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.

A case of Empty Sella syndrome with adrenal insufficiency masked by prednisolone after administration of immune checkpoint inhibitors.

INTRODUCTION: The use of immune checkpoint inhibitors (ICIs) is gradually increasing; ICIs produce a variety of immune-related adverse events (irAEs), especially ICI-induced hypoadrenocorticism, which can be a lethal complication if treatment is delayed. PATIENT CONCERNS: A 63-year-old man received chemotherapy with pembrolizumab for nonsmall cell lung cancer. He developed drug-induced interstitial pneumonia 366 days after receiving pembrolizumab and was treated with prednisolone. Five hundred thirty-seven days later, he developed drug-induced eosinophilic enteritis, and pembrolizumab was discontinued and prednisolone was continued. After discontinuation of prednisolone, general malaise and edema of the lower extremities appeared, and adrenal insufficiency was suspected. DIAGNOSIS: In blood tests on admission adrenocorticotropic hormone (ACTH) was 2.2 pg/mL and cortisol was 15 µg/dL, with no apparent cortisol deficiency. However, the cortisol circadian rhythm disappeared and remained low throughout the day; a corticotropin-releasing hormone stimulation test showed decreased reactive secretion of ACTH. Pituitary magnetic resonance imaging showed pituitary emptying, suggesting Empty Sella syndrome. INTERVENTIONS AND OUTCOMES: We started hydrocortisone and his symptoms were improved. CONCLUSIONS: The administration of high-dose steroids after ICI administration may mask the symptoms of hypoadrenocorticism as irAEs. Therefore, we should bear in mind the possibility of hypoadrenocorticism when we stop steroid therapy in patients who are treated with steroids after ICI administration.

Usefulness of Once-Weekly GLP-1 Receptor Agonist Semaglutide on Glycemic Control in Subjects with Type 2 Diabetes Mellitus: Switching from the Same Class Dulaglutide in a Retrospective Observation Study.

Recently, the development of once-weekly incretin-based injections dulaglutide and semaglutide has drawn a great deal of attention. This study is aimed at comparing the efficacy of once-weekly GLP-1 receptor activator (GLP-1RA) dulaglutide and semaglutide on glycemic control and several metabolic parameters in patients with type 2 diabetes mellitus. We compared various clinical parameters between before and after switching from dulaglutide to semaglutide in "study 1" (pre-post comparison) and set the control group using propensity score matching method in "study 2." In "study 1," six months after the switching, HbA1c was significantly reduced from 8.2% to 7.6% and body mass index was also decreased from 30.4 kg/m2 to 30.0 kg/m2. Such effects were more pronounced in subjects whose glycemic control was poor. In "study 2," after 1 : 1 propensity score matching, glycemic control and body weight management were improved in the switching group compared with the dulaglutide continuation group. In this study including obese subjects with poor glycemic control, switching dulaglutide to semaglutide showed more beneficial effects on both glycemic and weight control irrespective of age, body weight, and diabetes duration. Therefore, we should bear in mind that it would be better to start using a relatively new once-weekly GLP-1RA semaglutide in clinical practice, especially in obese subjects with poor glycemic control with other GLP-1RAs.

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.

Comparison of clinical efficacy and safety of weekly glucagon-like peptide-1 receptor agonists dulaglutide and semaglutide in Japanese patients with type 2 diabetes: Randomized, parallel-group, multicentre, open-label trial (COMING study).

AIM: To compare the clinical usefulness of once-weekly glucagon-like peptide-1 receptor agonists dulaglutide and semaglutide at the doses approved for use in Japanese patients with type 2 diabetes. METHODS: In total, 120 patients with glycated haemoglobin (HbA1c) ≥7% were randomly assigned to dulaglutide (n = 59) or semaglutide group (n = 61), and 107 participants (dulaglutide/semaglutide = 53/54) completed the 24-week trial. The primary endpoint was the difference of HbA1c level between the two groups at 24 weeks. RESULTS: HbA1c level at 24 weeks was significantly lower in the semaglutide group (7.9 ± 0.5%-6.7 ± 0.5%) compared with the dulaglutide group (8.1 ± 0.6%-7.4 ± 0.8%) (p < .0001). Reduction in body mass index and visceral fat area were also more significant in the semaglutide group (p < .05, respectively). The achievement rate of HbA1c <7% was higher in the semaglutide group (p < .0001). The parameters such as low-density lipoprotein cholesterol, alanine aminotransferase and γ-glutamyl transpeptidase were decreased in the semaglutide group. Surprisingly, only semaglutide group significantly improved the apolipoprotein B/A1 ratio, which is considered a useful myocardial infarction risk index. Using computed tomography, the liver to spleen ratio was significantly elevated only in the semaglutide group. In contrast, gastrointestinal symptoms were observed in 13.2% of dulaglutide and 46.3% of semaglutide group (p < .01). The Diabetes Treatment-Related Quality of Life scores related to pain and gastrointestinal symptoms were also superior in the dulaglutide group. CONCLUSIONS: This prospective trial showed that semaglutide has more pronounced glucose- and body mass index-lowering effects and reduces liver fat percentage and visceral fat area and that dulaglutide has less gastrointestinal symptoms and superior Diabetes Treatment-Related Quality of Life scores related to pain and gastrointestinal 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.

