Exploring the burden of mixed dyslipidemia in patients with type 2 diabetes mellitus: A cross-sectional study in Kashmir, India.

BACKGROUND: Diabetes-related dyslipidemia is a multifaceted, complicated disorder characterized by an abnormal lipid profile in individuals with diabetes. The incidence of different types of dyslipidemia, however, was not a focus of prior investigations. The patients were characterized into three categories of dyslipidemia. Different patterns of dyslipidemia were combined into single dyslipidemia (7 patterns), mixed dyslipidemia (16 patterns), and triple dyslipidemia (4 patterns). METHODS: In this cross-sectional study, 586 people suffering from type 2 diabetes mellitus (T2DM) were included. We assessed the serum lipid profile and used log (TG/HDL-C) to determine the atherogenic index of plasma (AIP). Dyslipidemia was examined as a categorical variable, and the findings were presented as percentages and numbers. To compare categorical variables, we either utilized Fisher exact tests or Chi square tests. RESULTS: The study comprised of 586 T2DM patients, with 310 (52.9%) women and 276 (47.1%) men. Women have significantly higher hypertension (33.6%) as compared to men (23.2%). 18.94% (111) of patients were having coronary artery disease (CAD) history consisting of 12.28% (72) females and 6.66% (39) males, a difference which is statistically significant. 98.12% of total individuals had as a minimum of one lipid abnormality. 4.61% (27) of study subjects were having isolated dyslipidemia and 93.51% (548) had dual or triple pattern of dyslipidemia (mixed dyslipidemia). High AIP >0.24 (94.8%) was the most predominant trend of dyslipidemia. The dual combination of AIP (>0.24) and HDL (<50 mg/dL in Females and <40 mg/dL in Males) was found to be the most common pattern of mixed dyslipidemia (68.08%). The most prevalent trend of isolated dyslipidemia was found to be high AIP (>0.24), In patients with CAD history. Among the mixed dyslipidemia, the common pattern of dyslipidemia (71.17%) was the dual combination of high AIP (>0.24) and low HDL (<50 mg/dL women and <40 mg/dL males). The triple combination of TG (≥200 mg/dL) and HDL (<40 and <50 mg/dL) and LDL (≥100 mg/dL) was only found in females. CONCLUSION: In conclusion, dyslipidemia is highly prevalent in T2DM patients, with mixed dyslipidemia being the most common type observed in the community of Kashmir valley, India. High AIP was the most prevalent pattern in the current investigation.

Long-term hepatic and cardiac health in patients diagnosed with Sheehan's syndrome.

PURPOSE: Sheehan's syndrome (SS) is characterised by chronic pituitary insufficiency following a vascular insult to the pituitary in the peripartum period. There is a lack of substantial evidence on the long-term hepatic and cardiac consequences in these patients, following hormone replacement. METHODS: Patients with a diagnosis of SS were recruited for the study. Detailed clinico-biochemical and radiological evaluation were performed in all patients (n = 60). Hepatic and cardiac complications were assessed using fibroscan and echocardiography (2D speckle-tracking) respectively, in a subset of patients (n = 29) as well as age-and BMI-matched controls (n = 26). Controlled attenuation parameter (for steatosis) and liver stiffness measurement (for fibrosis) were used to define non-alcoholic fatty liver disease (NAFLD). Diastolic cardiac function was evaluated using standard criteria and systolic function by ejection fraction and global longitudinal strain (GLS). RESULTS: The mean age of the cohort was 42.7 ± 11.6 years. Multiple (≥ 2) hormone deficiencies were present in 68.8% of patients, with hypothyroidism (91.4%), hypocortisolism (88.3%), and growth hormone (GH) deficiency (85.7%) being the most common. At a mean follow-up of 9.8 ± 6.8 years, NAFLD was present in 63% of patients, with 51% having severe steatosis, which was predicted by the presence of GH deficiency and higher body mass index. Though the ejection fraction was similar, increased left ventricular GLS (18.8 vs. 7.7%) was present in a significantly higher number of patients versus controls. CONCLUSION: NAFLD, especially severe hepatic steatosis, is highly prevalent in SS. Subclinical cardiac systolic dysfunction (impaired GLS) is also more common, but of mild intensity.

Prevalence of coronary calcium deposits in Sheehan's syndrome patients on long term replacement treatment.

