAC > 10) for incident CV events as against 1.6% controls. The mean Multi-Ethnic Study of Atherosclerosis (MESA) score was significantly higher in patients with SS than controls. CAC corelated significantly with fasting blood glucose (r = .316), ApoB (r = .549), LP(a) (r = .310) and FRS (r = .294). CONCLUSION: Significant number of asymptomatic SS patients have high coronary artery calcium score and are classified at risk for CAD.

Effect Modification of LHCGR Gene Variant (rs2293275) on Clinico-Biochemical Profile, and Levels of Luteinizing Hormone in Polycystic Ovary Syndrome Patients.

 Polycystic ovary syndrome (PCOS) is a common multifaceted endocrine disorder among reproductive-aged women. Deranged luteinizing hormone levels and associated downstream signaling cascade mediated by its receptor luteinizing hormone chorionic gonadotropin receptor (LHCGR) are pivotal in the etiopathogenesis of PCOS. Genetic variations in the LHCGR have been associated with PCOS risk. However, the results are mixed and inconclusive. We evaluated the association of the LHCGR rs2293275 polymorphic variant with PCOS risk and its association with clinico-biochemical features of PCOS. 120 confirmed PCOS cases and an equal number of age-matched controls were subjected to clinical, biochemical, and hormonal investigations. Genotyping for rs2293275 was performed using polymerase chain reaction-restriction fragment length polymorphism. Logistic regression models were used to calculate odds ratios (ORs) at 95% confidence intervals (95% CIs). In the current study, PCOS cases reported a lower number of menstrual cycles per year than respective controls. A significantly higher BMI, Ferriman Galway score, levels of serum testosterone, insulin, TSH, FSH, and fasting glucose were observed in cases than in controls (p < 0.01). Compared to GG carriers, we observed a higher risk of developing PCOS in the subjects who harbored GA (OR 10.4, p < 0.0001) or AA (OR 7.73, p = 0.02) genotype. The risk persisted in the dominant model (GA + AA) as well (OR 10.29, p = 0.01). On stratification, a higher risk of developing PCOS was observed in variant genotype carriers who had a family history of either type two diabetes mellitus (OR 117; p < 0.0001) or hirsutism (OR 79; p < 0.0001). We also found significantly elevated levels of serum LH levels in the subject harboring GA and AA genotypes when compared to GG carriers. In the present study, we report a significant association of the LHCGR rs2293275 variant with the PCOS risk.

TGF-ß signaling: A recap of SMAD-independent and SMAD-dependent pathways.

Transforming growth factor-ß (TGF-ß) is a proinflammatory cytokine known to control a diverse array of pathological and physiological conditions during normal development and tumorigenesis. TGF-ß-mediated physiological effects are heterogeneous and vary among different types of cells and environmental conditions. TGF-ß serves as an antiproliferative agent and inhibits tumor development during primary stages of tumor progression; however, during the later stages, it encourages tumor development and mediates metastatic progression and chemoresistance. The fundamental elements of TGF-ß signaling have been divulged more than a decade ago; however, the process by which the signals are relayed from cell surface to nucleus is very complex with additional layers added in tumor cell niches. Although the intricate understanding of TGF-ß-mediated signaling pathways and their regulation are still evolving, we tried to make an attempt to summarize the TGF-ß-mediated SMAD-dependent andSMAD-independent pathways. This manuscript emphasizes the functions of TGF-ß as a metastatic promoter and tumor suppressor during the later and initial phases of tumor progression respectively.

Differential Impact of Insulin Sensitizers vs. Anti-Androgen on Serum Leptin Levels in Vitamin D Replete PCOS Women: A Six Month Open Labeled Randomized Study.