Efficacy and safety of pemafibrate in patients with hypertriglyceridemia in clinical settings: A retrospective study.

BACKGROUND AND AIMS: Recently, pemafibrate, a selective PPARα modulator, has been developed as a treatment for hypertriglyceridemia and has attracted much attention. The aims of this study were to evaluate the efficacy and safety of pemafibrate in hypertriglyceridemia patients under clinical settings. METHODS AND RESULTS: We evaluated changes in lipid profiles and various parameters before and after 24-week pemafibrate administration in patients with hypertriglyceridemia who had not previously taken fibrate medications. There were 79 cases included in the analysis. 24 weeks after the treatment with pemafibrate, TG was significantly reduced from 312 ± 226 to 167 ± 94 mg/dL. In addition, lipoprotein fractionation tests using PAGE method showed a significant decrease in the ratio of VLDL and remnant fractionations, which are TG-rich lipoproteins. After pemafibrate administration, body weight, HbA1c, eGFR, and CK levels were not changed, but liver injury indices such as ALT, AST, and γ-GTP were significantly improved. CONCLUSION: In this study, pemafibrate improved the metabolism of atherosclerosis-induced lipoproteins in hypertriglyceridemia patients. In addition, it showed no off-target effects such as hepatic and renal damage or rhabdomyolysis.

A Male Subject with Congenital Adrenal Hyperplasia due to 21-Hydroxylase Deficiency Which Was Diagnosed at 31 Years Old due to Infertility.

INTRODUCTION: Congenital adrenal hyperplasia is caused by deficiencies in a number of enzymes involved in hormone biosynthesis in the adrenal glands or sexual glands. Adrenocorticotropic hormone (ACTH) secretion is enhanced by decreased cortisol production, leading to adrenal hyperplasia. The frequency of 21-hydroxylase deficiency (21-OHD) was the highest among congenital hyperplasias, and in 1989 it became one of the target diseases for newborn screening in Japan. CASE PRESENTATION: A 31-year-old Japanese male visited our institution due to infertility. On admission, his height was 151.7 cm (average ± SD in the same age, sex and population: 172.1 ± 6.1 cm). It was noted that his height had not changed since he was ten years old, and that pubic hair was observed when he was 7 years old. He had azoospermia and his gonadotropin level was low. He had low levels of both luteinizing hormone (LH) and follicle-stimulating hormone (FSH) but high levels of free testosterone. He had a low cortisol level and high ACTH level. Abdominal computed tomography (CT) showed swelling of bilateral adrenal glands, although morphology was normal. Based on these findings, he was diagnosed with primary adrenal insufficiency and admitted to our institution. His height had not changed since he was ten years old. In addition, pubic hair was observed when he was 7 years old. His sexual desire was decreased, although he had no general malaise or fatigue. He did not have pigmentation of the skin, genital atrophy or defluxion of pubic hair, although his body hair was relatively thin. In endocrinology markers, ACTH level was high (172.2 pg/mL) (reference range: 7.2-63.3 pg/mL), although his cortisol level was 6.9 µg/dL (4.5-21.1 µg/dL). These data suggest that he suffered from primary adrenal insufficiency. LH and FSH levels were both low, but free testosterone and estradiol levels were high. These data excluded the possibility of central hypogonadism. Furthermore, the level of 17a-hydroxyprogesterone, a substrate of 21-hydroxylase, and the level of pregnanetriol, a metabolite of progesterone in urine, were both markedly high. Based on these findings, we ultimately diagnosed this patient with 21-hydroxylase deficiency. CONCLUSIONS: We experienced a case of congenital adrenal hyperplasia due to 21-hydroxylase deficiency which was diagnosed in a 31-year-old male with infertility. Therefore, the possibility of 21-hydroxylase deficiency should be borne in mind in subjects with infertility who were born before 1989 and who had not undergone newborn screening for this disease.

