Japanese 17q12 Deletion Syndrome with Complex Clinical Manifestations.

17q12 deletion syndrome is a rare chromosomal anomaly with variable phenotypes, caused by the heterozygous deletion of chromosome 17q12. We herein report a 35-year-old Japanese patient with chromosomal 17q12 deletion syndrome identified by de novo deletion of the 1.46 Mb segment at the 17q12 band by genetic analyses. He exhibited a wide range of phenotypes, such as maturity-onset diabetes of the young (MODY) type 5, structural or functional abnormalities of the kidney, liver, and pancreas; facial dysmorphic features, electrolyte disorders; keratoconus, and acquired perforating dermatosis. This case report provides valuable resources concerning the clinical spectrum of rare 17q12 deletion syndrome.

Glucokinase Variant Proteins Are Resistant to Fasting-Induced Uridine Diphosphate Glucose-Dependent Degradation in Maturity-Onset Diabetes of the Young Type 2 Patients.

We previously reported that glucokinase undergoes ubiquitination and subsequent degradation, a process mediated by cereblon, particularly in the presence of uridine diphosphate glucose (UDP-glucose). In this context, we hereby present evidence showcasing the resilience of variant glucokinase proteins of maturity-onset diabetes of the young type 2 (MODY2) against degradation and, concomitantly, their influence on insulin secretion, both in cell lines and in the afflicted MODY2 patient. Hence, glucose-1-phodphate promotes UDP-glucose production by UDP-glucose pyrophosphorylase 2; consequently, UDP-glucose-dependent glucokinase degradation may occur during fasting. Next, we analyzed glucokinase variant proteins from MODY2 or persistent hyperinsulinemic hypoglycemia in infancy (PHHI). Among the eleven MODY2 glucokinase-mutated proteins tested, those with a lower glucose-binding affinity exhibited resistance to UDP-glucose-dependent degradation. Conversely, the glucokinaseA456V-mutated protein from PHHI had a higher glucose affinity and was sensitive to UDP-glucose-dependent degradation. Furthermore, in vitro studies involving UDP-glucose-dependent glucokinase variant proteins and insulin secretion during fasting in Japanese MODY2 patients revealed a strong correlation and a higher coefficient of determination. This suggests that UDP-glucose-dependent glucokinase degradation plays a significant role in the pathogenesis of glucose-homeostasis-related hereditary diseases, such as MODY2 and PHHI.

Unmasked insulinoma occasioned by severe hypoglycemic coma immediately postpartum: a case report.

BACKGROUND: Insulinoma in women during pregnancy and postpartum is very rare; approximately 65% of cases are diagnosed early in pregnancy and ~ 35% immediately after delivery, few being found in middle or late pregnancy, likely due to increased insulin resistance seen after early-stage pregnancy. We successfully treated a case of insulinoma in which severe hypoglycemic coma immediately after delivery occasioned detailed investigation and diagnosis. CASE PRESENTATION: Our patient experienced hypoglycemic coma in the 3rd month of pregnancy (initially considered due to her hyperemesis gravidarum) that improved spontaneously during the gestational period. No abnormalities of plasma glucose or body weight were found in regular checkups during her pregnancy; however, recurrence of hypoglycemic coma after delivery led us to suspect insulinoma. While contrast enhanced computer tomography and endoscopic ultrasonography (EUS) initially failed to detect a tumor in the pancreas, selective arterial calcium stimulation test revealed an insulin-secreting tumor localized in the pancreatic body. She then underwent spleen-preserving distal pancreatectomy; a 10-mm tumor positive for chromogranin A, synaptophysin and insulin was identified. CONCLUSIONS: Although pregnancy can mask insulinoma-associated symptoms and make diagnosis challenging, hypoglycemic episodes during early pregnancy, which were observed in this case, are suggestive of insulinoma. Importantly, in this case, accurate preoperative localization of the tumor enabled prompt curative surgery after delivery. Thus, clinical vigilance for the occurrence of insulinoma and its localization is appropriate for pregnant women suffering severe hypoglycemia.

Effectiveness of countermeasure for polypharmacy by multidisciplinary team review in patients with diabetes mellitus.

