Primary Epstein-Barr virus infection shortly after primary Cytomegalovirus infection: a case report.

BACKGROUND: Infectious mononucleosis (IM) and mononucleosis-like illnesses are common viral infectious diseases which are often accompanied by a high fever, pharyngitis and lymphadenopathy in adults, although such infection in childhood is generally subclinical. Most cases of IM are caused by the Epstein-Barr virus (EBV) or Cytomegalovirus (CMV). However, it is difficult to diagnose IM only with subjective symptoms, and thus EBV and CMV are nearly indistinguishable in clinical practice. CASE PRESENTATION: A 20-year-old healthy Japanese woman had a 2-day history of high fever and consulted us. She had sex for the first time 6 months earlier. Her virus antibodies showed that she was infected with primary CMV. About 5 months later, she again experienced high fever and lymph node enlargement at the posterior cervical region. Her virus antibodies showed that she was infected with primary EBV at that time. CONCLUSION: Herein, we report a healthy adult Japanese woman with primary EBV infection relatively soon after primary CMV infection. It is very interesting to compare the symptoms and/or clinical data after EBV and CMV infection in the same patient within a short period of time. Our patient was diagnosed based only on subjective symptoms, physical examination and laboratory data, without tests of such virus-related antibodies. Therefore, clinicians should bear in mind that primary EBV infection and/or primary CMV infection is possible when patients have symptoms such as high fever, pharyngitis and lymphadenopathy, even in healthy adults.

Basedow's disease with associated features of Hashimoto's thyroiditis based on histopathological findings.

BACKGROUND: Basedow's disease and Hashimoto's thyroiditis are autoimmune thyroid disorders and usually diagnosed with elevation of serum autoimmune antibodies. Thyrotropin receptor antibodies (TRAb) and/or thyroid-stimulating antibody (TSAb) are usually used for diagnosis of Basedow's disease, and thyroid peroxidase antibodies (TPOAb) and/or thyroglobulin antibodies (TgAb) are for diagnosis of Hashimoto's thyroiditis. However, it is difficult to diagnose a subject as Basedow's disease with associated features of Hashimoto's thyroiditis only with elevation of such autoimmune antibodies. CASE PRESENTATION: A 44-year-old woman with 5-year history of Basedow's disease underwent a total thyroidectomy. She did not have a goiter. TRAb, TSAb, TPOAg and TgAb were all positive before a total thyroidectomy. In histopathological macroscopic examination, diffuse hyperplasia of the thyroid gland was observed. Furthermore, in histopathological microscopic examination, both characteristics of Basedow's disease and Hashimoto's thyroiditis were observed. After a total thyroidectomy, titers of all thyroid-associated autoimmune antibodies were markedly reduced. CONCLUSION: Herein, we report a subject with Basedow's disease without a goiter whose TPOAb and TgAb were relatively high at the onset of Basedow's disease. In addition, interestingly, the histopathological findings of this subject showed direct signs of Basedow's disease and Hashimoto's thyroiditis in the same thyroid gland. Considering from such findings, she seemed to have Basedow's disease with associated features of Hashimoto's thyroiditis. In conclusion, we should bear in mind the possibility of Basedow's disease with associated features of Hashimoto's thyroiditis in subjects with Basedow's disease, particularly when TPOAb and TgAb as well as TRAb and TSAb are positive.

Comparison of the effects of three kinds of glucose-lowering drugs on non-alcoholic fatty liver disease in patients with type 2 diabetes: A randomized, open-label, three-arm, active control study.

AIMS/INTRODUCTION: Non-alcoholic fatty liver disease (NAFLD) is often observed in individuals with type 2 diabetes mellitus, and it is known that the presence of type 2 diabetes mellitus leads to the aggravation of NAFLD. The aim of this study was to compare the possible effects of three kinds of oral hypoglycemic agents on NAFLD in individuals with type 2 diabetes mellitus. MATERIALS AND METHODS: We carried out a prospective clinical trial (a randomized and open-label study) in patients with type 2 diabetes mellitus and NAFLD. A total of 98 patients were randomly allocated either to the dapagliflozin (n = 32), pioglitazone (n = 33) or glimepiride (n = 33) group, and the patients took these drugs for 28 weeks. The primary end-point was the change of the liver-to-spleen ratio on abdominal computed tomography. RESULTS: There was no difference in baseline clinical characteristics among the three groups. Dapagliflozin, pioglitazone and glimepiride ameliorated hyperglycemia similarly. Bodyweight and visceral fat area were significantly decreased only in the dapagliflozin group. Serum adiponectin levels were markedly increased in the pioglitazone group compared with the other two groups. Dapagliflozin and pioglitazone, but not glimepiride, significantly increased the liver-to-spleen ratio, and the effects of dapagliflozin and pioglitazone on the liver-to-spleen ratio were comparable. CONCLUSIONS: The present study showed that the decrease of visceral fat area and the increase of adiponectin level contributed to the improvement of NAFLD in patients with type 2 diabetes mellitus. Furthermore, dapagliflozin and pioglitazone exerted equivalent beneficial effects on NAFLD in patients with type 2 diabetes mellitus, although it seemed that these two drugs had different mechanisms of action.