PURPOSE: Sheehan's Syndrome (SS) is one of the most important causes of hypopituitarism in developing countries with patients having varying degrees and severity of anterior pituitary hormone deficiency including growth hormone deficiency (GHD). SS is characterized by increased clustering of metabolic and proinflammatory risk factors predisposing them to increased cardiovascular morbidity and mortality. Coronary calcium deposits (CCD), a marker for significant coronary atherosclerosis, is used for evaluation in asymptomatic individuals of global cardiac risk to develop events related to coronary heart disease (CHD). This study therefore aimed to evaluate the prevalence of coronary artery disease in patients with SS appropriately replaced for pituitary hormone deficiencies but untreated for GHD. METHODS: Thirty patients previously diagnosed with SS and stable on a conventional replacement treatment for at least 6 months before the study and thirty age and Body Mass Index (BMI) matched controls were enrolled in this observational study. The subjects underwent detailed clinical, biochemical, and hormone analysis. Coronary multidetector computed tomography was performed in 19 SS patients and 19 healthy participants by a 16-row multislice scanner. Non contrast acquisitions were performed to detect coronary calcifications. Calcium was quantified by the Agatston score (AS) in all subjects. AS > 10 indicates increased CHD risk. RESULTS: The mean (± SD) age was 38.30 ± 10.73 years and the diagnostic delay was 11.35 ± 4.74 years. Patients with SS had significantly higher mean triglyceride, total cholesterol, and low density lipoprotein (LDL) cholesterol and lower HDL cholesterol concentrations on conventional replacement therapy. The prevalence of CCD was significantly higher in patients of SS compared to controls (42.1% vs. 5.3%; P = 0.023). The presence of CCD and AS > 10 were detected in 42.1% and 31.6% of patients respectively. The presence of significant calcification (Agatston score > 10) was documented in 75% of patients (6/8) of the SS patients with CCD compared to none in the control group (P = 0.019). (Left anteriordescending, 1; left circumflex, 2; right coronary artery, 2 and posterior descending, 1) CONCLUSION: Since coronary artery calcium is an independent predictor of CHD events, the presence of significant prevalence of CCD in patients with SS compared to healthy matched controls, undermines the importance of early risk stratification of SS individuals with plethora of conventional cardiovascular risk factors that are at relatively high risk to avoid the adverse vascular consequences.

Sheehan's syndrome presenting as psychosis: a rare clinical presentation.

Sheehan's syndrome (SS) refers to the occurrence of varying degree of hypopituitarism after parturition (1). It is a rare cause of hypopituitarism in developed countries owing to advances in obstetric care and its frequency is decreasing worldwide. However, it is still frequent in underdeveloped and developing countries. Sheehan's syndrome is often diagnosed late as it evolves slowly (2,3). Reports of psychoses in patients with Sheehan's syndrome are rare. Herein, a case report of psychosis in a 31 year old woman who developed Sheehan's syndrome preceded by postpartum haemorrhage is presented. Treatment with thyroxine and glucocorticoids resulted in complete remission after attaining euthyroid and eucortisolemic state.

Variations in MAP kinase gladiators and risk of differentiated thyroid carcinoma.

Thyroid carcinoma (TC) accounts for ~2.1% of newly diagnosed cancer cases. Mutations in KRAS, HRAS, NRAS and BRAF are primary participants in the development and progression of various types of malignancy, including differentiated TC (DTC). Therefore, the present prospective cohort study aimed to screen patients with DTC for variations in RAS gene family and BRAF gene. Exon 1 and 2 of KRAS, HRAS, NRAS and exon 15 of BRAF gene were screened for hotspot mutations in 72 thyroid tumor and adjacent normal tissue samples using di-deoxy Sanger sequencing. HRAS T81C mutation was found in 21% (15 of 72) of DTC tissue samples, therefore this mutation was investigated in blood samples from patients with DTC and controls as a genetic polymorphism. In addition, HRAS T81C genotypes were determined in 180 patients with DTC and 220 healthy controls by performing restriction fragment length polymorphism. BRAF V600E mutation was confined to classical variant of papillary thyoid cancer (CPTC; 44.4%) and was significantly associated with multifocality and lymph node (LN) metastasis. No mutation was found in exons 1 and 2 of KRAS and NRAS and exon 2 of HRAS genes, however, mutation was detected in exon 1 of HRAS gene (codon 27) at nucleotide position 81 in 21% (15 of 72) of DTC tumor tissue samples. Furthermore, HRAS T81C single nucleotide polymorphism was significantly associated with the risk of DTC with variant genotypes more frequently detected in cases compared with controls (P≤0.05). Moreover, frequency of variant genotypes (TC+CC) was significantly higher among DTC cases with no history of smoking, males, greater age, multifocality and LN metatasis compared with healthy controls (P<0.05). BRAF V600E mutation was primarily present in CPTC and associated with an aggressive tumor phenotype but mutations in RAS gene family were not present in patients with DTC. HRAS T81C polymorphism may be involved in the etiopathogenesis of DTC in a Pakistani cohort. Furthermore, testing for the BRAF V600E mutation may be useful for selecting initial therapy and follow-up monitoring.

