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   Table of Contents - Current issue
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March-April 2017
Volume 21 | Issue 2
Page Nos. 261-363

Online since Tuesday, March 14, 2017

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EDITORIALS  

Patient-centered blood pressure: Thresholds, targets, and tools in diabetes p. 261
Sanjay Kalra, Kamal Kishor, Yashdeep Gupta
DOI:10.4103/ijem.IJEM_37_17  
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Transgenerational karma p. 265
Bharti Kalra, Sanjay Kalra, AG Unnikrishnan, Manash P Baruah, Deepak Khandelwal, Yashdeep Gupta
DOI:10.4103/ijem.IJEM_7_17  
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Interaction, information, involvement (the 3I strategy): Rebuilding trust in the medical profession p. 268
Sanjay Kalra, AG Unnikrishnan, Manash P Baruah
DOI:10.4103/ijem.IJEM_6_17  
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ORIGINAL ARTICLES Top

Perceptions about training during endocrinology residency programs in India over the years: A cross-sectional study (PEER India Study) Highly accessed article p. 271
Deepak Khandelwal, Deep Dutta, Rajiv Singla, Vineet Surana, Sameer Aggarwal, Yashdeep Gupta, Sanjay Kalra, Rajesh Khadgawat, Nikhil Tandon
DOI:10.4103/ijem.IJEM_530_16  
Background: Residents' perception on quality of endocrinology training in India is not known. This study aimed to evaluate the perceptions about endocrinology residency programs in India among current trainees as compared to practicing endocrinologists. Methods: Trainees attending a preconference workshop at the annual conference of Endocrine Society of India (ESI) were given a questionnaire designed to evaluate their perceptions on their training. These evaluated the reasons for choosing endocrinology, their experiences during residency, and career plans. Practicing endocrinologists attending ESICON with at least 5-year experience were evaluated as controls. Results: Questionnaires from 63 endocrine trainees and 78 practicing endocrinologists were analyzed. Endocrinology is perceived to be the super-specialty with the best quality of life (QOL) but fair with regard to financial remuneration. Among current trainees, 61.89%, 31.74%, and 34.91% are satisfied with training in clinical endocrinology, laboratory endocrinology, and clinical/translational research, respectively. The corresponding figures for practicing endocrinologists are 71.78%, 25.63%, and 30.75%, respectively. Exposure to national endocrinology conferences during their endocrinology residency was adequate. However, exposure to international endocrinology conferences, research publications, project writing, and grant application are limited. Laboratory endocrinology is rated as the most neglected aspect during endocrine residency. Most of the trainees want to establish their own clinical practice in the long run. Very few trainees (17.46%) wish to join the medical education services. Conclusion: There is a good perception of QOL in endocrinology in spite of average financial remuneration. There is dissatisfaction with the quality of training in laboratory endocrinology and clinical research. Very few endocrine trainees consider academics as a long-term career option in India.
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Improving bethesda reporting in thyroid cytology: A team effort goes a long way and still miles to go… p. 277
Subramanian Kannan, Nalini Raju, Vikram Kekatpure, Naveen Hedne Chandrasekhar, Vijay Pillai, A Renuka Keshavamurthy, Moni Abraham Kuriakose, Pobbisetty Radhakrishnagupta Rekha, Nisheena Raghavan, Akhila Lakhsmikantha, Srinivas Ramaiah, Brijal Dave
DOI:10.4103/ijem.IJEM_350_16  
Context: Fine-needle aspiration cytology is the first step in evaluation of thyroid nodules. Although the Bethesda classification for reporting thyroid cytology has been purported that this uniformity in reporting cytology thereby facilitating clinical decision-making, there are also studies indicating that the reporting percentage and the rates of malignancy in each category vary considerably from center to center making the clinical decision more difficult. Aim and Materials and Methods: We looked at our retrospective cytology and histopathology data of thyroid nodules operated between 2012 and 2014 and then prospectively collected data during 2015–2016. In the prospective arm, for every thyroid nodule that was sampled, there was a discussion between the endocrinologist and the cytopathologist on the risk of thyroid cancer (based on the patient's history, examination findings, sonographic pattern, and the cytological appearance). Results: We noted that there was considerable improvement in reporting standards with the rates of nondiagnostic cytology dropping from 11% to 5%, an increased reporting of Bethesda Category 2 and 6 which are the definitive strata of benign and malignant nodules (38% to 41% in Category 2 and 7% to 11% in Category 6) with a high specificity (100%). There was a decline in numbers of Category 4 and 5 (13% to 9% in Category 4 and 12% to 3% in Category 5). The reporting prevalence of Category 3 increased from 19% to 27%. Conclusions: We conclude that a team approach between the clinician who performs the ultrasound and the reporting cytopathologist improves Bethesda reporting, its predictive value, and thus potentially avoiding unnecessary thyroidectomies in benign thyroid nodules and hemithyroidectomies in thyroid cancers.
