Transient Central Diabetes Insipidus (Arginine Vasopressin Deficiency) Following SARS-CoV-2 Vaccination: A Case Report and Literature Review.

INTRODUCTION: Since December 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has affected millions of people, causing the COVID-19 global pandemic. The use of novel technologies led to the development of different types of SARS-CoV-2 vaccines that have reduced severe disease courses and related deaths. Besides the positive impact of vaccination on the pandemic, local and systemic side effects have been reported; they are usually mild to moderate, although also serious adverse events have been described. CASE PRESENTATION: A 21-year-old female was referred to our hospital for the recent onset of severe polyuria and polydipsia, with the need for about 8 liters of daily water intake. The symptoms developed seven days after the administration of the second dose of the mRNA-based (Pfizer-BioNTech® BNT162b2) SARS-CoV-2 vaccine. In the suspicion of central diabetes insipidus (DI) development, she started treatment with desmopressin (Minirin® tablets) 60 mg/day with an improvement of symptoms and thirst. A thickening of the pituitary stalk was observed at the pituitary MRI with loss of the posterior pituitary bright spot on T1 weighted images. To confirm the diagnosis of central DI, both the water deprivation test and arginine stimulated copeptin test were performed; whilst the former gave no clear-cut indication of DI, the latter showed a reduced copeptin peak after arginine infusion consistent with the diagnosis of partial central DI. Furthermore, the development of symptoms right after the second dose of the vaccine strengthened the hypothesis that DI was related to the vaccination itself. After our evaluation, there was a progressive reduction of desmopressin dose to a complete discontinuation with the maintenance of a normal hydroelectrolytic balance. Clinical and biochemical follow-up was performed by repeating a pituitary MRI and a second arginine-stimulated copeptin test 15 months after the diagnosis. This time, copeptin levels reached a significantly higher peak after arginine stimulation that completely excluded central DI and at pituitary MRI, the thickening of the pituitary stalk previously described was no longer visible. CONCLUSION: Neurohypophysitis can have an abrupt onset independently of the etiology. Central DI is a rather exceptional event after SARS-CoV-2 vaccination but should be recalled in case of sudden polyuria and polydipsia. DI is indeed reported even after SARS-CoV-2 infection, thus, this report should not discourage the use of mRNA-based vaccines. Furthermore, our case demonstrates that full recovery of posterior pituitary function is possible after immunization with anti-Covid-19 BNT162b2 vaccine. Further studies are needed to clarify the possible mechanism relating to SARS-CoV-2 vaccination and this rare adverse event.

Doege-Potter Syndrome; A Case of Solitary Fibrous Pleura Tumor Associated with Severe Hypoglycemia: A Case Report in Internal Medicine.

BACKGROUND: Doege-Potter syndrome is a rare paraneoplastic entity that is often diagnosed incidentally during the work-up of hypoglycemia of unclear etiology. It is characterized by a non-islet cell tumor hypoglycemia mostly associated with solitary fibrous tumors. These uncommon tumors have been reported in <5% of solitary fibrous tumors. Although not unique in its kind, this case is extremely important as this syndrome often conceals unrecognized tumors that can be surgically resolved. CASE PRESENTATION: We present the case of a 59-year-old non-diabetic man with a 2-month history of severe and recurrent fasting hypoglycaemia presenting with severe dyspnea and sweating. Further workup revealed low insulin, C-peptide, and IGF-1 levels and a large right in-trathoracic solitary fibrous tumor. Unfortunately, bioassays for IGF-2 were unavailable at our hos-pital. Nevertheless, as hypoglycemia completely resolved after resection of the mass, Doege-Potter syndrome was highly suspected. CONCLUSION: Doege-Potter syndrome is a complication of rare tumors. If hy-poglycemia is unexplained, this syndrome should always be suspected, and the presence of un-known masses should be investigated.

Low Pepsinogen I/II Ratio and High Gastrin-17 Levels Typify Chronic Atrophic Autoimmune Gastritis Patients With Gastric Neuroendocrine Tumors.

