C-peptide index at 2 h post-meal is a useful predictor of endogenous insulin secretory capacity and withdrawal from insulin therapy in subjects with type 2 diabetes.

AIMS: To evaluate the correlation between C-peptide index (CPI) at 2 h post-meal and endogenous insulin secretory capacity and to develop clinical models to predict the possibility of withdrawal from insulin therapy in patients with type 2 diabetes. METHOD: This was a single-centre retrospective study of patients with type 2 diabetes admitted to our hospital. Patients were divided into a withdrawal group (n = 72) and a non-withdrawal group (n = 75) based on whether they were able to withdraw from insulin therapy at discharge, and the correlation between CPI at 2 h after meal and diabetes-related parameters was evaluated. In addition, we created two clinical models to predict the possibility of withdrawal from insulin therapy using machine learning. RESULTS: The glycated haemoglobin values of the study participants were 87.8 ± 22.6 mmol/mo. The CPI at 2 h post-meal was 1.93 ± 1.28 in the non-withdrawal group and 2.97 ± 2.07 in the withdrawal group (p < 0.001). CPI at 2 h post-meal was an independent predictor of withdrawal from insulin therapy. In addition, CPI at 2 h post-meal was a better predictor than fasting CPI. Six factors associated with insulin therapy withdrawal (age, duration of diabetes, creatinine, alanine aminotransferase, insulin therapy until hospitalization, and CPI at 2 h post-meal) were used to generate two clinical models by machine learning. The accuracy of the generated clinical models ranged from 78.3% to 82.6%. CONCLUSION: The CPI at 2 h post-meal is a clinically useful measure of endogenous insulin secretory capacity under non-fasting conditions.

Clinical findings of acute necrotizing esophagitis complicated by diabetic ketoacidosis.

Acute necrotizing esophagitis (ANE) is a rare and potentially life-threatening complication of diabetic ketoacidosis (DKA). While its association with DKA is established, specific clinical characteristics that predict ANE in DKA patients remain less understood. This study aimed to identify these characteristics by analyzing data from 30 DKA patients admitted from January 2018 to September 2022. Seven patients in this study presented with ANE, forming the ANE group. The remaining 23 constituted the non-ANE group. We compared the clinical parameters and computed tomography (CT) between the groups. The mean age of participants was 57.7 ± 20.4 years, and their mean HbA1c was 11.1 ± 3.3%. Notably, ethanol intake was significantly higher in the ANE group (44.4 ± 25.4 g/day) compared to the non-ANE group (6.8 ± 14.0 g/day; p = 0.013). Additionally, sodium-glucose transport protein 2 inhibitor use was significantly more prevalent in the ANE group (p = 0.013). Gastrointestinal symptoms were also significantly more pronounced in the ANE group, with vomiting occurring in 85.7% of patients compared to only 13.0% in the non-ANE group. Admission CT scans revealed further distinguishing features, with the ANE group showing significantly higher rates of esophageal wall thickening, intra-esophageal effusion, and calcification of the celiac artery origin (p < 0.0001, 0.0038, 0.0038, respectively). In conclusion, our study suggests that heavy alcohol consumption and strong gastrointestinal symptoms in DKA patients warrant a heightened suspicion of ANE. Early consideration of CT or upper gastrointestinal endoscopy is recommended in such cases.

Obstructive pneumonia with bronchial foreign body: A case report.

The age of predilection for foreign body aspiration into the lower airway shows a bimodal distribution, with the majority of cases occurring in children or infants and in the elderly. Although several pediatric airway foreign bodies have been summarized, in adults, bronchial foreign bodies are relatively uncommon. There are a variety of symptoms induced by airway foreign bodies, although the typical symptoms of some bronchial foreign bodies are cough. Bronchial foreign bodies, especially in the elderly, may have few symptoms and it is necessary for careful identification. Therefore, it is very important to carefully perform medical consultations about current and past medical history. Herein, we report a case of an elderly Japanese with obstructive pneumonia with a bronchial foreign body of fish bone with a long history of cough. It is known that people in some countries such as Japan have a habit of eating fish. Therefore, it is necessary to more carefully explore the possibility of some bronchial foreign body such as a fish bone, when we observe symptoms of persistent cough in such countries.