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Cardiac autonomic neuropathy in patients with Type 2 diabetes mellitus at high risk for foot ulcers p. 282
Anil S Menon, Abhinav Dixit, MK Garg, R Girish
DOI:10.4103/ijem.IJEM_542_16  
Aim: To study the prevalence of cardiac autonomic neuropathy (CAN) in patients with Type 2 diabetes mellitus at high risk for foot ulcers. Materials and Methods: We screened patients attending diabetic clinic for identifying patients at high risk for foot ulcers. Those with foot risk category 1, 2 and 3 as per criteria of Foot Care Interest Group were subjected to battery of cardiovascular autonomic reflex tests. Those with one abnormal test were termed as probable CAN and those with two abnormal tests as definite CAN. Those with postural fall in blood pressure with one other abnormal test were termed to have advanced CAN. Results: A total of 74 patients were recruited in the study. The prevalence of abnormal cardiovascular autonomic reflex test was sustained hand grip 81%, E/I ratio 66.2%, 30:15 ratio 28.3% and orthostatic hypotension 13.5%. The prevalence of possible CAN was 31.0% (23/74) and definite CAN was 66.2% (49/74). Ten patients had advanced CAN. There was no observable difference in presence of probable or definite CAN in three risk category for foot ulcers. Conclusion: We found a high prevalence of CAN in subgroup of diabetic patients at increased risk for foot ulcer.
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Long-term efficacy and safety of empagliflozin monotherapy in drug-naïve patients with type 2 diabetes in Indian subgroup: Results from a 76-week extension trial of phase iii, double-blind, randomized study p. 286
Sunil Gupta, Shehla Shaikh, Pooja Joshi, Shraddha Bhure, Viraj Suvarna
DOI:10.4103/ijem.IJEM_517_16  
Background and Objectives: Empagliflozin, a sodium glucose cotransporter-2 inhibitor, was recently evaluated in a randomized, controlled trial (RCT) in drug-naïve Type 2 diabetes mellitus (T2DM) patients managed on diet and exercise therapy. Efficacy and safety of empagliflozin in Indian subgroup of patients from a 76-week extension study of the initial multicentric RCT are reported in this article. Materials and Methods: In this study, patients were randomized to empagliflozin 10 mg (E10, n = 24), empagliflozin 25 mg (E25, n = 29), placebo (n = 28) and sitagliptin 100 mg (S100, n = 27). Exploratory efficacy endpoints were changed from baseline to week 76 in glycosylated hemoglobin (HbA1c, %) and fasting blood glucose (mg/dL) along with body weight (kg) and blood pressure (BP) (mmHg) reduction. Safety analysis included clinically relevant adverse events (AEs). Results: In 108 randomized patients, adjusted mean reduction in HbA1c compared to placebo was significant with E10 (−0.81, 95% confidence interval (CI) −1.33, −0.28; P = 0.0029) and E25 (−1.11, 95% CI − 1.60, −0.61; P < 0.0001). HbA1c below 7% at week 76 was achieved in significantly higher number of patients with E10 (20.8%, P < 0.0001) and E25 (28.0%, P < 0.0001). There was significant reduction in adjusted mean weight as compared to placebo with E10 (−1.41, 95% CI − 2.51, −0.31; P = 0.0125) and E25 (−1.50, 95% CI − 2.54, −0.46; P = 0.0051) but nonsignificant with S100 (−0.75 95% CI − 1.86, −0.36; P = 0.1842). BP reduction was numerically higher with empagliflozin compared to placebo. AEs were similar in all treatment groups except for genital infections which were more common in E10 (20.8%) but not in E25 (3.4%) as compared to placebo (3.6%). All treatments were well tolerated with no severe AEs. Conclusion: Treatment with empagliflozin was well tolerated and resulted in sustained glycemic efficacy over long-term (76 weeks) in drug-naïve Indian T2DM patients.