Women with PCOS are linked to insulin resistance, inflammation, and vitamin D (VD) deficiency. The study endeavors to comprehend the differential impact of insulin sensitizers vs. anti-androgen on serum leptin levels among women with PCOS rendered vitamin D replete with high VD oral supplement. This was open-labeled randomized study that screened 180 eligible women presenting to Endocrine clinic with oligomenorrhea or features of hyperandrogenism. Ninety-nine women who furnished written informed consent and fulfilled the Rotterdam 2003 criteria for diagnosis of PCOS were randomized into 3 drug treatment arms to receive either spironolactone (50 mg/d; n=30), metformin (1000 mg/d; n=30) or pioglitazone (30 mg/d; n=30). These women were also administered oral VD (4000 IU/day) in addition to the allocated drug for a period of 6 months. Detailed history, clinical examination, and laboratory evaluation was carried out at baseline and 6 months after intervention. Number of menstrual cycles/year increased while as Ferriman-Gallwey score, blood glucose, HOMA-IR, and plasma insulin levels significantly decreased in all the three arms with better outcomes in spironolactone and pioglitazone arms (p<0.05). Similarly, serum leptin levels superiorly improved in spironolactone and pioglitazone group. Pioglitazone group showed better efficacy in lowering serum total testosterone (p<0.05). Co-supplementation of high dosage VD with spironolactone or pioglitazone are more effective in reducing plasma leptin levels than metformin, and thus might prove to be better therapeutic strategies for women with PCOS.

Effect of six-month use of oral contraceptive pills on plasminogen activator inhibitor-1 & factor VIII among women with polycystic ovary syndrome: An observational pilot study.

Background & objectives: Polycystic ovary syndrome (PCOS) is an endocrinopathy warranting lifelong individualized management by lifestyle and pharmacological agents mainly oral contraceptive pills (OCPs). This study was aimed to report the impact of six-month OCP use on plasminogen activator inhibitor-1 (PAI-1) and factor VIII (FVIII) in women with PCOS. Methods: PCOS women diagnosed on the basis of Rotterdam 2003 criteria, either treated with OCPs (ethinyl estradiol-0.03 mg, levonorgestrel-0.15 mg) for a period of six months (n=40) or drug-naïve (n=42), were enrolled in this study. Blood was drawn to estimate glucose, insulin levels and lipid profile. Chemiluminescence immunoassays were used to measure hormones (LH, FSH, PRL, T4). Plasma levels of PAI-I and FVIII were measured by commercially available kits. Results: Menstrual regularity, Ferriman-Gallwey score and serum total testosterone significantly improved in the OCP group compared to drug-naïve group (P<0.01). No significant difference was observed in PAI-1 levels of the two groups; however, significant decrease in FVIII levels was observed in OCP group as compared to drug-naïve group. PAI-1 levels of OCP group correlated positively with blood glucose two hours, triglycerides and insulin two hours, while FVIII levels of OCP group correlated negatively with fasting insulin and homoeostatic model assessment-insulin resistance. Interpretation & conclusions: OCPs use has differential effect on pro-coagulant markers among women with PCOS. Well-designed, long-term, prospective, large-scale studies are prerequisite to elucidate the efficacy and safety of OCP in the treatment of PCOS.

Evaluation of serum anti-nuclear antibody among women with PCOS: a hospital based single center cross sectional study.

Polycystic ovary syndrome (PCOS), a major endocrinopathy is associated with barrage of metabolic aberrations. Reports in literature on association of PCOS and autoimmunity are conflicting. We aim to evaluate serum levels of anti-nuclear antibody (ANA) among Indian women with PCOS. In this hospital-based single center cross-sectional study, women qualifying a diagnosis of PCOS by Rotterdam criteria 2003 were recruited. Eighty-nine eligible women who consented were enrolled. All these women along with 87 age-matched, healthy controls underwent, clinical (menstrual history, anthropometry, hirsutism scoring), biochemical, hormonal assessment and serum ANA estimation. OGTT after overnight (8-12 h) fast with 75 g oral glucose load was done for 1 h, 2 h glucose and insulin measurements. The mean age of cases and controls was comparable (22.67 ± 5.53 vs. 22.84 ± 3.64 years). The prevalence of ANA positivity was significantly higher among women with PCOS (18.4% vs. 2.29%; p < .001). Though significant correlation was observed between ANA positivity and clinical signs of hyperandrogenism and plasma glucose, no significant correlation was noted between ANA status and other hormonal parameters. Higher prevalence of ANA positivity among women with PCOS, being a marker of autoimmunity, suggests a possible role of autoimmunity in causation of PCOS and needs further elucidation.

Impact of hypovitaminosis D on clinical, hormonal and insulin sensitivity parameters in normal body mass index polycystic ovary syndrome women.