Structural and functional differences in auto-antibody positive compared to auto-antibody negative hypothyroid patients with chronic thyroiditis.

Most primary hypothyroidism in adults is caused by chronic thyroiditis. Autoantibodies such as anti-thyroglobulin antibody (TgAb) and anti-thyroid peroxidase antibody (TPOAb) are involved in the pathogenesis of chronic thyroiditis. On the other hand, the clinical features of antibody-negative hypothyroidism are not clear. In this study, we aimed to determine the prevalence of thyroid-related autoantibodies in patients with primary hypothyroidism and to evaluate the differences in thyroid structure between antibody-positive and antibody-negative hypothyroidism. Among 804 patients who attended Kawasaki Medical School Hospital for thyroid hormone abnormalities or thyroid gland enlargement between January 1, 2010 and December 31, 2021, 237 patients with primary hypothyroidism who underwent thyroid antibody measurement and thyroid ultrasound examination were included. Participants were divided into groups according to antibody positivity/negativity, and differences in antibody positivity and thyroid structure were evaluated. In this study, 34.6% of patients had antibody-negative hypothyroidism. The positive rate of each antibody was 62.0% for TgAb and 49.4% for TPOAb. The participants with antibody-positive hypothyroidism had significantly larger thyroid gland on thyroid ultrasound examination (p < 0.05). Thyroid-stimulating hormone was significantly higher in participants with antibody-positive compared to antibody-negative hypothyroidism. The present study reveals a positive rate of thyroid-related autoantibodies in patients with hypothyroidism and the differences in thyroid structure between patients with and without antibodies. This study clearly show that the prevalence of antibody-negative chronic thyroiditis is quite high among hypothyroid patients, although this point needs confirmation by further investigations. The data in this study would be useful for the treatment of antibody-negative hypothyroid patients.

Immune checkpoint inhibitor-induced hypothyroidism predicts treatment response in Japanese subjects.

Background: Immune checkpoint inhibitors (ICIs) cause a variety of immune-related adverse events (irAEs). Among them, thyroid dysfunction is most frequently observed. Patients with irAEs have higher survival rates than those without irAEs, but there is no certainty as to whether the degree of thyroid dysfunction is associated with treatment response or survival with ICIs. Method: This is a single-center, retrospective, observational study. The study included 466 patients who received ICI at Kawasaki Medical School Hospital from September 1, 2014, to May 31, 2022 and evaluated the degree of abnormal thyroid function and survival and remission rates after treatment with ICIs. Primary hypothyroidism of less than 10 µIU/mL TSH was classified as grade 1, and primary hypothyroidism requiring more than 10 µIU/mL TSH or levothyroxine as grade 2-4. Result: The mean age of the study participants was 68.2 ± 10.3 years, and the percentage of male participants was 72.6%. The frequency of ICI-induced thyroid dysfunction in the study participants was 28.2%. TSH levels were significantly higher in Grade 1 and Grades 2-4 when treated with ICI compared to NTF (p<0.0001). The survival rate at 1 year after ICI administration was significantly higher with 64.9% for grade 1 and 88.9% for grades 2-4 compared to 52.1% for NTF (p<0.0001). Cancer stage at the time of ICI administration did not differ among the groups (p=0.68). Nevertheless, the remission rate assessed by RECIST criteria was significantly higher in grades 2-4 compared to NTF (p<0.0001). Conclusion: ICI-induced thyroid dysfunction was significantly correlated with survival, mean observation time, and treatment remission rate. It is important to monitor thyroid hormone levels regularly in patients receiving ICIs.

Case Report: Repeated esophageal obstruction in a patient with type 3C diabetes mellitus.

Although diabetic neuropathy is a well-known cause of gastrointestinal motility disorders, it is rare that diabetic neuropathy brings about esophageal obstruction. Here, we report a case with Type 3C diabetes mellitus (DM) lasting over 15 years and repeated esophageal obstruction resulting in chicken-meat-induced esophageal obstruction and candidiasis. This case highlights the importance of management of DM to prevent the development of complications such as diabetic neuropathy and associated symptoms.

Simple standing test without furosemide is useful in the diagnosis of primary aldosteronism.

