Alok Sachan

High Prevalence of Associated Birth Defects in Congenital Hypothyroidism

Aim. To identify dysmorphic features and cardiac, skeletal, and urogenital anomalies in patients with congenital hypothyroidism. Patients and Methods. Seventeen children with congenital primary hypothyroidism were recruited. Cause for congenital hypothyroidism was established using ultrasound of thyroid and radionuclide thyroid scintigraphy. Malformations were identified by clinical examination, echocardiography, X-ray of lumbar spine, and ultrasonography of abdomen. Results. Ten (59%) patients (6 males and 4 females) had congenital malformations. Two had more than one congenital malformation (both spina bifida and ostium secundum atrial septal defect). Five (29%) had cardiac malformations, of whom three had only osteum secundum atrial septal defect (ASD), one had only patent ductus arteriosus (PDA), and one patient had both ASD and PDA. Seven patients (41%) had neural tube defects in the form of spina bifida occulta. Conclusion. Our study indicates the need for routine echocardiography in all patients with congenital hypothyroidism.

Association of lipid peroxidation with endothelial dysfunction in patients with overt hypothyroidism.

Hypothyroidism is associated with increased oxidative stress. The mechanism underlying the endothelial dysfunction in thyroid disease is not yet clear. This study aims to investigate lipid peroxidation and its association with endothelial dysfunction in overt hypothyroidism (OHT).Plasma malondialdehyde (MDA) as a marker of oxidative stress and plasma nitrates and asymmetric dimethyl arginine levels (ADMA) as markers of endothelial dysfunction were estimated in 25 OHT patients in comparison to 25 euthyroid controls. Plasma MDA, ADMA levels were significantly increased, whereas plasma nitrates were significantly decreased in the patient group compared to control group (p<0.01). Moreover, a significant positive association between plasma MDA and ADMA was found in the patient group (ρ=0.472, p=0.036). Our results reveal the presence of endothelial dysfunction in OHT patients as evidenced by decreased plasma nitrates and increased ADMA levels. Increased levels of MDA represent an increased generation of reactive oxygen species in these patients. A finding of significant direct relation of plasma MDA with ADMA indicates that oxidative stress has a strong impact on endothelial dysfunction in overt hypothyroidism. Further studies focusing on the role of oxidative stress in endothelial dysfunction and the effects of antioxidant supplementation on endothelial function in OHT patients are required.

Oxidative stress in non-obese women with polycystic ovarian syndrome.

BACKGROUND Polycystic ovarian syndrome (PCOS) is one of the most common endocrine diseases of women. Oxidative stress is an important component of the cardio-metabolic risk seen in these women. Oxidative stress has been reported in obese PCOS women. This study is taken up to study oxidative stress in non-obese PCOS women. MATERIALS AND METHODS Twenty five non-obese women with PCOS attending the Endocrinology outpatient Department of Sri Venkateswara Institute of Medical Sciences, Tirupati, India along with 25 healthy BMI matched controls were included in the study. The changes in the lipid peroxidation products (MDA), and total anti oxidant capacity (FRAP) as an index of anti oxidant status along with fasting glucose, insulin and uric acid levels were measured in both groups. Insulin resistance was evaluated by using homeostasis model assessment for insulin resistance [HOMA-IR)= [FPG (mg/dl) × insulin (mIU/L)]/ 405] in both groups. RESULTS Serum MDA and uric acid levels were increased in the study group compared with controls and FRAP levels were decreased in the study group compared to controls though statistically insignificant. CONCLUSION Oxidative stress is also present in non-obese women with PCOS. Oxidative stress further increases the CVD risk in these women.Correcting oxidative stress with antioxidants along with monitoring the antioxidant status using a simple assay like FRAP could have a beneficial effect on oxidative stress induced insulin resistance and hyperandrogenism seen in these women.

Effect of lifestyle modification and metformin therapy on emerging cardiovascular risk factors in overweight Indian women with polycystic ovary syndrome.

INTRODUCTION Polycystic ovarian syndrome (PCOS) is common among women of reproductive age. Although traditional cardiac risk factors are known to be altered and improved with short-term metformin therapy, not much is known about novel cardiac risk factors. OBJECTIVE The aim of this study was to evaluate the effects of lifestyle modification and short-term metformin therapy on the fasting serum lipids, homeostasis model assessment of insulin resistance (HOMA-IR), serum high-sensitivity C-reactive protein (hsCRP), and serum homocysteine. METHODS Native overweight [body mass index (BMI) >23 kg/m(2)] Indian women diagnosed with PCOS were evaluated and subjected to an oral glucose tolerance test and determination of insulin, homocysteine, hsCRP, and fasting lipids levels. They were started on maximally tolerated doses of metformin along with lifestyle modification. Following 3 months of therapy, they were resampled. RESULTS Out of 36 consecutive patients included, 25 women completed 3 months of metformin treatment and were eligible for repeat evaluation. The age of study group was 22.2 ± 5 years. Twenty-two (61%) women were obese (BMI >25 kg/m(2)). Improvement was seen in body weight, BMI, serum total cholesterol, triglycerides, high-density lipoprotein cholesterol (HDL-C), hsCRP, and serum testosterone on metformin therapy. However, no improvement was seen in serum fasting insulin, HOMA-IR, or homocysteine. CONCLUSION Serum hsCRP improved with lifestyle modification and metformin therapy for 3 months in overweight subjects from India with PCOS, along with serum total cholesterol, triglycerides, and HDL-C. However, markers of insulin resistance and serum homocysteine did not improve.

