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Cureus Apr 2024Insulin autoimmune syndrome (IAS) or Hirata disease is a rare condition presenting as recurrent hypoglycemia, and associated with elevated insulin levels in the presence...
Insulin autoimmune syndrome (IAS) or Hirata disease is a rare condition presenting as recurrent hypoglycemia, and associated with elevated insulin levels in the presence of insulin autoantibodies (IAAs) in patients who were never exposed to exogenous insulin and with no evidence of pancreatic abnormalities. IAS is much more frequent in East Asians, especially the Japanese population, compared to the lower incidence in Caucasians. However, it can be associated with other autoimmune diseases or drug use like methimazole and alpha-lipoic acid (ALA). We report a case of a 47-year-old Caucasian male presenting with a 12-month history of worsening episodes of fasting and post-prandial hypoglycemia associated with symptoms of dizziness, tremors, palpitations, and unconsciousness associated with hypoglycemia. Symptoms resolved with the administration of carbohydrate-containing foods, establishing Whipple's triad. At an outside facility, he had initial labs that showed elevated insulin levels (141 µU/ml) with normal glucose, C-peptide, and proinsulin levels, but there was no availability of an IAA lab assay. Given his symptoms, severity, and frequency of hypoglycemia, he was admitted to the hospital for a 72-hour fast, which showed the lowest glucose level of 64 mg/dl with inappropriately high insulin of 22.2 µU/ml, low C-peptide of 0.57 ng/ml, and undetectable proinsulin of <1.6 pmol/L, but with IAA being >50 U/ml (0.0-0.4 U/ml). He was treated with intensive dietary counseling with a low-carbohydrate diet and prednisone 20 mg twice daily initially. Additionally, he could not tolerate octreotide, diazoxide, and acarbose due to side effects. He is currently on prednisone 10 mg daily and nifedipine with no further hypoglycemic episodes, but still has a high IAA of >50 U/ml and serum insulin levels of 70-112 µU/ml. Our case highlights the importance of recognizing hypoglycemia and checking for IAA levels as first-line diagnostic tests, in the absence of which there could be a delay in diagnosis and leading to unnecessary lab and imaging testing. Our case is unique since it happened in a Caucasian without any prior exposure to a triggering factor and has not undergone self-remission yet, which happens in most of IAS cases.
PubMed: 38623323
DOI: 10.7759/cureus.58270 -
Journal of Neuroendocrinology Jun 2024Peptide receptor radionuclide therapy (PRRT) can be a very useful treatment for patients with neuroendocrine neoplasms and metastatic castration-resistant prostate... (Review)
Review
Peptide receptor radionuclide therapy (PRRT) can be a very useful treatment for patients with neuroendocrine neoplasms and metastatic castration-resistant prostate cancer but it is routinely avoided in those with advanced kidney disease because it can adversely affect the renal function. Accordingly, no clear guidelines exist on the use of PRRT for patients on hemodialysis (HD). We performed a literature review to identify publications on HD patients who received PRRT with Lutetium-177 (Lu) Dotatate and Y-90 and obtained information on Lu pharmacokinetics and early testing data from the manufacturer. We also perused the most recent North American Neuroendocrine Tumor Society (NANETS)/European Neuroendocrine Tumor Society (ENETS) recommendations. Seven relevant publications with a total of 15 patients were included. Patients received dose-adjusted fractions of PRRT with HD occurring usually within 24 h. There were no immediate or long-term serious adverse events attributed to the radioligand, although data was limited. Using available evidence and input from a multidisciplinary group, we have created an institutional workflow. Dose-adjusted PRRT can be offered to patients undergoing HD under careful, multidisciplinary supervision.
Topics: Humans; Radiopharmaceuticals; Lutetium; Neuroendocrine Tumors; Kidney Failure, Chronic; Algorithms; Male; Octreotide; Radioisotopes; Renal Dialysis; Receptors, Peptide; Organometallic Compounds
PubMed: 38622851
DOI: 10.1111/jne.13393 -
Annals of Surgical Oncology Jun 2024
Comparative Study
Topics: Humans; Octreotide; Vasoconstrictor Agents; Carcinoid Tumor; Intraoperative Complications; Antineoplastic Agents, Hormonal; Malignant Carcinoid Syndrome; Prognosis
PubMed: 38619707
DOI: 10.1245/s10434-024-15264-2 -
The American Journal of Case Reports Apr 2024BACKGROUND Tumor-induced osteomalacia (TIO) is a paraneoplastic syndrome caused by aberrant fibroblast growth factor-23 (FGF-23)-producing tumors. Early surgical...