Inter-relationship of Pro- and Anti- inflammatory Biomarkers with the development of Type 2 Diabetes Mellitus.

Purpose: There has been growing evidence that inflammatory markers play a role in the development as well as severity of Type 2 diabetes mellitus (T2DM). This study has been designed to decipher the involvement of C-Reactive Protein (CRP), Tumor Necrosis Factor (TNFα), Interleukin-6 (IL-6) and Interleukin-10 (IL-10) in the etiopathogenesis of T2DM. Basic procedures: A total of 480 T2DM cases and 540 healthy controls were recruited for the study. Blood samples were collected from each study subject to measure the serum levels of CRP, TNFα, IL-6 and IL-10. Main findings: We found that serum levels of CRP in mg/dl (4.2 ± 0.9), TNFα in pg/ml (34.5 ± 8.8), IL-6 in pg/ml (19.2 ± 7.2) in T2DM patients were significantly high as compared to control participants (CRP; 1.4 ± 0.6, TNFα; 12.7 ± 3.4, IL-6; 3.1 ± 1.4; P < 0.0001). The serum levels of IL-10 in pg/ml were lower in T2DM cases compared to controls (4.35 ± 1.2 vs. 9.6 ± 1.2). In addition, we observed a significant association of CRP levels with insulin resistance, obesity and dyslipidemia. Increased TNFα levels were strongly associated with female gender, Poor glycemic control and strong family history of diabetes. Poor glycemic control was significantly associated with elevated IL-6 levels. Moreover, significantly reduced IL-10 levels were found in T2DM patients with sedentary lifestyle; low educational and rural background. Conclusions: This study showed a strong relationship between TNFα, IL-6, CRP, IL-10 and T2DM patients of Kashmiri ethnicity, treated at SMHS Hospital. Thus, supporting other studies and showing that cytokines may be good markers for T2DM development.

Association between T2DM and the lowering of testosterone levels among Kashmiri males.

OBJECTIVE: The objective of this study is to study association between testosterone and diabetes in Kashmiri males. METHODS: A total of 300 males with Type 2 diabetes visited an outpatient and inpatient clinic at Shri Maharaja Hari Singh (SMHS) hospital, Srinagar, J&K India. The blood sugar and HbA1c, which are the markers of diabetes, and sérum testosterone levels were measured. The blood samples from both the cases and controls were collected. RESULTS: Out of 300 subjects, 42% had a testosterone deficiency. A relationship between type 2 diabetic males and healthy males was observed, and testosterone levels were determined to be significantly lower among diabetic males (p < 0.001) when compared to healthy males. Then, we compared diabetic markers among testosterone deficient and normal testosterone level groups; the mean fasting plasma glucose (p = 0.0019) and glycated haemoglobin (HbA1c; p = 0.0449) levels were significantly higher in the testosterone deficient group than in the control group. To elucidate the relationship between the serum total testosterone level and fasting plasma glucose and HbA1c values, Pearson's correlation test was performed. Fasting plasma glucose levels (r = -0.252, p = 0.001) and HbA1c values (r = -0.697, p = 0.001) showed a significant negative correlation with serum testosterone levels among diabetic males. CONCLUSION: This study shows that diabetes causes low testosterone levels among males, and lower testosterone levels can act as a marker for diabetes. Thus, with timely intervention, mortality and co-morbidity associated with diabetes can be prevented.

Graves' disease in a Down's syndrome patient.

Thyroid dysfunction in patients with Down's syndrome is well known. Although the majority of children with Down's syndrome appear to have normal thyroid function, however, hypothyroidism is commonly seen. The presence of hyperthyroidism is rare. The etiology is believed to be autoimmune. We report a patient with Down syndrome and Graves' disease who responded well to antithyroid drugs. The rarity of this association, especially in a child younger than eight years of age, has prompted us to report this case.

Polycystic Ovary Syndrome in Bipolar Affective Disorder: A Hospital-based Study.

