Introduction: 177Lu-DOTATATE-based peptide receptor radionuclide therapy (PRRT) is a promising therapy for metastatic and/ 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/ 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 PCC (4), sPGL (4), HNPGL (5), PCC+sPGL (1), HNPGL+sPGL (1) 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 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 haematotoxicity. 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.

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.

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.

U‐500 insulin is five times the concentration of conventional U‐100 insulin, which is routinely used in the United Kingdom. Its use has been reported in severely resistant patients with type 2 diabetes requiring large insulin doses, with its use improving glycaemic control. There are no clear guidelines or indications on its use. This article discusses the practical aspects on the use of U‐500 insulin. Copyright © 2006 John Wiley & Sons, Ltd.

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 aimed 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 GITS (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&lt;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 GITS 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 GITS), and tachycardia (6 in prazosin GITS and 3 in amlodipine). Interpretation 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 α-blockers like phenoxybenzamine and/or doxazosin in PPGL patients are warranted.