Primary aldosteronism (PA) is a well-known cause of secondary hypertension. We have long performed the simple standing test in patients with PA. On the other hand, there are few reports on the usefulness of the simple standing test in PA. This study is a single-center, retrospective, observational study. A total of 173 patients with hypertension or adrenal tumor admitted to Kawasaki Medical School were included. Eighty patients who met the exclusion criteria were excluded, and 31 patients without PA (non-PA), 26 patients with unilateral PA, and 36 patients with bilateral PA were included in the study. The simple standing test was performed after 120 min of standing or sitting followed, and the aldosterone/renin ratio (ARR) and percentage of increase plasma aldosterone concentration (%increase of PAC) was calculated. The mean ARR in the simple standing test in unilateral PA (1143 (528-2200)) and bilateral PA subjects (521 (374-765)) were significantly higher compared to non-PA subjects (152 (102-240)) (p < 0.0001, p = 0.0013, respectively). The percentage increase of PAC after standing loading was significantly lower in unilateral PA subjects (110 (96-140)) compared to non-PA subjects (187 (155-244)) (p = 0.0003), with no difference between non-PA and bilateral PA subjects (p = 0.99). The cutoff value of the ARR in the simple standing test for diagnosis of PA in this study was 364 (AUC = 0.948, sensitivity = 83.8%, specificity = 93.5%, false positive rate = 3.7%, false negative rate = 25.6%, p < 0.001), which was not inferior to the diagnostic performance of the captopril loading test. The diagnostic performance of the simple standing test for PA was not inferior to that of the captopril loading test. The percentage increase of PAC in unilateral PA subjects was significantly lower compared to bilateral PA subjects. These results demonstrate the usefulness of the simple standing test, which can be performed simultaneously with general screening tests of PA.

Ectopic PTH-producing parathyroid cyst inside the thymus: a case report.

BACKGROUND: The hallmark of hyperparathyroidism is hypersecretion of parathyroid hormone (PTH) which results in hypercalcemia and hypophosphatemia. While hypercalcemia due to malignancy is often brought about by PTH-related protein in adults, PTH-producing tumors are quite rare in clinical practice. Additionally, from the point of embryology, it is very difficult to examine ectopic PTH-producing tissue such as ectopic parathyroid glands. Furthermore, clear histopathological criteria are not present. CASE PRESENTATION: A 57-year-old woman was referred to our hospital for hypercalcemia. Her parathyroid hormone (PTH) level was elevated, but there were no enlarged parathyroid glands. Although 99mTc-MIBI confirmed a localized and slightly hyperfunctioning parathyroid tissue in the anterior mediastinum, it was not typical as hyperfunctioning parathyroid. We finally diagnosed her as ectopic PTH-producing cyst-like tumor with venous sampling of PTH. She underwent anterosuperior mediastinal ectopic PTH-producing cyst-like tumor resection. It is noted that intact-PTH concentration of the fluid in the cyst was very high (19,960,000 pg/mL). Based on histopathological findings, we finally diagnosed her as ectopic PTH-producing parathyroid cyst inside the thymus. After resection of anterosuperior mediastinal thymus including ectopic PTH-producing parathyroid cyst, calcium and intact-PTH levels were decreased, and this patient was discharged without any sequelae. CONCLUSIONS: We should know the possibility of superior mediastinal ectopic PTH-producing parathyroid cyst inside the thymus among subjects with ectopic PTH-producing parathyroid glands. Particularly when the cyst is present in the superior mediastinum, it is necessary to do careful diagnosis based on not only positive but also negative findings in 99mTc-MIBI. It is noted that the patient's bloody fluid in the cyst contained 19,960,000 pg/mL of intact-PTH, and its overflow into blood stream resulted in hyperparathyroidism and hypercalcemia. Moreover, in such cases, the diagnosis is usually confirmed after through histological examination of ectopic PTH-producing parathyroid glands. We think that it is very meaningful to let clinicians know this case.

Correlation of Baba's diabetic neuropathy classification with various diabetes-related complications.

It is known that Baba's diabetic neuropathy classification (BDC) is useful in quantitative evaluation of Diabetic polyneuropathy (DPN). In this study, we aimed to investigate the possible association between BDC and various diabetic microvascular and macrovascular complications in patients whose neuropathy was evaluated with BDC. As the results, BDC was significantly correlated with the severity of diabetic retinopathy and nephropathy. BDC was also significantly correlated with history of myocardial infarction or cerebral infarction, carotid IMT, and ABI. These data suggest that BDC may be useful in predicting the presence of various diabetic microvascular and macrovascular complications. The data also support the idea that we should perform further investigation of other diabetes-related complications in patients with severe DPN.