BACKGROUND: Preliminary studies suggest a multidimensional relationship of mood pathology with endocrine disturbances. Studies have found an increased risk of mood disorders in polycystic ovary syndrome (PCOS), and conversely, many of the medications commonly used in the treatment of bipolar affective disorder (BPAD) can have deleterious effects on blood levels of reproductive hormones and consequently on the hypothalamic-pituitary-gonadal (HPG) axis and reproductive function. Furthermore, there is evidence of reproductive dysfunction in women with BPAD before treatment. OBJECTIVES: To assess the comorbidity of PCOS in patients of BPAD and to study risk factors associated with this comorbidity. MATERIALS AND METHODS: Two hundred female patients with the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition diagnosis of BPAD, between ages of 15 and 45 years, were evaluated by an endocrinologist. Patients reporting menstrual disturbances or having any stigmata of PCOS were further subjected to hormonal analysis, which included luteinizing hormone, follicle-stimulating hormone, prolactin, and testosterone, in the early follicular phase of menstrual cycle. Diagnosis of PCOS was made as per the NIH criteria. RESULTS: Of 200 patients, 46 (23%) were diagnosed as having PCOS. Forty-five percent (n = 90) reported menstrual disturbances while 27% (n = 54) had polycystic ovaries on ultrasonography. 19.2% of the patients diagnosed as PCOS had a history of valproate intake while 27.90% patients had no such history (P = 0.15). No significant difference (P = 0.07) was found in the prevalence of PCOS among various drug groups (including group on multiple mood stabilizers). CONCLUSION: A higher prevalence of PCOS is seen in BPAD, irrespective of pharmacotherapy, suggesting a common link between the disorders which might be in the form of disturbance in HPG axis.

Colorectal neoplasm and acromegaly.

The risk for colorectal carcinoma in acromegaly remains controversial. In our earlier study, we have demonstrated that the risk of colorectal carcinoma in Asian Indians with acromegaly is not increased and after this report, routine colonoscopy in our patients with acromegaly was abandoned. Subsequently, two consecutive young men aged 30 and 35, one 6 years after and other at the time of diagnosis of acromegaly had colorectal carcinoma respectively. None of them had family history of colonic neoplasm. These two younger patients with no other predisposition for colorectal neoplasm suggests that colonoscopy should be done in all patients with acromegaly at diagnosis and they should remain under surveillance.

Association between T2DM and the lowering of testosterone levels among Kashmiri males

ABSTRACT Objective: The objective of this study is to study association between testosterone and diabetes in Kashmiri males. Subjects and methods: A total of 300 males with Type 2 diabetes visited an outpatient and inpatient clinic at Shri Maharaja Hari Singh (SMHS) hospital, Srinagar, J&K India. The blood sugar and HbA1c, which are the markers of diabetes, and sérum testosterone levels were measured. The blood samples from both the cases and controls were collected. Results: Out of 300 subjects, 42% had a testosterone deficiency. A relationship between type 2 diabetic males and healthy males was observed, and testosterone levels were determined to be significantly lower among diabetic males (p < 0.001) when compared to healthy males. Then, we compared diabetic markers among testosterone deficient and normal testosterone level groups; the mean fasting plasma glucose (p = 0.0019) and glycated haemoglobin (HbA1c; p = 0.0449) levels were significantly higher in the testosterone deficient group than in the control group. To elucidate the relationship between the serum total testosterone level and fasting plasma glucose and HbA1c values, Pearson's correlation test was performed. Fasting plasma glucose levels (r = −0.252, p = 0.001) and HbA1c values (r = −0.697, p = 0.001) showed a significant negative correlation with serum testosterone levels among diabetic males. Conclusions: This study shows that diabetes causes low testosterone levels among males, and lower testosterone levels can act as a marker for diabetes. Thus, with timely intervention, mortality and co-morbidity associated with diabetes can be prevented.

Prevalence of gestational diabetes mellitus in Kashmiri women from the Indian subcontinent.

This prospective study was carried out to determine the prevalence of gestational diabetes mellitus (GDM) in Kashmiri women and to assess the effect of various demographic factors. Two thousand pregnant women (divided into groups A and B, being the first and last 1000 consecutive women) attending various antenatal clinics in six districts of Kashmir valley were screened for GDM by 1 h 50 g oral glucose challenge test. Four hundred and fourteen (20.8%) women (216 from group A and 198 from group B) had an abnormal screening test and proceeded to oral glucose tolerance testing. Women from group A had a 3 h 100 gram oral glucose tolerance test (OGTT) and GDM was as classified by Carpenter and Coustan. A 2 h 75 g OGTT was performed on group B subjects and WHO criteria applied for diagnosis of GDM. The overall prevalence of GDM was 3.8% (3.1% in group A versus 4.4% in group B-P-value 0.071). GDM prevalence steadily increased with age (from 1.7% in women below 25 years to 18% in women 35 years or older). GDM occurred more frequently in women who were residing in urban areas, had borne three or more children, had history of abortion(s) or GDM during previous pregnancies, had given birth to a macrosomic baby, or had a family history of diabetes mellitus. Women with obesity, hypertension, osmotic symptoms, proteinuria or hydramnios had a higher prevalence of GDM.