BACKGROUND Tumor-induced osteomalacia (TIO) is a paraneoplastic syndrome caused by aberrant fibroblast growth factor-23 (FGF-23)-producing tumors. Early surgical resection is the optimal strategy for preventing TIO progression. Thus, tumor localization is a priority for successful treatment. A simple and safe examination method to identify functional endocrine tumors is essential to achieve better outcomes in patients with TIO. CASE REPORT A 64-year-old Japanese man with recurrent fractures, hypophosphatemia, and elevated alkaline phosphatase and FGF-23 levels (109 pg/mL) was admitted to our university hospital and was diagnosed with FGF23-related hypophosphatemic osteomalacia. Notably, the superficial dorsal vein in the patient's left foot exhibited a high FGF-23 level (7510 pg/mL). Octreotide and ¹⁸F-fluorodeoxyglucose (FDG) scintigraphy and systemic venous sampling revealed that the tumor in the third basal phalanx of the left foot was responsible for FGF-23 overproduction. Tumor resection resulted in a rapid decrease in serum FGF-23 levels and an increase in serum phosphorus levels. CONCLUSIONS Octreotide scintigraphy, FDG-positron emission tomography, and systemic venous sampling are the standard methods for localizing functional endocrine tumors. However, the limited availability and invasive nature of these examinations hinder effective treatment. Here, we highlight the importance of peripheral superficial blood sampling as an alternative to conventional systemic methods for confirming the presence of FGF-23-producing tumors. Clinicians should consider TIO as a potential cause of acquired hypophosphatemic osteomalacia. Furthermore, peripheral superficial vein blood sampling may be useful for confirming the localization of FGF-23-producing tumors.
Topics: Male; Humans; Middle Aged; Osteomalacia; Fibroblast Growth Factor-23; Fluorodeoxyglucose F18; Octreotide; Neoplasms; Paraneoplastic Syndromes
PubMed: 38613142
DOI: 10.12659/AJCR.943152 -
International Journal of Molecular... Mar 2024Somatostatin receptor ligands (SRLs) with high affinity for somatostatin receptors 2 and 5 (SSTR2 and SSTR5) are poorly efficacious in NF-PitNETs, expressing high levels...
Somatostatin receptor ligands (SRLs) with high affinity for somatostatin receptors 2 and 5 (SSTR2 and SSTR5) are poorly efficacious in NF-PitNETs, expressing high levels of SSTR3. ITF2984 is a pan-SSTR ligand with high affinity for SSTR3, able to induce SSTR3 activation and to exert antitumoral activity in the MENX rat model. The aim of this study was to test ITF2984's antiproliferative and proapoptotic effects in NF-PitNET primary cultured cells derived from surgically removed human tumors and to characterize their SSTR expression profile. We treated cells derived from 23 NF-PitNETs with ITF2984, and a subset of them with octreotide, pasireotide (SRLs with high affinity for SSTR2 or 5, respectively), or cabergoline (DRD2 agonist) and we measured cell proliferation and apoptosis. SSTR3, SSTR2, and SSTR5 expression in tumor tissues was analyzed by qRT-PCR and Western blot. We demonstrated that ITF2984 reduced cell proliferation (-40.8 (17.08)%, < 0.001 vs. basal, = 19 NF-PitNETs) and increased cell apoptosis (+41.4 (22.1)%, < 0.001 vs. basal, = 17 NF-PitNETs) in all tumors tested, whereas the other drugs were only effective in some tumors. In our model, SSTR3 expression levels did not correlate with ITF2984 antiproliferative nor proapoptotic effects. In conclusion, our data support a possible use of ITF2984 in the pharmacological treatment of NF-PitNET.
Topics: Humans; Antimitotic Agents; Neuroendocrine Tumors; Octreotide; Pituitary Neoplasms; Receptors, Somatostatin
PubMed: 38612419
DOI: 10.3390/ijms25073606 -
Case Reports in Gastroenterology 2024Ampullary neuroendocrine tumors (NETs) are usually diagnosed in the 5th-6th decades of life, and no cases were reported in <20 years of age. We report a rare case,...