Earlier data on the relationship of 25 hydroxyvitamins (25OHD) levels with various components of polycystic ovary syndrome (PCOS) has been conflicting. We studied 122 normal body mass index (BMI) women with PCOS (cases) and 46 age and BMI-matched healthy women (controls) and assessed the impact of serum 25OHD levels on clinical, biochemical and insulin sensitivity parameters in these lean Indian women with PCOS. The mean age and BMI of the cases and controls were comparable. Mean serum 25OHD levels respectively were 10.1 ± 9.9 and 7.9 ± 6.8 ng/ml with 87.7% and 91.1% vitamin D (VD) deficient. No significant correlation was noted between 25OHD levels and clinical, biochemical and insulin sensitivity parameters except with the total testosterone levels (p = 0.007). Also, no significant difference in these parameters was observed once the PCOS women were stratified into various subgroups based on the serum 25OHD levels. We conclude that VD deficiency being common in normal BMI Indian women with or without PCOS does not seem to alter the metabolic phenotype in these women.

Insulin resistance, metabolic syndrome and chronic low grade inflammation in Sheehan's syndrome on standard replacement therapy: a case control study.

BACKGROUND: Increased clustering of metabolic risk factors has been demonstrated in patients with hypopituitarism on standard replacement therapy. This usually has been attributed to persistent growth hormone deficiency, though contribution from underlying etiology of hypopituitarism cannot be underestimated. We, therefore, studied conventional metabolic risk factors and pro inflammatory markers in a cohort of hypopituitary patients in whom the etiology was Sheehan's syndrome. MATERIAL & METHODS: We studied 30 GH naive patients with Sheehan's syndrome (SS) on standard replacement therapy and compared with healthy age, BMI and parity matched controls. All subjects were normotensive, non-diabetic, non-smokers and none had history of any acute or chronic illness. We recorded height, weight, BMI, waist circumference and waist hip ratio, besides measuring biochemical parameters like lipid profile, fasting plasma glucose and insulin, sVCAM-1, ICAM-1 and hsCRP. RESULTS: Metabolic syndrome and impaired glucose tolerance were more common with SS patients. Similarly total cholesterol (mean ± SD, 5.21 ± 0.98 vs 4.57 ± 0.88, P = 0.00), LDL-cholesterol (3.15 ± 0.90 vs 2.67 ± 0.75, P = 0.02), triglycerides (2.14 ± 1.00 vs 1.43 ± 0.45, P = 0.00) and pro-inflammatory markers i.e. hsCRP (3.95 ± 2.58 vs 1.45 ± 2.77, P = 0.00) were significantly higher in patients with SS. hsCRP positively correlated with fasting insulin (r = 0.40, P = 0.02), HOMA-IR (r = 0.38, P = 0.03) and negatively with HDL (r = - 0.33, P = 0.05). CONCLUSIONS: GH naïve SS patients on standard replacement therapy have increased clustering of metabolic and pro-inflammatory risk factors.

Pattern of adrenal morphology and function in pulmonary tuberculosis: response to treatment with antitubercular therapy.

OBJECTIVE: Although previous studies have shown enlargement of adrenal glands in patients with tuberculosis, only few have studied its natural history. Similarly, there have been variable reports of adrenal function in these patients. Some but not all the studies revealed a high prevalence of adrenal insufficiency. The aim of this study was to prospectively study the adrenal cortical function and morphology before and after treatment of pulmonary tuberculosis. DESIGN AND PATIENTS: In a prospective case-control study, 45 patients with acute pulmonary tuberculosis and 45 healthy age- and gender-matched controls were studied. Adrenal function was tested using a short Synacthen test at the baseline and after 6 months of antitubercular treatment. Size of both adrenal glands was studied using 64 slice MDCT (Somatom Sensation, Siemens) before and after 6 months of antitubercular treatment. The findings were compared with a group of healthy controls. RESULTS: The mean age of cases was 42·4 ± 20·4 years and that of controls was 41·1 ± 17·7 years. The various clinical and biochemical parameters were comparable between cases and controls. The mean cortisol both basal and one-hour postintravenous Synacthen was significantly lower in cases as compared to controls (mean ± SD basal cortisol of 413·57 ± 108·42 nmol/l in cases vs 615·26 ± 108·15 nmol/l in controls and post Synacthen cortisol of 685·61 ± 83·87 nmol/l in cases vs 1497·30 ± 734·44 nmol/l in controls). Both the adrenal length and thickness of the right and left adrenal gland were greater in patients with active tuberculosis compared with controls and reversed to baseline after completion of antitubercular treatment. CONCLUSION: Adrenal enlargement demonstrated by CT is common in active tuberculosis and is reversible. Basal and stimulated cortisol is less in patients with pulmonary tuberculosis as compared with healthy controls and increases after antitubercular treatment, although unlike previous studies, none of the patients had adrenal insufficiency.

