Adrenal morphology and cortical function in patients with extrapulmonary tuberculosis: response to antituberculosis treatment.

Objective: Enlargement of the adrenal glands and variable adrenocortical function have been reported in patients with pulmonary tuberculosis and, in a few studies, in patients with extrapulmonary tuberculosis (EPTB). However, none of the studies have evaluated the course of the adrenal morphology in these patients. Subjects and methods: Prospective study including 37 patients with EPTB and 37 healthy age- and sex-matched controls. The adrenal function was evaluated by measurement of cortisol levels at baseline and after stimulation with ACTH (Acton Prolongatum) before and 6 months after antituberculosis treatment. The size of both adrenal glands was evaluated using 64-slice computed tomography (CT) scanning before and 6 months after treatment. The findings were compared with those in a group of healthy matched controls. Results: Clinical and biochemical parameters were comparable between groups. The mean baseline serum cortisol level was significantly lower in the EPTB group (397.1 ± 184.9 nmol/L) compared with the control group (696.3 ± 101.8 nmol/L). Compared with controls, patients with EPTB had significantly lower mean cortisol levels at baseline and 1 hour after ACTH, both before (397 ± 184.9 nmol/L and 750.7 ± 176.8 nmol/L, respectively) and after (529.7 ± 100.4 nmol/L and 1017.2 ± 119.7 nmol/L, respectively) antituberculosis treatment. Both the length and thickness of the right and left adrenal glands were greater in patients with EPTB than in controls but became comparable to those in controls after treatment completion. Conclusion: Patients with EPTB have an enlarged adrenal size and low baseline and stimulated serum cortisol levels. After treatment completion, cortisol levels increased significantly, and the adrenal size normalized in these patients.

Gender Disparities in Prolactinomas: Unravelling Clinical Patterns, Metabolic Variations, and Treatment Responses.

Background and objective Individuals with prolactinoma exhibit elevated rates of obesity, metabolic syndrome (MS), and dyslipidemia compared to their healthy counterparts. However, there is a lack of data regarding metabolic variance between male and female prolactinoma patients. Consequently, this study aimed to investigate and compare sex-specific discrepancies in metabolic abnormalities among individuals diagnosed with prolactinoma. Methods In this prospective study, 80 treatment-naïve patients with prolactinoma (12 males and 68 females) underwent clinical assessments and laboratory investigations. The measured parameters included blood glucose, total cholesterol (TC), triglycerides (TG), LDL cholesterol (LDL-C), HDL cholesterol (HDL-C), urea, creatinine, uric acid, and blood glucose levels. The patients were treated with cabergoline, a dopamine agonist, and reevaluated after 12 weeks. Results Forty-eight patients had microprolactinomas (all females), and 32 had macroprolactinomas (20 females, 12 males). The mean age was 28.30±7.49 years for females and 28.91±7.12 years for males (p=0.71). The median symptom duration was 12 months (range 1-72 months, IQR 4-16 months), with no significant difference between males (median 12 months, IQR 5-54 months) and females (median 12 months, IQR 10-24 months, p=0.620). The median serum prolactin (PRL) was 988 ng/mL (IQR 471-1,439) in males and 165 ng/mL (IQR 90-425) in females (p<0.05). Males showed higher HbA1c, BGF, TC, TG, LDL-C, and higher rates of obesity, MS, and diabetes mellitus. Treatment with cabergoline resulted in significant improvements in the HbA1c, BGF, TC, TG, and LDL-C levels. Conclusion Males with prolactinomas had larger tumor sizes and higher serum PRL levels than females. Additionally, males exhibited worse metabolic parameters than females. However, there was no significant difference in the duration of symptoms or age at diagnosis between the two groups.

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.

Cardioprotection by Citrus grandis (L.) Peel Ethanolic Extract in Alloxan-Induced Cardiotoxicity in Diabetic Rats.