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Footboards: Indigenous and novel method of screening for diabetes peripheral neuropathy – A pilot study p. 293
Akram Hussain Bijli, Altaf Rasool, Adil Hafeez Wani, Mir Yasir, Tanveer Ahmad Bhat, Bashir Ahmad Laway
DOI:10.4103/ijem.IJEM_549_16  
Background: To validate the effectiveness of indigenously designed “footboard (FB)” in early diagnosis of diabetic peripheral neuropathy (PNP) by comparing it with Semmes–Weinstein monofilament (SWM) and vibration perception (VP). Materials and Methods: Two hundred and forty-four patients with diabetes were examined for PNP using SWM and 128 Hz tuning fork. The findings were compared with indigenously designed FBs with 1, 2, and 3 mm elevations. Results: Out of 108 patients who did not have protective sensation as per SWM, only 10 (9.2%) felt 1 mm board bearings, and out of 72 patients who did not feel vibration, only 8 (11.1%) felt 1 mm board bearings. Out of 136 patients who had protective sensation, 128 (94.11%) felt 2 mm elevated board bearings, and out of 172 patients who had VP, only 152 patients (88.3%) felt 2 mm board bearings. With SWM as standard, the sensitivities and specificities, respectively, were 63% and 90% (1 mm board), and 94% and 60% (2 mm board). With VP, the sensitivities and specificities, respectively, were 59% and 90% (1 mm board), and 88% and 61% (2 mm board). Conclusions: FB, which simultaneously tests touch and pressure sensation, shows a high level of performance in detecting at-risk feet. FB may be simple, time-efficient, and inexpensive test for detection of neuropathy and needs further validation in a larger study.
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Association of fat mass and obesity-associated gene variant with lifestyle factors and body fat in Indian Children p. 297
Lavanya S Parthasarthy, Nikhil Phadke, Shashi Chiplonkar, Anuradha Khadilkar, Kavita Khatod, Veena Ekbote, Surabhi Shah, Vaman Khadilkar
DOI:10.4103/ijem.IJEM_372_16  
Context: Common intronic variants of the fat mass and obesity-associated (FTO) gene have been associated with obesity-related traits in humans. Aims: (1) The aim of this study is to study the distribution of FTO gene variants across different body mass index (BMI) categories and (2) to explore the association between FTO gene variants and lifestyle factors in obese and normal weight Indian children. Subjects and Methods: Fifty-six children (26 boys, mean age 10.3 ± 2.2 years) were studied. Height, weight, and waist and hip circumference were measured. Physical activity (questionnaire) and food intake (food frequency questionnaire) were assessed. Body fat percentage (%BF) was measured by dual-energy X-ray absorptiometry. FTO allelic variants at rs9939609 site were detected by SYBR Green Amplification Refractory Mutation System real-time polymerase chain reaction using allele-specific primers. Generalized linear model was used to investigate the simultaneous influence of genetic and lifestyle factors on %BF. Results: Mean height, weight, and BMI of normal and obese children were 130.6 ± 7.1 versus 143.2 ± 15.6, 24.0 ± 5.2 versus 53.1 ± 15.8, and 13.9 ± 2.1 versus 25.3 ± 3.2, respectively. The frequency of AA allele was 57% among obese children and 35% in normal weight children. Children with the AA allele who were obese had least physical activity, whereas children with AT allele and obesity had the highest intake of calories when compared to children who had AT allele and were normal. %BF was positively associated with AA alleles and junk food intake and negatively with healthy food intake and moderate physical activity. Conclusions: Healthy lifestyle with high physical activity and diet low in calories and fat may help in modifying the risk imposed by FTO variants in children.
