Utility of Simple and Non-Invasive Strategies Alternative to Inferior Petrosal Sinus Sampling and Peripheral CRH Stimulation in Differential Diagnosis of ACTH-Dependent Cushing Syndrome.

We aimed to evaluate the utility of simple, cost-effective, and non-invasive strategies alternative to BIPSS and peripheral CRH stimulation in differential diagnosis of ACTH-dependent CS. First, we performed ROC analysis to evaluate the performance of various tests for differential diagnosis of ACTH-dependent CS in our cohort (CD, n=76 and EAS, n=23) and derived their optimal cut-offs. Subsequently, combining various demographic (gender), clinical (hypokalemia), biochemical (plasma ACTH, HDDST, peripheral CRH stimulation) and imaging (MRI pituitary) parameters, we derived non-invasive models with 100% PPV for CD. Patients with pituitary macroadenoma (n=14) were excluded from the analysis involving non-invasive models. Relative percent ACTH (AUC: 0.933) and cortisol (AUC: 0.975) increase on peripheral CRH stimulation demonstrated excellent accuracy in discriminating CD from EAS. Best cut-offs for CD were plasma ACTH<97.3 pg/ml, HDDST≥57% cortisol suppression, CRH stimulation≥77% ACTH increase and≥11% cortisol increase. We derived six models that provided 100% PPV for CD and precluded the need for BIPPS in 35/85 (41.2%) patients with ACTH-dependent CS and no macroadenoma (in whom BIPSS would have otherwise been recommended). The first three models included basic parameters and avoided both peripheral CRH stimulation and BIPSS in 19 (22.4%) patients, while the next three models included peripheral CRH stimulation and avoided BIPSS in another 16 (18.8%) patients. Using simple and non-invasive alternative strategies, BIPSS can be avoided in 41% and peripheral CRH stimulation in 22% of patients with ACTH-dependent CS and no macroadenoma; such patients can be directly referred for a pituitary surgery.

A Randomized Controlled Trial of Intrathecal versus Caudal Morphine-Bupivacaine on Postoperative Analgesia and Cortisol Levels in Pediatric Patients.

BACKGROUND: Morphine is commonly used in pediatric caudal blocks. We compared the analgesic efficacy and effect on cortisol levels of intrathecal morphine and bupivacaine with caudal morphine and bupivacaine in children undergoing lower abdominal surgeries. METHODS: Forty children undergoing lower abdominal surgeries were randomized to receive 4 µg/kg of intrathecal morphine and 0.5% hyperbaric bupivacaine (n = 20), or caudal morphine 40 µg/kg and 0.25% bupivacaine (n = 20). Postoperative analgesia was provided with intravenous (IV) paracetamol (PCM). The primary outcome was time to reach Face, Legs, Activity, Cry, and Consolability (FLACC) score ≥4 postoperatively. Secondary outcomes were perioperative serum cortisol levels, analgesic requirement, and parent satisfaction. RESULTS: Since seventy 5% of patients receiving intrathecal morphine and bupivacaine did not reach a FLACC score ≥4 within 24 hours, the primary outcome was presented as the Kaplan-Meier curve. The probability of FLACC score <4 was significantly higher with intrathecal morphine and bupivacaine than with caudal morphine and bupivacaine (P < .001). The unadjusted and adjusted (for gender) hazard ratio (95% confidence interval [CI]) of occurrence of pain (FLACC score ≥4) was 0.07 (0.03-0.15, P < .001) and 0.06 (0.03-0.14, P < .001), respectively. The difference in means (95% CI) of cortisol levels between caudal morphine (with bupivacaine) and intrathecal morphine (with bupivacaine) groups were after intubation -0.667 (-4.99 to 3.65, P = .76), at 2 hours intraoperatively 7.88 (3.55-12.2, P < .001), 6 hours postoperatively 16.8 (12.5-21.1, P < .001), and 24 hours postoperatively 15.4 (11.1-19.7, P < .001) µg/dL. Intraoperatively, rescue fentanyl was required by 60% of patients on caudal morphine and bupivacaine against 20% of patients receiving intrathecal morphine and bupivacaine (absolute risk-reduction [95% CI] of 40% [12%-68%]; P = .010). Postoperative rescue fentanyl was required in 45% of patients on caudal morphine and bupivacaine and 5% of patients on intrathecal morphine and bupivacaine. All (100%) patients on caudal morphine and bupivacaine required postoperative PCM against 6 (30%) patients on intrathecal morphine and bupivacaine (absolute risk-reduction [95% CI] of 70% [50%-90%]; P < .001).The median (interquartile range [IQR]) parent satisfaction score for patients on caudal morphine (with bupivacaine) and intrathecal morphine (with bupivacaine) was 0(0-0) and 2(2-2) at 12 hours postoperatively (P < .001) and 0(0-1) and 2(1.5-2) at 24 hours postoperatively (P < .001). One patient in each group developed nausea and vomiting, and 1 patient in the intrathecal group developed pruritus. There was no incidence of respiratory depression. CONCLUSIONS: Intrathecal morphine and bupivacaine results in longer duration of analgesia, lower analgesic consumption, prevents surgical-stress-related elevation of serum cortisol, and improves parent satisfaction compared to caudal morphine with bupivacaine in children undergoing lower abdominal surgeries.