AIMS/INTRODUCTION: Polypharmacy in diabetes patients is related to worse clinical outcomes. The aim of this study was to evaluate the usefulness of our countermeasure for polypharmacy, which combines a pharmacist check followed by a multidisciplinary team review in diabetic patients with polypharmacy. METHODS: A single-center, retrospective observational study was conducted at Gifu University Hospital. Study participants included diabetic patients taking six or more drugs on admission to the diabetes ward between July 2021 and June 2022. Drugs which were discontinued by the present countermeasure were examined, and the number of drugs being taken by each patient was compared between admission and discharge. RESULTS: 102 of 308 patients were taking six or more drugs on admission. The drugs being taken by these patients were evaluated by pharmacists using a checklist for polypharmacy. Eighty-four drugs which were evaluated as inappropriate or potentially inappropriate medications by pharmacists were discontinued following the multidisciplinary team review. The median and mean number of drugs taken by the 102 patients significantly decreased from 9.0 (IQR: 8-12) and 9.26 ± 2.64 on admission to 9.0 (IQR: 6-10) and 8.42 ± 2.95 on discharge (P = 0.0002). We followed up with these patients after discontinuation of the drugs and confirmed that their clinical status had not deteriorated. CONCLUSION: The present countermeasure for polypharmacy, which combines a pharmacist check based on a checklist for evaluating polypharmacy followed by a multidisciplinary team review, was useful for reducing the number of inappropriate or potentially inappropriate medications taken by diabetes patients with polypharmacy.

Comprehensive Genome profile testing in head and neck cancer.

OBJECTIVE: Head and neck cancer (HNC) is a tumor occurring in various primary sites with limited chemotherapy options for its treatment. Recently, comprehensive genomic profiling (CGP) testing has become clinically widespread. In this study, we examined the utility of CGP in diagnosing and treating HNC. METHODS: This study included 29 patients with HNC who underwent CGP testing at the Gifu University Hospital between December 2019 and April 2022. We analyzed the types of gene mutations and tumor mutational burden (TMB) based on the CGP results. Squamous cell carcinoma accounted for 55.2%, and other cancers accounted for 44.8%. And we investigated the correlation of prognosis with gene mutations and TMB. RESULTS: Gene mutations were detected in TP53(48.3%), CDKN2A (27.6%), CDKN2B (17.2%), NOTCH1 (17.2%), PIK3CA (17.2%), ARID1A (13.8%), and NF1 (13.8%). TP53, CDKN2A and CDKN2B mutations significantly decreased survival rate in HNC. Five cases (17.2%) were TMB-high and 82.8% were TMB-low. In SCC cases treated with immune checkpoint inhibitors, TMB-high had better Overall survival than TMB-low. And all patients with TMB-high were oropharyngeal cancer. CONCLUSION: Although there were no cases in which effective treatment was actually performed based on the results of CGP, many gene mutations have been detected and several gene mutations correlated with prognosis. Furthermore, TMB can be used as a biomarker to predict the therapeutic effects of immune checkpoint inhibitors in cases of SCC.

Two cases of systemic lupus erythematosus after administration of severe acute respiratory syndrome coronavirus 2 vaccine.

Although there is a great demand for increased coronavirus disease 2019vaccination worldwide, rare side effects of the vaccines in susceptible individuals are attracting attention. We recently treated two patients who developed systemic lupus erythematosus after administration of a severe acute respiratory syndrome coronavirus 2 vaccine from Pfizer-BioNTech or Moderna. While causal relationships between vaccination and adverse events are difficult to discern due to both confounding and masking factors, our findings suggest that attention to possible adjuvant-related autoimmune diseases in certain individuals receiving severe acute respiratory syndrome coronavirus 2 vaccines is appropriate.

A Case of Thyroid Carcinoma Showing Thymus-Like Differentiation With Breast Cancer Susceptibility Gene 2 Mutation: A Case Report and Literature Review.

Carcinoma showing thymus-like differentiation (CASTLE) is a rare malignant tumor that originates from ectopic thymic or residual embryonic tissues. CASTLE is specified as a synonym for intrathyroidal thymic carcinoma. The patient is a 66-year-old male. Surgery was performed on the thyroid tumor with tracheal infiltration, and pathological examination revealed CASTLE. Multidisciplinary treatment, including chemoradiotherapy, was performed for recurrent tumors, and he has been alive for 90 months since the initial treatment. The cancer genome panel identified mutations in AT-rich interaction domain 1A(ARID1A)and breast cancer susceptibility gene 2 (BRCA2), but there were no available clinical trials or recommended drugs. BRCA2 may be involved in CASTLE. Herein, we review the literature and report the treatment method and gene mutation for recurrent metastatic cases of CASTLE, for which standard treatment has not been established.