Thyroid Autoimmunity and Subclinical Hypothyroidism in Prolactinoma: A Case Control Study.

Background: This study was aimed at determining the frequency of thyroid autoimmunity and subclinical hypothyroidism in patients with hyperprolactinemia due to prolactinoma compared to well-matched healthy controls. Methods: This was a cross-sectional study wherein 78 treatment naïve prolactinoma patients and ninety-two healthy control subjects were recruited. Serum prolactin (PRL), thyroid-stimulating hormone (TSH), total thyroxine (T4), circulating anti-thyroid peroxidase (anti-TPO), and anti-thyroglobulin (anti-Tg) antibody levels were measured in all study subjects. Progression of the antibody-positive population to subclinical hypothyroidism was determined. Results: The median PRL level among patients was 166 ng/ml (IQR 85-467) compared to 11.4 ng/ml (IQR 8.5-15.9) in controls (P < 0.001). There was no significant difference in levels of T4 (P = 0.83) and TSH (P = 0.82) between the cases and controls. Overall, 25% of patients had the presence of anti-thyroid antibodies as compared to 20% of controls (P = 0.56). SCH was more common in antibody-positive hyperprolactinemia subjects compared with antibody-positive controls. Conclusion: We did not find an increased prevalence of thyroid autoimmunity among untreated prolactinoma patients compared to healthy controls. At the same time, subclinical hypothyroidism was more common in thyroid antibody-positive patients with hyperprolactinemia than positive controls.

Analysis of molecular aberrations of Wnt pathway gladiators in colorectal cancer in the Kashmiri population.

The development and progression of colorectal cancer (CRC) is a multi-step process, and the Wnt pathways with its two molecular gladiators adenomatous polyposis coli (APC) and ß-catenin plays an important role in transforming a normal tissue into a malignant one. In this study, we aimed to investigate the role of aberrations in the APC and ß-catenin genes in the pathogenesis of CRC in the Kashmir valley, and to correlate it with various clinicopathological variables. We examined the paired tumour and normal-tissue specimens of 86 CRC patients for the occurrence of aberrations in the mutation cluster region (MCR) of the APC gene and exon 3 of the ß-catenin gene by polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) and/or PCR-direct sequencing. Analysis of promoter hypermethylation of the APC gene was also carried out using methylation-specific PCR (MS-PCR). The overall mutation rate of the MCR of the APC gene among 86 CRC cases was 12.8 per cent (11 of 86). Promoter hypermethylation of APC was observed in 54.65 per cent (47 of 86) of cases. Furthermore, we found a significant association between tumour location, tumour grade and node status and the methylation status of the APC gene (p ≤ 0.05). Although the number of mutations in the APC and ß-catenin genes in our CRC cases was very low, the study confirms the role of epigenetic gene silencing of the pivotal molecular gladiator, APC, of the Wnt pathway in the development of CRC in the Kashmiri population.

SMAD4--molecular gladiator of the TGF-beta signaling is trampled upon by mutational insufficiency in colorectal carcinoma of Kashmiri population: an analysis with relation to KRAS proto-oncogene.

BACKGROUND: The development and progression of colorectal cancer has been extensively studied and the genes responsible have been well characterized. However the correlation between the SMAD4 gene mutations with KRAS mutant status has not been explored by many studies so far. Here, in this study we aimed to investigate the role of SMAD4 gene aberrations in the pathogenesis of CRC in Kashmir valley and to correlate it with various clinicopathological variables and KRAS mutant genotype. METHODS: We examined the paired tumor and normal tissue specimens of 86 CRC patients for the occurrence of aberrations in MCR region of SMAD4 and exon 1 of KRAS by PCR-SSCP and/or PCR-Direct sequencing. RESULTS: The overall mutation rate of mutation cluster region (MCR) region of SMAD4 gene among 86 patients was 18.6% (16 of 86). 68.75% (11/16) of the SMAD4 gene mutants were found to have mutations in KRAS gene as well. The association between the KRAS mutant genotype with SMAD4 mutants was found to be significant (P = or < 0.05). Further more, we found a significant association of tumor location, tumor grade, node status, occupational exposure to pesticides and bleeding PR/Constipation with the mutation status of the SMAD4 gene (P = or < 0.05). CONCLUSION: Our study suggests that SMAD4 gene aberrations are the common event in CRC development but play a differential role in the progression of CRC in higher tumor grade (C+D) and its association with the KRAS mutant status suggest that these two molecules together are responsible for the progression of the tumor to higher/advanced stage.