Late-night salivary cortisol cut-offs for diagnosis of Cushing syndrome using second-generation electrochemiluminescence immunoassay kits.

CONTEXT: Late-night salivary cortisol (LNSC) is a simple and reliable screening test for Cushing syndrome (CS). With improved analytical performance of the current second-generation electrochemiluminescence immunoassay (ECLIA; Elecsys Cortisol-II; Roche Diagnostics), there is a need to revisit the LNSC cut-offs, especially in a South-Asian population. OBJECTIVE: To derive LNSC cut-offs for diagnosis of CS using second-generation ECLIA kits. DESIGN: Diagnostic accuracy study. METHODS: We prospectively recruited 155 controls aged 18-60 years, including, normal-weight (body mass index [BMI] < 25 kg/m2 and no hypertension or diabetes [n = 53]) and overweight/obese (BMI 25-30 kg/m2 and hypertension and/or diabetes [n = 52] or BMI ≥ 30 kg/m2 with/without comorbidities [n = 50]) participants. All participants submitted LNSC samples collected at home; overweight/obese controls additionally underwent dexamethasone suppression test to exclude CS. We also reviewed records of adults with endogenous CS (cases, n = 92) and a valid LNSC result using the same method. RESULTS: The 95th percentile for LNSC in controls was 6.76 nmol/L. The mean ± SD LNSC levels were 40.47 ± 49.63 nmol/L in cases and 3.37 ± 1.18 nmol/L in controls (p < 0.001). Receiver operating characteristic (ROC) analysis showed excellent diagnostic performance of LNSC for CS, with area under curves (AUCs) of 0.994 (cases vs. all controls) and 0.993 (cases vs. overweight/obese controls), respectively. The best diagnostic performance was achieved at cut-offs ≥6.73 nmol/L (sensitivity: 97.8%, specificity: 94.8%) and ≥7.26 nmol/L (sensitivity: 97.8%, specificity: 95.1%), respectively. CONCLUSIONS: LNSC measured using second-generation ECLIA demonstrated high diagnostic accuracy for CS. Based on this study, we propose a LNSC cutoff ≥6.73 nmol/L to diagnose CS.

Clinical profile and treatment outcomes among patients with sporadic and multiple endocrine neoplasia syndrome-related primary hyperparathyroidism.

OBJECTIVE: Accurate demarcation between multiple endocrine neoplasia, type 1 (MEN1)- related primary hyperparathyroidism (MPHPT) and sporadic PHPT (SPHPT) is important to plan the management of primary parathyroid disease and surveillance for other endocrine and nonendocrine tumours. The objective of this study is to compare the clinical, biochemical and radiological features and surgical outcomes in patients with MPHPT versus SPHPT and to identify the predictors of MEN1 syndrome in PHPT. DESIGN, PATIENTS AND MEASUREMENTS: This was an ambispective observationalstudy involving 251 patients with SPHPT and 23 patients with MPHPT evaluated at the endocrine clinic of All India Institute of Medical Sciences, New Delhi, India between January 2015 and December 2021. RESULTS: The prevalence of MEN1 syndrome among patients with PHPT was 8.2% and a genetic mutation was identified by Sanger sequencing in 26.1% of patients with MPHPT. Patients with MPHPT were younger (p < .001), had lower mean serum calcium (p = .01) and alkaline phosphatase (ALP; p = .03) levels and lower bone mineral density (BMD) Z score at lumbar spine (p < .001) and femoral neck (p = .007). The prevalence of renal stones (p = .03) and their complications (p = .006) was significantly higher in MPHPT group. On multivariable analysis, factors predictive of MPHPT were hyperplasia on histopathology [OR 40.1, p < .001], ALP levels within reference range [OR 5.6, p = .02] and lumbar spine BMD [OR 0.39 per unit increase in Z score, p < .001]. CONCLUSIONS: Patients with MPHPT have more severe, frequent and early onset of bone and renal involvement despite milder biochemical features. A normal serum ALP, low BMD for age and gender at lumbar spine and histopathology evidence of hyperplasia are predictive factors for MEN1 syndrome in PHPT.

