Etiological Profile of Galactorrhoea.

BACKGROUND: Recent increase in the non-specific use of prokinetics in clinical practice may alter the etiological profile of hyperprolactinemia and galactorrhea. Hence, we have studied the etiological profile of patients presenting with galactorrhea and characteristics of drug-induced galactorrhea. MATERIALS AND METHODS: This retrospective study was conducted at a tertiary health care center from South India. Patients who presented with or referred for galactorrhea and/or hyperprolactinemia to the Department of Endocrinology between January 2017 and December 2017 were included in the study. RESULTS: Forty women presented with or referred for galactorrhea to the Department of Endocrinology during the study period. Thirty-two patients had received drugs that are associated with hyperprolactinemia (levosulpiride in 15, domperidone in 13, ranitidine in 2, oral contraceptive pill in 1, and amisulpiride in 1) of whom etiology was proved in 27 patients, whereas in four patients the cause was inconclusive due to lack of follow-up. The patient on amisulpiride was found to have concomitant pituitary microadenoma. Idiopathic galactorrhea (n = 2), idiopathic hyperprolactinemia (n = 2), and prolactinoma (n = 4) accounted for the remaining cases. Six patients with prokinetic-induced galactorrhea had received cabergoline inspite of which hyperprolactinemia and/or galactorrhea persisted and six patients had also undergone pituitary magnetic resonance imaging (MRI) for evaluation of galactorrhea. CONCLUSIONS: Prokinetic use is the most common cause of galactorrhea in our study and often was investigated with costly tests and treated with D2 agonists unnecessarily. Hence, there is a need to ensure measures to reduce the non-specific use of prokinetics and increase awareness regarding the occurrence of galactorrhea with prokinetics use, to reduce unnecessary investigations and treatment.

Impairment of Health-related Quality of Life among Indian Patients with Hypothyroidism.

CONTEXT: Health-related quality of life (HRQL) is an important outcome measure for various diseases, although there are sparse data regarding HRQL among Indian patients with hypothyroidism. AIMS: This study aimed to assess HRQL among Indian patients with hypothyroidism using the SF-36 questionnaire. METHODS: This cross-sectional study evaluated 244 consecutive patients with hypothyroidism who were treated at the Vydehi Institute of Medical Sciences and Research Centre in Bengaluru. All patients were >18 years old and visited the outpatient department for endocrine treatment. Perceived health status was evaluated using the SF-36 questionnaire. The patients' data were compared to data from 250 age-matched and sex-matched healthy controls. RESULTS: Compared to the healthy controls, the patients with hypothyroidism had significantly lower scores for six of the eight SF-36 scales. No significant intergroup differences were observed in the "role emotional" and "social functioning" dimensions. INTERPRETATION AND CONCLUSIONS: Hypothyroidism was associated with reduced HRQL among Indian patients. These patients generally experienced greater reductions in physical dimensions, compared to social and emotional dimensions.

Normative Values for Electrochemical Skin Conductance Measurements for Quantitative Assessment of Sudomotor Function in Healthy Indian Adults.

CONTEXT: Electrochemical skin conductance (ESC) test is a widely accepted objective technique for quantitatively assessing sudomotor dysfunction, which is one of the earliest-detected neurophysiologic abnormalities in diabetic patients with distal symmetric polyneuropathy. AIMS: This study aimed to provide normative data for ESC values among healthy Indian participants and assess the potential influence of age, sex, and body mass index (BMI) on ESC measurements. SETTINGS AND DESIGN: A sample of 217 healthy participants aged 18-75 years were recruited and assessed for parameters including age, gender, BMI, and ESC measurements of the hands and feet. STATISTICAL ANALYSIS USED: The Shapiro-Wilk test was used to assess the normality of the data. Pearson's correlation was used to evaluate the association between age, gender, and BMI, and ESC measurements. RESULTS: The mean age of the participants was 43.3 ± 13.2 years, and mean BMI was 26.0 ± 4.3 kg/m2. Mean ESC for the hands and feet was 68.9 ± 13.1 and 71 ± 12.9 micro-Siemens, respectively, and there was a significant correlation between values from the right and left hands and feet (r = 0.9, P < 0.0001). A significant correlation was also observed between ESC measurements of the hands and feet (r = 0.94, P < 0.0001). ESC values of both hands and feet declined with age. A weak but significant inverse correlation between ESC and age was observed for the hands (r = 0.02, P = 0.01) and for the feet (r = 0.12, P < 0.0001). There was no significant difference in hand or feet ESC measurement between male and female participants. No significant correlation was observed between BMI and ESC of hands or feet. Only age was identified as a significant determinant of ESC on multivariate logistic regression analysis. CONCLUSIONS: Normative values for Indians are lower than that reported for Caucasians.

