Impact of empagliflozin add-on therapy on quality of life in patients of type 2 diabetes mellitus with hypertension: A prospective study.

Background: Diabetes has a negative impact on patient's quality of life (QoL). Comorbidities and polypharmacy further worsen their QoL. Thus, in addition to glycemic control, assessment of QoL is also gaining importance. Objective: The objective of this study was to evaluate QoL in patients of type 2 diabetes mellitus (T2DM) with hypertension after add-on empagliflozin to triple drug therapy (metformin, teneligliptin, and glimepiride). Materials and Methods: A prospective research was done on T2DM patients with hypertension, who visited a tertiary care referral institute's endocrine outpatient clinic. For 3 months, empagliflozin, 25 mg once daily, was administered as an add-on treatment with metformin, teneligliptin, and glimepiride. In addition to clinical assessment, an Urdu-translated QoL instrument for Indian diabetes patients was used to conduct QoL study. The QoL outcomes prior to empagliflozin add-on were compared with those obtained at the conclusion of the 3 months of treatment. Results: Empagliflozin as an add-on therapy significantly improved various aspects of QoL like role limitation due to physical health, physical endurance, general health, symptom botherness, financial worries, emotional/mental health, and diet satisfaction (P < 0.001). It also improved glycemic and blood pressure parameters significantly. Conclusion: QoL is an essential measure with respect to patient-centered treatment approach. Empagliflozin, as an add-on medication, improved QoL, glycemic parameters and blood pressure in T2DM patients with hypertension. It can be recommended as an add-on, but more research with a larger sample size is required.

Coadministration of metformin or spironolactone enhances efficacy of rosiglitazone in management of PCOS.

The aim of this study was to compare the efficacy and safety of adding metformin or spironolactone to rosiglitazone in women with polycystic ovary syndrome (PCOS). This is a prospective non-randomized study in a tertiary care with at in a tertiary care endocrine clinic. Women (n = 138) diagnosed with PCOS on the basis of Rotterdam criteria 2003 were categorized into three groups on the basis of drug intake as - rosiglitazone (R), rosiglitazone with spironolactone (R + S), and rosiglitazone with metformin (R + M). Clinical, biochemical, hormonal, and insulin sensitivity parameters were assessed at baseline and after six months of follow up. There was a significant improvement in number of menstrual cycles per year and Ferriman Gallwey (FG) score in all three groups after 6 months. Plasma insulin (0, 2 h), HOMA-IR and serum total testosterone levels decreased after six months in all the three groups. The inter group comparison showed higher efficacy of R + S in improving hyperandrogenism whereas R + M was most effective in decreasing body weight and plasma insulin levels compared to R and R + S (p<.05). Treatment of women with PCOS using rosiglitazone alone and in combination with spironolactone or metformin is safe and efficacious with limited adverse events however randomized trials with longer duration of follow up are warranted.

Healthcare-Associated Pneumonia and Hospital-Acquired Pneumonia: Bacterial Aetiology, Antibiotic Resistance and Treatment Outcomes: A Study From North India.

BACKGROUND: Data regarding the comparative profiling of HCAP and HAP from developing countries like India are scant. We set out to address the microbial aetiology, antibiotic resistance and treatment outcomes in patients with HCAP and HAP. METHODS: 318 consenting patients with HCAP (n = 165, aged 16-90 years; median 60 years; 97 males) or HAP (n = 153; aged 16-85 years; median 45 years; 92 males) presenting to a tertiary care hospital in North India from 2013 to 2015 were prospectively recruited for the study. Data on patient characteristics, microbial aetiology, APACHE II scores, treatment outcomes and mortality were studied. Clinical outcomes were compared with various possible predictors employing logistic regression analysis. RESULTS: Patients in HCAP had more comorbidity. Escherichia coli (30, 18%) and Acinetobacter baumannii (62, 41%) were the most commonly isolated bacteria in HCAP and HAP, respectively. Multidrug-resistant bacteria were isolated more frequently in HCAP, only because the incidence of extensively drug-resistant bacteria was markedly high in HAP (p = 0.00). The mean APACHE II score was lower in HCAP (17.55 ± 6.406, range 30) compared to HAP (19.74 ± 8.843, range 37; p = 0.013). The length of stay ≥ 5 days (p = 0.036) and in-hospital mortality was higher in HAP group (p = 0.002). The most reliable predictors of in-hospital mortality in HCAP and HAP were APACHE II score ≥ 17 (OR = 14, p = 0.00; HAP: OR = 10.8, p = 0.00), and septic shock (OR = 4.5, p = 0.00; HAP: OR = 6.9, p = 0.00). CONCLUSION: The patient characteristics in HCAP, treatment outcomes, bacterial aetiology, and a higher incidence of antibiotic-resistant bacteria, suggest that HCAP although not as severe as HAP, can be grouped as a separate third entity.