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The thyroid registry: Clinical and hormonal characteristics of adult indian patients with hypothyroidism p. 302
Bipin Sethi, Sumitav Barua, MS Raghavendra, Jagdish Gotur, Deepak Khandelwal, Upal Vyas
DOI:10.4103/ijem.IJEM_387_16  
Objectives: Appropriate treatment of hypothyroidism requires accurate diagnosis. This registry aimed to study the disease profile and treatment paradigm in hypothyroid patients in India. Materials and Methods: We registered 1500 newly diagnosed, treatment-naïve, adult hypothyroid males and nonpregnant females across 33 centers and collected relevant data from medical records. The first analysis report on baseline data is presented here. Results: The mean age of the study population was 41.1 ± 14.01 years with a female to male ratio of 7:3. The most frequently reported symptoms and signs were fatigue (60.17%) and weight gain with poor appetite (36.22%). Menstrual abnormalities were reported in all women (n = 730) who had not attained menopause. Grades 1 and 2 goiter (as per the WHO) were observed in 15.41% and 3.27% patients, respectively. Comorbidities were reported in 545 patients (36.36%), type 2 diabetes mellitus being the most prevalent (13.54%) followed by hypertension (11.34%). Total serum thyroxine (T4) and thyroid-stimulating hormone (TSH) levels were assessed in 291 (19.47%) patients only. In majority of patients (81%), treatment was based on serum TSH levels alone. The dose of levothyroxine ranged from 12.5 to 375 mcg. Conclusions: Guidelines suggest a diagnosis of hypothyroidism based on TSH and T4 levels. However, most of the patients as observed in this registry received treatment with levothyroxine based on TSH levels alone, thus highlighting the need for awareness and scientific education among clinicians in India. The use of standard doses (100, 75, and 25 mcg) of levothyroxine may point toward empirical management practices.
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Occurrence of diabetes mellitus in obese nondiabetic patients, with correlative analysis of visceral fat, fasting insulin, and insulin resistance: A 3-year follow-up study (mysore visceral adiposity in diabetes follow-up study) p. 308
M Premanath, H Basavanagowdappa, M Mahesh, M Suresh Babu
DOI:10.4103/ijem.IJEM_418_16  
Objective: To assess the occurrence of diabetes in obese nondiabetic patients over a 3-year follow-up period with a correlative analysis of visceral fat (VF), fasting insulin levels, (FILs) and insulin resistance (IR). Material and Methods: Thirty-seven obese and nineteen nonobese nondiabetics of our previous study, Mysore Visceral Adiposity in Diabetes were followed for the next 3 years. Their blood pressure, body mass index, waist circumference (WC), fasting blood sugar (FBS), FIL, lipid profile and subcutaneous fat (SCF), and VF measurement by US method were repeated every 6 months for the next 3 years. The findings were analyzed with appropriate statistical methods. Results: Twenty-three obese and 18 nonobese nondiabetics completed the study. There were 17 dropouts. The changes in the physical and biochemical characteristics of the two groups before and after the study were not significant. SCF had no correlation with IR whereas VF correlated with FIL and IR. There were three diabetics in the obese group and two from the control group at the end of the study. There were 12 impaired glucose tolerance (IGT) in the test group and 2 in the control group. Those who developed diabetes had higher VF, WC, FBS, FIL, and IR. Those who showed IGT also had these at higher levels compared to others. There was no change in the VF at the end of the study. Conclusions: This follow-up study on South Indians has shown that VF is a significant risk factor for the development of IR. IR can develop without any increase in the volume of the VF, is the essential finding of this study. SCF has not shown any significant relationship with IR. We recommend FBS and FIL in all the obese nondiabetics to calculate IR, which has given much insight in the development of IGT and diabetes. Large multicentric, longitudinal studies are required to establish the cause of IR.
