A case of Cushing’s syndrome detected by repeated fragility fractures

A ３８-year-old woman had suffered from an avulsion fracture of the left cuboid bone, a rib fracture, a fatigue fracture of the left second metatarsal bone and a pubic fracture within the last ４ years. She also realized that her face was getting rounded and became aware of edema on extremities. She had repeated fragile fractures before menopause and was referred to our department on suspicion of secondary osteoporosis. The patients showed physical signs of moon face, central obesity, and abdominal violaceous striae. Cushing’s syndrome was suspected, therefore confirmatory studies were performed. Circadian variation of cortisol : serum cortisol１９．３μg／dL（at７：００）, ２１．４μg／dL（at２３：００）, urinary free cortisol :２４７．４μg／２４h, ACTH :２．５pg／mL. Low-dose（１mg） dexamethasone did not suppress cortisol level（１８．９μg/dL）. Based on these findings, we diagnosed as Cushing’s syndrome and glucocorticoid excess seemed to be the cause of secondary osteoporosis. Abdominal CT identified a ２．７ cm tumor in the left adrenal gland, and in-phase T１‐weighted MRI showed decreased signal compared to out-phase, suggesting an adrenocortical adenoma. She underwent laparoscopic left adrenalectomy. Postoperative fasting serum cortisol decreased to２．２ μg/dL, and glucocorticoid replacement therapy was started. It is necessary to find out any secondary causes for premenopausal women with fragility fractures. It is well known that endocrine disorders including Cushing’s syndrome are the most frequent associated diseases in patients with premenopausal osteoporosis. Cushing’s syndrome should be considered as a causative disease in premenopausal women with osteoporosis

Adult T-cell leukemia/lymphoma with multiple intracranial masses and CMV and HHV-6 reactivation at initial presentation

症例は55歳，男性。1ヶ月前からの咽頭痛の精査目的で紹介された。意識障害と項部硬直，口腔内の多発性有痛性潰瘍，全身に米粒大の紅斑を認めた。白血球数7,910/μL (異常リンパ球2%)，LDH 203U/L，補正カルシウム11.2mg/dL,可溶性IL-2受容体11,800U/mL，サイトメガロウイルス抗原(C10，C11)43/49。末梢血や骨髄，皮膚にCD4，25陽性の異常リンパ球あり，末梢血でHTLV-1プロウイルスDNAのモノクローナルな組み込みを確認し，成人T細胞白血病リンパ腫(ATLL)と診断した。CTで，脳実質内にリング状造影効果を有する腫瘤が多発し，髄液検査で細胞数1,320/mm3 (フローサイトメトリー法でATLL細胞が79%)，蛋白244mg/dL，HHV-6 DNA陽性を認めた。ヘルペスウイルス属感染症に対する治療や髄注を併用してmodified LSG15療法を行うも，意識障害が急速に進行し，入院21日目で死亡した。ATLLでは，中枢神経浸潤のさらなる病態の解明と標準治療の確立が求められる。A 55-year-old man, suffering from a sore throat for a month was referred to our hospital. Physical examination revealed disturbance of consciousness, nuchal rigidity, painful multiple ulcers in the oral cavity and rice grain sized erythema on the whole body. Hematological examination showed the following: white blood cell 7,910/μL (abnormal lymphocytes 2%), LDH 203U/L, corrected calcium 11.2mg/dL, soluble IL-2 receptor 11,800U/mL, and cytomegalovirus antigenemia (C10,C11) 43/49. Abnormal lymphocytes (CD4+CD25+) were found in the peripheral blood, bone marrow and skin samples. Southern blotting of peripheral blood confirmed monoclonal integration of HTLV-1 provirus DNA, consequently, he was diagnosed with adult T-cell leukemia/lymphoma (ATLL). Contrast-enhanced computed tomography revealed multiple tumors with ringed contrast effect in the brain parenchyma. Examination of the cerebrospinal fluid showed that the cell number was 1,320/mm3 (ATLL cells were 79% in flow cytometry), and the protein level was 244mg/dL; further, the examination revealed a positive result for human herpesvirus 6 DNA. Although treatment for herpesvirus genus and modified LSG15 therapy combined with intrathecal chemotherapy were performed, the patient became comatose, and he died on day 21 of hospitalization. A deeper understanding of the pathogenesis of and the establishment of standard treatment for ATLL with CNS involvement are required

Phase angle and extracellular water-to-total body water ratio estimated by bioelectrical impedance analysis are associated with levels of hemoglobin and hematocrit in patients with diabetes

Background: Anemia is one of the common complications of diabetes and is associated with mortality. Phase angle (PhA), ratio of extracellular water to total body water (ECW/TBW) and skeletal muscle mass index (SMI) estimated by bioelectrical impedance analysis (BIA) have been used as prognostic indicators for various chronic diseases and frailty. We aimed to clarify the clinical significance of PhA, ECW/TBW and SMI for anemia in patients with diabetes. Materials and methods: The values of PhA, ECW/TBW and SMI were estimated by a portable BIA device and blood samples were collected in 371 Japanese patients with diabetes. The relationships of PhA, ECW/TBW and SMI with hemoglobin (Hgb) and hematocrit (Hct) were statistically evaluated. Results: In simple linear regression analysis, PhA and SMI were positively correlated with Hgb and Hct levels in total subjects, male subjects and female subjects. In contrast, ECW/TBW was negatively correlated with Hgb and Hct levels regardless of sex. Multivariate regression analysis showed that both PhA and ECW/TBW but not SMI independently contributed to Hgb and Hct levels after adjustment of clinical confounding factors in both males and females. Conclusions: PhA and ECW/TBW but not SMI were associated with levels of Hgb and Hct in patients with diabetes. Therefore, aberrant values of PhA and ECW/TBW suggest a risk of anemia in diabetic patients