Usefulness of cortisol/ACTH ratio (CAR) for diagnosis of cushing's syndrome: comparison of CAR with findings in dexamethasone suppression test.

Cushing's syndrome and subclinical Cushing's syndrome (SCS) are conditions of increased cortisol secretion from the adrenal glands. Cushing's syndrome includes adrenocorticotropic hormone (ACTH)-dependent Cushing's syndrome (Cushing's disease) and ACTH-independent Cushing's syndrome (AICS). The purpose of this study was to investigate the diagnostic potential of the cortisol / adrenocorticotropic hormone (ACTH) ratio (CAR) for diagnosis of Cushing's syndrome or SCS in adult subjects. This was a single-center, retrospective, observational study. This study enrolled 44 subjects with SCS, 14 AICS, 10 CD, and 248 non-Cushing's syndrome subjects who had undergone a 1 mg dexamethasone suppression test (1 mg DST). Definition of SCS was as follows: no physical signs characteristic of Cushing syndrome and cortisol was ≥ 83 nmol/L in 1 mg DST. The diagnostic potential of CAR for diagnosis of Cushing's syndrome was evaluated by comparing the correlation between CAR and after-load cortisol level in 1 mg DST. As the results, there was a strong positive correlation between CAR and after-load cortisol level in subjects with AICS (r = 0.800, p < 0.005). CAR was 10,040 ± 4170 nmol/pmol in subjects with NCS, 17,535 ± 10,246 nmol/pmol in SCS, 101,221 ± 18,009 nmol/pmol in AICS, and 4324 ± 2051 nmol/pmol in CD, all of which were significantly higher compared to those with AICS (p < 0.0005). The cutoff values of CAR for screening at our institution were 11,849.6 nmol/pmol for AICS (AUC 0.935, p < 0.005, sensitivity 92.3%, specificity 83.5%) and 7006.1 nmol/pmol for CD (AUC 0.714, p < 0.05, sensitivity 100.0%, specificity 46.8%). There was a positive correlation between CAR and adrenal adenoma diameter in subjects with AICS (r = 0.508, p < 0.05), but there was no correlation between tumor diameter and CAR in subjects with SCS and CD. In conclusion, high CAR indicates increased cortisol secretion from the adrenal glands. Since CAR is a simple indicator that can be easily evaluated by general practitioners as well as endocrinologists, we think CAR would be useful for the early detection of Cushing's syndrome.

IgG4-related lung disease with multifocal pulmonary consolidations near the pleura: A case report.

RATIONALE: Immunoglobulin G4 (IgG4)-related disease (IgG4-RD) is a systemic immune-mediated condition that can cause fibroinflammatory lesions in multiple organs. Approximately 35% of IgG4-RD patients have some symptoms in the chest and IgG4-related lung disease (IgG4-RLD) is observed in about 10% of IgG4-RD cases. In addition, it is thought that glucocorticoid therapy is effective for IgG4-RD and IgG4-RLD. It is difficult to diagnose IgG4-RLD complicated with another lung disease. PATIENT CONCERNS: An 85-year-old Japanese man was hospitalized due to pulmonary consolidations just below the pleura in chest computed tomography while being treated with antibiotics. Previously, an upper lobectomy of the right lung was performed for an upper lung mucinous adenocarcinoma, and he was diagnosed with chronic obstructive pulmonary disease. Although he took antibiotics before admission, C-reactive protein levels were elevated. DIAGNOSIS: IgG4 levels were also elevated (IgG4; 733 mg/dL), and lung biopsy histology showed an abundance of IgG4-positive plasma cell infiltration; about 40% of the affected area was occupied by such infiltration. Based on such findings, we finally diagnosed him as IgG4-RLD. INTERVENTIONS: We administered 20 mg/d prednisolone. OUTCOMES: About 2 weeks after administration of prednisolone by intravenous injection, his multifocal pulmonary consolidations just below the pleura were markedly improved and his pulmonary symptoms disappeared. Four weeks after glucocorticoid therapy, IgG4 levels decreased from 831 mg/dL (peak) to 547 mg/dL. LESSONS: We should consider IgG4-RLD, a rare disease, when lesions are detected as pulmonary consolidations near the pleura and are unresponsive to antibiotic therapy. Glucocorticoid therapy, however, is very effective for such IgG4-RLD.