Alteration of ACTH and Cortisol Levels After Estradiol Valerate Treatment in a Male Subject With Gender Dysphoria: A Case Report.

Background: The number of subjects with gender dysphoria has been increasing. In general, male-to-female transsexual subjects are treated with estradiol valerate therapy. In this report, we showed the time course of ACTH and cortisol levels after estradiol valerate injection in a male subject with gender dysphoria. It seemed that alteration of estradiol levels influenced ACTH and cortisol levels via some pathway. Case presentation: A 31-year-old man with estradiol valerate therapy for gender dysphoria was referred due to an elevation of serum cortisol levels. She started hormone therapy at 26 years old. Her laboratory analyses showed an elevation of plasma ACTH and cortisol levels. There were no remarkable changes in the adrenal gland and pituitary gland. Her estradiol levels were elevated 7 days after estradiol valerate injection, but they were not detected 18 days after such treatment. Interestingly, plasma ACTH and serum cortisol levels were moderately decreased 7 days after estradiol valerate injection, but both were markedly elevated 18 days after such treatment. Conclusions: We should bear in mind the possibility of elevation in plasma ACTH and serum cortisol levels when we start estradiol valerate injection in subjects with gender dysphoria. In addition, we may need to check ACTH and cortisol levels when we use estrogen replacement therapy for a long period of time in subjects with gender dysphoria.

Severe hypertriglyceridemia in a subject with disturbed life style and poor glycemic control without recurrence of acute pancreatitis: a case report.

BACKGROUND: Hypertriglyceridemia is often observed as the result of lipid abnormality and frequently associated with other lipid and metabolic disorders. Aggravation of hypertriglyceridemia is caused by various conditions. However, severe hypertriglyceridemia is usually induced by an addition of some secondary clinical conditions such as uncontrolled type 2 diabetes mellitus (T2DM) and obesity with insulin resistance. CASE PRESENTATION: A 40-year-old man with 4-year history of dyslipidemia and T2DM visited after his interruption of therapy for about 1.5 years. His past history was acute pancreatitis. His life style was markedly disturbed, and he had a lot of risk factors for hypertriglyceridemia. Surprisingly, his serum triglyceride level was as high as 16,900 mg/dL. His aggravation and remission of hypertriglyceridemia were closely associated with the alteration of RLP-cholesterol levels in dyslipidemia and glycoalbumin and ketone body levels in T2DM. CONCLUSION: We report very severe hypertriglyceridemia, which seemed to be caused by markedly disturbed life style and poorly controlled T2DM. Total therapy with diet and drug for each disease is very important for the improvement of very severe hypertriglyceridemia. This case report suggests that very severe hypertriglyceridemia alone does not necessarily bring out acute pancreatitis, although it is very important to check pancreatitis markers in such a situation.

Dramatic Improvement of Glycemic Control by Promptly Starting Steroid Therapy at an Early Stage of Autoimmune Pancreatitis in a Subject with Type 2 Diabetes.

Glucocorticoid therapy is effective for treating autoimmune pancreatitis, but autoimmune pancreatitis itself and steroid therapy aggravate glycemic control. A 77-year-old man with type 2 diabetes was consulted due to aggravation of glycemic control. He was diagnosed with autoimmune pancreatitis. We promptly started glucocorticoid therapy for autoimmune pancreatitis and insulin therapy for glycemic control. Subsequently, both pancreatitis and diabetes were markedly ameliorated. After stopping glucocorticoid therapy, good glycemic control continued with diet therapy alone. Starting glucocorticoid therapy at an early stage of autoimmune pancreatitis is very important for preserving the insulin secretory capacity and improving glycemic control.

Acute exacerbation of chronic osteomyelitis triggered by aggravation of type 2 diabetes mellitus: a case report.