A case-control study of tumor necrosis factor-alpha promoter polymorphism and its serum levels in patients with chronic obstructive pulmonary disease in Kashmir, North India.

AIM: Data about polymorphism in tumor necrosis factor-alpha (TNF-α) and its serum levels in chronic obstructive pulmonary disease (COPD) are conflicting. We aimed to evaluate the association of TNF-α-308 G > A polymorphism in patients with COPD in Kashmir (North India), a high burden area and also determined the serum TNF-α levels in these patients. MATERIALS AND METHODS: One hundred spirometrically confirmed COPD patients and 163 controls resident from Kashmir valley (North India) were recruited. Genotyping of the promoter region of TNF-α was carried out using polymerase chain reaction-restriction fragment length polymorphism. The serum TNF-α was quantified using the Cytometric Bead Array flex system by flow cytometry. Results were subjected to appropriate statistical treatment andP < 0.05 was considered statistically significant. RESULTS: Ninety-one COPD patients (91%) had G/G (wild homozygous) genotype and nine patients (9%) had G/A (heterozygous) genotype. Among the control population, 150 (92%) had G/G genotype and 13 (8%) had G/A genotype. The variant allele "A" was not detected in either of the two groups. Serum levels of TNF-α were significantly higher in patients compared to control group (8.0 ± 10.1 pg/ml vs. 3.3 ± 0.42 pg/ml, respectively,P = 0.0001). CONCLUSION: While serum levels of TNF-α are higher in COPD patients compared to the controls, there was no difference in the prevalence of TNF-α-308 polymorphism in the ethnic Kashmiri population with COPD.

Polymorphic analysis of MHClinked Heat Shock Protein 70 genes: Their susceptibility and prognostic implication in Kangri cancer cases of Kashmiri population.

Kangri cancer is a unique thermally-induced squamous cell carcinoma (SCC) of skin that develops due to persistent use of Kangri (a brazier), used by Kashmiri people, to combat the chilling cold during winter months. We designed a large scale case-control study to characterize the frequency of two polymorphisms within the MHC class III-linked HSP70genes, Hsp70-2 and Hsp70-hom, in order to find any association of these genotypic variants for predisposition to and clinical outcome of Kangri cancer patients from Kashmir valley in North India. Polymerase Chain Reaction and restriction enzymes were utilized to characterize the frequency of two polymorphisms with in Hsp70-2 and Hsp70-hom genes in 118 Kangri carcinoma cases and 95 healthy controls from the same population of Kashmir. Association of high frequency allelic variants of Hsp70genes with various clinicopathological features of prognostic significance was assessed by Chi-square test using SPSS software. In this study, allelic frequency of Hsp70-2 A/G heterozygote (0.87) (P = 0.012) was found to be significantly high in Kangri cancer cases compared to control (0.736) with a Relative Risk of 2.45 fold. Conversely, the allelic frequency of Hsp70-2 A/A allele in homozygous condition was significantly low in Kangri cancer cases and worked out to be 0.084 (Vs 0.252 in control) with P is equal to 0.001, implicating it as a protective allele against Kangri cancer in subjects with this genotype. Similarly, significantly high frequency of 0.50 (Vs 0.29 in control) of Hsp70-homC/C allele was found in homozygous condition in Kangri cancer cases suggestive of a positive relative risk associated with this genotype (RR is equal to 2.47) (P is equal to 0.002). The overall allele frequency data analysis of Hsp70-2 and Hsp70-hom genes was significant (chi(2) is equal to 12.38, P is equal to 0.002; and chi(2) is equal to 12.21, P is equal to 0.002). The study also reveals considerable association of high frequency alleles of HSP70 genes, especially of Hsp70-2 A/G or G/G in Kangri tumors with clinico-pathological features of poor prognosis. These results indicate that the relative risk of Kangri cancer associated with Hsp70-2 and Hsp70- hom gene polymorphisms is confined to Hsp70-2 A/G or G/G and Hsp70homC/C haplotype in our population. The study, therefore, suggests Hsp70-2 A/G or G/G and Hsp70homC/C genotypes as potential susceptibility markers and independent prognostic indicators in Kangri carcinoma patients in Kashmiri population.