INTRODUCTION: Chronic atrophic autoimmune gastritis (CAAG) can lead to the development of gastric neuroendocrine tumors (gNETs) and can be accompanied by other autoimmune diseases. This study aimed to determine, in CAAG patients, the association of gNET development, the prevalence of autoimmune diseases other than CAAG, the association of autoimmunity, and gNET development with pepsinogen I, II, gastrin-17, and Helicobacter pylori infection analysis. METHODS: We determined the prevalence of gNETs and other autoimmune diseases and analyzed pepsinogen I and II, gastrin-17 serum levels, and H. pylori infection in all patients diagnosed with CAAG at our hospital between 2013 and 2017. RESULTS: A total of 156 patients were studied and in 15.4% was observed concomitant gNET. Approximately 68.6% had at least 1 other autoimmune disease at diagnosis of CAAG. Approximately 60.9% had autoimmune thyroiditis, followed by diabetes (19.9%) and autoimmune polyendocrine syndrome (12.8%). CAAG patients with and without gNET had similar rates of comorbidity with other autoimmune diseases, but the pepsinogen I/II ratio was lower in patients with gNET (1.6 vs 4.5, P = 0.018). Receiver operating characteristic curve analyses identified a pepsinogen I/II ratio <2.3 and gastrin-17 levels >29.6 pmol/L as cutoffs distinguishing CAAG patients with gNET from those without. The combined use of these cutoff correctly identified 16 of the 18 CAAG patients with gNET (P = 0.007). H. pylori infection was observed in 28.7% of cases tested but did not associate with gNET. DISCUSSION: This study suggests that a low pepsinogen I/II ratio and high gastrin-17 levels characterize patients with CAAG and gNET and confirms the frequent coexistence of CAAG with other autoimmune diseases.

Polymorphism in Toll-Like Receptors and Helicobacter Pylori Motility in Autoimmune Atrophic Gastritis and Gastric Cancer.

Autoimmune atrophic gastritis (AAG) is associated with an increased risk of certain types of gastric cancer (GC). Helicobacter pylori (H. pylori) infection may have a role in the induction and/or maintenance of AAG and GC. Toll-like receptors (TLR) are essential for H. pylori recognition and subsequent innate and adaptive immunity responses. This study therefore aimed to characterize TLR polymorphisms, and features of bacterial flagellin A in samples from patients with AAG (n = 67), GC (n = 114) and healthy donors (HD; n = 97). TLR5 rs5744174 C/C genotype was associated with GC, lower IgG anti H. pylori response and a higher H. pylori flagellin A abundance and motility. In a subset of patients with AAG, H. pylori strains showed a reduction of the flagellin A abundance and a moderate motility compared with strains from GC patients, a prerequisite for active colonization of the deeper layers of the mucosa, host immune response and inflammation. TLR9 rs5743836 T allele showed an association with serum gastrin G17. In conclusion, our study suggests that alterations of flaA protein, moderate motility in H. pylori and two polymorphisms in TLR5 and TLR9 may favor the onset of AAG and GC, at least in a subset of patients. These findings corroborate the function of pathogen-host cell interactions and responses, likely influencing the pathogenetic process.

Pepsinogens to Distinguish Patients With Gastric Intestinal Metaplasia and Helicobacter pylori Infection Among Populations at Risk for Gastric Cancer.