Effects of thyroid hormone replacement on glycated hemoglobin levels in non diabetic subjects with overt hypothyroidism.

OBJECTIVE Glycated hemoglobin (HbA1c) may not accurately reflect the level of glycemia in conditions of altered erythrocyte turnover. Hypothyroidism is one condition associated with sluggish erythropoesis. To assess changes in HbA1c, independent of changes in plasma glucose after initiation of thyroxine replacement in patients with overt hypothyroidism. MATERIALS AND METHODS In this prospective longitudinal study carried out in a tertiary care centre, adult non-diabetic patients with overt hypothyroidism recruited between March 2012 to August 2013 were rendered euthyroid on thyroxine. They underwent testing for hemoglobin, HbA1c, reticulocyte count, thyroxine, thyrotropin and a standard oral glucose tolerance test, both before and at 3 months after restoration to the euthyroid state. Main outcome assessed was the change in HbA1c independent of the change in glucose parameters. RESULTS Thirty eight patients (35 female and 3 male) aged 37.8 ± 10.2 years with overt hypothyroidism (thyroxine 12.6 ± 13.4 ng/mL and thyrotropin -98.1 ± 63.7 µIU/mL respectively) were recruited. While HbA1c fell from 5.8 ± 0.7% to 5.6 ± 0.5% (p = 0.009) at 3 months following the correction of hypothyroidism, there were no changes in the fasting and the 2 hr post oral glucose tolerance test glucose (p = 0.67 and 0.56 respectively). The number of patients with dysglycemia diagnosed by HbA1c (i.e HbA1c ≥ 5.7%) fell from 25 (65.78%) to 17 (44.7%) after treatment (p = 0.008). There were 7 (18.4%) patients with HbA1c ≥ 6.5% at baseline, but this fell to just 4 (10.5%) (p < 0.001) after 3 months of euthyroidism. CONCLUSION HbA1c is not a reliable diagnostic test for diabetes in the presence of hypothyroidism.

Effect of oral hypoglycaemic agents on bone metabolism in patients with type 2 diabetes mellitus & occurrence of osteoporosis

Background & objectives: Type 2 diabetes mellitus (T2DM) is considered to be a protective factor against development of osteoporosis. But oral hypoglycaemic agents (OHA) are likely to increase the risk of osteoporosis. This study was carried out to evaluate the effect of various OHA on bone mineral density (BMD) in patients with T2DM. Methods: Forty one patients (study group) with T2DM (mean age 51.9±5.5 yr; 31 females) receiving treatment with oral hypoglycaemic agents (OHA) [thiazolidinediones alone (n=14) or in combination with other OHA (n=27)] for a period of at least three consecutive years and 41 age- and gender-matched healthy controls (mean age 51.4±5.1 yr) were included in the study. A detailed clinical history was taken and all were subjected to physical examination and recording of anthropometric data. BMD was assessed for both patients and controls. Results: The mean body mass index (kg/m2) (26.5±4.90 vs 27.3 ±5.33) and median [inter-quartile range (IQR)] duration of menopause (yr) among women [6(2-12) vs 6(1-13)] were comparable between both groups. The bone mineral density (BMD; g/cm2) at the level of neck of femur (NOF) (0.761±0.112 vs 0.762±0.110), lumbar spine antero-posterior view (LSAP) (0.849±0.127 vs 0.854±0.135); median Z-score NOF {0.100[(-0.850)-(0.550)] vs -0.200[(-0.800)-(0.600)]}, LSAP {-1.200[(-1.700)-(-0.200)] vs -1.300 [(-1.85)-(-0.400)]} were also similar in study and control groups. Presence of normal BMD (9/41 vs 8/41), osteopenia (16/41 vs 18/41) and osteoporosis (16/41 vs 15/41) were comparable between the study and control groups. No significant difference was observed in the BMD, T-scores and Z-scores at NOF and LSAP among T2DM patients treated with thiazolidinediones; those treated with other OHA and controls. Interpretation & conclusions: The present findings show that the use of OHA for a period of three years or more does not significantly affect the BMD in patients with T2DM.

Should we apply suction during fine needle cytology of thyroid lesions? A prospective study of 200 cases.