Comparison between peak systolic velocity of the inferior thyroid artery and technetium-99m pertechnetate thyroid uptake in differentiating Graves' disease from thyroiditis.

OBJECTIVES: The differentiation between the various etiologies of thyrotoxicosis, including those with hyperthyroidism (especially Graves' disease [GD], the most common cause of hyperthyroidism) and without hyperthyroidism (like thyroiditis), is an important step in planning specific therapy. Technetium-99m (99mTc) pertechnetate thyroid scanning is the gold standard in differentiating GD from thyroiditis. However, this technique has limited availability, is contraindicated in pregnancy and lactation, and is not helpful in cases with history of recent exposure to excess iodine. The aim of this study was to identify the diagnostic value of the peak systolic velocity of the inferior thyroid artery (PSV-ITA) assessed by color-flow Doppler ultrasound (CFDU) and compare the sensitivity and specificity of this method versus 99mTc pertechnetate thyroid uptake. SUBJECTS AND METHODS: We prospectively analyzed 65 patients (46 with GD and 19 with thyroiditis). All patients were evaluated with clinical history and physical examination and underwent 99mTc pertechnetate scanning and measurement of TRAb levels and PSV-ITA values by CFDU. The diagnosis was based on findings from signs and symptoms, physical examination, and 99mTc pertechnetate uptake. RESULTS: Patients with GD had significantly higher mean PSV-ITA values than those with thyroiditis. At a mean PSV-ITA cutoff value of 30 cm/sec, PSV-ITA discriminated GD from thyroiditis with a sensitivity of 91% and specificity of 89%. CONCLUSION: Measurement of PSV-ITA by CFDU is a good diagnostic approach to discriminate between GD and thyroiditis, with sensitivity and specificity values comparable to those of 99mTc pertechnetate thyroid uptake.

Oral contraceptive use increases risk of inflammatory and coagulatory disorders in women with Polycystic Ovarian Syndrome: An observational study.

Polycystic ovarian syndrome (PCOS) is a multispectral disorder requiring lifelong management. Its pathophysiology is still being explored which makes its treatment options restrained. Present study explores impact of oral contraceptive mode of treatment on metabolic, hormonal, inflammation and coagulation profile of PCOS women. 50 subjects diagnosed with Rotterdam criteria receiving no drug treatment served as controls whereas 50 subjects receiving only OCPs (Ethinyl estradiol 0.03 mg, Levonorgestrel 0.15 mg) as a mode of treatment at least for six-months served as cases. Ferriman-Gallwey score and hormonal profile improved on OCP treatment. However, parameters like weight, Body mass index, waist-hip ratio, Oral glucose tolerance test, lipid profile, insulin, HOMA-IR, adiponectin, interleukin1ß, visfatin, resistin, tissue factor, PT and APTT showed considerable derangements in OCP group. All above parameters are associated with the risk of diabetes mellitus, dyslipidemia, coronary vascular disease, cancers, hypercoagulable state, venous thromboembolism and thrombotic events. Long-term use of OCPs needs to be considered carefully for PCOS patients who are already burdened with associated risk factors. This study was conducted in a region where women do not have much access to high-end screening and diagnostic facilities that further exacerbates their clinical outcomes. Large scale, long-term studies need to be designed to further evaluate safety use of OCPs in PCOS women.

Calcitonin gene-related peptide (CGRP) concentrations outside migraine attacks in peripheral blood as a potential biomarker for chronic migraine / Concentrações de peptídeo relacionado ao gene da calcitonina (CGRP) fora dos ataques de enxaqueca no sangue periférico como um potencial biomarcador para enxaqueca crônica

Introduction: Chronic migraine is a debilitating condition that affects a significant portion of the population. Accurate diagnosis and treatment of chronic migraine remain a challenge due to the lack of objective biomarkers. Calcitonin gene-related peptide (CGRP) is a neuropeptide involved in the pathophysiology of migraine and has been proposed as a potential biomarker for migraine. Methods: We measured CGRP levels in peripheral blood samples collected from 142 participants with chronic or episodic migraine and 24 healthy controls during ictal periods, i.e., outside migraine attacks. We compared CGRP levels between the three groups and assessed the correlation between CGRP levels and clinical features of chronic migraine. Conclusion: Our study provides evidence that CGRP levels in peripheral blood during ictal periods may serve as a potential biomarker for chronic migraine. Further studies are needed to validate these findings and to explore the clinical utility of CGRP as a biomarker for chronic migraine.