Frequent Occurrence of Faulty Practices, Misconceptions and Lack of Knowledge among Hypothyroid Patients.

INTRODUCTION: Hypothyroidism is a common endocrine disorder with a reported prevalence of 4%-10%. Previous studies have reported significant gaps in the basic knowledge about the condition in hypothyroid patients. It has also been observed that faulty practices prevail among these patients. There is paucity of data on the assessment of knowledge and practices among treated hypothyroid patients. AIM: The present study was aims to assess the knowledge, awareness and practices in treated hypothyroid patients. MATERIALS AND METHODS: The current cross-sectional study was conducted on 244 consecutive hypothyroid patients, attending the Endocrinology Outpatient Department (OPD). The patients were asked to fill a structured questionnaire pertaining to knowledge and practices about various aspects of hypothyroidism. RESULTS: Only two-thirds of the participants correctly identified thyroid as a gland and 41% were aware that hypothyroidism is caused due to decreased function of the thyroid gland. The most common symptom attributed to hypothyroidism was weight gain (139 responses). Nearly 45% of the patients believed alternative forms of medicine can be used for treatment of hypothyroidism. It was believed by 42% of the patients that hypothyroidism runs in the family and about 10% believed it could be transferred to their spouses. Only 33% of the patients gave one hour gap between levothyroxine and food intake. CONCLUSION: The study demonstrates the lack of knowledge about basic aspects of hypothyroidism among the patients. In addition, there is a high prevalence of misconceptions and faulty practices. The study highlights the need for comprehensive patient education to improve therapeutic outcomes and compliance among hypothyroid patients.

High Prevalence of Serine Protease Inhibitor Kazal Type 1 Gene Variations Detected by Whole Gene Sequencing in Patients with Fibrocalculous Pancreatic Diabetes.

AIM OF STUDY: The aim is to study the prevalence and pattern of serine protease inhibitor Kazal type 1 (SPINK1) gene variations in patients with fibrocalculous pancreatic diabetes (FCPD) using whole gene sequencing. MATERIALS AND METHODS: A total of 56 consecutive patients of FCPD were recruited for the study. Diagnosis of FCPD was based on the presence of diabetes mellitus in patients having chronic pancreatitis with radiological evidence of ductal calcifications, in the absence of other known causes for pancreatitis. Ethylenediaminetetraacetic acid samples were collected from all patients, and complete gene sequencing was performed for SPINK1 gene using Sanger technique. RESULTS: Overall 35 patients (62.5%) were detected to have genetic alterations in SPINK1 gene. N34S polymorphism was seen in 23 participants (41.07%) out of which 3 were homozygous. N34S was seen to be in linkage disequilibrium with IVS1 - 37T>C (18/23) and IVS3-69insAAAA (19/23) polymorphisms. Seven patients (12.5%) had a 272 C>T 3'UTR polymorphism while one patient (1.8%) had a P55S polymorphism. Two patients (3.5%) had an IVS3 + 2T>C mutation which has been shown to be associated with loss of function of SPINK protein. Overall 48.2% of FCPD patients had genetic variations that were significant compared to the control population. There was no difference in anthropometric and biochemical parameters between those with or without SPINK1 gene variations. CONCLUSIONS: Variations in SPINK1 gene are frequently observed in FCPD. N34S polymorphism was the most common variation followed by intronic variations. Two patients had the pathogenic intronic IVS3 + 2T>C mutation. Whole gene sequencing of the SPINK1 gene enabled detection of an additional 7.1% of patients with significant SPINK1 gene variations as compared to targeted screening for the N34S variation.

Preoperative zoledronic acid therapy prevent hungry bone syndrome in patients with primary hyperparathyroidism.