Diabetic cardiomyopathy (DCM) pathogenesis is multifarious, and there are insufficient therapeutic options to treat DCM. The present research explored the effects of Citrus grandis peel ethanolic extract (CGPE) in alloxan-induced DCM in rats. Diabetes was triggered by intraperitoneal (i.p.) injection of alloxan (150 mg/kg) in Wistar rats (200-250 g). CGPE (100, 200, and 400 mg/kg) or glibenclamide (Glib, 10 mg/kg) were administered orally for 2 weeks. After the treatment schedule, prooxidants (thiobarbituric acid reactive substances), antioxidants (glutathione, catalase, and superoxide dismutase), and inflammatory markers (tumor necrosis factor-α) were determined in cardiac tissues. Biomarkers of cell death, viz., lactate dehydrogenase (LDH), creatine kinase MB (CK-MB) activity, glucose levels, total cholesterol (TC), and high-density lipoproteins (HDL), were assessed in the blood. Rats administered with alloxan showed a consistent increase in blood glucose level (days 7 and 14) that was lowered considerably (p < 0.001) by CGPE or Glib. Alloxan-induced increase in LDH, CK-MB, TC, and decline in HDL was attenuated (p < 0.001) in rats that were treated with CGPE or Glib. Alloxan significantly (p < 0.001) elevated oxidative stress, inflammation, and reduced antioxidants in the cardiac tissue of rats, and these pathogenic abnormalities were ameliorated (p < 0.001) by CGPE. Histopathological studies showed a decrease in morphological disruptions by alloxan in CGPE-treated rats. CGPE (400 mg/kg) significantly ameliorated biochemical parameters in comparison to the lower doses against alloxan cardiotoxicity. Citrus grandis peel extract can be an alternative in the management of DCM.

Comparison of clinical, biochemical, and polysomnographic parameters between obese and nonobese obstructive sleep apnea.

Background: Obstructive sleep apnea (OSA) occurs in both obese and nonobese individuals. This study was designed to compare clinical, metabolic profile, and polysomnographic parameters among obese and nonobese OSA patients. Material and Methods: This cross-sectional retro-prospective study involved 148 OSA patients. OSA patients were classified as nonobese (body mass index [BMI] <27.5 kg/m2) and obese (BMI ≥27.5 kg/m2) to determine the influence of BMI on its risks, clinical, metabolic, and polysomnographic parameters. For statistical comparisons, continuous variables were analyzed by Student's t-test and categorical variables by Chi-square. Results: Of 148 patients, 106 patients were of a retrospective group and 42 in the prospective group. 116 patients were obese and 32 were nonobese with a mean BMI of 33.66 ± 5.3 versus. 25.17 ± 2.2 kg/m2 respectively. Female sex (70.7% vs. 43.4%), larger neck circumference (37.99 ± 3.93 vs. 33.67 ± 5.5 cm), loud snoring (94.8% vs. 81.3%), excessive daytime sleepiness (53.4% vs. 9.4%), fatigability (94.8% vs. 75%), high Epworth Sleepiness Scale score (16% vs. 8%), and hypertension (77.6% vs. 46.9%) were significantly (P < 0.05) more common among obese OSA patients while as smoking and sedative use was more prevalent among nonobese OSA group. However, no significant difference in median apnea-hypopnea index and severity of OSA between obese and nonobese group was observed. At the same time, the median oxygen desaturation index was significantly higher in obese patients (26.1 vs. 12.7, P = 0.005). Conclusion: Nonobese OSA patients depicted less severe disease symptoms and thus require high index of suspicion for early identification due to associated cardiovascular risk.

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.

Thyroid Function, Urinary Iodine, and Thyroid Antibody Status Among the Tribal Population of Kashmir Valley: Data From Endemic Zone of a Sub-Himalayan Region.

Background: There are scarce data on the prevalence of thyroid disorders and urinary iodine status among tribal populations of India, with no reported data from Kashmir valley. Objectives: To estimate the prevalence of thyroid disorders and evaluate urinary iodine concentration (UIC) and thyroid autoantibody status among Gujjar and Bakerwal tribes of Kashmir valley. Methods: This cross-sectional study recruited tribal subjects using multistage cluster sampling from 5 out of 22 districts of Jammu and Kashmir (J&K). Using a predesigned questionnaire, the details of past or current medical history and drug intake, including thyroid hormone medication etc. were recorded after obtaining an informed consent. Examination included anthropometry (height, weight, waist circumference), blood pressure measurement, and relevant general physical examination focusing on goiter palpation, while as laboratory assessment included estimation of serum thyroid hormone levels, antithyroid peroxidase antibody (anti-TPO Ab), and urinary iodine concentration. Results: A total of 763 subjects (56.4% women and 43.6% men) with a mean(±SD) age of 39.46 (±17.51) ranging from 10 to 85 years and mean(±SD) body mass index (BMI) of 21.28 (±4.16) kg/m2 were studied. Goiter was detected in 6.8%, while 33.2% subjects had some form of thyroid dysfunction (including 24.1% subclinical and 6.8% overt hypothyroidism). Subclinical and overt hyperthyroidism were observed in 1.3 and 0.9% of cases, respectively. Anti-TPO Ab was elevated in 13.6%, while the median [interquartile range (IQR)] for UIC was 154.50 (135) µg/L [156.13 (134) µg/L in men and 147.26 (136) µg/L in women]. A negative correlation was observed between UIC and anti-TPO Ab (r = -0.087, P = <0.05). Conclusion: These novel data on iodine and thyroid status among a tribal population of India generally inhabiting in remote sub-Himalayan belts demonstrate high prevalence of subclinical hypothyroidism (SCH) with persistent iodine deficiency. These preliminary data may warrant large well-designed studies to carry out comprehensive assessment of the problem in this high-risk and marginalized population.