Calcitriol-mediated Reversible Hypercalcemia in a Patient with Primary Adrenal Lymphoma.

Primary adrenal lymphomas (PAL) are rare occurrences with only less than 150 cases reported in the literature. Two-thirds of these cases were reported in the last decade due to the advancements in imaging techniques and immunohistochemistry. The non-specific signs and symptoms have resulted in a delayed onset of symptoms and diagnosis of these tumors. Reports of the results of chemotherapy are not gratifying, and most patients die within one year of the diagnosis. We report a 65-year-old male with adrenal non-Hodgkin's lymphoma (NHL), who presented with hypercalcemia and renal failure. We reviewed all adrenal NHL cases presented with hypercalcemia and attempted to comprehend its etiology and overall survival effect.

Goitre and urinary iodine excretion survey in schoolchildren of Kashmir Valley.

BACKGROUND: An extensive survey on schoolchildren in Kashmir Valley in 1995 showed a high prevalence of goitre, making it imperative to have a relook at our iodine status, 15 years postiodization. OBJECTIVE: To study the total prevalence of goitre and urinary iodine excretion (UIE) in Kashmiri schoolchildren, 15 years postiodization. DESIGN: A cross-sectional survey, covering 9576 schoolchildren, aged 5-15 years (5988 in 6-12 year age group) was conducted. Goitres were graded as per WHO/UNICEF/ICCIDD. UIE was measured by the arsenic acid reduction in ceric ions method and was estimated in 208 subsampled children. Results were compared with that of 1995 survey. RESULTS: The overall prevalence of goitre in the present study was 3·8% (95% CI: 3·4-4·2) and 3·7% (95% CI: 3·2-4·2) in those aged 6-12 years. No significant difference in prevalence of goitre was observed between boys and girls overall (3·6% vs 4·1%. P > 0·2), nor in the 6-12 year age group (3·3% vs 4·0%, P > 0·1). There was a significant trend of increasing prevalence of goitre with age (P < 0·005). UIE ranged from 12 to 397 µg/g.creatinine (median, 104); 11% subjects had UIE of <50 µg/g.creatinine. Overall, prevalence of goitre was significantly lower (3·8% vs 45·2%, P < 0·001), and mean UIE was significantly higher (123·6 ± 5·3 vs 49·60 ± 3·55 µg/g.creatinine, P < 0·001), compared to that in the 1995 survey. CONCLUSION: The marked improvement in overall iodine nutrition in Kashmir Valley- one and a half decades after implementation of salt iodization should encourage healthcare providers to make tangible efforts for implementation of iodization programmes in areas with iodine deficiency.

Pituitary stalk interruption syndrome due to novel ROBO1 mutation presenting as combined pituitary hormone deficiency and central diabetes insipidus.

OBJECTIVES: The genetic causes of pituitary stalk interruption syndrome (PSIS) remain elusive in 95 % of cases. The roundabout receptor-1 gene (ROBO1) plays critical roles in axonal guidance and cell migration. Recently, mutations in the ROBO1 gene have been reported patients with PSIS. CASE PRESENTATION: We report a 2.9-year-old boy with PSIS who presented with combined pituitary hormone deficiency, central diabetes insipidus, and the classical triad of MRI findings. Through clinical exome sequencing using next-generation sequencing techniques, a previously unidentified novel heterozygous frame shift mutation in the ROBO1 gene was identified. This is the first report of ROBO1 mutation associated with posterior pituitary dysfunction. CONCLUSIONS: We conclude and emphasize that ROBO1 should be investigated in patients with PSIS. Our case is unique in the published literature in that we are first time reporting posterior pituitary dysfunction as manifestation of ROBO1 mutation. The full clinical spectrum of the mutations may not be fully known.