Correlation of Levator-Muller's Complex Thickness on Ultrasound Biomicroscopy to Botulinum Toxin A Injection in Thyroid-Related Upper Eyelid Retraction.

OBJECTIVES: To study the thickness of levator palpebra superioris-Muller's muscle complex (LMC) on ultrasound biomicroscopy (UBM) and to correlate with the clinical response to botulinum toxin A (BTA) injection in patients with inactive-stage of thyroid-related upper eyelid retraction (UER). We also studied the correlation of clinical parameters, preinjection with postinjection values. METHODS: This was a prospective, interventional study. Patients with thyroid-related UER who underwent subconjunctival injection of BTA were recruited. Demographic data and clinical details were evaluated. UBM (50 MHz) was done to measure the thickness of LMC. Patient's satisfaction was graded at each follow-up. Follow-up was done at 1 week, 1 month, and 3 months' time intervals. RESULTS: A total of 13 patients were recruited and 26 eyes were divided into two groups; group 1 included eyes with UER (n = 17), and group 2 included eyes without UER (n = 9). There was a statistically significant reduction in margin reflex distance 1 (MRD1) after BTA injection at 1-week, 1-month, and 3-months follow-up with maximum reduction at 1 month. The mean LMC thickness of 26 eyes was 0.96 mm which was found to be significantly more than normal controls. On comparison of mean LMC thickness with the amount of UER and reduction in MRD1, we did not find a significant difference. CONCLUSIONS: Patients with TED have significantly thicker LMC on UBM than controls. Further studies are needed with a larger sample size on the correlation of UBM features of levator aponeurosis with response to BTA injection.

Pattern of Lipid Abnormalities Among South Asian Indians With Cushing's Syndrome and the Short Term Impact of Surgical Correction of Hypercortisolism.

Atherosclerotic cardiovascular events are one of the common causes of mortality in patients with Cushing's syndrome (CS). Atherogenic dyslipidemia is more common among South Asian Indians as compared to other ethnicities and is likely to worsen among patients with CS. This retrospective study was done over 5 years at a single institute to evaluate the pattern of lipid abnormalities in subjects with CS and the changes in lipid parameters after surgical control of hypercortisolemia. The study was done in two parts. In the first part, records of patients with CS diagnosed over 3 years were retrospectively reviewed. Hormonal and metabolic parameters including fasting plasma glucose (FPG), post prandial plasma glucose (PPPG), HbA1c, serum lipids, serum cortisol and plasma ACTH were recorded. In the second part, lipid parameters were rechecked among patients who underwent surgery and a median follow up of 4±2 months after remission. Out of the 126 patients diagnosed with endogenous CS over 3 years, 100 patients were eligible for inclusion in the study. At baseline, sixty five (65%) patients had dyslipidemia as defined by the NCEP-ATPIII criteria. 47 out of 63 (74.6%) subjects achieved remission after surgical management of CS. 32 (68.1%) of these patients had dyslipidemia prior to surgery. After excluding 1 death, 26 of 46 (56.5%) subjects had dyslipidemia after the follow up period. Lipid abnormalities are common among South Asian Indian subjects with endogenous CS and the pattern persists in most of them, 3 months after surgical correction of hypercortisolism.

Novel Heterozygous Genetic Variants in Patients with 46,XY Gonadal Dysgenesis.