Semaglutide is effective in type 2 diabetes and obesity with schizophrenia.

Background: Prevention and treatment of type 2 diabetes and obesity are problematic for individuals with schizophrenia partly because atypical antipsychotics and mental distress themselves increase appetite, thus promoting subsequent body weight gain and deterioration of glycemic control. Glucagon-like peptide-1 (GLP-1) receptor agonists have been gaining attention for their glucose-lowering and body weight-reducing effects in obese individuals with type 2 diabetes generally, but their effects in those also having schizophrenia have not been adequately addressed. Case presentation: This case was a 50-year-old obese woman having type 2 diabetes and schizophrenia. Although she was receiving oral anti-diabetes treatment, her HbA1c remained inadequately controlled (8.0-9.0%) partly due her difficulty in following instructions on heathy diet and exercise. In addition, she was repeatedly hospitalized due to suicide attempts by overdosing on her anti-psychotic and anti-diabetes drugs. Her HbA1c was elevated to as high as 10.2% despite the use of multiple anti-diabetes drugs including the GLP-1 receptor agonist dulaglutide, and she was hospitalized in our department. We chose the GLP-1 receptor agonist semaglutide to replace dulaglutide along with a multidisciplinary team approach that included a cognitive-behavioral therapist. The patient perceived that her hunger was suppressed when she started receiving semaglutide 0.5 mg. After discharge, semaglutide was remarkably more effective than dulaglutide in that it reduced and maintained the patient's HbA1c and body weight for 6 months after initiation of the drug. Conclusion: The GLP-1 receptor agonist semaglutide can be effective in maintaining appropriate control of glycemia and body weight in diabetes and obesity with schizophrenia.

A case of familial hypocalciuric hypercalcemia type 1 due to CASR p.Pro55Leu mutation.

BACKGROUND: Familial hypocalciuric hypercalcemia (FHH) is a rare autosomal dominant disease, which requires differential diagnosis from relatively common primary hyperparathyroidism (PHPT) in order to avoid unnecessary surgery. CASE PRESENTATION: A 16-year-old female had been followed by the department of psychosomatic medicine at our institution. Throughout the follow-up period, her plasma calcium levels were high, plasma Pi levels were relatively low, and plasma intact PTH was relatively high. She was referred to our department to determine the cause of her hypercalcemia. Her 24 h urinary calcium excretion was as low as 100 mg/day, and calcium creatinine clearance ratio was below 0.01. Moreover, she had a family history of hypercalcemia (proband, her brother, and her father). The genetic testing for her family revealed that she, her brother, and her father were definitively diagnosed with FHH type 1 due to the heterozygous calcium-sensing receptor mutation (NM_00388:4:c.164C > T:p.Pro55Leu). CONCLUSION: We experienced a 16-year-old female with FHH, in whom genetic testing identified the heterozygous calcium-sensing receptor mutation (NM_00388:4:c.164C > T:p.Pro55Leu) as pathogenic, permitting a definitive diagnosis of FHH type 1. The genetic testing for calcium sensing receptor is beneficial to distinguish asymptomatic primary hyperparathyroidism from FHH.

Graves' Disease after Administration of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Vaccine in a Type 1 Diabetes Patient.

Although there is a great demand for increased coronavirus disease 2019 (COVID-19) vaccination worldwide, rare side effects of the vaccine in susceptible individuals are attracting attention. We recently treated a patient with type 1 diabetes who had HLA-A*240201/A*020101, B*5401/B*5601, DRB1*0405/DRB1*0405, DPB1*0501/DPB1*0501 and DQB1*0401/DQB1*040 and developed Graves' disease soon after the administration of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine. While causal relationships between vaccinations and adverse events are difficult to discern due to both confounding and masking factors, our findings suggest that attention to possible adjuvant-related endocrinological diseases in certain individuals receiving SARS-CoV-2 vaccines is appropriate.

Graves' Disease with Thymic Hyperplasia: The Response of the Thyroid Function, Thyrotropin Receptor Autoantibody, and Thymic Size to Thiamazole Treatment.

We treated a 22-year-old woman suffering from Graves' disease and thymic hyperplasia. She was referred to our institution for a close investigation of thyrotoxicosis and thymic mass. Thyroid tests and magnetic resonance imaging resulted in a diagnosis of Graves' disease and thymic hyperplasia. The thyroid function and thyroid-stimulating hormone receptor antibody (TRAb) were normalized one and five months after thiamazole initiation, respectively. The thymic size began to decrease after 1 month and was further decreased after 5 months; it was normalized after 12 months. The correlation between TRAb titers and the thymic size (R2=0.99) suggested that the patient's autoimmunity might have contributed to the thymic hyperplasia.