Autoimmune polyglandular syndrome type 1 with reversible dilated cardiomyopathy: complete recovery after correction of hypocalcemia and hypocortisolemia.

Autoimmune polyglandular syndrome type 1 (APS1) - characterized by the triad of mucocutaneous candidiasis, hypoparathyroidism, and primary adrenal insufficiency - is an uncommon entity. In this case report we describe the case of a young girl who presented with classic features of APS1 and dilated cardiomyopathy, which were missed during her presentation to the children's hospital. Her condition improved only when appropriate replacement therapy in the form of calcium, calcitriol and hydrocortisone was instituted. Hypocalcemia and hypocortisol state are curable causes of myocardial dysfunction and subsequent congestive cardiac failure, and should always be considered in the differential diagnosis of resistant congestive cardiac failure, especially in children. To the best of our knowledge, cardiomyopathy in the setting of APS1 has never been described previously and can remain unrecognized for a long time and present with life threatening complications.

VDR downregulation and promoter hypermethylation as one of the causes for triggering type 2 diabetes mellitus: Clinical and molecular studies.

Background: Our present study was to investigate the methylation and Gene expression of the vitamin D receptor (VDR) gene in the causing T2DM and to determine the inflammatory biomarkers in exaggerating T2DM in Kashmiri population. Methods: In this study, T2DM cases (n = 100) and controls (n = 100) of Kashmiri population were designed. Blood samples were taken from both groups, and serum vitamin D levels, inflammatory biomarkers (TNF-α, IL-6, IL-10, CRP, Leptin and adiponectin) were estimated by ELISA. By using methylation-specific PCR (MS-PCR) and RT-PCR, respectively, the levels of methylation and expression were measured after the extraction of DNA and RNA. Results: Studies using RT-PCR demonstrated that patients with diabetes had a lower degree of VDR expression than control subjects (P > 0.05). The T2DM was shown to be strongly correlated with hypermethylation (p-value < 0.001, OR 2.9; 95%CI 1.6-5.54). When compared to control groups, T2DM patients' levels of vitamin D in their serum were considerably lower (p < 0.01). Pro-inflammatory mediators like TNF-α, CRP, IL-6, and leptin levels were discovered to be higher, and concentrations of anti-inflammatory mediators like IL-10 and adiponectin were observed to be lower in people with T2DM than in people without the condition (p < 0.05). Conclusions: This study suggests the hypermethylation and down expression of VDR as one of the basis for causing T2DM in kashmiri individuals, exaggerated by enhanced degree of TNF-α, CRP, IL-6 and leptin and diminished concentration of IL-10 and adiponectin in T2DM. Supplementary Information: The online version contains supplementary material available at 10.1007/s40200-023-01266-6.

Weight homeostasis & its modulators in hyperthyroidism before & after treatment with carbimazole.

BACKGROUND & OBJECTIVES: Hyperthyroidism is associated with increased food intake, energy expenditure and altered body composition. This study was aimed to evaluate the role of adipocytokines in weight homeostasis in patients with hyperthyroidism. METHODS: Patients (n=27, 11men) with hyperthyroidism (20 Graves' disease, 7 toxic multinodular goiter) with mean age of 31.3±4.2 yr and 28 healthy age and body mass index (BMI) matched controls were studied. They underwent assessment of lean body mass (LBM) and total body fat (TBF) by dual energy X-ray absorptiometer (DXA) and blood sample was taken in the fasting state for measurement of leptin, adiponectin, ghrelin, insulin, glucose and lipids. Patients were re-evaluated after 3 months of treatment as by that time all of them achieved euthyroid state with carbimazole therapy. RESULTS: The LBM was higher (P<0.001) in healthy controls as compared to hyperthyroid patients even after adjustment for body weight (BW), whereas total body fat was comparable between the two groups. Serum leptin levels were higher in patients with hyperthyroidism than controls (22.3±3.7 and 4.1±0.34 ng/ml, P<0.001), whereas adiponectin levels were comparable. Plasma acylated ghrelin was higher in patients than in controls (209.8±13.3 vs 106.2±8.2 pg/ml, P<0.05). Achievement of euthyroidism was associated with significant weight gain (P<0.001) and significant increase in lean body mass (P<0.001). The total body fat also increased but insignificantly from 18.4±1.8 to 19.9±1.8 kg. There was significant decrease (P<0.05) in serum leptin and acylated ghrelin but adiponectin levels remained unaltered after treatment. Serum leptin positively correlated with TBF and this correlation persisted even after adjustment for BW, BMI, gender and age (r=0.62, P=0.001). However, serum leptin and acylated ghrelin did not correlate with the presence or absence of hyperphagia. INTERPRETATION & CONCLUSION: Patients with hyperthyroidism predominantly had decreased lean body mass which increased after achievement of euthyroidism with carbimazole. The hyperphagia and the alterations in weight homeostasis associated with hyperthyroidism were independent of circulating leptin and ghrelin levels.