46,XY gonadal dysgenesis (GD) constitutes a rare group of disorders characterized by the presence of dysfunctional testes in genotypic males. The molecular etiology is not known in about 2 thirds of instances. The aim of this study was to identify the genetic cause in patients with 46,XY gonadal dysgenesis. Based on clinical, cytogenetic, and biochemical screening, 10 patients with 46,XY GD were recruited. Direct sequencing of SRY, NR5A1, SOX9, DAX1, DHH, DMRT1 genes was carried out for molecular analysis. Among 10 patients, 5 were diagnosed with complete gonadal dysgenesis (CGD), 3 with partial gonadal dysgenesis (PGD), and 3 with testicular agenesis. Molecular analysis revealed 12 heterozygous genetic changes, 4 of which were novel. One (c.416T>A) was observed in evolutionary conserved region of DMRT1 gene in a patient with CGD and was found to be probably damaging on in silico analysis. Other 3 were identified in NR5A1 gene (c.990+22 C>A, c.1387+1403T>A and p.131P), but their association with gonadal dysgenesis is not evident from our study. These genetic changes were absent in parents and 50 healthy control samples, which were also studied. With targeted sequencing approach, a molecular diagnosis was made in only one patient with 46,XY GD. The application of new genomic technologies is required for the precise evaluation of these rare genetic defects.

T372R Mutation Status in Yin Yang 1 Gene in Insulinoma Patients.

Insulinomas are rare pancreatic neuroendocrine tumors. The genetic causes underlying insulinoma are still being investigated. Recently, 3 independent studies reported a recurrent somatic mutation in YY1 gene (C>G; Thr372Arg) among insulinoma patients belonging to Chinese and Western Caucasian populations, which was found to increase insulin secretion by ß-cells. However, the status of this key gene variation remains unknown in patients of other ethnicities. We, therefore, screened Indian sporadic insulinoma patients for YY1 T372R mutation in the present study. Seventeen patients diagnosed with insulinoma were recruited retrospectively and their records of family history and clinical parameters were collected. Formalin-fixed paraffin-embedded tumor tissues were used to extract genomic DNA, which was subjected to PCR amplification of YY1 exon 5, followed by Sanger sequencing. Nucleotide sequences thus obtained were aligned against the documented sequence of YY1 exon 5. We found absence of C to G mutation at YY1 codon 372 in all 17 (100%) insulinoma tissues analyzed. On comparison with the mutation frequency observed in the Chinese patients, our results point to genetic heterogeneity in the pathogenesis of insulinoma. This is the first report on the status of YY1 T372R in insulinoma cases of Indian origin. This also warrants analysis of other documented as well as novel mutations in genes in insulinoma tumorigenesis.

Evolving management of insulinoma: Experience at a tertiary care centre.

BACKGROUND & OBJECTIVES: Since our previous study in 2006, several new modalities for localization of cause of endogenous hyperinsulinemic hypoglycaemia such as multiphasic computed tomography (CT), multiphasic magnetic resonance imaging (MRI), endoscopic ultrasound (EUS), intraoperative ultrasound, and intra-arterial calcium infusion with arterial stimulation venous sampling (ASVS) have become available. Therefore, to evaluate the relative usefulness of various imaging modalities to guide future management in terms of diagnosis and patient care, we analyzed presentation and management of patients of endogenous hyperinsulinemic hypoglycaemia. METHODS: In this retrospective study, medical records of patients admitted with endogenous hyperinsulinemic hypoglycaemia were retrieved. Data pertaining to clinical features, diagnosis, imaging, surgery and patient outcome were extracted. The localization of insulinoma by preoperative imaging techniques was compared with the findings at surgery to assess the accuracy of localization. RESULTS: Fasting hypoglycaemia was present in all, and post-prandial hypoglycaemia (plasma glucose ≤50 mg/dl within four hours of meal) in 25.8 per cent. Mean duration of symptoms before reaching a diagnosis of hyperinsulinemic hypoglycaemia was 3.9 years. Mean duration of provocative fast was 21.8 h (range 6-48 h). Among the currently used imaging modalities, the sensitivity of localizing tumour was 79.3 per cent for multiphasic CT, 85 per cent for multiphasic MRI and 95 per cent for EUS. EUS detected tumour missed by both CT and MRI. All, except one of the operated patients, were cured by surgery. INTERPRETATION & CONCLUSIONS: Our results suggest that patients with insulinoma have a varied presentation. Multiphasic contrast-enhanced MRI/CT scan, EUS and ASVS may be complimentary in pre-operative localization.

Novel MEN 1 gene findings in rare sporadic insulinoma--a case control study.