INTRODUCTION
Ampullary neuroendocrine tumors (NETs) are usually diagnosed in the 5th-6th decades of life, and no cases were reported in <20 years of age. We report a rare case, presenting at a very young age, of well-differentiated NET involving the ampulla of Vater with lymph node metastasis.
CASE PRESENTATION
An 18-year-old man presented with a 3-month history of upper abdominal pain and jaundice. Abdominal ultrasound showed a dilated common bile duct, and endoscopic retrograde cholangiopancreatography revealed two duodenal polypoid lesions, one of them overlying the ampulla of Vater, with an erythematous and ulcerated surface. Histopathological examination confirmed the diagnosis of NET grade 1. Octreotide scan revealed 2 para-aortic lymph nodes with intense radiotracer uptake. The patient had undergone Whipple surgery with para-aortic lymph node dissection. Histopathological examination of the surgical specimens was confirmatory of NET grade 2 and paraganglioma in a few of the dissected lymph nodes. Postoperatively, the patient was kept on monthly intramuscular octreotide. Follow-up gallium-68 DOTATATE is unremarkable apart from an avid left para-aortic lymph node which is showing stability over 12 months of follow-up.
CONCLUSION
This case demonstrates that NETs of the ampulla of Vater can present at a very young age. Radical surgical excision with extended lymph node dissection and postoperative octreotide is associated with better patient outcomes and survival.
PubMed: 38590835
DOI: 10.1159/000538260 -
Journal of Neuroendocrinology May 2024Metastases outside the liver and abdominal/retroperitoneal lymph nodes are nowadays detected frequently in patients with neuroendocrine tumours (NETs), owing to the high...
Metastases outside the liver and abdominal/retroperitoneal lymph nodes are nowadays detected frequently in patients with neuroendocrine tumours (NETs), owing to the high sensitivity of positron emission tomography (PET) with Gallium-68-DOTA-somatostatin analogues (Ga-SSA) and concomitant diagnostic computed tomography (CT). Our aim was to determine the prevalence of extra-abdominal metastases on Ga-DOTATOC-PET/CT in a cohort of patients with small intestinal (Si-NET) and pancreatic NET (Pan-NET), as well as that of pancreatic metastasis in patients with Si-NET. Among 2090 patients examined by Ga-DOTATOC-PET/CT at two tertiary referral centres, a total of 1177 patients with a history of Si- or Pan-NET, were identified. The most recent Ga-DOTATOC-PET/CT report for each patient was reviewed, and the location and number of metastases of interest were recorded. Lesions outside the liver and abdominal nodes were found in 26% of patients (n = 310/1177), of whom 21.5% (255/1177) were diagnosed with Si-NET and 4.5% (55/1177) Pan-NET. Bone metastases were found in 18.4% (215/1177), metastases to Virchow's lymph node in 7.1% (83/1177), and lung/pleura in 4.8% (56/1177). In the subset of 255 Si-NET patients, 5.4% (41/255) manifested lesions in the pancreas, 1.5% in the breast (18/255), 1.3% in the heart (15/255) and 1% in the orbita (12/255). In Si-NET patients, the Ki-67 proliferation index was higher in those with ≥2 metastatic sites of interest, than with 1 metastatic site, (p <0.001). Overall, extra-abdominal or pancreatic metastases were more often found in patients with Si-NET (34%) than in those with Pan-NET (13%) (p <0.001). Bone metastases were 2.6 times more frequent in patients with Si-NET compared to Pan-NET patients (p <0.001). Lesions to the breast and orbita were encountered in almost only Si-NET patients. In conclusion, lesions outside the liver and abdominal nodes were detected in as many as 26% of the patients, with different prevalence and metastatic patterns in patients with Si-NET compared to Pan-NET. The impact of such metastases on overall survival and clinical decision-making needs further evaluation.
Topics: Adult; Aged; Aged, 80 and over; Female; Humans; Male; Middle Aged; Intestinal Neoplasms; Intestine, Small; Lymph Nodes; Lymphatic Metastasis; Neuroendocrine Tumors; Octreotide; Organometallic Compounds; Pancreatic Neoplasms; Positron Emission Tomography Computed Tomography; Prevalence; Retrospective Studies
PubMed: 38590270
DOI: 10.1111/jne.13391 -
Clinical Case Reports Apr 2024Treatment of congenital chyloperitoneum is a challenge. Conservative methods may be ineffective. Preoperative visualization of the site of lymphatic leakage is crucial,...
