Context Data on the overnight 1 mg-dexamethasone suppression test (ONDST) in renal dysfunction are limited.Objective We aim to determine the normative range of ONDST cortisol across chronic kidney disease (CKD) stages and reasons for its alteration.Methods Prospectively, 180 CKD (30 each in G2-G5/5D) patients and 30 healthy controls underwent ONDST 8 Am serum cortisol (chemiluminescent immunoassay [CLIA]). In an exploratory cohort, 45 (15 each: G3b/G4, G5/G5D, and healthy controls) individuals' blood biochemistry for basal (8 Am) cortisol and adrenocorticotropin (ACTH), post-ONDST 8 Am dexamethasone, ACTH, cortisol (CLIA and liquid chromatography-tandem mass spectrometry), and 4 Pm cortisol was collected.Results Post-ONDST cortisol (mu g/dL) correlated inversely (r = 0.47; P < .005) with estimated glomerular filtration rate (eGFR) (mL/min/1.73 m2), with 95th percentile being 1.2 in controls, 3.0 in G2, 3.2 in G3a, 4.3 in G3b, 4.7 in G4, 5.7 in G5, and 7.1 in G5D. In the exploratory cohort, basal 8 Am cortisol and ACTH, and post-ONDST dexamethasone were similar among controls and CKD subgroups. ONDST ACTH (for evaluating the hypothalamo-pituitary-adrenal axis) was slightly higher in G5/5D vs controls (8.9 vs 6.1 pg/mL), while it was similar in G3b/G4 vs controls. Median 8 Am ONDST cortisol was similar on CLIA and LC-MS/MS in controls and higher on CLIA in G3b/4 (1.7 vs 1.1 mu g/dL; P = .012) and G5/5D (2.4 vs 1.7 mu g/dL; P = .002) than LC-MS/MS. Post-ONDST serum cortisol drop from 8 Am to 4 Pm was significant in controls (0.5-<0.2 mu g/dL) and G3b/4 (1.7-1.2 mu g/dL), but not in G5/5D (2.4-2.2 mu g/dL).Conclusion The normative data of ONDST serum cortisol with eGFR-based cutoffs are useful in evaluating Cushing syndrome in CKD. Prolonged cortisol half-life and immunoassay-related assay cross-reaction are likely contributors to higher ONDST cortisol.
Alopecia in hereditary vitamin D resistant rickets (HVDRR) has some correlation with severe rickets and poor overall response. However, these observations are based on small series. Hence, we aim to assess the genotypic spectrum of HVDRR and its correlation with alopecia and clinical response. Seven genetically-proven HVDDR patients from five unrelated families and 119 probands from systematic review were analysed retrospectively for phenotypic and genotypic data and overall response to therapy. In our cohort mean age at rickets onset was 12 (± 3.4) months. Alopecia was present in all patients but one. All patients had poor overall response to oral high-dose calcium and calcitriol and most required intravenous calcium. Genetic analyses revealed four novel variants. On systematic review, alopecia was present in majority (81.5
Literature regarding utility of 68Ga‐DOTATATE PET/CT in insulinoma localization across various subgroups [benign/malignant/multiple endocrine neoplasia‐1 (MEN‐1) syndrome associated] remains scarce. In this study, the performance of 68Ga‐DOTATATE PET/CT was compared with contrast‐enhanced computed tomography (CECT) and 68Ga‐NODAGA‐Exendin‐4 PET/CT (whenever available) in an endogenous hyperinsulinemic hypoglycemia (EHH) cohort.