BACKGROUND: Osteomyelitis is an infection in a bone. Acute osteomyelitis is observed mainly in the long leg bones of children and is usually treated with antibiotics. On the other hand, in adults, subacute or chronic osteomyelitis is more common. Antibiotics therapy is not necessarily effective for chronic osteomyelitis, and sometimes a surgical operation is performed for its remission. Furthermore, in classification of osteomyelitis by cause, type 2 diabetes mellitus is one of most common conditions associated with osteomyelitis. It isCase presentation well known that a variety of complications are induced in patients with type 2 diabetes mellitus due to chronic hyperglycemia, inflammatory reaction, and immunodeficiency, especially when glycemic control is poor. CASE PRESENTATION: A 58-year-old Japanese man had acute exacerbation of chronic osteomyelitis triggered by aggravation of type 2 diabetes mellitus. He had acute osteomyelitis in his right lower leg in his babyhood. After this episode, he did not experience any pain in his leg for approximately 50 years; he felt acute pain in his right lower leg at the age of 50 when his glycemic control was very poor. He then started undergoing medical therapy for type 2 diabetes mellitus and, after an improvement in glycemic control, his pain was gradually mitigated. However, he did not take medicine for approximately 8 months at the age of 58. After the interruption, glycemic control became very poor and he felt the similar acute pain again in the same area. After improving glycemic control, his pain was gradually mitigated again as observed at the age of 50. CONCLUSIONS: Here we report a case of chronic osteomyelitis under poorly controlled diabetic conditions. Interestingly, chronic osteomyelitis was observed at the same position where acute osteomyelitis was observed in his babyhood. In addition, chronic osteomyelitis was repeatedly observed, and it seemed that its acute exacerbation was closely associated with aggravation of type 2 diabetes mellitus. We should bear in mind that type 2 diabetes mellitus is one of the major risk factors of osteomyelitis and that acute exacerbation of chronic osteomyelitis could be triggered by a disturbance of glycemic control in patients with type 2 diabetes mellitus.

There is a Close Association Between the Recovery of Liver Injury and Glycemic Control after SGLT2 Inhibitor Treatment in Japanese Subjects with Type 2 Diabetes: A Retrospective Clinical Study.

INTRODUCTION: Sodium-glucose co-transporter 2 (SGLT2) inhibitors function not only to reduce hyperglycemia but also to ameliorate liver injury and reduce body weight. The aim of this study was to examine in which subjects SGLT2 inhibitors are more effective for glycemic control, liver injury, and obesity in Japanese subjects with type 2 diabetes mellitus. METHODS: We enrolled a total of 156 subjects with type 2 diabetes who initiated SGLT2 inhibitor treatment after September 1, 2014 in Kawasaki Medical School (Protocol No. 2375). We evaluated the alteration of glycemic control, liver injury, body mass composition, and various clinical parameters. RESULTS: SGLT2 inhibitors significantly ameliorated glycemic control and improved liver injury in Japanese subjects with type 2 diabetes. SGLT2 inhibitors were more effective for liver injury when glycemic control was improved with SGLT2 inhibitors. In multivariate analyses, the amelioration of glycemic control was an independent determinant factor for the improvement of liver damage in Japanese subjects with type 2 diabetes. The reverse was also correct; the improvement of liver damage was an independent determinant factor for the amelioration of glycemic control. CONCLUSION: Recovery of liver injury with SGLT2 inhibitor treatment was closely associated with their effects on glycemic control in Japanese subjects with type 2 diabetes.

Efficacy and Safety of Switching from Insulin Glargine 100 U/mL to the Same Dose of Glargine 300 U/mL in Japanese Type 1 and 2 Diabetes Patients: A Retrospective Analysis.

Objective Insulin glargine [300 U/mL (Gla-300)] achieved better glycemic control and reduced the risk of hypoglycemia in comparison to glargine [100 U/mL; (Gla-100)] in phase 3 trials. This is the first study to retrospectively evaluate the efficacy and safety of Gla-300 in Japanese type 1 and 2 diabetes patients in a routine clinical setting. Methods We analyzed 20 type 1 diabetes patients and 62 type 2 diabetes patients who switched from Gla-100 to the same dose of Gla-300. Sixty type 2 diabetes patients who continued the use of Gla-100 during the study were included as controls. Results At three months after switching, the HbA1c levels were decreased in the patients with type 1 diabetes, but not to a significant extent. In the type 2 diabetes patients, the HbA1c levels were significantly decreased after switching (p<0.01). In contrast, there was no change in the HbA1c levels of the type 2 diabetes patients who continued the use of Gla-100 over the same period. The BMI values of the type 1 diabetes patients tended to decrease (p=0.06) and there was a significant decrease in the BMI values of the type 2 diabetes patients (p<0.05). There was no change in the BMI values of the type 2 diabetes patients who continued the use of Gla-100. The rates of hypoglycemia and adverse events did not change during the follow-up period. Conclusion In the clinical setting, switching from Gla-100 to the same dose of Gla-300 had a favorable effect on glycemic control and body weight control in Japanese type 1 and type 2 diabetes patients, without any increase in adverse events; however, a prospective study should be performed to confirm these findings.