BACKGROUND: Insulinomas, which are rare tumors causing hyperinsulinemic hypoglycemia are usually sporadic but may also occur in association with multiple endocrine neoplasia type 1 (MEN-1) syndrome an autosomal dominant disorder caused by MEN1 gene mutations. MEN1 encodes a nuclear protein Menin, a tumor suppressor which acts as an adapter and interacts with partner proteins involved in crucial activities like transcriptional regulation, cell division, proliferation and genome stability. This study reports on clinical findings and mutation screening in sporadic insulinoma patients. METHODS: Seventeen patients diagnosed with insulinoma were recruited along with 30 healthy volunteers who acted as controls for the present study. The patients presented with symptoms of sweating, tremors, drowsiness, palpitations, loss of consciousness, abnormal behavior, seizures and weight gain. Detailed clinical and family history was collected from all the participants along with 5 ml of blood sample after taking informed consent. Genomic DNA isolated from blood was subjected to MEN1 gene amplification followed by direct sequencing. Nucleotide sequences obtained were compared with published MEN1 cDNA sequences. Prediction of functional effects of novel changes was done using various bioinformatics algorithms. RESULTS: Molecular analysis revealed presence of three novel exonic mutations (M561K, Q192K and Q261Q), two novel intronic variations c.445-44G → A and c.913-42G → C in introns two and six respectively and three reported exon SNPs; H433H (rs540012), D418D (rs2071313), A541T (rs2959656) and one intronic SNP (rs669976). CONCLUSIONS: The study identified presence of novel pathogenic MEN1 mutations in sporadic cases of insulinoma. The new mutations identified were in regions involved in defective binding of menin to proteins implicated in genetic and epigenetic mechanisms. The outcome of the study extends the growing list of MEN1 pathogenic mutations even in sporadic cases providing consequential insight into phenotypic heterogeneity and in the expression of individual mutations.

Coeliac disease in patients with short stature: A tertiary care centre experience.

BACKGROUND: We aimed to determine the prevalence of coeliac disease among children with short stature at a tertiary care centre and to define the predictors for coeliac disease, if any, in them. METHODS: In this retrospective study, we reviewed the case records of children and adolescents with growth retardation attending the Paediatric Endocrinology Clinic from January 2008 to June 2011. All patients underwent the multi-tier stratified diagnostic protocol for complete evaluation of short stature. Coeliac disease was screened using IgA-anti-tissue transglutaminase antibody. The diagnosis of coeliac disease was made on the basis of the modified European Society of Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) criteria. RESULTS: Of 432 patients (238 boys) who presented with short stature, 72 (16.7%) had physiological, while 360 (83.3%) had pathological causes. Endocrine causes were growth hormone deficiency (86 patients, 19.9%), hypopituitarism (31, 7.2%), hypothyroidism (22, 5.1%) and others (7, 1.6%). The systemic causes were: coeliac disease (47, 10.9%), haematological diseases (14, 3.2%), renal diseases (11, 2.5%) and others (24, 5.6%). Chronic diarrhoea (OR 15.7, 95% CI 7.8-31.5) and anaemia (OR 4.9, 95% CI 1.9-12.7]) were significant predictors for coeliac disease in patients with short stature. There was a definite response to gluten-free diet in them and the mean (SD) growth velocity measured over at least 6 months of gluten-free diet was 8.1 (3.0) cm/year. CONCLUSION: Nearly 11% of patients presenting with short stature have coeliac disease. In these patients chronic diarrhoea and anaemia were significant predictors of coeliac disease.

Pragmatic Evaluation of Growth Hormone Stimulation Tests in Short Stature.

Introduction: To assess the performance of growth hormone stimulation tests (GHSTs) in the evaluation of short stature. Methods: It was a single-centre retrospective study carried out in children evaluated for short stature between January 2005 to March 2020. The clonidine stimulation test (CST) and glucagon stimulation test (GST) were used to assess growth hormone (GH) reserve (GST was performed only when peak GH levels were between 5 to ≤10 ng/mL on CST). A GH level of <5 ng/mL on CST or ≤10 ng/ml on both was used to corroborate GH deficiency. Results: A total of 556 children were eligible for this study. The mean (SD) age was 12.9 (3.5) years, and 66.3% were male. The peak GH level [median (IQR)] was 5.50 ng/ml (1.90 - 7.50) on CST (at 60 minutes) and 7.45 ng/ml (2.15 - 10.77) on GST (at 120 minutes). On restricting sampling to two time points, the false positive rate was 13.6% on CST (60, 90 minutes) and 11.5% on GST (120, 150 minutes). Similarly, restricting to three time points was associated with a false positive rate of 8.5% on CST (60, 90, 120 minutes) and 3.8% on GST (90, 120, 150 minutes). Using the treating clinician-determined diagnosis of GHD as a reference standard, the optimal cut-off of peak GH on CST was 7.79 ng/ml (sensitivity: 83.8%; specificity: 89.4%). Conclusion: Restricting the GH sampling to fewer time points is associated with an increase in the false positivity rate (FPR).

