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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.

Context Data regarding prevalence, predictors, and mechanisms of persistent hypogonadotropic hypogonadism (HH) in males with a macroprolactinoma who achieve normoprolactinemia on dopamine-agonist therapy is limited. None of the previous studies provide cut-offs to predict the achievement of eugonadism. Objective To evaluate the prevalence of persistent HH and its determinants in males with a macroprolactinoma who achieve normoprolactinemia on cabergoline monotherapy Design Retrospective study with prospective cross-sectional evaluation. Setting Tertiary health care center. Patients Males with a macroprolactinoma and baseline HH who achieve normoprolactinemia on cabergoline monotherapy Intervention None. Main outcome measures Prevalence of persistent HH and its predictors. Results Thirty subjects (age: 38.3±10.1 years) with baseline tumor size of 4.08±1.48 cm and median (IQR) prolactin of 2871 (1665-8425) ng/ml were included. Eight of 30 participants achieved eugonadism after a median follow-up of three years. Patients with persistent HH had suppression of LH-testosterone axis with sparing of other anterior pituitary hormonal axes including FSH-Inhibin B. Baseline prolactin (1674 vs. 4120 ng/ml; p=0.008) and maximal tumor diameter (2.55±0.36 vs. 4.64±1.32 cm; p=0.003) were lower in patients who achieved eugonadism. Baseline maximal tumor diameter ≤ 3.2 cm (sensitivity: 75%, specificity: 63.6%) and serum prolactin ≤ 2098 ng/ml (sensitivity: 87.5%, specificity: 77.3%) best predicted reversal of HH. Conclusion Recovery of LH-testosterone axis occurred in 26.7% of males with a macroprolactinoma who achieved normoprolactinemia on cabergoline monotherapy. Higher baseline tumor size and serum prolactin predict persistent HH. Our data favors chronic functional modification of hypothalamic-pituitary-gonadal axis over gonadotroph damage as the cause of persistent HH.

Background: Awareness about Insulin Autoimmune Hypoglycaemia (IAH) and its management remains limited. Methodology:We describe two cohorts: Cohort 1 (n = 7) included patients with IAH from a tertiary care centre in India and Cohort 2 (n = 294) included systematic review of published English literature from PubMed. They were compared with our insulinoma patients (n = 41). Results: Cohort 1 included seven female patients where two had drugs (carbimazole and thiocolchicoside) as triggering factors. Except for one patient requiring oral prednisolone, others had spontaneous remission. The unique features from our series are being first case series of IAH from India and reporting of second case of thiocolchicoside triggered IAH.Cohort 2 had 294 patients identified from 149 publications. Mean age was 54 ± 19 years. Thirty-five different triggers were identified from 160 cases.Antithyroid drugs were most common triggers in Japanese patients and most common HLA allele was DRB1*0406, while it was alpha-lipoic acid and HLA DRB1*0403 in non-Asians. Serum Insulin >100 µIU/mL and insulin to C-peptide molar ratio (ICMR) >0.25 had specificity of 100% and 97.5%, respectively, for IAH as compared to insulinoma. 56% patients had remission with complex carbohydrate diet and trigger removal while 43% required immunosuppressants. 70% achieved remission within 6 months. Conclusions:Middle age remains most common age group. Sulfhydryl drugs are most common triggers. Serum Insulin >100 µIU/mL and ICMR > 0.25 in critical sample are good predictors for diagnosis of IAH, which needs to be confirmed by IAA.Conservative management with dietary modification and trigger removal usually suffices in majority. Rests need immunosuppressants. K E Y W O R D Scase series of IAH, insulin auto-antibodies, insulin autoimmune hypoglycaemia, insulin autoimmune syndrome, management of IAH, systematic review of IAH