Hypoglycemic coma in an elderly adult switched from twice-daily vildagliptin to once-daily glimepiride to improve drug adherence.

BACKGROUND: Elderly adults with diabetes are at increased risk of severe hypoglycemia and hypoglycemic coma due to various conditions including decline in cognitive function, reduced activity of daily living (ADL) and reduced renal function; special cautions are, therefore, recommended to avoid these life-threatening events. CASE PRESENTATION: A 92-year-old female was admitted to our institution because of severe coma. Upon arrival, her serum C-peptide was 1.64 ng/mL despite low plasma glucose (24 mg/dL) and serum glimepiride (40.85 ng/mL). She had past history of compression fracture of her lumbar spine, which substantially affected her ADL. Her score on the dementia assessment sheet for community-based integrated care system-8 items (DASC-8) was 26 points. She had been receiving 12 oral medications for diabetes, essential hypertension, chronic gastritis and constipation from her nearby clinic. Her physician-in-charge had found that she was not taking her medications properly and simplified her prescription regimen to 3 oral medications with vildagliptin 50 mg twice daily replaced by glimepiride 3 mg once daily and asked her son to assist in taking the drugs 6 days before her admission to our hospital. While her consciousness level was improved to some extent, she was transferred to a long-term care bed hospital because it had become too difficult to care for her at home. CONCLUSIONS: It is important to note that anti-diabetes drugs should be carefully selected based on each patient's cognitive function and ADL, and that the reasoning should be shared with the general practitioners involved to avoid severe hypoglycemic events. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13340-021-00510-9.

First Japanese Family With PDX1-MODY (MODY4): A Novel PDX1 Frameshift Mutation, Clinical Characteristics, and Implications.

CONTEXT: The PDX1 gene encodes pancreatic and duodenal homeobox, a critical transcription factor for pancreatic ß-cell differentiation and maintenance of mature ß-cells. Heterozygous loss-of-function mutations cause PDX1-MODY (MODY4). CASE DESCRIPTION: Our patient is an 18-year-old lean man who developed diabetes at 16 years of age. Given his early-onset age and leanness, we performed genetic testing. Targeted next-generation sequencing and subsequent Sanger sequencing detected a novel heterozygous frameshift mutation (NM_00209.4:c.218delT. NP_000200.1: p.Leu73Profs*50) in the PDX1 transactivation domain that resulted in loss-of-function and was validated by an in vitro functional study. The proband and his 56-year-old father, who had the same mutation, both showed markedly reduced insulin and gastric inhibitory polypeptide (GIP) secretion compared with the dizygotic twin sister, who was negative for the mutation and had normal glucose tolerance. The proband responded well to sitagliptin, suggesting its utility as a treatment option. Notably, the proband and his father showed intriguing phenotypic differences: the proband had been lean for his entire life but developed early-onset diabetes requiring an antihyperglycemic agent. In contrast, his father was overweight, developed diabetes much later in life, and did not require medication, suggesting the oligogenic nature of PDX1-MODY. A review of all reported cases of PDX1-MODY also showed heterogeneous phenotypes regarding onset age, obesity, and treatment, even in the presence of the same mutation. CONCLUSIONS: We identified the first Japanese family with PDX1-MODY. The similarities and differences found among the cases highlight the wide phenotypic spectrum of PDX1-MODY.

Glucokinase-maturity onset diabetes mellitus in the young suggested by factory-calibrated glucose monitoring data: a case report.

Glucokinase has an important role in regulating glycolysis as a glucose sensor in liver and pancreatic ß cells. Glucokinase-maturity onset diabetes in young (GCK-MODY also known as MODY2) is caused by autosomal dominant gene mutation of the GCK gene; it is characterized by mild fasting hyperglycemia and small 2-h glucose increment during 75 g-oral glucose tolerance test (OGTT) as well as near-normal postprandial glucose variabilities. A 10-year-old girl with family history of diabetes visited her physician after being found positive for urinary glucose by school medical checkup. She received a diagnosis of diabetes based on the laboratory data: 75 g-OGTT (mild fasting hyperglycemia and small 2-h glucose increment) and factory-calibrated glucose monitoring (mild elevation of average glucose level and near-normal glycemic variability), which raised suspicion of GCK-MODY. She was then referred to our institution for genetic examination, which revealed a GCK heterozygous mutation (NM_000162: exon10: c.1324G>T: p.E442X) in the proband as well as in her mother and maternal grandmother, who had been receiving anti-diabetes medications without knowing that they had GCK-MODY specifically. GCK-MODY cases show incidence of microvascular and macrovascular diseases similar to that of normal subjects, and their glucose levels are adequately controlled without anti-diabetes drug use. Thus, early and definitive diagnosis of MODY2 by genetic testing is important to avoid unnecessary medication.