Utility of an in-house real-time PCR in whole blood samples as a minimally invasive method for early and accurate diagnosis of invasive mould infections.

INTRODUCTION: Invasive mould infections (IMIs) are a leading cause of death in patients with compromised immune systems. Proven invasive mould infection requires detection of a fungus by histopathological analysis of a biopsied specimen, sterile culture, or fungal DNA amplification by PCR in tissue. However, the clinical performance of a PCR assay on blood samples taken from patients suspected of invasive mould disease has not been fully evaluated, particularly for the differential diagnosis of invasive aspergillosis (IA) and invasive Mucormycosis (IM). OBJECTIVES: To assess the diagnostic utility of our previously validated in-house real-time PCR in blood samples for diagnosis of invasive aspergillosis and mucormycosis in patients with suspected invasive mould infection. METHODS: All patients with suspected invasive mould infection were prospectively enrolled from May 2021 to July 2021. Conventional fungal diagnosis was performed using tissue and respiratory samples. In-house PCR was performed on blood samples and its diagnostic performance evaluated. RESULTS: A total of 158 cases of suspected invasive mould infection were enrolled in the study. The sensitivity and specificity of in-house PCR performed on blood samples was found to be 92.5% and 81.4% respectively for diagnosis of probable IA, and 65% and 84.62% respectively for diagnosis of proven and probable IM. It was also able to detect 3 out of 5 cases of possible IM where no other microbiological evidence of IM was obtained. CONCLUSIONS: This assay could be helpful in minimally invasive diagnosis of IMIs for patients in whom invasive sampling is not feasible, especially as a preliminary or screening test. It can help in early diagnosis, anticipating conventional laboratory confirmation by days or weeks. Possible correlation between fungal load and mortality can help in initiating aggressive treatment for patients with high initial fungal load.

Decreased autonomic modulation of heart rate and altered cardiac sympathovagal balance in patients with Cushing's syndrome: role of endogenous hypercortisolism.

BACKGROUND/AIMS: Endogenous Cushing's syndrome is associated with a higher risk of cardiovascular morbidity and mortality. Previous literature suggested multiple possible links by which hypercortisolism may alter the autonomic control of cardiovascular functions. We investigated the impact of chronic endogenous hypercortisolism on the autonomic regulation of cardiac functions by short-term heart rate variability analysis. METHODS: Eighteen patients with endogenous Cushing's syndrome and 20 age-, gender- and BMI-matched controls participated in the study. ECG signal was acquired in lead II configuration for 5 min and heart rate variability assessment was made in both time and frequency domain using the extracted RR interval data. RESULTS: All time and frequency domain measures of heart rate variability were significantly (p < 0.05) lower in the patient group compared to the control group. The patient group had an altered sympathovagal balance with low frequency/high frequency band ratio significantly higher than the control group [1.857 (0.6747-2.610) vs. 0.8581 (0.4779-1.352); p = 0.0253]. A significant negative correlation was obtained between normalized high frequency power of heart rate variability and basal cortisol levels (r = -0.6594; p = 0.0029). Multiple linear regression analysis identified age, disease duration (in months), basal cortisol levels and systolic blood pressure as independent predictors of normalized high frequency power. CONCLUSION: Findings of the study clearly portrayed the diminished autonomic modulation of heart rate in endogenous Cushing's syndrome and its possible relationship with hypercortisolism as the main causative factor. Diminished heart rate variability may be an indicator of the increased risk of cardiac mortality in these patients.

Prevalence of depression among type 2 diabetes compared to healthy non diabetic controls.