Treatment of congenital chyloperitoneum is a challenge. Conservative methods may be ineffective. Preoperative visualization of the site of lymphatic leakage is crucial, but radiological imaging is technically complicated and may not provide sufficient information, especially in small patients. To ease the detection of lymphatic leakage during surgery, preoperative feeding with fat-rich formula with Sudan Black has been recommended. However, administration of Sudan Black may result in life-threatening methemoglobinemia and liver damage without any advantage of revealing leakage during surgery. We recommend preoperative feeding with pure fat-rich formula.
PubMed: 38585587
DOI: 10.1002/ccr3.8676 -
Current Oncology Reports May 2024This paper aims to address the latest findings in neuroendocrine tumor (NET) theranostics, focusing on new evidence and future directions of combined diagnosis with... (Review)
Review
PURPOSE OF REVIEW
This paper aims to address the latest findings in neuroendocrine tumor (NET) theranostics, focusing on new evidence and future directions of combined diagnosis with positron emission tomography (PET) and treatment with peptide receptor radionuclide therapy (PRRT).
RECENT FINDINGS
Following NETTER-1 trial, PRRT with [177Lu]Lu-DOTATATE was approved by FDA and EMA and is routinely employed in advanced G1 and G2 SST (somatostatin receptor)-expressing NET. Different approaches have been proposed so far to improve the PRRT therapeutic index, encompassing re-treatment protocols, combinations with other therapies and novel indications. Molecular imaging holds a potential added value in characterizing disease biology and heterogeneity using different radiopharmaceuticals (e.g., SST and FDG) and may provide predictive and prognostic parameters. Response assessment criteria are still an unmet need and new theranostic pairs showed preliminary encouraging results. PRRT for NET has become a paradigm of modern theranostics. PRRT holds a favorable toxicity profile, and it is associated with a prolonged time to progression, reduction of symptoms, and improved patients' quality of life. In light of further optimization, different new strategies have been investigated, along with the development of new radiopharmaceuticals.
Topics: Humans; Neuroendocrine Tumors; Radiopharmaceuticals; Octreotide; Positron-Emission Tomography; Receptors, Peptide; Theranostic Nanomedicine; Radioisotopes; Organometallic Compounds
PubMed: 38581469
DOI: 10.1007/s11912-024-01526-5 -
Molecular Medicine Reports Jun 2024The intestinal mucosal barrier is of great importance for maintaining the stability of the internal environment, which is closely related to the occurrence and...
The intestinal mucosal barrier is of great importance for maintaining the stability of the internal environment, which is closely related to the occurrence and development of intestinal inflammation. Octreotide (OCT) has potential applicable clinical value for treating intestinal injury according to previous studies, but the underlying molecular mechanisms have remained elusive. This article is based on a cell model of inflammation induced by lipopolysaccharide (LPS), aiming to explore the effects of OCT in protecting intestinal mucosal barrier function. A Cell Counting Kit‑8 assay was used to determine cell viability and evaluate the effectiveness of OCT. Gene silencing technology was used to reveal the mediated effect of somatostatin receptor 2 (SSTR2). The changes in intestinal permeability were detected through trans‑epithelial electrical resistance and fluorescein isothiocyanate‑dextran 4 experiments, and the alterations in tight junction proteins were detected using immunoblotting and reverse transcription fluorescence‑quantitative PCR technology. Autophagosomes were observed by electron microscopy and the dynamic changes of the autophagy process were characterized by light chain (LC)3‑II/LC3‑I conversion and autophagic flow. The results indicated that SSTR2‑dependent OCT can prevent the decrease in cell activity. After LPS treatment, the permeability of monolayer cells decreased and intercellular tight junctions were disrupted, resulting in a decrease in tight junction protein zona occludens 1 in cells. The level of autophagy‑related protein LC3 was altered to varying degrees at different times. These abnormal changes gradually returned to normal levels after the combined application of LPS and SSTR2‑dependent OCT, confirming the role of OCT in protecting intestinal barrier function. These experimental results suggest that OCT maintains basal autophagy and cell activity mediated by SSTR2 in intestinal epithelial cells, thereby preventing the intestinal barrier dysfunction in inflammation injury.
Topics: Humans; Caco-2 Cells; Octreotide; Lipopolysaccharides; Intestinal Mucosa; Tight Junction Proteins; Autophagy; Inflammation; Tight Junctions; Permeability
PubMed: 38577927
DOI: 10.3892/mmr.2024.13214