A novel RFX6 heterozygous mutation (p.R652X) in maturity-onset diabetes mellitus: A case report.

Heterozygous RFX6 mutation has emerged as a potential cause of maturity-onset diabetes mellitus of the young (MODY). A 16-year-old female was diagnosed with diabetes by her family doctor and was referred to our institution for genetic examination. Genetic testing revealed a novel RFX6 heterozygous mutation (NM_173560: exon17: c.1954C>T: p.R652X) in the patient and in her mother and brother. She had no islet-specific autoantibodies and showed a reduced meal-induced response of insulin, glucose-dependent insulinotropic polypeptide, and glucagon-like peptide-1, which is consistent with the phenotype of MODY due to heterozygous RFX6 mutation. In conclusion, we report a case of MODY due to a novel heterozygous mutation, p.R652X.

Effects of ChREBP deficiency on adrenal lipogenesis and steroidogenesis.

Carbohydrate response element-binding protein (ChREBP) is critical in the regulation of fatty acid and triglyceride synthesis in the liver. Interestingly, Chrebp-/- mice show reduced levels of plasma cholesterol, which is critical for steroid hormone synthesis in adrenal glands. Furthermore, Chrebp mRNA expression was previously reported in human adrenal glands. Thus, it remains to be investigated whether ChREBP plays a role directly or indirectly in steroid hormone synthesis and release in adrenal glands. In the present study, we find that Chrebp mRNA is expressed in mouse adrenal glands and that ChREBP binds to carbohydrate response elements. Histological analysis of Chrebp-/- mice shows no adrenal hyperplasia and less oil red O staining compared with that in WT mice. In adrenal glands of Chrebp-/- mice, expression of Fasn and Scd1, two enzymes critical for fatty acid synthesis, was substantially lower and triglyceride content was reduced. Expression of Srebf2, a key transcription factor controlling synthesis and uptake of cholesterol and the target genes, was upregulated, while cholesterol content was not significantly altered in the adrenal glands of Chrebp-/- mice. Adrenal corticosterone content and plasma adrenocorticotropic hormone and corticosterone levels were not significantly altered in Chrebp-/- mice. Consistently, expression of genes related to steroid hormone synthesis was not altered. Corticosterone secretion in response to two different stimuli, namely 24-h starvation and cosyntropin administration, was also not altered in Chrebp-/- mice. Taking these results together, corticosterone synthesis and release were not affected in Chrebp-/- mice despite reduced plasma cholesterol levels.

Diagnosis and treatment of primary central nervous system lymphoma with the primary lesion in the hypothalamus: a case report.

BACKGROUND: Primary central nervous system lymphoma is a rare extra-nodal lymphoma of the central nervous system. Primary central nervous system lymphoma lesions usually appear in the vicinity of the ventricle, and there are few reports of primary central nervous system lymphoma with hypothalamic-pituitary lesions. CASE PRESENTATION: We treated a 56-year-old male with primary central nervous system lymphoma with the primary lesion in the hypothalamus, which was found by magnetic resonance imaging after sudden onset of endocrinological abnormalities. Initially, he was hospitalized to our department for hyponatremia. Endocrinological examination in conjunction with head magnetic resonance imaging and endoscopic biopsy revealed hypothalamic hypopituitarism and tertiary hypoadrenocorticism caused by a rapidly growing, diffuse large B-cell lymphoma in the hypothalamus. Remission of the tumor was achieved by high-dose methotrexate with whole brain radiotherapy, and some of the hormone responses were normalized. CONCLUSIONS: While primary central nervous system lymphoma is rare, it is important to note that hypopituitarism can result and that the endocrinological abnormalities can be partially restored by its remission.

Effect of hypertriglyceridemia in dyslipidemia-induced impaired glucose tolerance and sex differences in dietary features associated with hypertriglyceridemia among the Japanese population: The Gifu Diabetes Study.