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Antiretroviral therapy-induced insulin resistance and oxidative deoxy nucleic acid damage in human immunodeficiency virus-1 patients p. 316
Vaishali Kolgiri Honnapurmath, VW Patil
DOI:10.4103/2230-8210.202029  
Background and Objectives: Insulin resistance (IR) is frequent in human immunodeficiency virus (HIV) infection and may be related to antiretroviral therapy (ART). Increased oxidative stress parameters and carbonyl protein are linked to insulin sensitivity. The present study is aimed to determine IR, its association with oxidative deoxy nucleic acid (DNA) damage in HIV-1-infected patients with different ART status. Materials and Methods: In this case–control study, a total 600 subjects were included. We used plasma levels of the oxidized base, 8-hydroxy-2-deoxyguanosine (8-OHdG), as our biomarker of oxidative DNA damage. 8-OHdG was measured with the highly sensitive 8-OHdG check enzyme-linked immunosorbent assay kit. IR was determined using homeostasis model assessment. Results: All subjects were randomly selected and grouped as HIV-negative (control group) (n = 300), HIV-positive without ART (n = 100), HIV-positive with ART first line (n = 100), and HIV-positive with ART second line (n = 100). IR and oxidative DNA damage were significantly higher in HIV-positive patients with second-line ART and HIV-positive patients with first-line ART than ART-naive patients. In a linear regression analysis, increased IR was positively associated with the increased DNA damage (odds ratio: 3.052, 95% confidence interval: 2.595–3.509) P < 0.001. Interpretation and Conclusions: In this study, we observed that ART plays a significant role in the development of IR and oxidative DNA damage in HIV-positive patients taking ART. Awareness and knowledge of these biomarkers may prove helpful to clinicians while prescribing ART to HIV/AIDS patients. Larger studies are warranted to determine the exact role of ART in the induction of IR and DNA damage.
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Patient and health-care professional satisfaction with a new, simple, high accuracy blood glucose meter with color range indicator p. 322
Laurence B Katz, Mike Grady, Lorna Stewart, Hilary Cameron, Pamela A Anderson, Anish Desai
DOI:10.4103/2230-8210.202030  
Background: Accurate self-monitoring of blood glucose (BG) is a key component of effective self-management of glycemic control. Methods: The OneTouch Select Plus Simple™ (OTSPS) BG monitoring system (BGMS) was evaluated for accuracy in a clinical setting. Results: OTSPS was accurate over a wide glucose range and met lay user and system accuracy BG standards described in ISO 15197:2013. Patients also used OTSPS for a 1-week trial period and reported their level of satisfaction with meter features. In a separate study, health-care professionals (HCPs) in India naïve to OTSPS experienced OTSPS online using a variety of interactive demonstrations of the BGMS and answered questions about its potential utility to their patients. Summary: Patients and HCPs felt the features of OTSPS, including a color range indicator, could provide significant benefits to them and their patients.
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Lack of association of B-type raf kinase V600E mutation with high-risk tumor features and adverse outcome in conventional and follicular variants of papillary thyroid carcinoma p. 329
C Gopalakrishnan Nair, Misha Babu, Lalitha Biswas, Pradeep Jacob, Riju Menon, AK Revathy, Krishnanunni Nair
DOI:10.4103/ijem.IJEM_353_16  
Introduction: Somatic B-type Raf kinase (BRAF) V600E mutation in exon 15 was frequently found in high frequencies associated with papillary thyroid cancer (PTC). The phenotype of these cancers expressed aggressive clinical and pathological features. The present study aimed to assess the prevalence of BRAF V600E mutation among conventional and follicular variants of PTC and its association with aggressive tumor factors and outcome. Study Design: Patients who were operated and received further treatment for PTC during 2012 were included in the study. BRAF V600E mutation analysis was done by extracting genomic DNA from tumor tissue. Results: Of the 59 patients included in the study, 51% harbored BRAF V600E mutation, but the mutation status was not associated with aggressive tumor factors and adverse outcome. Conclusion: BRAF V600E mutation was not significant predictor of aggressive tumor behavior in conventional and follicular variants of PTC.
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REVIEW ARTICLES Top

Mobile health technology in the prevention and management of Type 2 diabetes p. 334
Shruti Muralidharan, Harish Ranjani, Ranjit Mohan Anjana, Steven Allender, Viswanathan Mohan
DOI:10.4103/ijem.IJEM_407_16  
Essential steps in diabetes prevention and management include translating research into the real world, improving access to health care, empowering the community, collaborative efforts involving physicians, diabetes educators, nurses, and public health scientists, and access to diabetes prevention and management efforts. Mobile phone technology has shown wide acceptance across various ages and socioeconomic groups and offers several opportunities in health care including self-management as well as prevention of Type 2 diabetes mellitus (T2DM). The future seems to lie in mobile health (mHealth) applications that can use embedded technology to showcase advanced uses of a smartphone to help with prevention and management of chronic disorders such as T2DM. This article presents a narrative review of the mHealth technologies used for the prevention and management of T2DM. Majority (48%) of the studies used short message service (SMS) technology as their intervention while some studies (29%) incorporated applications for medication reminders and insulin optimization for T2DM management. Few studies (23%) showed that, along with mHealth technology, health-care professionals' support resulted in added positive outcomes for the patients. This review highlights the fact that an mHealth intervention need not be restricted to SMS alone.