Saibokuto as a Possible Therapy for Type B Insulin Resistance Syndrome: The Disappearance of Anti-insulin Receptor Antibody and a Marked Amelioration of Glycemic Control by Saibokuto Treatment.

Type B insulin resistance syndrome is a rare autoimmune disease and no effective therapy has yet been established. On the other hand, it is known that Saibokuto, one type of Japanese Kampo medicine, may have beneficial effects on various symptoms associated with this disease and it is therefore occasionally prescribed for various immune disorders. We herein describe a case of type B insulin resistance syndrome in which anti-insulin receptor antibody disappeared and the patient's glycemic control markedly improved after the administration of Saibokuto. At first, we administered various anti-oral diabetic drugs and insulin therapy, but the patient's glycemic control became further aggravated. In addition, Helicobacter pylori eradication therapy was not effective, although its benefit has been reported. Interestingly, after the patient started taking Saibokuto, her glycemic control markedly improved. In addition, the patient's plasma insulin levels markedly decreased and anti-insulin receptor antibody became negative after taking Saibokuto. Taken together, there is a possibility that Saibokuto may one of the options for type B insulin resistance syndrome therapy.

Werner Syndrome and Diabetes Mellitus Accompanied by Adrenal Cortex Cancer.

Werner syndrome is a rare genetic disease characterized by progeria, diabetes mellitus, cataracts and various types of malignancy. However, there are few reports showing adrenal cortex cancer in subjects with Werner syndrome. We herein report an extremely rare case of Werner syndrome accompanied by adrenal cortex cancer. Based on the data obtained from blood samples, computed tomography, magnetic resonance imaging and 131I adosterol scintigraphy, we diagnosed this subject with adrenal cortex cancer and Cushing's syndrome. Since the prognosis of adrenal cancer is very poor, we should be aware of the possibility of adrenal cancer occurring in subjects with Werner syndrome.

Hypoglycemic Coma Induced by the Use of Succinic Acid Cibenzoline in Frail Late-stage Elderly Subjects.

Succinic acid cibenzoline (CZ) is an antiarrhythmic agent often used for the treatment of tachyarrhythmia. However, hypoglycemia should be avoided in the treatment of diabetes. We herein report two late-stage elderly subjects who experienced a severe and prolonged hypoglycemic coma after the usage of CZ. These cases suggest that, when CZ is administered to elderly subjects with renal dysfunction and/or frailty, we should be aware of the possibility that this medicine may induce hypoglycemia and should adjust the dose as appropriate and monitor the concentration of CZ to avoid severe hypoglycemia.

Inadequate Triglyceride Management Worsens the Durability of Dipeptidyl Peptidase-4 Inhibitor in Subjects with Type 2 Diabetes Mellitus.

Dipeptidyl peptidase-4 (DPP-4) inhibitors are often used all over the world and exert various beneficial effects including glucose-lowering effect in many subjects with type 2 diabetes. It is poorly understood, however, which factors are closely related with the durability of glucose-lowering effect by DPP-4 inhibitor. In this study, we examined retrospectively which factors could mainly influence the durability of DPP-4 inhibitor. We enrolled 212 participants with type 2 diabetes to whom DPP-4 inhibitor was administered for over 1 year without an addition or increase of other hypoglycemic agents. Age and baseline HbA1c level were significantly higher in the effective group than those in the ineffective group. The effective group had a tendency of smaller amounts of weight change, average total cholesterol, and average triglyceride compared with the ineffective group. Multiple logistic regression analysis showed that average triglyceride and baseline HbA1c were independent predictors associated with the durability of DPP-4 inhibitor. Moreover, an average triglyceride level contributed to the durability of DPP-4 inhibitor in the obese group (BMI ≥ 25 kg/m2) but not in the nonobese group (BMI < 25 kg/m2). These results suggest the importance of strict triglyceride management to maintain the durability of glucose-lowering effect by DPP-4 inhibitor, especially in obese subjects with type 2 diabetes.

Dramatic mitigation of bone pain after phosphorus replacement therapy in a subject with FGF23-related hypophosphatemic osteomalacia.