Adult acetonemic vomiting complicated with low body weight in a subject with Mycobacterium avium complex pulmonary disease: a case report.

Pulmonary diseases often cause significant health issues and nutritional disorders. Weight loss and malnutrition are related to the severity of obstructive disorders. Therefore, patients with such conditions often experience low nutritional energy. Acetonemic vomiting is caused by acetonemic syndrome. Previously, it was believe that acetonemic vomiting was observed only in childhood. However, it was recently suggested that acetonemic vomiting can also occur in adults. It is also considered that acetonemic vomiting can occur in subjects with low body weight because stored carbohydrate levels are reduced and fats are mainly used for energy. Consequently, large amounts of acetone are produced, ultimately resulting in nausea and vomiting. In this study, we report a case of adult acetonemic vomiting complicated by low body weight in a subject with Mycobacterium avium complex pulmonary disease.

Onset of Aortic Dissection Complicated with Cushing's Disease: A Case Report and Review of the Literature.

Cushing's syndrome and Cushing's disease cause various metabolic disorders associated with high cortisol levels. Some reports have shown that Cushing's syndrome is complicated with dissecting aortic aneurysm and aortic dissection after long-term exposure to high cortisol levels. We herein report a rare case of aortic dissection complicated with Cushing's disease. Aortic dissection may occur even under relatively short periods of high cortisol conditions. This case suggests that hypercortisolemia should be treated as soon as possible in order to prevent aortic dissection in subjects with Cushing's disease.

Case Report: Massive Hemoptysis From a Spontaneously Regression Inflammatory Bronchial Polyp.

Background: Bronchial inflammatory polyps are usually treated by surgical operation or with steroids and/or antibiotics, and it is quite rare that such polys spontaneously disappear without any treatment. This report shows a rare case with a bronchial inflammatory polyp which caused massive hemoptysis but spontaneously disappeared without any treatment. Case Presentation: A 66-year-old man with type 2 diabetes mellitus and a history of cough and asthma suddenly developed massive hemoptysis while smoking and was brought to an emergency room in our institution. In bronchoscopy on admission, a polypoidal elevated lesion was observed in the left upper lobe bifurcation. Pulsatile hemorrhage from a polypoidal elevated lesion was observed upon stimulation of passage of the bronchoscope. Bronchoscopy performed 25 days after discharge showed no evidence of active bleeding and a tendency toward reduction of the elevated lesion. In bronchoscopy performed 106 days after the initial hospitalization, the bronchial inflammatory polyp completely disappeared. Conclusions: We should bear in mind the possibility of spontaneous disappearance of bronchial inflammatory polyps causing some serious symptoms such as massive hemoptysis and repeated bloody sputum. Finally, we should select the best therapy for bronchial inflammatory polys based on each patient's background and conditions in clinical practice.

Serious diabetic ketoacidosis induced by insulin allergy and anti-insulin antibody in an individual with type 2 diabetes mellitus.

Diabetic ketoacidosis (DKA) is one of the most serious acute metabolic complications of diabetes mellitus, and is characterized by hyperglycemia, metabolic acidosis and increased total ketone body concentrations. The main mechanism of DKA is a lack of insulin in the body. It has been reported that some immunological response is associated with insulin therapy. Herein, we report a case of serious DKA, which was induced by insulin allergy and anti-insulin antibody. This case clearly shows that DKA can be induced by insulin allergy and anti-insulin antibodies in individuals with type 2 diabetes treated with insulin. Furthermore, we should know that as the required insulin dose might be very high under severe insulin resistance and serious DKA in such cases, we should increase the insulin dose appropriately while monitoring pH, base excess and other factors.

Case Report: A Patient With Neuroleptic Malignant Syndrome, Water Intoxication and Hyponatremia Associated With Severe Cerebral Edema and Coma.