Introdução: A enxaqueca crônica é uma condição debilitante que afeta uma parcela significativa da população. O diagnóstico preciso e o tratamento da enxaqueca crónica continuam a ser um desafio devido à falta de biomarcadores objetivos. O peptídeo relacionado ao gene da calcitonina (CGRP) é um neuropeptídeo envolvido na fisiopatologia da enxaqueca e foi proposto como um potencial biomarcador para enxaqueca. Métodos: Medimos os níveis de CGRP em amostras de sangue periférico coletadas de 142 participantes com enxaqueca crônica ou episódica e 24 controles saudáveis ​​durante períodos ictais, ou seja, fora das crises de enxaqueca. Comparamos os níveis de CGRP entre os três grupos e avaliamos a correlação entre os níveis de CGRP e as características clínicas da enxaqueca crônica. Conclusão: Nosso estudo fornece evidências de que os níveis de CGRP no sangue periférico durante os períodos ictais podem servir como um potencial biomarcador para enxaqueca crônica. Mais estudos são necessários para validar estes resultados e explorar a utilidade clínica do CGRP como biomarcador para enxaqueca crónica.

Prevalence, risk factors and consequences of overweight and obesity among schoolchildren: a cross-sectional study in Kashmir, India.

BACKGROUND: Obesity among children and adolescents is a growing public health problem. The objective of this study was to evaluate the prevalence, risk factors and metabolic consequences of obesity among schoolchildren from Kashmir, India. METHODS: The study subjects (n=2024) included 870 boys and 1154 girls, aged between 6 and 18 years. Data were collected by interviewer-administered questionnaires. Information was obtained about different lifestyles, anthropometric parameters and dietary habits. Obesity was defined as body mass index (BMI) percentile as per the guidelines of Centers for Disease Control, 2000. For the evaluation of different clinical parameters, blood samples were collected from the subjects in the fasting state at 8 to 9 am after an overnight (10-12 h) fast. RESULTS: The highest representation of subjects was from fee-paying private schools. Out of the total subjects, 6.69% were overweight and 4.64% were obese. The hip circumference, abdominal circumference, BMI, blood pressure (BP), use of ready-made foods as well as the clinical parameters like glucose, phosphorous, cholesterol and triglycerides were found significantly higher among girls than boys (p<0.05). Boys were taller and were physically more active than girls (p<0.01). Compared to the boys (3.33%), the girls were found to be more obese (5.63%). Rural dwelling subjects (4.22%) exhibited a lower percentage of obesity than urban population (5.00%). The difference in obesity among the different age groups was found statistically significant (p<0.05). Additionally, children with active lives in the form of vigorous (10.59%) or moderate (10.34%) exercise decreased their chances of gaining weight substantially. CONCLUSIONS: Results from the present study have shown that prevalence of obesity among children was high in our population.

ApoE gene polymorphism and its relationship with coronary artery disease in ethnic Kashmiri population.

Apolipoprotein E is a fundamental component of various lipoproteins and plays substantial role in cholesterol/lipid transport among cells of various tissues. The ApoE gene is polymorphic with three alleles ε2, ε3, and ε4, coding for isoforms E2, E3, and E4 having different binding inclination for corresponding receptors. This work aimed to investigate the association between ApoE gene polymorphism and coronary artery disease (CAD) in Kashmiri population. APOE genotyping was done by polymerase chain reaction-restriction fragment length polymorphism. Our study indicated ApoE ε3/ε3 to be the most common genotype in both CAD and control group. The frequency of ε2, ε3, and ε4 alleles of ApoE gene in cases was observed to be 0.06, 0.72, and 0.20, while in control subjects it was 0.075, 0.82, and 0.11, respectively. A significant difference was found between cases and controls with respect to TC, LDL, and HDL levels. Our data showed that frequency of ε4/ε4, ε4/ε3 genotype and ε4 allele was significantly higher in cases than in controls (p = 0.02, p = 0.004, p < 0.001 respectively). Moreover, the CAD patients carrying ε4 allele had significantly higher TC and LDL levels (p value <0.01). Thus our data showed a significant association of ApoE ε4 allele with the risk of CAD. The data revealed that ApoE ε4 allele is associated with increased risk of CAD and increased levels LDL and TC in Kashmiri population.