Context Preoperative blockade with alpha-blockers is recommended in patients with pheochromocytoma/paraganglioma (PPGL). The data on calcium channel blockade (CCB) in PPGL are scarce. Objective We aimed to compare the efficacy of CCB and alpha-blockers on intraoperative hemodynamic instability (HDI) in PPGL. Methods In the interim analysis of this monocentric, pilot, open-label, randomized controlled trial, patients with solitary, secretory, and nonmetastatic PPGL were randomized to oral prazosin gastrointestinal therapeutic system (GITS) (maximum 30 mg, n = 9) or amlodipine (maximum 20 mg, n = 11). The primary outcomes were the episodes and duration of hypertension (systolic blood pressure >= 160 mmHg) and hypotension (mean arterial pressure < 60 mmHg) and duration of HDI (hypertension and/or hypotension) as a percentage of total surgical time (from induction of anesthesia to skin closure). Results The median (IQR) episodes (2 [1-3] vs 0 [0-1]; P = 0.002) and duration of hypertension (19 [14-42] vs 0 [0-3] minutes; P = 0.001) and intraoperative HDI duration (22.85 +/- 18.4% vs 2.44 +/- 2.4%; CI, 8.68-32.14%; P 0.002) were significantly higher in the prazosin GITS arm than the amlodipine arm, whereas episodes and duration of hypotension did not differ between the 2 groups. There was no perioperative mortality. One patient had intraoperative ST depression on the electrocardiogram. The drug-related adverse effects were pedal edema (1 in amlodipine), dizziness (1 in prazosin GITS), and tachycardia (6 in prazosin GITS and 3 in amlodipine). Conclusion Preoperative blockade with amlodipine is an efficacious alternative to prazosin GITS in preventing intraoperative HDI in PPGL. Larger studies that compare preoperative blockade by amlodipine with other alpha-blockers like phenoxybenzamine and/or doxazosin in PPGL patients are warranted.
Abstract Background: Preoperative blockade with α-blockers is recommended in patients with pheochromocytoma/paraganglioma (PPGL). The data on calcium channel blockade (CCB) in PPGL is scarce. We aim to compare the efficacy of CCB and α-blockers on intraoperative haemodynamic instability (HDI) in PPGL. Methods: In the interim analysis of this monocentric, pilot, open-label, randomized controlled trial, patients with solitary, secretory, and nonmetastatic PPGL were randomized to oral prazosin (maximum 30mg, n=9) or amlodipine (maximum 20mg, n=11). The primary outcomes were the episodes and duration of hypertension (SBP≥160mmHg) and hypotension (MAP<60mmHg) and duration of HDI (hypertension and/or hypotension) as a percentage of total surgical time (from induction of anaesthesia to skin closure). Findings: The median (IQR) episodes (2 [1–3] vs. 0 [0–1], p 0·002) and duration of hypertension (19 [14–42] min vs. 0 [0–3] min, p 0·001) and intraoperative HDI duration (22·85±18.4% vs 2·44±2·4%, CI 8·68-32·14%, p 0·002) were significantly higher in the prazosin arm than the amlodipine arm whereas episodes and duration of hypotension did not differ between the two groups. There was no perioperative mortality whereas one patient had intraoperative ST depression on the electrocardiogram. The drug-related adverse effects were pedal edema (1 in amlodipine), dizziness (1 in prazosin), and tachycardia (6 in prazosin and 3 in amlodipine). Interpretation: Preoperative blockade with amlodipine was more efficacious than prazosin in preventing intraoperative HDI in PPGL. Larger studies that compare preoperative blockade with amlodipine and both competitive and noncompetitive α-blockers inPPGL patients of various biochemical phenotypes are warranted.
BACKGROUND AND CONTEXT:Glucagon-like peptide-1 receptor (GLP-1 R) based imaging has shown higher sensitivity for insulinoma localization as compared to other anatomic/functional imaging.METHODOLOGY:We reviewed the published English literature for GLP-1 R targeted imaging in insulinoma in PubMed until August 2020 in accordance with PRISMA guidelines using the MeSH terms "((Exendin-4 PET/CT) OR (Exendin-4 SPECT/CT) OR (GLP-1 R imaging)) AND (Insulinoma)". An individual patient data-metanalysis (IPD-MA) was performed, and performance parameters were calculated for the histopathological diagnosis of insulinoma.MAIN OUTCOME MEASURES:True-positive (TP), false-positive (FP), false-negative (FN), true-negative (TN), sensitivity (Sn), specificity (Sp), positive predictive value (PPV) and negative predictive value (NPV) for insulinoma localization.RESULTS:A total of 179 cases (316 lesions) from 16 publications were included for IPD-MA. For insulinoma localization, exendin-4-PET/CT (Sn & PPV: 94%) performed better than exendin-4-SPECT/CT (Sn: 63%, PPV: 94%). The Sn was lower in malignant insulinoma cases whereas the Sp was higher in cases with MEN-1 syndrome. With exendin-4-based imaging, FP uptakes in Brunner's gland, normal pancreas, and other β-cell pathologies and FN results in pancreatic tail lesions and malignancy were seen in a few patients. TN results suggested the correct diagnosis of other endogenous hyperinsulinemic hypoglycaemia (EHH) subtypes.CONCLUSION:For insulinoma localization, exendin-4 PET/CT should be preferred over exendin-4 SPECT/CT because of higher sensitivity and specificity. FP uptakes in Brunner's gland, normal pancreas, and other β-cell pathologies and FN results in tail lesions, and malignant insulinomas are limitations. Higher specificity for insulinoma localization is particularly useful in patients with MEN-1 syndrome.