BACKGROUND: Hungry bone syndrome is a common complication of surgery for primary hyperparathyroidism in India which often leads to prolonged hospitalization. There are varying reports on the use and efficacy of bisphosphonates in the prevention of hungry bone syndrome. METHODS: We retrospectively analyzed the effect of preoperative bisphosphonate therapy on rates of hungry bone syndrome in our patients with primary hyperparathyroidism. A total of 19 patients underwent surgery for primary hyperparathyroidism at our institute between January 2013 and June 2015 among whom eight did not receive preoperative bisphosphonates and 11 received intravenous zoledronic acid 4 mg, 24-48 h preoperatively. RESULTS: There was no significant difference between the two groups with respect to age, gender, duration of symptoms, preoperative serum calcium, phosphorus, parathyroid hormone, alkaline phosphatase, and the presence of radiological evidence of hyperparathyroid bone disease also did not differ between the groups. Three out of the eight patients who did not receive preoperative zoledronic acid therapy had hungry bone syndrome but none in the zoledronic acid group. The prevalence of hungry bone syndrome tended to be lower in the zoledronic acid group (P = 0.058). The need for intravenous calcium and duration of postoperative hospital stay were significantly lesser in the zoledronic acid group. CONCLUSION: Preoperative intravenous zoledronic acid significantly reduces the need for intravenous calcium therapy and duration of postoperative hospital stay and seems a promising option to reduce the rate of hungry bone syndrome in patients with primary hyperparathyroidism.

The seroprevalence of immunoglobulin A transglutaminase in type 1 diabetic patients of South Indian origin.

CONTEXT: Celiac disease (CD) is a commonly encountered autoimmune condition in patients with type 1 diabetes (T1D). There is sparse data on the seroprevalence of immunoglobulin A (IgA) transglutaminase (tTG) in T1D patients of South Indian origin. AIMS: To detect the prevalence of IgA tTG in T1D patients of South Indian origin. To evaluate the relation between the presence of autoimmunity and metabolic control and complications of diabetes. MATERIALS AND METHODS: We conducted a cross-sectional study on 258 T1D patients. All the patients were subjected to biochemical tests and evaluated for microvascular complications. IgA tTG was estimated by ELISA. IgA tTG levels >40 AU/ml was considered positive. RESULTS: Of the 258 participants, 12 (4.65%) were found to be positive for IgA tTG antibodies. Distribution of IgA positivity was equal in both sexes. There was a significant negative correlation of IgA tTG positivity with hemoglobin and glycated hemoglobin (HbA1c). CONCLUSIONS: The seropositivity of CD in South Indian patients with T1D has been observed to be 4.68%. This is much lower compared to studies from North India. This can be explained by both the genetic and dietary factors. The seropositivity correlated negatively with hemoglobin and HbA1c.

Pancreatic exocrine insufficiency in type 1 and type 2 diabetics of Indian origin.

BACKGROUND: Pancreatic exocrine insufficiency has been frequently described in both type 1 and type 2 diabetes. Fecal elastase test has been demonstrated to have good correlation with direct tests for exocrine function, especially in moderate to severe cases. There are no data on the prevalence of pancreatic exocrine insufficiency in Indian patients with diabetes utilizing FEC concentrations. The objective of our study is to evaluate the prevalence of pancreatic exocrine insufficiency (PEI) in type 1 and type 2 diabetes and study the impact of PEI on glycemic control and metabolic parameters in diabetes. METHODS AND MATERIALS: We conducted a cross sectional study on 89 T1D, 95 T2D patients and 90 healthy controls. Biochemical parameters including FBS, HbA1c, serum albumin and serum calcium were estimated. Fecal elastase concentrations (FEC) were estimated by ELISA. Patients with FEC <200 µg/g were considered to have pancreatic exocrine insufficiency. RESULTS: The prevalence of PEI was 31.4% in T1D, 29.4% in T2D and 4.4% in controls (P < 0.01). A significant negative correlation was observed between FEC levels and, both FBS and HbA1c in diabetic patients. There was also a significant positive correlation between BMI and FEC. There was no significant association between low FEC and other biochemical parameters. CONCLUSION: Nearly one third of patients with both T1D and T2D showed evidence of impaired exocrine function utilizing FEC test. Presence of PEI correlated with lower BMI and higher HbA1c.