Biomarkers: Tools for Discriminating MODY from Other Diabetic Subtypes.

Maturity Onset Diabetes of Young (MODY), characterized by the pancreatic b-cell dysfunction, the autosomal dominant mode of inheritance and early age of onset (often ≤25 years). It differs from normal type 1 and type 2 diabetes in that it occurs at a low rate of 1-5%, three-generational autosomal dominant patterns of inheritance and lacks typical diabetic features such as obesity. MODY patients can be managed by diet alone for many years, and sulfonylureas are also recommended to be very effective for managing glucose levels for more than 30 years. Despite rapid advancements in molecular disease diagnosis methods, MODY cases are frequently misdiagnosed as type 1 or type 2 due to overlapping clinical features, genetic testing expenses, and a lack of disease understanding. A timely and accurate diagnosis method is critical for disease management and its complications. An early diagnosis and differentiation of MODY at the clinical level could reduce the risk of inappropriate insulin or sulfonylurea treatment therapy and its associated side effects. We present a broader review to highlight the role and efficacy of biomarkers in MODY differentiation and patient selection for genetic testing analysis.

Environmental Factors as Diabetic Mediators: A Mechanistic Approach.

Despite substantial investment in research and treatment options, diabetes mellitus remains a pressing public health concern with potential epidemic proportions globally. There are reports that by the end of 2040, 642 million people will be suffering from diabetes. Also, according to an estimation, 1.6 million deaths were caused directly by diabetes in 2016. Diabetes is a metabolic disorder characterized by impaired glucose regulation in the body due to the destruction of pancreatic ß-cells or insulin resistance. Genetic propensity, unhealthy and imbalanced diet, obesity and increasing urbanization are the common risk factors for diabetes. Besides this, it has been reported that environmental pollutants like organic pesticides, heavy metals, and air pollutants act as strong predisposing factors for diabetes owing to their highly bio-accumulative nature. These pollutants disturb glucose homeostasis either by up-regulating or down-regulating the expression of diabetic marker genes like insulin (INS) and glucokinase (GCK). Unfortunately, the molecular mechanism of the role of pollutants in causing diabetes is not very clear. This mechanistic review provides evidence of different environmental determinants, including persistent organic pollutants (POPs), air pollutants, toxic metals, etc., in inducing diabetes and proposes a framework for the possible mechanisms involved. It also illuminates the current status and future challenges, which will not only broaden our understanding but can also be a reasonable platform for further investigation.

Clinical profiling and screening for HNF4α and GCK gene mutations in Kashmiri patients with maturity-onset diabetes of the young (MODY).

AIM: Maturity-onset Diabetes of Young (MODY) is a monogenic form of diabetes affecting 1-5% of young (often ≤25 years) diabetic patients exhibiting an autosomal dominant mode of inheritance. Considering the significance of genetic polymorphisms in a variety of diseases, this study aimed to determine the association between HNF4α and GCK gene polymorphisms and the risk of MODY in the Kashmir community, as well as their clinical differences. METHOD: The study was conducted on clinically confirmed MODY patients (n = 50), and age and gender-matched controls (25 T1DM and 25 non-diabetic) recruited from the endocrinology department of the hospital, for evaluating the HNF4α and GCK mutation. Under standard conditions, PCR-mediated amplification was done to evaluate the respective exons. Preliminary mutations were detected using restriction enzymes (BfaI and HhaI), which were then followed by sequencing of representative samples. The diabetic history, clinical and biochemical data were obtained after proper consent. RESULTS: Our data revealed no association of HNF4α (exon7) and GCK (exon8) gene mutation with MODY disease susceptibility in the Kashmiri population. On diagnosis, no MODY patient was given immediate insulin; instead, metformin (68%) or sulphonyl-urea (28%) and dietary changes (4%) were recommended. Later in life, 54% of MODY patients develop insulin dependency. The MODY probability was calculated to be 73.88% (±4.56). HbA1c levels were lower [7.48% (±1.64)] than in T1DM [9.17(±2.29%)]. CONCLUSIONS: Young early-onset diabetic patients were able to keep their HbA1c and blood glucose levels stable with a modified diet and metformin/sulphonyl-urea, but they may become insulin-dependent in the future, as seen in our study. As a result, prompt diagnosis and management are essential for avoiding complications. Furthermore, no HNF4α (exon7) or GCK (exon 8) mutations were found in MODY patients or T1DM/healthy non-diabetic controls.