Incidence of endocrine-related immune-related adverse events in Japanese subjects with various types of cancer.

Background: Immune checkpoint inhibitors (ICIs), such as cytotoxic T lymphocyte antigen-4 (CTLA-4) inhibitors, programmed cell death protein 1 (PD-1) inhibitors, and programmed cell death protein 1 ligand 1 (PD-L1) inhibitors, are often used to treat a variety of malignancies. ICIs are known to cause endocrine-related immune-related adverse events (irAEs), but the incidence varies among reports and/or agents. This study evaluated the incidence of endocrine-related irAEs in patients who were treated with ICIs in Japan. Method: This single-center, retrospective, observational study examined the incidence and clinical characteristics of endocrine-related irAEs in 466 participants who were treated with ICIs at Kawasaki Medical School Hospital. Result: The mean age of participants with and without endocrine-related irAEs was 69.1 ± 1.8 years and 68.1 ± 1.1 years, respectively, with no difference between them. The overall incidence of any endocrine-related irAEs among the participants was 25.5%. Hypothyroidism was prevalent in 24.3%, hypoadrenocorticism in 3.2%, hypopituitarism in 0.9%, and insulin-dependent diabetes mellitus in 1.1%. Participants receiving combination therapy with CTLA-4 and PD-1 inhibitors had a significantly higher incidence of endocrine-related irAEs than those receiving monotherapy. Conclusion: Endocrine-related irAEs correlated significantly with survival and mean observation period. There was substantial difference in the incidence of endocrine-related irAEs among various types of ICIs and types of cancer. We should bear in mind that endocrine testing is necessary during the treatment with ICIs.

Influence of Nutritional Guidance/Consulting on Glycemic Control during the Coronavirus Disease 2019 Pandemic in Patients with Type 2 Diabetes Mellitus.

Objective The coronavirus disease 2019 (COVID-19) pandemic has led to a global restriction of public behavior due to lockdowns in various major cities. Lifestyle changes and reduced rates of outpatient lifestyle guidance/consulting may have had some impact on glycemic control in patients with type 2 diabetes. This study analyzed the impact of changes in the frequency of nutritional guidance/consulting (NGC) during the COVID-19 pandemic on outpatient care for type 2 diabetes. Methods Among 785 patients, 67 who received regular NGC during the COVID-19 pandemic were assigned to the continuation group (CG), 143 whose NGC was discontinued after the pandemic were assigned to the discontinuation group (DG), and 575 who did not receive regular NGC regardless of the COVID-19 pandemic status were assigned to the irregular NGC group (IGG). The three groups were followed up for two years. Analyses among the three categories were performed using the chi-square test or an analysis of covariance. Results The number of diabetes medications after the declaration of the COVID-19 emergency did not markedly increase in the CG (2.0±1.4 to 2.1±1.5, p>0.05) but significantly increased from 2.2±1.4 to 2.6±1.4 in the DG (p<0.005) and from 2.2±1.4 to 2.4±1.4 in the IGG (p<0.005). The increase in HbA1c adjusted for confounders was unchanged at 0.12±1.06% for the CG and -0.07±1.29% for the IGG but was significantly increased at 0.19±1.49% for the DG (p<0.05). Conclusion In patients with type 2 diabetes mellitus, regular nutritional guidance may be important for maintaining good glycemic control, even during the COVID-19 pandemic.

Case report of severe hypoglycemic alcoholic ketoacidosis: A possible pitfall in diagnosis of ketoacidosis.

BACKGROUNDS: Hypoglycemic alcoholic ketoacidosis is known to be one of the emergent diseases but its frequency is very low compared to hyperglycemic ketoacidosis or hyperosmolar hyperglycemic syndrome observed in subjects with diabetes mellitus. CASE PRESENTATION: We experienced a case who had alcoholic ketoacidosis and severe hypoglycemia after drinking too much alcohol without taking enough food for a long period of time. In this subject, plasma glucose level was as low as 25 mg/dL, and ketone bodies, especially 3-hydroxybutyrate, were markedly increased. In addition, in blood gas analysis, severe acidosis was observed and anion gap was increased. These points were compatible with hypoglycemia alcoholic ketoacidosis. CONCLUSIONS: When we examine subjects with ketoacidosis and hypoglycemia, we should bear in mind the possibility of hypoglycemic alcoholic ketoacidosis especially in subjects who drink too much alcohol without taking enough food for a long period of time.