Long-term carbimazole pretreatment reduces the efficacy of radioiodine therapy.

INTRODUCTION: Data from several studies suggest that pretreatment with antithyroid drugs (ATD) before (131)I increases the risk of treatment failure. This effect has been demonstrated more consistently with propylthiouracil than with carbimazole (CMZ) or methimazole (MMI). Men with Graves' disease (GD) have a lower rate of remission with (131)I compared to women and the impact of long-term ATD pretreatment on the success of (131)I is unknown. The objective of our study was to compare the efficacy of fixed doses of radioiodine between patients with and without long-term CMZ pretreatment. MATERIALS AND METHODS: We performed a retrospective study on 335 male patients with GD treated with (131)I from 1998 to 2008. 148 patients had been pretreated with CMZ, and the remaining 187 patients received (131)I without pretreatment. We compared the success rate of a single dose of (131)I, between patients with and without long-term CMZ pretreatment. RESULTS: The success rate of a single dose of (131)I was significantly higher in patients without pretreatment than in patients who were pretreated with CMZ (91.4% vs. 82.3%, P = 0.01). The rate of hypothyroidism in the first 6 months after (131)I therapy was significantly higher in patients without pretreatment (55.1% vs. 44.6%, P = 0.05). There was also a trend for higher cumulative rate of hypothyroidism at last follow-up in nonpretreated patients (78.1% vs. 69.7%). CONCLUSION: Male patients with Graves' hyperthyroidism pretreated with CMZ have lower efficacy with 131I therapy compared to nonpretreated patients. CMZ pretreatment given for a prolonged period reduces the efficacy of (131)I therapy.

Zinc transporter-8 autoantibodies can replace IA-2 autoantibodies as a serological marker for juvenile onset type 1 diabetes in India.

INTRODUCTION: Zinc transporter-8 (ZnT8) is an islet cell secretory granule membrane protein recently identified as an autoantigen in type 1 diabetes (T1D). The aim of this study was to estimate the prevalence of antibodies to ZnT8 (ZnT8A) in juvenile onset T1D and to determine the utility of ZnT8A as an independent marker of autoimmunity either alone in antibody-negative subjects or in conjunction with glutamic acid decarboxylase (GAD) and insulinoma-2 antigen antibodies (GADA and IA2A). RESEARCH DESIGN: ZnT8A, GADA, and IA2A were measured in sera of consecutive T1D patients (n = 88, age range 2-18 years) within 4 years of diagnosis and 88 sex-matched controls. RESULTS: The prevalences of GADA, ZnT8a, and IA2A were 64.7%, 31.8% and 19.3%, respectively. In newly diagnosed patients, the frequency of ZnT8A was 45%. ZnT8A were positive in 26% of patients negative for both GADA and IA2A. IA2A were positive only in two patients who were negative for other two antibodies. Combined use of ZnT8A and GADA could detect 97% of antibody positive patients. In receiver operating characteristic (ROC) analysis, the performances of GADA and ZnT8As were better than that of IA2A; and AUCs of GADA, ZnT8A, and IA2A for the prediction of T1D were 0.8, 0.65, and 0.59, respectively. CONCLUSIONS: ZnT8A complements GADA and increases the diagnostic sensitivity for detection of autoimmunity in juvenile-onset T1D. Inclusion of ZnT8A increases the proportion of patients with antibody positivity to nearly 80%. ZnT8A can replace IA2A as a serological marker for autoimmunity in Indian T1D patients without loss of sensitivity and specificity.

Aspergillus and mucormycosis presenting with normal chest X-ray in an immunocompromised host.

Invasive aspergillus and mucormycosis infection are not uncommon in immunocompromised individuals. Endobronchial fungal infections have been reported in the literature, especially in patient's with diabetes complicated by diabetic ketoacidosis, but end bronchial coinfection with aspergillus and mucormycosis without pulmonary involvement has not been described in the literature. We report the case of a woman with diabetes who presented with gastrointestinal symptoms, ketoacidosis and respiratory distress, with an apparently normal chest X-ray. Investigations revealed a cavitatory lesion in the left lower lobe of the lungs on CT scan. Bronchoscopy revealed intense mucosal oedema and whitish plaques at the lower end of the trachea and right main stem bronchus with a normal left bronchial tree. Microbiological and pathological results confirmed aspergillus and mucormycosis. Despite aggressive medical management, the patient deteriorated and died of respiratory failure. Strong suspicion of invasive fungal infections in immunocompromised patients with respiratory failure and minimal chest infiltrates, early fibreoptic bronchoscopy and early aggressive treatment is crucial for the patient's survival.