Introduction: 177Lu-DOTATATE-based peptide receptor radionuclide therapy (PRRT) is a promising therapy for metastatic and/or inoperable pheochromocytoma and paraganglioma (PPGL). We aim to evaluate the efficacy and safety of and identify predictors of response to 177Lu-DOTATATE therapy in metastatic and/or inoperable PPGL. Methods: This retrospective study involved 15 patients of metastatic or unresectable PPGL, who received 177Lu-DOTATATE PRRT therapy. Clinical, biochemical (plasma-free normetanephrine), and radiological (anatomical and functional) responses were compared before and after the last therapy. Results: A total of 15 patients (4 PCC, 4 sPGL, 5 HNPGL, 1 PCC + sPGL, 1 HNPGL + sPGL) were included. The median duration of follow up was 27 (range: 11–62) months from the start of PRRT. Based on the RECIST (1.1) criteria, progressive disease was seen in three (20%), stable disease in eight (53%), partial response in one (7%), and minor response in three (20%) and controlled disease in 12 (80%). On linear regression analysis the presence of PGL (P= 0.044) and baseline SUVmax >21 (P < 0.0001) were significant positive predictors of early response to PRRT. Encouraging safety profiles were noted with no long term nephrotoxicity and hematotoxicity. Conclusion: 177Lu-DOTATATE therapy is an effective and safe modality of treatment for patients with metastatic/inoperable PPGL. Although it is not prudent to withhold PRRT in metastatic PPGL with baseline SUVmax < 21, baseline SUVmax >21 can be used to predict early response to PRRT.
A 38-year-old female presented with recurrent episodes of hypoglycemia for 5 years. On 72-h fast test, critical sample biochemistry was suggestive of endogenous hyperinsulinemic hypoglycemia. Both constrast-enhanced computed tomography and 68Ga-DOTATATE positron emission tomography/computerized tomography (PET/CT) revealed no pancreatic lesion but showed a jejunal lesion suggestive of neuroendocrine tumor (NET) but not confirmatory of insulinoma. 68Ga-Exendin-4 PET/CT showed intense uptake in the proximal jejunum, and this being a specific scan for insulinoma, confirmed it as an ectopic insulinoma. The patient attained normoglycemia after excision of this NET confirming it to be a case of ectopic insulinoma located in the jejunum. Although most insulinomas are located in the pancreas, rarely ectopic cases have been described in the spleen, perisplenic tissue, duodenohepatic ligament, adjacent to the ligament of Treitz, duodenum, and the jejunum. Functional scanning with 68Ga-Exendin-4 PET/CT scan aids the localization of ectopic insulinoma.