AIMS: Successful diabetes management depends on patient behaviour. Diabetes is a significant risk factor for depression which itself is a risk factor for poor metabolic control. Data on this association is scarce from India--which is fast becoming the diabetes capital of the world. This study was done to see the prevalence of depression in adult patients with type 2 diabetes diagnosed within the previous 5 years and treated with oral hypoglycaemic agents compared to healthy persons without diabetes. Also, to evaluate Becks depression inventory (BDI) in terms of Mini International Neuropsychiatric Interview (MINI) as a tool to assess depression in diabetes. METHODS: Patients with diabetes within 5 year of diagnosis and on oral anti-diabetic drugs were included. Controls were healthy relatives of these patients without diabetes. These patients underwent clinical examination, biochemical tests, assessment of depression by BDI and MINI BDI and MINI were used to assess depression in controls as well. Prevalence of depression was found in both groups and compared. BDI was evaluated considering the MINI as gold standard in detecting depression in diabetes. RESULTS: The prevalence of co-morbid depression was 27.05% according to the MINI. In the non-diabetic healthy patient relatives, this was 11.11%. Those having depression had a lower educational attainment and a higher prevalence of retinopathy, compared to subjects without depression. The relative risk for the diabetics to have co-morbid depression was 2.97 (95% confidence interval 1.41-6.24). The BDI score with best sensitivity and specificity for diagnosing depression in diabetes was > or = 21. For healthy controls, a score of > or = 14 had best sensitivity and specificity. Diabetic patients had a higher score of BDI even without a diagnosis of depression on the MINI. CONCLUSION: Prevalence of depression was 27.05% diabetic patients and 11.11% healthy controls. A BDI score of 21 had the best sensitivity and specificity for diagnosing depression in adult type 2 diabetic patients. BDI can be used as a simple screening tool for the detection of depression in diabetic patients.

Prevalence and Predictors of Osteoporosis/BMD Below Expected Range for Age in Pheochromocytoma/Paraganglioma and BMD, TBS Change Post-Operatively: A Prospective Cohort Study.

Context: Pheochromocytomas/paragangliomas (PPGLs) have recently been shown to be associated with lower bone mineral density (BMD) and trabecular bone score as compared to healthy controls suggesting low bone mineral concentration and disrupted bone microarchitecture. There is paucity of data on prevalence and clinical predictors of low BMD/osteoporosis in PPGL from India and the extent of change in BMD post-operatively. Aims: This study aimed to find prevalence of low BMD/osteoporosis and trabecular bone score (TBS)-adjusted FRAX score in subjects with PPGL and to see the post-operative change in BMD and TBS at follow-up. Material and Methods: 32 consecutively diagnosed adult cases with PPGL were enrolled. Although the provisional diagnosis of PPGL was made based on imaging consistent with PPGL supported by biochemical evidence of catecholamine excess, its confirmation was made histopathologically before final analysis. Results: We found significantly low average BMD T-score/Z-score at spine, hip or wrist. Osteoporosis was evident in 87.5% of subjects (nine of 11 post-menopausal women or men >50 years of age) and BMD below the expected range for age in 42.9% of subjects (nine of 21 pre-menopausal women or men <50 years of age) by International Society for Clinical Densitometry criteria. Conclusions: 87% of older subjects with PPGL had osteoporosis while 43% of younger subjects had BMD below expected range for age (Z-score ≤-2.0), more at lumbar spine than at hip. Decreased body weight was associated with osteoporosis in older or Z-score ≤-2.0 in younger subjects. There was no significant change in BMD and TBS scores at a median of four months post-operatively.

Clinical profile and treatment outcomes of patients with ectopic ACTH syndrome compared to Cushing disease: a single-center experience.

PURPOSE: We aimed to evaluate and compare the clinical, biochemical and radiological profile and outcomes of patients with ectopic ACTH syndrome (EAS) and Cushing disease (CD) treated over a period of 10 years (2013-2022). METHODS: In this ambispective observational study, we collected data for 146 patients with ACTH-dependent CS (EAS, n = 23; CD, n = 94; occult ACTH source, n = 29). Relevant details were filled in a predesigned proforma and outcomes were ascertained at the most recent visit. RESULTS: EAS was more common in males (65.2 vs. 27.6%, p < 0.001). Patients with EAS had a shorter duration of symptoms [12 (6-12) vs. 31.5 (15-48) months, p < 0.001] and were more likely to have hypokalemia (82.6 vs. 21.0%, p = 0.001), pedal edema (65.2 vs. 34.2%, p = 0.015), weight loss (34.8 vs. 4.0%, p < 0.001) and systemic infection (30.4 vs. 6.5%, p = 0.006). They also had significantly higher 8 a.m. serum cortisol, midnight serum and salivary cortisol and 8 a.m. plasma ACTH levels. Bronchial carcinoid (n = 10, 43.5%) was the most common etiology of EAS. Bilateral adrenalectomy was performed in 11 (47.8%) patients with EAS. Eight patients (34.8%) with EAS died at the last follow-up, of whom 7 (87.5%) had metastatic disease. In CD group, overall remission rate was 69.4% (56.1%, early and 13.3%, delayed) and 26.3% of patients with an initial remission had recurrence. CONCLUSIONS: Bronchial carcinoid was the most common cause of EAS in our cohort. Bilateral adrenalectomy was performed in approximately every 1 in 2 patients with EAS and approximately every 1 in 3 patients expired till the last follow-up.