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.

The Clinical Spectrum of Fibrocalculous Pancreatic Diabetes in Kashmir Valley and Comparative Study of the Clinical Profile of Fibrocalculous Pancreatic Diabetes and Type 2 Diabetes Mellitus.

BACKGROUND: Fibrocalculous pancreatic diabetes (FCPD) is a secondary form of diabetes, described from several tropical countries, including India. We described the existence of this entity in the subtropical region-the Kashmir valley of the Indian subcontinent and compared the clinical characteristics of these patients with type 2 diabetes mellitus (T2DM) patients. AIM: The present study aimed to compare the clinical characteristics of patients with FCPD and those with T2DM to identify the characteristics distinctive of FCPD. MATERIALS AND METHODS: A total of 124 patients with FCPD were compared with 124 patients with T2DM matched for age and duration of diabetes. Biochemical parameters and microvascular and macrovascular complications were assessed in all patients. Multivariate regression analyses were performed to study the determinants of microvascular complications in both groups. RESULTS: FCPD patients had significantly lower serum cholesterol, serum triglyceride, and serum calcium levels but higher glycosylated hemoglobin levels compared to T2DM patients. FCPD participants were significantly leaner. The prevalence of retinopathy, neuropathy, and nephropathy was similar between the two. Five T2DM patients had documented cardiovascular disease compared to one in FCPD patients (P < 0.05). Multiple logistic regression analysis revealed glycosylated hemoglobin and duration of diabetes to be significantly associated with retinopathy and nephropathy in T2DM. Among FCPD patients, glycosylated hemoglobin showed a strong association with retinopathy as well as nephropathy. BMI showed a significant negative association with nephropathy in FCPD patients. Age and age at onset showed a strong association with neuropathy in FCPD patients while the duration of diabetes showed the association with neuropathy (P = 0.015) in T2DM. CONCLUSION: There are several differences in the phenotype, biochemical parameters, and prevalence of diabetic complications between patients with FCPD and T2DM.

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.

Evaluation of serum anti-nuclear antibody among women with PCOS: a hospital based single center cross sectional study.

Polycystic ovary syndrome (PCOS), a major endocrinopathy is associated with barrage of metabolic aberrations. Reports in literature on association of PCOS and autoimmunity are conflicting. We aim to evaluate serum levels of anti-nuclear antibody (ANA) among Indian women with PCOS. In this hospital-based single center cross-sectional study, women qualifying a diagnosis of PCOS by Rotterdam criteria 2003 were recruited. Eighty-nine eligible women who consented were enrolled. All these women along with 87 age-matched, healthy controls underwent, clinical (menstrual history, anthropometry, hirsutism scoring), biochemical, hormonal assessment and serum ANA estimation. OGTT after overnight (8-12 h) fast with 75 g oral glucose load was done for 1 h, 2 h glucose and insulin measurements. The mean age of cases and controls was comparable (22.67 ± 5.53 vs. 22.84 ± 3.64 years). The prevalence of ANA positivity was significantly higher among women with PCOS (18.4% vs. 2.29%; p < .001). Though significant correlation was observed between ANA positivity and clinical signs of hyperandrogenism and plasma glucose, no significant correlation was noted between ANA status and other hormonal parameters. Higher prevalence of ANA positivity among women with PCOS, being a marker of autoimmunity, suggests a possible role of autoimmunity in causation of PCOS and needs further elucidation.