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.

Association between changes in pancreatic morphology and vascular complications in subjects with type 2 diabetes mellitus: a retrospective study.

Decreased pancreatic volume, increased pancreatic fat mass, and serrated pancreatic margins are characteristic morphological changes of the pancreas in subjects with type 2 diabetes mellitus. This retrospective study aimed to clarify the clinical significance of pancreatic morphological changes in subjects with type 2 diabetes mellitus who underwent abdominal magnetic resonance imaging. The mean age and HbA1c value were 59.1 ± 16.3 years old and 8.9 ± 2.3%, respectively. Pancreatic body mass corrected for body surface area (BSA) in subjects with diabetes mellitus was lower compared to those in normal glucose tolerance (49.4 ± 15.3 cm3 vs. 60.9 ± 7.8 cm3), although it did not reach a statistic significance. There was a negative correlation between BSA-corrected pancreatic volume and age, duration of diabetes, glycoalbumin, mean and max IMT, and there was a positive correlation between BSA-corrected pancreatic volume and HOMA2-ß. Serration of the pancreatic limbus was more often observed in subjects with diabetes mellitus compared to those in normal glucose tolerance (74.1% vs. 14.3%). Subjects with serrated changes were older and had higher HbA1c, and visceral fat area was significantly larger in subjects with serrated changes. BSA-corrected pancreatic volume in subjects with serrated changes was significantly smaller, and mean IMT was significantly thicker in subjects with serrulation. Furthermore, advanced diabetic retinopathy and diabetic nephropathy were more often observed in subjects with serrated changes. Taken together, decreased BSA-corrected pancreatic volume and serrated changes were associated with the progression of vascular complications in subjects with type 2 diabetes mellitus.

Addison's disease triggered by infection with mycobacterium abscessus, but not by adrenal tuberculosis or MAC pulmonary disease, in a subject with type 2 diabetes mellitus: case report.

BACKGROUND: Addison's disease is primary adrenal dysfunction and is characterized by decrease of cortisol level and increase of adrenocorticotropic hormone (ACTH) level. It is known that infection is one of main causes of Addison's disease. Among various infections, tuberculous infection accounts for the majority of them. Recently the number of subjects with non-tuberculous mycobacterial infection has been increased, and the infection can also bring about Addison's disease. Mycobacterium avium complex (MAC) pulmonary disease accounts for the majority of non-tuberculous mycobacterial infection. CASE PRESENTATION: An 83-year-old female was suspected of having adrenal failure in our outpatient care and hospitalized in our institution. There was pigmentation in her face, hands and legs, especially in auricle and nail beds in her hands and legs. In rapid ACTH load test (0.25 mg of 1-24 ACTH), cortisol level was not increased at all. An abdominal computed tomography (CT) showed swelling of both adrenal glands accompanied by calcification. QuantiFERON test was negative and mycobacterium tuberculosis complex was negative in PCR test using bronchial lung lavage fluid. These data ruled out the possibility of adrenal tuberculosis. It is known that MAC pulmonary disease accounts for the majority of non-tuberculous mycobacterial infection. In this subject, however, anti-MAC antibody was negative and MAC-related bacteria were not detected in PCR test using bronchial lung lavage fluid. These data ruled out the possibility of MAC pulmonary disease. Mycobacterium abscessus (Mab) was positive in bronchial lung lavage fluid culture. Based on these data, we diagnosed this subject with Addison's disease triggered by infection with mycobacterium abscessus, but not by adrenal tuberculous or MAC pulmonary disease. Decreased sodium level and increased eosinophil number were normalized and appetite loss was markedly mitigated after starting hydrocortisone therapy. A chest CT which was taken about 6 months later showed drastic reduction of consolidation in the upper lobe of the left lung although calcification in the adrenal gland was still observed. CONCLUSIONS: We should bear in mind the possibility of Addison's disease triggered by another type of infection rather than adrenal tuberculosis or MAC pulmonary disease.

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.

Sudden extensive bloody pleural and pericardial effusion in a subject with untreated known hypothyroidism after total thyroidectomy, triggered by pneumonia.