AIMS/INTRODUCTION: The mechanisms underlying hypertriglyceridemia-induced impaired glucose tolerance in Japanese individuals remain unclear. We aimed to evaluate the effect of hypertriglyceridemia on glucose metabolism in comparison with that of increased low-density lipoprotein or decreased high-density lipoprotein levels and to elucidate the sex differences in hypertriglyceridemia-related dietary intake among Japanese individuals. MATERIALS AND METHODS: We randomly selected 898 (384 men and 514 women) participants aged 40-78 years in the Gifu Diabetes Study; those taking medication for dyslipidemia or diabetes mellitus were excluded. Serum levels of glucose metabolism parameters and the food frequency were measured cross-sectionally. The glycated hemoglobin was measured again after 5 years. RESULTS: Glucose metabolism parameters and the percentage of individuals with impaired glucose tolerance were significantly higher in the high triglyceride group in men and women. Similar trends were observed in the low high-density lipoprotein group, but only in men. Meanwhile, only the homeostasis model assessment of insulin resistance was higher in the high low-density lipoprotein group. In non-obese men, the percentage of energy intake from alcohol per total daily energy intake was significantly greater in the high triglyceride group. In obese women, the total energy intake was significantly greater in the high triglyceride group. At the 5-year follow up, the risk of elevated glycated hemoglobin levels with hypertriglyceridemia was increased in men. CONCLUSIONS: Hypertriglyceridemia is a stronger risk factor for impaired glucose tolerance than increased low-density lipoprotein or decreased high-density lipoprotein. For dietary habits, increased daily alcohol energy intake in non-obese men and increased total energy intake in obese women were associated with hypertriglyceridemia.

L-Arginine prevents cereblon-mediated ubiquitination of glucokinase and stimulates glucose-6-phosphate production in pancreatic ß-cells.

We sought to determine a mechanism by which L-arginine increases glucose-stimulated insulin secretion (GSIS) in ß-cells by finding a protein with affinity to L-arginine using arginine-immobilized magnetic nanobeads technology. Glucokinase (GCK), the key regulator of GSIS and a disease-causing gene of maturity-onset diabetes of the young type 2 (MODY2), was found to bind L-arginine. L-Arginine stimulated production of glucose-6-phosphate (G6P) and induced insulin secretion. We analyzed glucokinase mutants and identified three glutamate residues that mediate binding to L-arginine. One MODY2 patient with GCKE442* demonstrated lower C-peptide-to-glucose ratio after arginine administration. In ß-cell line, GCKE442* reduced L-arginine-induced insulin secretion compared with GCKWT. In addition, we elucidated that the binding of arginine protects glucokinase from degradation by E3 ubiquitin ligase cereblon mediated ubiquitination. We conclude that L-arginine induces insulin secretion by increasing G6P production by glucokinase through direct stimulation and by prevention of degradation.

A case of MODY5-like manifestations without mutations or deletions in coding and minimal promoter regions of the HNF1B gene.

Pancreatic tail hypoplasia is a common manifestation of maturity onset diabetes of the young (MODY) 5 that can cause reno-genito-urinary malformations such as renal cysts and bicornuate uterus. A 69-year-old female was admitted to our hospital for consultation on her relatively high HbA1c value. At age 20, she was diagnosed with uterus bicornis. At age 68, she was diagnosed with pancreas tail hypoplasia, renal cysts and non-functioning pancreatic neuroendocrine tumor (NET) in addition to right hydronephrosis due to multiple ureteral bladder carcinomas. She received total right nephrectomy, ureterectomy and partial cystectomy for multiple ureteral bladder carcinomas [non-invasive papillary urothelial carcinoma, low grade (G1), pTa, LV10, u-rtx, RM0, and pN0 (0/8)]. She also received distal pancreatomy for pancreatic NET [NET G1]. She then was referred to our department at age 69 due to increase in her HbA1c value from 6.2 to 7.2%; 75 g oral glucose tolerance test revealed impaired glucose tolerance. Her clinical characteristics (uterus bicornis, pancreas hypoplasia, and renal cysts) closely resembled the phenotype of MODY5, in which mutations in the HNF1B gene have been reported. Our genetic testing failed to detect any mutation or microdeletion in the coding or minimal promoter regions of the HNF1B gene. Although there remains a possibility that genetic mutations in introns and regulatory regions of the HNF1B gene might cause the MODY5-like manifestations in this patient, these results might suggest involvement of genes other than HNF1B in the pathogenesis of our patient's disease.