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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

Background Most common incidentally detected sellar-suprasellar region (SSR) masses are pituitary adenomas, followed by craniopharyngioma, rathke’s cleft cyst, hypophysitis, and meningioma. Besides these, certain unusual SSR lesions can sometimes present as diagnostic challenges, where diagnosis is often made post-operatively on histopathology, the pre-operative suspicion of which might have influenced the management strategies. Series describing such masses are few. Objective To present clinical, biochemical, and radiological characteristics and management outcomes of rare SSR lesions other than pituitary adenomas, craniopharyngioma, rathke’s cleft cyst, hypophysitis, and meningioma. Design, setting, patients Retrospective case record analysis of patients with uncommon SSR masses (from January 2006 to December 2016). Results Our series consisted of ten patients, five with neoplastic and five with non-neoplastic lesions. Neoplastic masses included granular cell tumor (n = 2), astrocytoma (n = 1), malignant peripheral nerve sheath tumor (MPNST, n = 1), and metastasis from occult papillary carcinoma of thyroid (n = 1), while non-neoplastic masses were aspergillus abscess (n = 1), sterile abscess (n = 1), and tubercular abscess (n = 1), aneurysm of left internal carotid artery (n = 1), and ruptured dermoid cyst (n = 1). All patients (except one) presented with headache and/or visual disturbance. Only one patient had acromegaly while most others had hypopituitarism. We describe detailed MRI characteristics of each of the lesion. Seven patients underwent trans-sphenoidal surgery. Post-operatively, five patients had permanent diabetes insipidus, while two patients died in early post-operative period. Conclusion Our series expand the differential diagnostic considerations of SSR lesions. Most of the rare SSR masses present with symptoms of mass effects and hypopituitarism. Except for some non-neoplastic lesions like sellar abscesses, aneurysms, and dermoid cysts which can have some specific imaging characteristics that can provide clue to pre-operative diagnosis, most of the other neoplastic masses have overlapping radiological features, and pre-operative suspicion remains difficult.

Context: Conventional fractionated radiotherapy (CRT) achieves control of pathological hypercortisolism in 75%-80% of patients with persistent or recurrent Cushing's disease (CD), over a mean period of 18-24 months. Medical therapy is recommended as bridge therapy while awaiting RT effect.Objective: To determine long-term outcome of CRT and its predictors in CD patients. Design, Setting and Patients:This is a retrospective case record analysis of 42 patients with CD who received CRT as a treatment modality and had at least 12 months post-RT follow-up. The dose delivered was 45 Gy in 25 fractions over 5 weeks.Demographic details, hormonal evaluation and radiological data were extracted from case records. Dexamethasone suppressed cortisol at cut-off of 1.8 µg/dL was used to define remission or recurrence. Possible predictors for remission and recurrence were analysed. Results:The mean age at the time of CRT administration was 23.7 ± 10.7 (range: 12-48) years. A total of 29 (69%) patients achieved remission 26.5 ± 28.5 (median: 18, range: 3-120) months after RT, while 13 (31%) patients had persistent disease at last follow-up. There were no significant predictors of disease remission after CRT.Six (20.7%) patients had recurrence after a documented initial remission. Recurrence occurred 66.6 ± 25.9 (median: 74; range: 18 to 90) months after documented remission. Recurrence of the disease was exclusively seen in patients who received peri-RT cabergoline. Peri-CRT use of cabergoline was significantly associated with increased recurrence rates (P = .016).Conclusion: Use of cabergoline in the peri-CRT period did not affect initial remission after CRT but was associated with increased recurrence after initial remission in CD. K E Y W O R D Scabergoline, conventional/conformal fractionated radiotherapy, ketoconazole, overnight dexamethasone suppression test, recurrence, remission

ObjectiveWe report a case of pediatric thoracic tumor-induced osteomalacia (TIO) causing severe hypophosphatemic rickets with delayed diagnosis and emphasize on timely management of this rare entity.Case presentationA young boy presented with rickets since five years of age. Biochemical evaluation revealed hypophosphatemia, hyperphosphaturia, elevated alkaline phosphatase and normal calcium levels. Initially managed as hereditary hypophosphatemic rickets, he was given phosphorus supplements and calcitriol. Despite the therapy, skeletal deformities worsened requiring surgical corrections. Subsequently, he developed iatrogenic tertiary hyperparathyroidism for which he underwent total parathyroidectomy. Later on, he was found to have fibroblast growth factor-23 secreting thoracic mass (10.5 cm in largest dimension) which was excised with significant post operative improvement. Histopathology showed phosphaturic mesenchymal tumor-mixed connective tissue variant, confirming the diagnosis of TIO.ConclusionTIO, a correctable cause of hypophosphatemic rickets, should be considered in children presenting with hypophosphatemic rickets with evident mass on examination/imaging and in refractory cases.