1-(4-Methyl-phenyl-sulfon-yl)-2-{[3-methyl-4-(2,2,2-tri-fluoro-eth-oxy)pyridin-2-yl]methyl-sulfan-yl}-1H-1,3-benzimidazole.

In the title compound, C23H20F3N3O3S2, the benzo-imidazole unit makes dihedral angles of 5.02 (1) and 76.42 (1)°, respectively, with the pyridine and methyl-benzene rings; the dihedral angle between the pyridine and methyl-benzene rings is 72.19 (1)°. In the crystal, mol-ecules are connected by weak C-H⋯F, C-H⋯O and C-H⋯N hydrogen bonds. Weak C-H⋯π inter-actions and π-π stacking [centroid-centroid distance = 3.6485 (14) Å] are also observed. The overall packing shows a three-dimensional architecture. The crystal structure contains a void of 51 Å(3), but no solvent mol-ecule (hexane or ethyl acetate) is located within it.

Acute community acquired Aspergillus pneumonia in a presumed immunocompetent host.

Infection from Aspergillus results in a wide range of diseases from simple Aspergillus pneumonia to fatal invasive Aspergillosis. Though the fungus is known to predominantly affect the immunocompromised host, it has also been known to cause acute pneumonia in immunocompetent hosts which is invariably fatal. It presents as an acute pneumonia with bilateral chest infiltrates on radiograph. Early clinical suspicion and microbiological identification by measures such as broncho alveolar lavage and initiation of therapy with voricanozole significantly increase the chances of survival. In this article the authors discuss a case of acute community acquired Aspergillus pneumonia in an immunocompetent host who survived due to early identification and prompt treatment with appropriate antifungal medication.

Sheehan's syndrome: Newer advances.

Sheehan's syndrome (SS) is postpartum hypopituitarism caused by necrosis of the pituitary gland. It is usually the result of severe hypotension or shock caused by massive hemorrhage during or after delivery. Patients with SS have varying degrees of anterior pituitary hormone deficiency. Its frequency is decreasing worldwide and it is a rare cause of hypopituitarism in developed countries owing to advances in obstetric care. However, it is still frequent in underdeveloped and developing countries. SS often evolves slowly and hence is diagnosed late. History of postpartum hemorrhage, failure to lactate and cessation of menses are important clues to the diagnosis. Early diagnosis and appropriate treatment are important to reduce morbidity and mortality of the patients.

Bromocriptine in type 2 diabetes mellitus.

Bromocriptine mesylate quick-release was approved by the Food and Drug Administration (FDA) in May 2009, for the treatment of type 2 diabetes. Bromocriptine is thought to act on the circadian neuronal activities in the hypothalamus, to reset an abnormally elevated hypothalamic drive for increased plasma glucose, free fatty acids, and triglycerides in insulin-resistant patients. Randomized controlled trials have shown that bromocriptine-QR lowers glycated hemoglobin by 0.4 - 0.8% either as monotherapy or in combination with other anti-diabetes medications. The doses used to treat diabetes (up to 4.8 mg daily) are much lower than those used to treat Parkinson's disease, and apart from nausea, the drug is well-tolerated. The novel mechanism of action, good side effect profile, and its effects to reduce cardiovascular event rates make it an attractive option for the treatment of type 2 diabetes.

Nationwide reference data for height, weight and body mass index of Indian schoolchildren.