Prevalence and Clinical Profile of Maturity Onset Diabetes of the Young among People with Diabetes Attending a Tertiary Care Centre.

Background: Maturity onset diabetes of young (MODY) is considered to be the most underdiagnosed condition. The correct diagnosis of MODY has a definite bearing on the outcome and clinical course of the disease. We aim to determine the prevalence and clinical profile of MODY among young diabetic patients attending at Department of Endocrinology, a tertiary care institute in North India. Methods: It was a cross-sectional study involving all consecutive consenting patients with diabetes and age of onset ≤35 years. A total of 1,094 patients were included in this study, of whom 858 were having age of onset of diabetes <25 years. All patients were screened for MODY using clinical criteria and MODY Probability calculator (available on diabetesgenes.org). Patients with high clinical probability of MODY having negative anti-GAD65 antibody and fasting serum C-peptide levels >0.6 ng/mL were subjected to the Ala98 Val polymorphism (SNP) in hepatocyte nuclear factor (HNF) 1a gene. Results: The prevalence of MODY among the study cohort as per clinical criteria was found to be 7.7%. Males constituted the majority of patients (male vs female, 56% vs. 44%; P < 0.001). The patients with MODY were younger (p < 0.001), leaner (p < 0.001), had younger age at onset of diabetes mellitus (p < 0.001), and lower frequency of features of insulin resistance in the form of skin tags and acanthosis nigricans. Among the 40 patients who were subjected to Ala98Val polymorphism of HNF1α gene (MODY 3), the mutant genotype was seen in 20 (50%) patients. Conclusion: We report a higher prevalence of MODY in our young diabetic patients. A high index of suspicion is required to diagnose MODY as misdiagnosis and inappropriate treatment may have a significant impact on quality-of-life (QOL) with increased cost and unnecessary treatment with insulin.

Lactic Acidosis in Diabetic Ketoacidosis: A Marker of Severity or Alternate Substrate for Metabolism.

PURPOSE: The lactate level is being increasingly used as a marker of severity of illness and prognosis in multitude of critical conditions. However, its role in diabetic ketoacidosis (DKA) is not well defined. AIM: To determine the prevalence and clinical importance along with the underlying role of metformin in lactic acidosis (LA) in patients admitted with DKA. METHODS: A 2-year prospective and observational study involving 62 consenting in hospital DKA patients. Plasma lactate level on arrival, its clinical significance and relationship with morbidity and mortality in patients with DKA was evaluated. RESULTS: The prevalence of LA (lactate ≥2.5 mmol/l) among the study cohort was found to be 55% with significant LA (≥5 mmol/l) documented in 16%. The median lactate level was 2.55 mmol/l (interquartile range, 1.70-3.20). No significant difference in the severity of LA was seen with metformin use. Lactate correlated positively with initial plasma glucose (IPG) (P = 0.001) and APACHE-II Score (P = 0.002); correlated negatively with systolic blood pressure (P = 0.003), pH (P = 0.002) and severity of DKA (P = 0.001). After controlling for AKI, APACHE II score and blood pressure, lactate continued to correlate positively with IPG (P = 0.002). No mortality or significant morbidity was documented in the entire cohort. CONCLUSIONS: LA has a significant presence in patients with DKA; however, it is not associated with mortality or significant morbidity. Moreover, there was no significant difference in severity of LA with metformin use. Elevated lactate levels may be an adaptation to provide alternate substrate for metabolism in the presence of hypoinsulinemic state. The study results provide rationale for large well-designed studies evaluating in-depth clinical relationship of lactate in DKA.

Hypercalciuria and nephrolithiasis on long-term follow-up of pseudo-vitamin D deficiency rickets.