BACKGROUND: In subjects with hypothyroidism, edema is often observed, and pleural effusion and pericardial fluid could be also observed. The color of such fluid retention is usually yellow. Here we show a very rare case with hypothyroidism who had bloody pleural effusion and bloody pericardial fluid. CASE PRESENTATION: A 42-year-old male noticed chest pain and the aggravation of exertional dyspnea, and he was transported to our institution by emergency. He had Graves' disease and underwent total thyroidectomy about 4 years before. After then, he had been treated with 200 µg/day of levothyroxine sodium for the maintenance of thyroid function. However, he self-interrupted such medication about 2 years before. Thyroid function on admission was reduced as follows: free triiodothyronine, 1.60 pg/mL; free thyroxine < 0.40 ng/dL; thyroid-stimulating hormone 25.50 µU/mL. Inflammation markers were increased: white blood cells 25,280 /µL; C-reactive protein 18.66 mg/dL. A large amount of pericardial fluid and pleural effusion were observed in chest and abdominal computer tomography and echocardiography. In addition, we performed pleural effusion and pericardial fluid collection. Pleural effusion in this subject showed bloody color, but not yellow. In cell block specimen of pleural effusion and pericardial fluid, red blood cells, neutrophils and lymphocyte component were observed. In this subject, however, we were unable to find any obvious background disease causing bloody pericardial effusion. Finally, we concluded that bloody pleural effusion and bloody pericardial fluid were brought about in a subject with untreated known hypothyroidism after total thyroidectomy, triggered by pneumonia. CONCLUSIONS: In subjects with hypothyroidism, fluid and mucopolysaccharide are stored in interstitial space and protein osmolality is increased, thus leading to edema and fluid retention. It is noted here that pleural effusion and pericardial fluid in this subject showed bloody color and included red blood cells. There are no reports of bloody pericardial fluid with hypothyroidism. Therefore, it is important to keep in mind that a subject with some trigger, such as infection, may have a hematologic fluid retention that is not seen when hypothyroidism is present alone, as observed in this subject.

Effect of Hyperglycemia-Related Acute Metabolic Disturbance on Thyroid Function Parameters in Adults.

Non-thyroidal illness (NTI) is a condition in which the hypothalamic-pituitary-thyroid system and thyroid hormone metabolism are abnormal due to non-thyroidal diseases. Although NTI has been reported to occur in hyperglycemic emergencies in children, there have been few studies in adult cases. In this study, we examined adult patients with hyperglycemia regarding the frequency of NTI and its triggers. Adult diabetic patients who were hospitalized for diabetic ketosis (DK), diabetic ketoacidosis (DKA), or hyperglycemic hyperosmolarity syndrome (HHS) were included in the study. Compared with the DK group, the DKA and HHS groups had higher admission blood glucose, Anion Gap, serum osmolality, creatinine, and urea nitrogen, and lower pH and eGFR. The frequency of NTI in the DKA, HHS, and DK groups was 80%, 70%, and 50%, respectively, and thyroid stimulating hormone (TSH) and free thyroxine 3 (FT3) were significantly improved after treatment for hyperglycemia. Multiple regression analysis showed a significant correlation between the decrease in FT3 level and 3-hydroxybutyrate and albumin. Acute metabolic failure associated with hyperglycemia tends to be associated with a high rate of NTI and low FT3 levels at the start of treatment. The data in this study clearly shows that transient NTI is frequently observed in subjects with acute metabolic disorders such as DKA, HHS and DK. In addition, we should bear in mind that thyroid hormone replacement therapy is not necessary in subjects with NTI due to DKA, HHS and DK, especially when overt symptoms of hypothyroidism are not observed.

Central Diabetes Insipidus Due to IgG4-related Hypophysitis That Required over One Year to Reach the Final Diagnosis Due to Symptoms Being Masked by Sialadenitis.

Pituitary inflammation due to IgG4-related disease is a rare condition and is sometimes accompanied by central diabetes insipidus. Central diabetes insipidus produces a strong thirst sensation, which may be difficult to distinguish when complicated by salivary insufficiency. A 45-year-old man was admitted to our department for a thorough examination of his thirst and polyuria. He had suddenly developed these symptoms more than one year earlier and visited an oral surgeon. Swelling of the left submandibular gland, right parotid gland, and cervical lymph nodes had been observed. Since his IgG4 level was relatively high at 792 mg/dL and a lip biopsy showed high plasmacytoid infiltration around the gland ducts, he had been diagnosed with IgG4-related disease. He had started taking 0.4 mg/kg/day of prednisolone, and his chief complaint temporarily improved. However, since the symptom recurred, he was referred to our institution. After admission, to examine the cause of his thirst and polyuria, we performed a water restriction test, vasopressin loading test, hypertonic saline loading test and pituitary magnetic resonance imaging. Based on the findings, we diagnosed him with central diabetes insipidus due to IgG4-related hypophysitis. We increased the dose of prednisolone to 0.6 mg/kg/day and started 10 µg/day of intranasal desmopressin. His symptoms were subsequently alleviated, and his serum IgG4 level finally normalized. We should remember that IgG4-related disease can be accompanied by hypophysitis and that central diabetes insipidus is brought about by IgG4-related hypophysitis. This case report should remind physicians of the fact that pituitary inflammation due to IgG4-related disease is very rare and can be masked by symptoms due to salivary gland inflammation, which can lead to pitfalls in the diagnosis in clinical practice.

