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

BackgroundImmune 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.MethodThis 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.ResultThe 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.ConclusionEndocrine-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

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

Administration of RAS Inhibitor before the Onset of Diabetic Nephropathy Counteracts the Adverse Effect of Chronic Hyperglycemia and Reduces the Augmentation of Urinary Albumin Excretion: A Retrospective Clinical Study

It is very important to explore how we can reduce urinary albumin excretion which is an independent risk factor for ischemic heart disease. In this study, we retrospectively evaluated the effects of RAS inhibitor therapy on diabetic nephropathy in Japanese subjects whose urinary albumin levels were within normal range. We enrolled 100 subjects with type 2 diabetes who did not take any renin-angiotensin system (RAS) inhibitor. We defined the subjects taking RAS inhibitor for more than 3 years as RAS inhibitor group. RAS inhibitor exerted protective effect on the progression of urinary albumin excretion in subjects with type 2 diabetes without diabetic nephropathy. In addition, RAS inhibitor exerted more protective effects on renal function especially in subjects with poor glycemic control. In conclusion, RAS inhibitor could protect renal function against the deleterious effect of chronic hyperglycemia in Japanese subjects with type 2 diabetes even before the onset of diabetic nephropathy

A case of tamoxifen-induced hypertriglyceridemia monitoring the changes in lipoprotein fractions over time

Abstract Background Tamoxifen, which is one of the selective estrogen receptor modulators (SERMs), can bring out life-threatening complication, e.g. hypertriglyceridemia-induced acute pancreatitis, although it is rare. We precisely report changes in lipoprotein metabolism before and after tamoxifen discontinuation because there have been few reports of it. Case presentation 47-year-old premenopausal woman with dyslipidemia, type 2 diabetes, nonalcoholic fatty liver disease and chronic kidney disease was prescribed tamoxifen as adjuvant therapy after operation of breast cancer. She experienced severe tamoxifen-induced hypertriglyceridemia several months after dosing tamoxifen. Before cessation of tamoxifen, lipoprotein fraction test revealed marked stagnation of VLDL and IDL metabolisms, resulting in severe hypertriglyceridemia (serum triglyceride level was 1881 mg/dL). Seven days after tamoxifen withdrawal, lipoprotein fraction test showed that the metabolisms of endogenous lipoproteins were changed drastically. Conclusions From these results, we confirmed that tamoxifen certainly changes lipoprotein metabolism through suppression of post-heparin lipolytic activity. It is very important to evaluate the balance between benefit and risk before dosing tamoxifen and survey lipid profiles constantly during treatment to avoid life-threatening complication when prescription of tamoxifen is planned

Eicosapentaenoic acid increases proportion of type 1 muscle fibers through PPARδ and AMPK pathways in rats

Summary: Muscle fiber type composition (% slow-twitch and % fast-twitch fibers) is associated with metabolism, with increased slow-twitch fibers alleviating metabolic disorders. Previously, we reported that dietary fish oil intake induced a muscle fiber-type transition in a slower direction in rats. The aim of this study was to determine the functionality of eicosapentaenoic acid (EPA), a unique fatty acid in fish oil, to skeletal muscle fiber type and metabolism in rats. Here, we showed that dietary EPA promotes whole-body oxidative metabolism and improves muscle function by increasing proportion of slow-twitch type 1 fibers in rats. Transcriptomic and metabolomic analyses revealed that EPA supplementation activated the peroxisome proliferator-activated receptor δ (PPARδ) and AMP-activated protein kinase (AMPK) pathways in L6 myotube cultures, which potentially increasing slow-twitch fiber share. This highlights the role of EPA as an exercise-mimetic dietary component that improves metabolism and muscle function, with potential benefits for health and athletic performance

Effect of Tofogliflozin on Body Composition and Glycemic Control in Japanese Subjects with Type 2 Diabetes Mellitus

Sodium-glucose cotransporter 2 inhibitor tofogliflozin is a new type of antidiabetic drug for individuals with type 2 diabetes mellitus (T2DM). The aim of this study was to examine in which type of individuals and/or under which conditions tofogliflozin could exert more beneficial effects on body composition and/or glycemic control in Japanese individuals with T2DM. We retrospectively evaluated the effects of tofogliflozin on body composition and/or glycemic control in individuals with T2DM who newly started taking tofogliflozin. After tofogliflozin treatment, body weight was significantly reduced and HbA1c levels were significantly decreased. Body fat mass, skeletal muscle mass, and skeletal muscle index, a marker for sarcopenia, were also reduced after the treatment. In univariate analyses, there was a statistically significant association between the decrease of HbA1c level after tofogliflozin treatment (Δ HbA1c) and the following parameters such as HbA1c levels at baseline, visceral fat area (VFA) at baseline, and reduction of VFA after the treatment (Δ VFA). Furthermore, in multivariate analyses, HbA1c levels at baseline and duration of diabetes were independently associated with Δ HbA1c. These results suggest that tofogliflozin would be more suitable for relatively obese individuals whose duration of diabetes is relatively short