INTRODUCTION: Fibroblast growth factor 23 (FGF23) is secreted from bone and suppresses the absorption of phosphorus in renal proximal tubule and in intestinal tract. Therefore, the increase of serum FGF23 levels leads to hypophosphatemic situations. Tumor-induced osteomalacia is often induced by various tumors, but it is often difficult to identify the localization of tumor, because most of the FGF23-producing tumors are small and could be observed in any part of the body. CASE DESCRIPTION: Here we report a case of elderly female subject with FGF23-related hypophosphatemic osteomalacia who repeatedly experienced severe bone pain and fragility fracture in various parts of the body. Although we failed to identify the localization of tumor in this subject even with various examination, after starting phosphorus replacement therapy with relatively small amounts of calcium phosphate (1.5 g/day) (phosphorus content: 270 mg), hypophosphatemia was ameliorated and repeated bone pain was dramatically mitigated without any surgical operation. DISCUSSION AND EVALUATION: Even when we fail to identify the localization of tumor in subjects with FGF23-related hypophosphatemic osteomalacia, phosphorus replacement therapy for hypophosphatemia could reduce the bone pain. CONCLUSIONS: We should be aware of the possibility that phosphorus replacement therapy exert marked beneficial effects for the reduction of bone pain in subjects with FGF23-related hypophosphatemic osteomalacia even when we fail to identify tumor localization.

Association of GA/HbA1c ratio and cognitive impairment in subjects with type 2 diabetes mellitus.

AIMS: The aim of this study was to search for factors influencing cognitive impairment and to clarify the association between the fluctuation of blood glucose levels and cognitive impairment in elderly Japanese subjects with type 2 diabetes. METHODS: We recruited 88 relatively elderly subjects (≥65years old) with type 2 diabetes who were hospitalized in Kawasaki Medical School from January 2014 to December 2015. We evaluated the fluctuation of blood glucose levels with glycoalbumin (GA)/hemoglobin A1c (HbA1c) ratio, and estimated cognitive impairment with Hasegawa dementia scale-revised (HDS-R) score and mini mental state examination (MMSE) score. RESULTS: Multivariate analyses showed that GA/HbA1c ratio and urinary albumin excretion, but not hypoglycemia, were independent determinant factors for cognitive impairment in elderly Japanese subjects with type 2 diabetes. CONCLUSIONS: The fluctuation of blood glucose levels per se is closely associated with cognitive impairment in elderly subjects with type 2 diabetes even when hypoglycemia is not accompanied. Since it is very easy to calculate GA/HbA1c ratio, we should check this ratio so that we can reduce the fluctuation of blood glucose levels especially in elderly subjects with type 2 diabetes.

Case of disseminated pyomyositis in poorly controlled type 2 diabetes mellitus with diabetic ketoacidosis.

Primary pyomyositis is a pyogenic and uncommon infection of skeletal muscle, which is mainly observed in tropical areas and/or human immunodeficiency virus patients. In non-human immunodeficiency virus infected patients, the most common cause is diabetes mellitus. Because of its rarity, the accurate diagnosis is often challenging. Staphylococcus aureus is the most common causative bacteria. According to the severity, pyomyositis is divided into three stages, and the late stage is occasionally lethal. The present case was compatible with the most advanced stage. Therefore, it was very difficult to save her life without precise and timely diagnosis. Furthermore, in the invasive stage, surgical drainage and broad-spectrum antibiotics should be given for a long enough period. Here, we report a case of a Japanese woman who developed disseminated abscesses under poorly controlled diabetic conditions accompanied by ketoacidosis, but was successfully treated without any sequelae.

Rapid onset of syndrome of inappropriate antidiuretic hormone secretion induced by duloxetine in an elderly type 2 diabetic patient with painful diabetic neuropathy.

Diabetic neuropathy is the most common diabetic complication. Duloxetine, a serotonin noradrenaline reuptake inhibitor (SNRI), is widely used for the treatment of diabetic painful neuropathy (DPN) because of the efficacy and safety profile. Syndrome of inappropriate antidiuretic hormone secretion, which is strongly associated duloxetine, is a rare but occasionally life-threatening adverse effect. Here, we report a case of syndrome of inappropriate antidiuretic hormone secretion that rapidly developed after starting duloxetine in an elderly Japanese female type 2 diabetes mellitus patient. Furthermore, we discuss the possible relationship between the onset of syndrome of inappropriate antidiuretic hormone secretion and the gene polymorphism of cytochrome P450 isoform 1A2 and 2D6, both of which are responsible for duloxetine metabolism.