Glucagon Test Is a Useful Predictor of Withdrawal From Insulin Therapy in Subjects With Type 2 Diabetes Mellitus.

There are many tests for evaluating endogenous insulin secretory capacity. However, there are only a limited number of studies that have examined in detail in clinical practice which method most accurately reflects the ability to secrete endogenous insulin especially in hyperglycemic state. The purpose of this study was to find the endogenous insulin secretory capacity and a possible predictor of insulin withdrawal in subjects with type 2 diabetes requiring hospitalization due to hyperglycemia. In the endogenous insulin secretory test during hospitalization, CPR, CPR index, and ΔCPR after glucagon loading were all significantly higher in the insulin withdrawal group. On the other hand, there were no difference in fasting CPR index, HOMA-ß, SUIT, and 24-hour urinary CPR excretion between the two groups. In the glucagon test of the insulin withdrawal group, the cutoff value of ΔCPR was 1.0 ng/mL, the withdrawal rate of ΔCPR of 1.0 ng/mL or more was 69.2%, and the withdrawal rate of less than 1.0 ng/mL was 25.0%. In conclusion, it is likely that glucagon test is the most powerful tool for predicting the possibility of insulin withdrawal as well as for evaluating endogenous insulin secretory capacity in subjects with type 2 diabetes requiring hospitalization due to hyperglycemia.

Vitamin D deficiency osteomalacia triggered by long-term social withdrawal and unbalanced diet in a Japanese middle-aged subject: A case report.

INTRODUCTION: Osteomalacia is caused by an increase in the number of osteoids owing to mineralization failure. There are various causes of osteomalacia, such as hypophosphatemia due to excess production of fibroblast growth factor 23, vitamin D deficiency, insufficient vitamin D action, and renal tubular disorders. PATIENT CONCERNS: A 53-year-old man with bone pain and gait disturbance was referred to our institution. At the age of 35, he developed atopic dermatitis. He had eyesight deterioration due to atopic cataracts when he was 37 years old. Subsequently, he stayed home all the time, and his eating habits were unbalanced for a long period of time. Although he had atopic dermatitis, he did not take allergen-free diets, and he did not use sunscreen. Furthermore, when he was 43 years old, he failed to flex his legs and suffered gait disturbance. DIAGNOSIS: Hypocalcemia and hypophosphatemia were observed as follow: calcium, 5.5 mg/dL; adjusted calcium, 6.9 mg/dL; inorganic phosphorous, 1.9 mg/dL. In addition, intact parathyroid hormone levels were as high as 277.4 pg/mL, and 1, 25-(OH)2 vitamin D and 25-(OH) vitamin D levels were markedly reduced: 1, 25-(OH)2 vitamin D, ≤4 pg/mL; 25-(OH) vitamin D, 11.0 ng/mL. Fibroblast growth factor 23 levels did not increase. Alkaline phosphatase (ALP) and bone-type ALP (BAP) levels were high: ALP, 784 U/L; BAP, 159.2 µg/L (reference range: 3.7-20.9 µg/L). Based on these findings, we diagnosed this patient with vitamin D-deficient osteomalacia triggered by long-term social withdrawal and an unbalanced diet. INTERVENTIONS AND OUTCOMES: After hospitalization, to treat vitamin D-deficient osteomalacia, we started to administer 1 µg/day of alfacalcidol and 3 g/day of calcium lactate. Approximately one month later, 1,25-(OH)2 vitamin D levels increased to 214 pg/mL. Consequently, calcium and inorganic phosphorus were also increased up to 7.8 mg/dL and 3.9 mg/dL, respectively, and intact parathyroid hormone was decreased to 132.0 pg/mL. CONCLUSIONS: We should bear in mind the possibility of osteomalacia triggered by social withdrawal and vitamin D deficiency even in middle-aged subjects.