Utility of in-house and commercial PCR assay in diagnosis of Covid-19 associated mucormycoss in an emergency setting in a tertiary care center.

Introduction. Invasive mucormycosis (IM) is a potentially fatal infection caused by fungi of the order Mucorales. Histopathology, culture, and radiology are the mainstays of diagnosis, but they are not sufficiently sensitive, resulting in delayed diagnosis and intervention. Recent studies have shown that PCR-based techniques can be a promising way to diagnose IM.Hypothesis/Gap Statement. Early diagnosis of fungal infections using molecular diagnostic techniques can improve patient outcomes, especially in invasive mucormycosis.Aim. The aim of this study was to evaluate the utility of our in-house mould-specific real time PCR assay (qPCR) in comparison with the commercially available real time PCR (MucorGenius PCR), for the early diagnosis of mucormycosis in tissue samples from patients with suspicion of invasive mucormycosis (IM). This in-house assay can detect and distinguish three clinically relevant mould species, e.g. Aspergillus spp., Mucorales and Fusarium spp. in a single reaction with only one pair of primers, without the need for sequencing.Methodology. We enrolled 313 tissue samples from 193 patients with suspected IM in this prospective study. All cases were classified using EORTC/MSGERC guidelines. All samples were tested using traditional methods, in-house qPCR, and MucorGenius PCR.Results. Using direct microscopy as a gold standard, the overall sensitivity and specificity of in-house qPCR for detection of IM was 92.46% and 80% respectively, while that of the MucorGenius PCR was 66.67% and 90% respectively. However, co-infection of IM and IA adversely affected the performance of MucorGenius PCR in detection of IM.The in-house PCR detected Aspergillus spp. in 14 cases and Fusarium spp. in 4 cases which showed clinical and radiological features of fungal sinusitis. The in-house qPCR also performed better in detecting possible cases of IM. This aids early diagnosis and appropriate treatment to improve patient outcomes.Conclusion. Because the in-house PCR is not only sensitive and specific, but also entirely based on SYBR Green for detection of targets, it is less expensive than probe-based assays and can be used on a regular basis for the diagnosis of IM in resource-constrained settings. It can be used to distinguish between mucormycosis and fungal sinusitis caused by Aspergillus and Fusarium in high-risk patients, as well as to accurately detect Mucorales in fungal co-infection cases.

Bone mineral density in patients of Graves disease pre- & post-treatment in a predominantly vitamin D deficient population.

BACKGROUND & OBJECTIVES: Hyperthyroidism causes bone loss, and its treatment may restore bone mass, however, concomitant vitamin D deficiency may prevent this. We undertook this study to measure the bone mineral density (BMD) 25 (OH) vitamin D levels in patients with Graves disease in our population which is predominently vitamin D deficient and how we change with when patients become euthyroid. METHODS: The biochemical, thyroid functions, serum vitamin D levels and BMD were estimated in 80 consecutive patients with Graves and 80 euthyroid controls. Patients were treated and rendered euthyroid. Fifty four completed one year, and 27 completed two years of follow up. RESULTS: Patients had significant reduced BMD during hyperthyroid state compared to normal healthy controls. The mean vitamin D levels at baseline were in the insufficient range both patients (12.67 ± 6.24 ng/ml) and controls (10.99 ± 7.05 ng/ml). The BMD improved at all sites with antithyroid treatment. But, the BMD adjusted for body mass index (BMI) and age at all sites showed significant decrease with time. INTERPRETATION & CONCLUSIONS: Age and body mass index positively correlated with BMD. There was improvement in absolute BMD of patients at one and two years of follow up. When the BMD was adjusted for age and BMI, there was a decrease in BMD at one year which was less in the second year including that the damage in BMD caused by thyroid hormone excess is not made up even after two years of patient being euthyroid. Whether vitamin D replacement would change this needs to be studied.