OBJECTIVES: The objectives of this study were to investigate the serum pepsinogen test for the prediction of OLGIM (Operative Link on Gastric Intestinal Metaplasia Assessment) stages in first-degree relatives (FDR-GC) of patients with gastric cancer (GC) and autoimmune chronic atrophic gastritis (ACAG). METHODS: In 67 consecutive patients with ACAG, 82 FDR-GC, and 53 controls (CTRL) without gastric disease (confirmed by biopsy), serum levels of pepsinogen 1 (PG1), pepsinogen 2 (PG2), G17, and the PG1/2 ratio were assessed by enzyme-linked immunosorbent assay kit. All ACAG patients had positive antiparietal cell antibody levels, estimated by indirect immunofluorescence. Biopsies taken in duplicate from the antrum, corpus, and fundus were stained with Giemsa for Helicobacter pylori detection. Endoscopic detection of metaplasia was confirmed by histological diagnosis. Histological classification of OLGIM stages was applied by using the criteria of severity and topography of intestinal metaplasia (IM). RESULTS: The highest discrimination capacity for distinguishing ACAG from other groups of patients was the gastrin G17 test. The lowest mean for PG1 and PG2 serum levels was found in ACAG. In multivariate analysis by age, PG1 and PG1/PG2 were independent prognostic factors for metaplasia, and PG2 also for the presence of a histological H. pylori infection. The serum PG1 level was significantly lower in individuals with IM at OLGIM stage >2 than in those with IM at OLGIM stage <2, resulting in a useful method for the prediction of OLGIM stage. With the inclusion of patient age at diagnosis in the prediction of ≥2 vs. 0-1 OLGIM stages, the receiver operating characteristic (ROC) curve at 47.9 ng/ml PG1 level reached a significant area under the curve (AUC) value (0.978, P<0.001). We also observed a slight difference in PG2 serum levels between histological H. pylori-positive and H. pylori-negative subjects (ROC AUC: 0.599). CONCLUSIONS: This study demonstrated an important increase in gastrin G17 serum level in autoimmune gastritis. PG1 serum level corrected by patient age can be used in the management of patients at risk for GC with a high predicted probability of having an OLGIM stage ≥2. Using a cutoff of 47.9 ng/ml, PG1 testing in FDR-GC and ACAG patients had a sensitivity of 95.83% and a specificity of 93.37. Although these results could be validated in a prospective study, the known importance of higher OLGIM stages in increasing the risk of GC development supports the rationale of proposing PG1 algorithm as a diagnostic tool for the selection of high-risk FDR-GC and ACAG patients at high-risk stages for subsequent detailed endoscopic examination to detect dysplasia and asymptomatic GC. In addition, serum PG1 and PG2 levels could stratify patients based on both H. pylori infection and OLGIM risk in consideration of the increased acknowledge regarding the role of H. pylori in the progression of gastritis to GC.

Concomitance of diabetic retinopathy and proteinuria accelerates the rate of decline of kidney function in type 2 diabetic patients.

OBJECTIVE: To evaluate the rate of progression of renal disease in proteinuric type 2 diabetic patients with and without retinopathy. RESEARCH DESIGN AND METHODS: Thirty-eight proteinuric type 2 diabetic patients with diabetic retinopathy and 27 without were enrolled in an observational study for the evaluation of rate of glomerular filtration rate (GFR) decline and followed up for a median period of 6 years. GFR was determined at least once per year, and blood pressure, glycated hemoglobin, and proteinuria were determined every 4 months. RESULTS: Although the two groups had comparable GFR, albuminuria, blood pressure, and HbA(1c) at entry of the study, the rate of decline of GFR was higher in type 2 diabetic patients with retinopathy (-6.5 +/- 4.4 ml/year) than in those without (-1.8 +/- 4.8 ml/year; P < 0.0001). Protein and albumin excretion rate increased significantly in patients with retinopathy, while they did not change in those without. Mean blood pressure between the two groups of patients were similar both at entry and during the follow-up, although the proportion of patients treated with at least two antihypertensive drugs was higher in patients with retinopathy. On a multiple regression analysis, only mean blood pressure and proteinuria were significant determinants of progression of renal disease in type 2 diabetic patients with retinopathy. CONCLUSIONS: The rate of progression of renal disease in proteinuric type 2 diabetic patients with retinopathy is faster than that observed in those without retinopathy. The screening for retinopathy identifies patients at high risk for rapid deterioration of kidney function.