BACKGROUND. The assessment of growth is crucial for child care and reference data are central to growth monitoring. We aimed to assess the height, weight and body mass index (BMI) of Indian schoolchildren in order to develop genderappropriate growth charts for children 5-18 years of age. METHODS. Cross-sectional evaluation of anthropometric parameters (height, weight and BMI) was done in Indian schoolchildren (3-18 years) randomly selected from both fee-paying (upper socioeconomic strata) and non-fee paying (lower socioeconomic strata) schools from 4 regions (north, south, east and west) of India. A total of 106 843 children were evaluated, of which 42 214 children (19 303 boys, 22 911 girls) were from the lower socioeconomic strata and 64 629 children (34 411 boys, 30 218 girls) were from the upper socioeconomic strata. Normative charts, using the lambda-mu-sigma (LMS) method to smoothen the curves, were drawn from children belonging to the upper socioeconomic strata, in view of the gross discrepancy between the two socioeconomic strata. RESULTS. Height, weight and BMI percentile (3rd, 5th, 10th, 25th, 50th, 75th, 90th, 95th and 97th) data were calculated and charts generated. The height of boys and girls was consistently higher at all ages when compared with earlier India data, but the final height was 2-4 cm lower than that reported in the WHO multicentre study of 2007. Weight centiles showed a rising trend both in boys and girls compared not only to earlier Indian data published in 1992, but also to that reported by the WHO multicentre study. The median weight at all ages in both boys and girls was approximately 4 kg more than that reported in affluent Indian children two decades earlier. CONCLUSION. This large nationwide study indicates secular trends in height, weight and BMI in Indian children from the upper socioeconomic strata. We suggest that the height and weight percentiles reported by us may be used as reference standards for India.

Identification of a novel mutation in an Indian patient with CAII deficiency syndrome.

Carbonic anhydrase II (CAII) deficiency syndrome characterized by osteopetrosis (OP), renal tubular acidosis (RTA), and cerebral calcifications is caused by mutations in the carbonic anhydrase 2 (CA2) gene. Severity of this disorder varies depending on the nature of the mutation and its effect on the protein. We present here, the clinical and radiographic details along with, results of mutational analysis of the CA2 gene in an individual clinically diagnosed with renal tubular acidosis, osteopetrosis and mental retardation and his family members to establish genotype-phenotype correlation. A novel homozygous deletion mutation c.251delT was seen in the patient resulting in a frameshift and a premature stop codon at amino acid position 90 generating a truncated protein leading to a complete loss of function and a consequential deficiency of the enzyme making this a pathogenic mutation. Confirmation of clinical diagnosis by molecular methods is essential as the clinical features of the CAII deficiency syndrome are similar to other forms of OP but the treatment modalities are different. Genetic confirmation of the diagnosis at an early age leads to the timely institution of therapy improving the growth potential, reduces other complications like fractures, and aids in providing prenatal testing and genetic counseling to the parents planning a pregnancy.

Peak bone mineral density of physically active healthy Indian men with adequate nutrition and no known current constraints to bone mineralization.

We undertook this study to characterize peak bone density and evaluate its determinants in a healthy cohort of young adult male paramilitary personnel. Bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry in 473 healthy men aged 21-40 yr. The effect of anthropometry and biochemical parameters on BMD was determined. Mean BMD values of L1-L4, forearm, total hip, and femoral neck were 1.170+/-0.137, 0.755+/-0.089, 1.129+/-0.130, and 1.115+/-0.133 g/cm(2), respectively. BMD values for 31- to 40-yr age group were lower than those of 20- to 30-yr age group except for forearm, which was higher in the former. Significant positive correlation was observed between height, weight, and body mass index with BMD. On multivariate regression analysis, weight was the most consistent contributor to variance in the BMD. Compared with age-matched US males, BMD of total hip and femoral neck were higher for Indian paramilitary personnel by 3.58% and 4.2%, whereas lumbar spine BMD was lower by 4.1%. In conclusion, peak BMD in healthy Indian males was achieved by 30 yr of age at lumbar spine and hip, with weight being the most consistent contributor to variance in BMD. Peak BMD in this population was comparable to that reported in white US males.

Fatal aluminium phosphide poisoning due to myocardial depression refractory to high dose inotropic support and intra-aortic balloon counterpulsation.

We report a case of aluminium phosphide poisoning that presented to us with refractory myocardial depression. This patient developed worsening circulatory failure that did not respond to inotropic or vasopressor support and intra-aortic balloon counterpulsation. She went on to develop progressive metabolic acidosis, renal failure and died within 48 hours of admission to the intensive care unit.