CONTEXT:Insulinoma needs accurate preoperative localization for minimally invasive surgery. Exendin-4-based imaging has shown promising results.OBJECTIVE:To evaluate performance parameters of exendin-4-based imaging in insulinoma localization and compare with other imaging modalities.DESIGN:Retrospective cross-sectional study.PATIENTS:We report 14 patients with endogenous hyperinsulinemic hypoglycaemia (EHH) managed at our centre; in whom, the final diagnosis was insulinoma (n = 11), Munchausen syndrome (MS) (n = 2) and inconclusive (n = 1). Retrospective reporting of CECT, 68 Ga-DOTATATE PET/CT and 68 Ga-NODAGA-exendin-4-PET/CT was done. With per-lesion analysis, performance parameters were calculated for the histopathological diagnosis of insulinoma.MAIN OUTCOME MEASURES:True positive (TP), false positive (FP), false negative (FN), true negative (TN), sensitivity (Sn), specificity (Sp), positive predictive value (PPV), negative predictive value (NPV) for insulinoma localization.RESULTS:In our cohort, 12 histopathologically proven insulinoma lesions [(TP): 11 primary lesions, 1 metastasis] were detected in 11 patients, whereas two patients had MS (TN). Sn and PPV were 75% and 100%, 33.3% and 80% and 83.3% and 71.4% for CECT, 68 Ga-DOTATATE PET/CT and 68 Ga-NODAGA-exendin-4-PET/CT, respectively. With exendin-4-based imaging, FP uptake in normal pancreatic tissue and FN results in the pancreatic tail lesion was seen. In one patient, TN result suggested the correct diagnosis of MS.CONCLUSION:68 Ga-NODAGA-exendin-4-PET/CT has higher sensitivity than 68 Ga-DOTATATE PET/CT and CECT for insulinoma localization. FP uptake in normal pancreas and FN result in tail lesions are limitations of currently utilized exendin-4-based imaging.
Background: Helicobacter pylori (H.pylori) colonization is the main main risk factor for peptic ulceration as well as for gastric adenocarcinoma and gastric MALT (mucosa-associated lymphoid tissue) lymphoma.Till date optimal therapeutic regimen has not been defined for H.pylori eradication, so present study is being conducted to compare efficacy of 10-day sequential triple therapy versus 14-days sequential therapy for the eradication of H. pylori.Methods.Four hundred H. pylori positive patients (diagnosed by rapid urease test and histology), were randomized to receive 10-day sequential therapy as follows with Omeprazole (20 mg) plus Amoxicillin (1 g) twice⁄day for five days, followed by Omeprazole (20 mg) with Tinidazole (500 mg) twice⁄day and Clarithromycin (500 mg) twice⁄day for five consecutive days and 14 Days Sequential Therapy with Omeprazole (20mg bid), Amoxicillin (1gm bid) for seven days, followed by Omeprazole (20mg) with Clarithromycin (500mg) and Tinidazole (500mg twice/day) for seven consecutive days respectively.Eradication rates were determined four weeks after treatment by rapid urease test.Results.Though the eradication rate was 80 % and 86 in 10 days sequential therapy group and 14 days sequential therapy group respectively, there was no statistically significant difference in eradication rates in these two groups ('p'value>0.05).Conclusions.14 days Sequential therapy group had better eradication rates as compared to 10 days Sequential therapy group but results were not statistically significant when both the groups were compared together.
Mediastinal lymph node enlargement commonly seen in sarcoidosis, lung cancer, lymphoma and tuberculosis in children’s. Tuberculosis in adult mostly involve parenchyma of lung and very rarely involve mediastinal lymph nodes, here we report a 27-year-old male, non-diabetic, non-hypertensive, non-alcoholic and non-smoker who present with low grade fever and dry cough. Search for the cause of morbidity revealed him to be suffering from mediastinal tuberculosis. He was treated for tuberculosis with ATT.