Systemic amyloidosis by LPL

We present the case of an 81-year-old woman with right shoulder discomfort and right supraclavicular lymph node swelling who referred to our hospital. Blood tests results showed normal immunoglobulin levels, but free light chain assay showed abnormal κ/λ ratio. Serum immunoelectrophoresis detected immunoglobulin G-λ type M proteins. 18F-fluorodeoxyglucose computed tomography revealed swelling of the right supraclavicular and mediastinal lymph nodes. Biopsy of the right supraclavicular lymph node showed a mixture of small lymphocytes with plasma cell-like round cells that were positive for cell surface CD20, CD138, CD56, IgG and λ, and negative for transthyretin and amyloid A. They had a Congo red stain-positive, glass-like surrounding structure and apple-green birefringence was observed under polarized light. Duodenal, gastric, and skin biopsies also showed amyloid deposits. We diagnosed the patient with lymphoplasmacytic lymphoma complicated by systemic light-chain amyloidosis. Rituximab monotherapy led to complete metabolic response. Systemic amyloidosis is a rare complication of B-cell lymphoma; however, the possibility of amyloidosis should be considered, even in patients with lymphadenopathy

Cross-Sectional and Longitudinal Associations between Skin Autofluorescence and Tubular Injury Defined by Urinary Excretion of Liver-Type Fatty Acid-Binding Protein in People with Type 2 Diabetes

It has previously been unclear whether the accumulation of advanced glycation end products, which can be measured using skin autofluorescence (SAF), has a significant role in diabetic kidney disease (DKD), including glomerular injury and tubular injury. This study was therefore carried out to determine whether SAF correlates with the progression of DKD in people with type 2 diabetes (T2D). In 350 Japanese people with T2D, SAF values were measured using an AGE Reader®, and both urine albumin-to-creatinine ratio (uACR), as a biomarker of glomerular injury, and urine liver-type fatty acid-binding protein (uLFABP)-to-creatinine ratio (uL-FABPCR), as a biomarker of tubular injury, were estimated as indices of the severity of DKD. Significant associations of SAF with uACR (p p p p p p p = 0.026). In conclusion, SAF is positively correlated with uL-FABP but not with uACR in people with T2D. Thus, there is a possibility that SAF can serve as a novel predictor for the development of diabetic tubular injury

Dehydroepiandrosterone Sulfate, an Adrenal Androgen, Is Inversely Associated with Prevalence of Dynapenia in Male Individuals with Type 2 Diabetes

Dehydroepiandrosterone sulfate (DHEAS) is thought to be associated with life expectancy and anti-aging. Although skeletal muscle disorders are often found in diabetic people, the clinical significance of DHEAS in skeletal muscle remains unclear. Therefore, we aimed to determine whether DHEAS is associated with the development of skeletal muscle disorders in individuals with type 2 diabetes (T2D). A cross-sectional study was conducted in 361 individuals with T2D. Serum DHEAS levels, skeletal muscle mass index (SMI), handgrip strength (HS), and gait speed (GS) were measured in the participants. Pre-sarcopenia, sarcopenia, and dynapenia were defined according to the definitions of the AWGS 2019 criteria. DHEAS level was positively associated with HS but not with SMI or GS after adjustment of confounding factors. Multiple logistic regression analyses in total subjects showed that DHEAS level had an inverse association with the prevalence of dynapenia but not with the prevalence of pre-sarcopenia or sarcopenia. Furthermore, a significant association between DHEAS level and dynapenia was found in males but not in females. ROC curve analysis indicated that cutoff values of serum DHEAS for risk of dynapenia in males was 92.0 μg/dL. Therefore, in male individuals with T2D who have low serum levels of DHEAS, adequate exercise might be needed to prevent dynapenia

Causes of In-Hospital Death and Pharmaceutical Associations with Age of Death during a 10-Year Period (2011–2020) in Individuals with and without Diabetes at a Japanese Community General Hospital

Since diabetes and its complications have been thought to exaggerate cardiorenal disease, resulting in a short lifespan, we investigated causes of death and lifespans in individuals with and without diabetes at a Japanese community general hospital during the period from 2011 to 2020. Causes of death and age of death in individuals with and those without diabetes were compared, and associations between medications used and age of death were statistically analyzed. A total of 2326 deaths were recorded during the 10-year period. There was no significant difference between the mean ages of death in individuals with and those without diabetes. Diabetic individuals had higher rates of hepato-pancreatic cancer and cardio-renal failure as causes of death. The prescription rates of antihypertensives, antiplatelets, and statins in diabetic individuals were larger than those in non-diabetic individuals. Furthermore, the use of sulfonyl urea or glinides and insulin was independently and inversely associated with the age of death. In conclusion, individuals with diabetes were treated with comprehensive pharmaceutical interventions and had life spans comparable to those of individuals without diabetes. This study’s discovery of an inverse relationship between the use of insulin secretagogues or insulin and the age of death suggests that the prevention of life-threatening hypoglycemia is crucial for individuals with diabetes