A case of pseudovitamin D deficiency (Vitamin D dependent rickets type I) is presented, who initially responded to physiological doses of calcitriol but developed nephrolithiasis and hypercalciuria around puberty. Hypercalciuria was corrected after stopping calcitriol. Pseudo vitamin D deficiency rickets also called vitamin D dependent rickets type I (VDDR 1) is an uncommon cause of rickets. Patients appear normal at birth and manifests with signs between the ages of two months to two years. Muscle weakness is prominent, radiographic features are striking and response to calciferols is complete. Hypercalciuria and nephrolithiasis are uncommon in the untreated disease but can develop due to overtreatment with calcitriol or oral calcium. Here we report a patient who developed hypercalciuria and nephrolithiasis around puberty while on maintenance dose of calcitriol and oral calcium.

Effects of Single Dose of Dexamethasone on Perioperative Blood Glucose Levels in Patients Undergoing Surgery for Supratentorial Tumors - An Observational Study.

INTRODUCTION: Dexamethasone is commonly administered in intracranial tumors to reduce the cerebral edema. Its administration may be associated with hyperglycemia. The primary objective of this study was to study the magnitude of rise in blood sugar levels following the administration of a single 10 mg dose of dexamethasone. METHODS: Seventy patients who underwent various neurosurgical procedures were enrolled in the study. Group D (n = 35 undergoing surgery for intracranial tumors) were administered injection dexamethasone 10 mg while as Group P (n = 35 undergoing surgery for subarachnoid hemorrhage) received placebo. Blood samples were obtained through the arterial line at baseline (before dexamethasone administration), 60, 120, 180, and 240 min after the dexamethasone administration and blood glucose concentrations noted. RESULTS: Glucose concentrations were significantly increased in patients who received dexamethasone compared with those who received placebo (P < 0.05). Blood glucose concentrations at different time intervals were greater when compared with the baseline blood sugar levels in both the placebo and dexamethasone group (P < 0.05). The arterial blood glucose concentration in those who received 10 mg dexamethasone (n = 35) increased from 95.29 ± 13.69 mg.dl-1 to 139.97 ± 10.34 mg.dl-1 over 4 h, compared with a change from 94.74 ± 10.05 mg.dl-1 to 122.34 ± 10.68 mg.dl-1 in those who received placebo (n = 35) (P < 0.05). CONCLUSION: The administration of a single intravenous dose of 10-mg dose dexamethasone caused a significant increase in the blood glucose concentrations at different point intervals when compared with the placebo over a 4-h period. We recommend intensive monitoring of the blood sugar levels during the intraoperative period to prevent the development of severe hyperglycemia and its associated complications.

Variations in the inhibin gene in Kashmiri women with primary ovarian insufficiency.

Inhibin is a glycoprotein produced by granulosa cells and its main function is the negative feedback control of follicle stimulating hormone (FSH) which has an important role in folliculogenesis. Mutation in the INHα gene leading to decreased bioactive inhibin has been associated with primary ovarian insufficiency (POI). The aim of this study was to investigate the role of variations in the INHα gene in increasing the susceptibility to POI in Kashmiri women. INHα c.769G > A mutation was analysed in 100 POI cases and 100 controls using PCR-RFLP and agarose gel electrophoresis. The INHα c.769G > A mutation was found in 10% of POI cases with 8% having heterozygous mutation and 2% having a homozygous mutation. The frequency of mutation in healthy controls was zero. Statistically, a very significant association was found between INHα c.769G > A mutation and the occurrence of POI (p = 0.0015). Moreover, the mutation was also significantly associated with high levels of FSH in POI patients (p < 0.0001). Given the significant association of INHα c.769G > A mutation with the increased FSH levels and POI in Kashmiri population, we suggest this mutation can be used to identify POI variants for screening of women susceptible to POI before the disease onset and can further facilitate putative therapy for such patients.

Presentation, Morbidity and Treatment Outcome of Acromegaly Patients at a Single Centre.