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Consensus statement on dose modifications of antidiabetic agents in patients with hepatic impairment p. 341
Kalyan Kumar Gangopadhyay, Parminder Singh
DOI:10.4103/ijem.IJEM_512_16  
Liver disease is an important cause of mortality in type 2 diabetes mellitus (T2DM). It is estimated that diabetes is the most common cause of liver disease in the United States. Virtually, entire spectrum of liver disease is seen in T2DM including abnormal liver enzymes, nonalcoholic fatty liver disease, cirrhosis, hepatocellular carcinoma, and acute liver failure. The treatment of diabetes mellitus (DM) in cirrhotic patients has particular challenges as follows: (1) about half the patients have malnutrition; (2) patients already have advanced liver disease when clinical DM is diagnosed; (3) most of the oral antidiabetic agents (ADAs) are metabolized in the liver; (4) patients often have episodes of hypoglycemia. The aim of this consensus group convened during the National Insulin Summit 2015, Puducherry, was to focus on the challenges with glycemic management, with particular emphasis to safety of ADAs across stages of liver dysfunction. Published literature, product labels, and major clinical guidelines were reviewed and summarized. The drug classes included are biguanides (metformin), the second- or third-generation sulfonylureas, alpha-glucosidase inhibitors, thiazolidinediones, dipeptidyl peptidase-4 inhibitors, sodium-glucose co-transporter 2 inhibitors, glucagon-like peptide-1 receptor agonists, and currently available insulins. Consensus recommendations have been drafted for glycemic targets and dose modifications of all ADAs. These can aid clinicians in managing patients with diabetes and liver disease.
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BRIEF COMMUNICATION Top

Levosulpiride and serum prolactin levels Highly accessed article p. 355
Mohammad Shafi Kuchay, Ambrish Mithal
DOI:10.4103/ijem.IJEM_555_16  
Levosulpiride is the levorotatory enantiomer of sulpiride used in dyspeptic syndromes of various etiologies. The prokinetic effect of levosulpiride is mediated through the blockade of enteric inhibitory dopaminergic type 2 (D2) receptors. The antagonism of central D2 receptors leads to both therapeutic (e.g. antiemetic effect due to D2 receptor blockade in the chemoreceptor trigger zone) and adverse (including hyperprolactinemia) effects. Dopamine is the main endogenous inhibitor of prolactin synthesis and secretion in the anterior pituitary. Levosulpiride causes significant elevation of serum prolactin levels in significant number of patients. The resultant hyperprolactinemia often manifests as distressing menstrual abnormalities and galactorrhoea in females. A significant number of patients who use levosulpiride develop serum prolactin levels of > 200 ng/mL that goes against the classical textbook teaching where pituitary tumor is supposed to be the mostly likely cause. Careful drug history in patients presenting with high serum prolactin levels will be of great help in reaching the exact diagnosis and avoiding unnecessary brain imaging.
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LETTERS TO THE EDITOR Top

Tuberculosis and diabetes mellitus, tackling dual maladies: Comment on Bangladeshi tuberculosis-diabetes mellitus guidelines p. 359
Jyothi Idiculla
DOI:10.4103/ijem.IJEM_465_16  
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Cytochrome P450 oxidoreductase deficiency: Novel cause of ambiguity with primary amenorrhea p. 360
Kranti Shreesh Khadilkar, Varsha Jagtap, Anurag Lila, Tushar Bandgar, Nalini S Shah
DOI:10.4103/2230-8210.202031  
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Utility of cinacalcet in familial hypocalciuric hypercalcemia p. 362
Bipin Kumar Sethi, V Sri Nagesh, Jayant Kelwade, Harsh Parekh, Vaibhav Dukle
DOI:10.4103/2230-8210.202034  
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