Background: Water intoxication is typically caused by primary or psychogenic polydipsia that potentially may lead to fatal disturbance in brain functions. Neuroleptic malignant syndrome (NMS) is a serious complication induced by administration of antipsychotics and other psychotropic drugs. The combination of inappropriate secretion of antidiuretic hormone (SIDAH), NMS and rhabdomyolysis have been rarely reported. Our patient also developed severe water intoxication. Case presentation: Herein we report a comatose case of NMS complicated with water intoxication, syndrome of SIADH and rhabdomyolysis. This patient had severe cerebral edema and hyponatremia that were improved rapidly by the correction of hyponatremia within a couple of days. Conclusions: Malignant neuroleptic syndrome water intoxication, SIADH and rhabdomyolysis can occur simultaneously. Comatose conditions induced by cerebral edema and hyponatremia can be successfully treated by meticulous fluid management and the correction of hyponatremia.

Case Report: Emphysematous Cystitis and Pyelonephritis Induced by Uterine Prolapse in a Subject With Untreated Diabetes Mellitus.

Type 2 diabetes mellitus (T2DM) is often accompanied by a lot of complications due to chronic hyperglycemia and inflammation. Emphysematous cystitis and pyelonephritis are rare types of urinary tract infections and are often complicated with DM. Herein, we report a case of emphysematous cystitis and pyelonephritis complicated with untreated DM. In addition, this case was very rare and interesting in that her emphysematous cystitis and pyelonephritis were induced by severe uterine prolapse, obstructive uropathy and urination disorders. Both uterine prolapse and DM should be appropriately treated because both can lead to the development of emphysematous cystitis and pyelonephritis.

Case Report: Severe Edema and Marked Weight Gain Induced by Marginal Thiamine Deficiency in a Patient With Alcohol Dependency and Type 2 Diabetes Mellitus.

Background: Patients with alcohol use disorder (AUD) may develop peripheral edema due to alcohol-related liver, renal, or heart disease. Thiamine deficiency is reported to occur in AUD and type 2 diabetes mellitus (T2DM). Thiamine deficiency may also cause peripheral edema. Thiamine is essential for optimal glucose metabolism through its role as an essential co-factor for key enzymes in intermediary metabolism. Since glucose metabolism worsens under diabetic conditions, it seems that a relative shortage of thiamine may occur more easily in patients with diabetes mellitus. Case Presentation: A 59-year-old Japanese man was admitted to the hospital with severe peripheral edema. His background history included alcohol liver disease (ALD), chronic renal failure (CRF), and T2DM. His body mass index (BMI) at admission was 37.7 kg/m2 and this represented a 30 kg increase in body weight over 2 months. Laboratory investigations showed anemia, liver and renal injury, hyperglycemia, and marginal hypothyroidism. The plasma thiamine diphosphate concentration was 20 ng/mL (reference range: 24-66 ng/mL). Diet therapy of 1,600 kcal/day and intravenous fursultiamine hydrochloride therapy (50 mg/once a day, seven days) was commenced in combination with intravenous diuretics. After one week, the plasma thiamine concentration was 853 ng/mL, and the patient's body weight had reduced by 18 kg. Conclusions: Patients with T2DM and AUD may develop severe peripheral edema in the context of marginal thiamine deficiency. Fursultiamine hydrochloride (50 mg/once a day, seven days) restored normal plasma thiamine concentrations and may have contributed to the rapid resolution of severe peripheral edema in this case. Empirical treatment with thiamine should be considered in patients with severe peripheral edema in the context of AUD and T2DM.

Pyogenic psoas abscess on the dorsal side, and bacterial meningitis and spinal epidural abscess on the ventral side, both of which were induced by spontaneous discitis in a patient with diabetes mellitus: A case report.

Type 2 diabetes mellitus patients are immunocompromised, particularly under poorly controlled conditions, and thereby they could develop rare inflammatory diseases, such as spontaneous discitis, pyogenic psoas abscess, spinal epidural abscess and bacterial meningitis. Herein we report a pyogenic psoas abscess on the dorsal side, and bacterial meningitis and spinal epidural abscess on the ventral side, both of which were induced by spontaneous discitis in a patient with poorly controlled type 2 diabetes mellitus. This case was very rare and interesting, because we successfully treated various infections with antibiotics over a long period of time, complicated by hyperglycemic crises, although the patient suffered severe bone destruction and required rehabilitation for a long time.