Increased prevalence of subclinical hypothyroidism in females in mountainous valley of Kashmir.

BACKGROUND: Iodine-rich diet is necessary for proper thyroid gland function. Subclinical hypothyroidism (SCH) is associated with serious complications. Substantial numbers of patients have risk of SCH getting converted into primary hypothyroidism. OBJECTIVES: The objectives of the present study are to survey dietary iodine intake pattern in ethnic population of Kashmir and to study the prevalence of SCH. MATERIALS AND METHODS: A retrospective, cross-sectional referral hospital study was conducted. Sample size comprised of 2550 patients who were referred to Department of Biochemistry, Government Medical college, Srinagar diagnostic laboratory from OPD and IPD of associated SMHS hospital. Assessment of thyroid function over a period of one year from March 2010 to March 2011 in the serum has been performed by electro-chemiluminescence immunoassay method on ECLIA 2010 fully automatic analyzer. Interview cum questionnaire methods were used to record the patient history and dietary iodine intake pattern. Iodine status of these patients was assessed by measuring urinary iodine excretion. RESULTS: Total patients were 2550 comprising of 44.6% males and 56.4% females. Subjects with elevated and normal thyroid stimulating hormone (TSH) levels in the serum were 30.51 and 69.4% respectively. About 550 patients (21.56%) had subclinical hypothyroidism which includes both males and females. Prevalence of SCH was more in females (81.8%) than in males (18.2%). Most of the patients presenting with SCH were in the age group of 20-65 years. CONCLUSION: The percentage of SCH amongst the study sample patients was 21.56%, which is much higher as compared to other parts of the world. The highest percentage of SCH was found in females (81.8%) as compared to males (18.2%). On the basis of the present study, we suggest that routine screening of selected populations, especially women between 20 and 65 years of age, may be advocated. Further community level awareness programs need to be organized wherein people in mountainous valley of Kashmir are motivated to take salt in iodized form and diet rich in iodine to ensure proper thyroid gland functioning.

A clinical study of the cutaneous manifestations of hypothyroidism in kashmir valley.

BACKGROUND: Thyroid disorders are known to involve all the organ systems of the body, the skin being no exception. The association of thyroid disorders with cutaneous manifestations is complex. Both hypothyroidism and hyperthyroidism are known to cause these changes. AIMS: The present study was designed to ascertain the varied cutaneous manifestations of hypothyroidism. MATERIALS AND METHODS: This study was a hospital based clinical study conducted in collaboration with the Endocrinology Division (Department of Medicine) of SMHS Hospital (associated teaching hospital of Government Medical College Srinagar), over a period of one year, from May 2010 to May 2011. Four hundred and sixty consecutive diagnosed cases of hypothyroidism constituted the subject material for the study and were evaluated for the presence of any cutaneous manifestation. RESULTS: In our study group of 460 patients, there were 416 females and 44 male patients. The predominant cutaneous symptom in our hypothyroid patients was dry coarse skin (65.22%), followed by hair loss (42.6%) and puffy edema (38.48%). The most common cutaneous sign observed in hypothyroid patients was xerosis (57.17%), followed by diffuse hair loss (46.09%), altered skin texture (31.74%), coarse scalp hair (29.35%) and puffy face (28.69%). CONCLUSIONS: The interaction between thyroid gland and skin is of profound clinical importance in dermatological practice. So, dermatologists need to be cognizant of the ways in which these two organs interact.

Cabergoline-induced tricuspid regurgitation: Case report and review of literature.

The increased risk of cardiac valve disease in patients treated for Parkinson's disease with cabergoline has raised concerns about the safety of treatment with ergot-derived dopamine agonists in patients with endocrine diseases, especially prolactinoma. Concern is raised because the use of cabergoline was associated in one study with an increased prevalence of moderate tricuspid regurgitation, and in two other studies with mild tricuspid regurgitation. Furthermore, the use of cabergoline was associated with increased frequencies of valvular thickening, calcifications, and increased mitral tenting area.

Suprasellar tubercular abscess presenting as panhypopituitarism: a common lesion in an uncommon site with a brief review of literature.

Following widespread use of imaging, detection rate of abnormal sites of parenchymal neuro-tuberculosis is on a rise. A handful of cases of tuberculomas/abscesses in hypothalamo-pituitary region have been reported and most of them are diagnosed on surgical histopathology. We describe a patient of suprasellar tubercular abscess, who presented with visual disturbances, diabetes insipidus with panhypopituitarism and on histopathology had granulomas and positive acid fast bacilli.