INTRODUCTION: The management of acromegaly, a rare and potentially curable disease, has undergone a paradigm shift in the past few decades. Many of the treatment modalities recommended for acromegaly are either too expensive or not available in many parts of India. There is a dearth of treatment and outcome data in Indian patients. AIM: Our aim was to study the clinical presentation, hormonal profile, radiology, management, and outcome of the disease at our center. MATERIALS AND METHODS: Fifty one patients with acromegaly who attended the Department of Endocrinology, SKIMS, Srinagar, between October 2015 and April 2017, were included in the study. Clinical and hormonal profiles, comorbidities, treatment modalities, and outcome were evaluated. RESULTS: The gender distribution was equal with the mean age of 42.3 ± 10.9 years at diagnosis. The majority (41) of the patients had macroadenoma. The most common presenting manifestations were acral enlargement and headache. Hypertension was present in 23, musculoskeletal manifestations in 19, and diabetes mellitus in 11 patients. Surgery was the most common method of treatment. Preoperatively only one patient with micro-adenoma had hypocortisolism, which was persistent in postoperative period, while no patient had preoperative or postoperative hypothyroidism or hypogonadism. As per the present consensus criteria, 23.7% patients achieved disease control (40% with microadenoma and only 19.5% with macroadenoma). The surgical complications occurred in 5 patients-CSF leak in 3 meningitis in 2 patients all except one having macroadenoma. CONCLUSIONS: The presentation of disease was generally comparable to that reported in literature. Cure rates were significantly lower than those reported from many large centers.

A Comparison between Silent and Symptomatic Renal Stones in Primary Hyperparathyroidism.

BACKGROUND: Nephrolithiasis is a common complication of primary hyperparathyroidism (PHPT), and in a subgroup of patients stones are clinically silent. Patients with silent and symptomatic stones may differ biochemically. There is a scarcity of data available comparing patients with silent and symptomatic renal stones in PHPT. AIMS: To characterize patients with PHPT with nephrolithiais and to compare patients with silent and symptomatic stones. MATERIALS AND METHODS: We reviewed clinical data of 186 patients with PHPT managed at our center from January 1996 to December 2017. Silent renal stones were defined as ultrasonography finding of renal stones without symptoms. Symptomatic renal stones were defined as those with symptoms or a history of graveluria or any procedure for nephrolithiasis. A 5-mm diameter was set as the cut-off between micro- and macrolithiasis. We compared those with (n = 95) and without (n = 91) stones, and, among stone formers, those with symptoms (n = 66) and silent (n = 29) were compared. RESULTS: There was no significant difference between stone formers and nonstone formers with respect to biochemical parameters. Patients with silent renal stones had significantly lower serum calcium and higher phosphate, than those with symptomatic stones. Most (75%) patients with silent renal stones had microlithiais, while only a fifth (22%) with symptomatic renal stones had microlithiasis. CONCLUSION: Nephrolithiasis is a common complication of PHPT. Most patients with silent renal stones had microlithiasis and biochemical features of less severe disease. Patients with silent renal stones may represent early mild stage of PHPT.

Disorders of Sex Development: A 10 Years Experience with 73 Cases from the Kashmir Valley.

PURPOSE: To present the clinical data, investigative profile, and management of patients with disorders of sex development (DSD) from the endocrine unit of a tertiary care university hospital. MATERIALS AND METHODS: This retrospective study included 73 cases of DSD, evaluated and managed at Department of Endocrinology, Sher-i-Kashmir Institute of Medical Sciences, Srinagar, Kashmir, over a period of 10 years from September 2008 to August 2018. RESULTS: Twenty-nine patients (39.7%) had 46 XY DSD and twenty-nine patients (39.7%) had 46 XX. Sex chromosome DSD was diagnosed in 15 (20.5%) patients. Of 29 patients with 46 XY DSD, 17 (58.6%) had 5α-reductase type-2 deficiency (5α-RD) and 6 (20.7%) had complete androgen insensitivity syndrome. In our patients with 5α-RD, the history of consanguinity was documented in nine (52.9%) patients. Two patients had testosterone biosynthetic defect and one patient had partial androgen insensitivity syndrome. Of 29 patients with 46 XX DSD, 16 (55.1%) had congenital adrenal hyperplasia (CAH). Of 15 patients with sex chromosome DSD, 7 patients had Turner's syndrome, 7 had Klinefelter's syndrome, and 1 patient had mixed gonadal dysgenesis. CONCLUSION: In our study, equal number of patients had 46 XY DSD and 46 XX DSD. We are for the first time reporting from India that the most common cause of 46 XY DSD is 5α-RD, whereas CAH is the most common cause of 46 XX DSD as reported previously.