INTRODUCTION Fine needle aspiration cytology (FNAC) is a well-established first line diagnostic tool in evaluating palpable thyroid lesions. However, the technique depends on suction and thus is at times painful, sometimes traumatic and yield haemorrhagic material for cytological study. In more recent times, a modified technique called fine needle sampling without aspiration (FNS) has come into vogue which obviates the use of suction and therefore is more patient friendly. AIMS/OBJECTIVES To investigate whether fine needle sampling without aspiration (FNS) gives quantitatively and qualitatively superior cytologic material as compared to the conventional technique of fine needle aspiration (FNAC) in thyroid lesions. MATERIALS AND METHODS It is a prospective study of 200 cases carried out in the Department of Pathology during two years period. Both techniques were executed on the same thyroid swelling / nodule in the same clinical session beginning with FNS followed by FNAC. The observation recorded by two pathologists were based on the scoring system proposed by Mair et al., Statistical analysis was done by Students paired t-test using SPSS 13 software. Observation/Results: A total of 200 cases were studied. The non-aspiration technique yielded less diagnostically adequate but more diagnostically superior smears when compared with aspiration technique. The average score per case was 5.31 by aspiration technique and 6.35 by non-aspiration technique. CONCLUSION Both the techniques have their own merits and demerits and neither is absolutely superior to the other. A combination of both the technique gives better result.

High-density lipoprotein cholesterol: How High.

The high-density lipoprotein cholesterol (HDL-C) is considered anti-atherogenic good cholesterol. It is involved in reverse transport of lipids. Epidemiological studies have found inverse relationship of HDL-C and coronary heart disease (CHD) risk. When grouped according to HDL-C, subjects having HDL-C more than 60 mg/dL had lesser risk of CHD than those having HDL-C of 40-60 mg/dL, who in turn had lesser risk than those who had HDL-C less than 40 mg/dL. No upper limit for beneficial effect of HDL-C on CHD risk has been identified. The goals of treating patients with low HDL-C have not been firmly established. Though many drugs are known to improve HDL-C concentration, statins are proven to improve CHD risk and mortality. Cholesteryl ester transfer protein (CETP) is involved in metabolism of HDL-C and its inhibitors are actively being screened for clinical utility. However, final answer is still awaited on CETP-inhibitors.

Heterogenous origins of hyperandrogenism in the polycystic ovary syndrome in relation to body mass index and insulin resistance

Abstract Background: Insulin resistance and obesity are not universal features of polycystic ovary syndrome (PCOS). We planned to assess the differences between patients with nonobese /insulin-sensitive phenotype vs. obese/ insulin-resistant phenotype in terms of the potential mechanisms underlying their hyperandrogenism. Materials and methods: A total of 52 women satisfying Androgen Excess Society (AES) criteria were included. Hormonal and metabolic profile including prolactin, dehydroepiandrosterone sulfate (DHEAS), free testosterone, sex hormone binding globulin (SHBG), fasting plasma glucose and insulin were measured in follicular phase. Results: DHEAS was found to be higher in the nonobese patients as compared to the obese (p = 0.01). There was also a strong trend for a higher DHEAS among patients with lower insulin resistance by homeostatic model assessment (HOMA-IR< 2.3) (p = .06).While the total testosterone (p = .044) and SHBG (p = .007) were found to be lower in the more insulin-resistant group (HOMA-IR ≥ 2.3), the free testosterone levels were similar. However, the percentage of free testosterone was higher in the more insulin-resistant group (p = .005). Conclusions: The hyperandrogenic state in PCOS appears to have heterogenous origins. Nonobese patients with PCOS have adrenal hyperandrogenism as the underlying mechanism while their obese/ insulin-resistant counterparts have low SHBG and hence an increased fraction of free testosterone.

Malignancy in solitary thyroid nodule: A clinicoradiopathological evaluation

Background: Thyroid nodules are common. They can be either benign or malignant. Solitary thyroid nodules (STN) have a high likelihood of being malignant. They should be characterized properly for optimum management. Materials and Methods: In this study, we have analyzed our departmental data over a period of 5 years. All the patients who presented to the outpatient department with a clinically detected STN were included in the study group. Our approach was individualized. Preoperative ultrasonography (USG) and fine-needle aspiration cytology were planned in all these patients. Hemi thyroidectomy and total thyroidectomy with and without neck dissection were performed wherever appropriate. Results: There were 162 cases of clinically detected STN. USG findings were available in 146 cases. Postoperative histopathology was reported as malignant in 58 cases. Malignant STN was more likely in males. Ultrasonographically detected solid STN were more prone for malignancy as compared to multinodular goiter (P = 0.000) Presence of micro calcification and cervical lymphadenopathy were more commonly noted in malignant thyroid swellings. Conclusion: Solitary thyroid nodules do have a high likelihood of harboring a malignancy. Solid echogenicity, micro calcification and cervical lymphadenopathy on USG were seen more frequently in malignant nodules.