BACKGROUNDThe average life expectancy of Women is at least five years more than Men across all age groups and in most nations. Traditionally, this difference has been attributed to the protective role played by Oestrogen in Women. However, the role of Serum Testosterone has not yet been as extensively evaluated. Initially it was believed that serum testosterone has no protective role but recent studies have provided evidence contrary to that assumption.The objective is to study the relationship between Serum hsCRP, Testosterone and Carotid Atherosclerosis in Men with Type 2 Diabetes Mellitus.MATERIALS AND METHODSWe randomly assessed 100 patients of type 2 Diabetes Mellitus attending various OPDs and wards of the hospital for levels of Serum Testosterone. We then proceeded to compare the various atherosclerotic markers between the two groups (with normal Serum Testosterone vs. Low Serum Testosterone). The results were then statistically analysed.RESULTSPrevalence of Low Serum Testosterone was 34% in our study. A higher BMI (28 +/-2.5 kg/m(2)) seen in the Low Serum Testosterone group versus the normal Testosterone group (25.9 +/- 2.61 kg/m(2)). Increased Serum Cholesterol seen in the Low Serum Testosterone group (191.6 +/- 50.5 mg/dL) versus the normal Serum Testosterone (172 +/- 39.1 mg/dL) group. Raised Triglycerides seen in the Low Serum Testosterone group (157.1 +/-58.7 mg/dL) than the normal Serum Testosterone group (137.6 +/- 31.9 mg/dL). Non-HDL Cholesterol in the Low Serum Testosterone group (155.2 +/- 49.1 mg/dL) was higher compared to the normal Testosterone Group (134.4 +/- 38 mg/dL). HbA1c levels were marginally higher in the Low Serum Testosterone group (7.9 +/- 1.1%) when compared to the normal Testosterone Group (7.5 +/- 0.9%). Increased hsCRP levels were seen in the Low Serum Testosterone group (3.2 +/- 1.0 mg/dL) than in the normal Testosterone Group (1.9 +/- 0.8 mg/dL). CIMT in the Low Serum Testosterone group (0.82 +/- 0.1 mm) was significantly more than the normal Testosterone Group (0.65 +/-0.1 mm). IHD was more frequent in the Low Serum Testosterone group (29%) versus the normal Testosterone Group (20%).CONCLUSIONTo conclude, a Low Serum Testosterone can serve as an adverse prognostic marker contributing to an increased atherosclerotic burden. Serum Testosterone should be screened for in all newly diagnosed patients of Type 2 Diabetes Mellitus.
BACKGROUNDOesophageal varices (EV) development is among the major complications of liver cirrhosis. Therefore, the current guidelines recommend screening of all liver cirrhosis patients for EV by endoscopy, but repeated endoscopic examinations are unpleasant for the patients, are not cost-effective and pose additional burden to endoscopic units. Therefore, non-invasive predictors of EV have been studied.The aim is to comparatively evaluate platelet count/spleen diameter (PC/SD) ratio, right liver lobe diameter (RLLD)/albumin ratio & left liver lobe diameter (LLLD)/albumin ratio as the non-invasive predictors of EV & their grading in patients with liver cirrhosis.MATERIALS AND METHODSThis study included 100 patients of liver cirrhosis which were subjected to laboratory investigations including platelet count & serum albumin concentration, abdominal ultrasound including measurement of RLLD, LLLD & spleen diameter and upper gastrointestinal endoscopy. PC/SD ratio, RLLD/albumin ratio & LLLD/albumin ratio were then calculated & comparatively evaluated statistically for their correlation with the presence & grading of EV.RESULTSPC/SD ratio, RLLD/albumin ratio and LLLD/albumin ratio had highly significant correlations with the presence and grading of EV (p<0.001 for each). The sensitivity, specificity and accuracy of PC/SD ratio in prediction of EV was 90.2%, 88.9% and 90% respectively at the best cut-off value of 1167.25 as calculated by applying receiver operating characteristic (ROC) curve. [AUC (Area under curve) = 0.965]. The sensitivity, specificity and accuracy of RLLD/albumin ratio in prediction of EV was 74.4%, 94.4% and 78% respectively at the best cut-off value of 4.272 (AUC= 0.835). The sensitivity, specificity and accuracy of LLLD/albumin ratio in prediction of EV was 89%, 83.3% and 88% respectively at the best cut-off value of 1.939 (AUC= 0.931). PC/SD ratio, having the highest sensitivity, accuracy & area under ROC curve, was the best predictor of EV, followed by the LLLD/albumin ratio, which was further followed by RLLD/albumin ratio.CONCLUSIONPC/SD ratio, RLLD/albumin ratio & LLLD/albumin ratio are cost-effective noninvasive parameters that can provide accurate information pertinent to predict the presence & grading of EV in liver cirrhosis patients & amongst them PC/SD ratio is the best predictor of EV, followed by LLLD/albumin ratio, which is further followed by RLLD/albumin ratio.