Nivolumab has promising efficacy for treating various advanced malignant tumors, although it has been reported to induce a wide range of autoimmune adverse effects. We herein report the case of a ...patient with metastatic lung adenocarcinoma who developed adrenal insufficiency after 12 cycles of nivolumab treatment. Endocrine test results supported a diagnosis of isolated adrenocorticotropic hormone deficiency due to hypophysitis, and replacement therapy using hydrocortisone has been successful. Although hypophysitis is a rare immune-related adverse event that is associated with nivolumab therapy, clinical awareness is essential, as this condition can be life-threatening and requires prompt treatment.
We herein report the case of a 38-year-old Japanese woman with antithyroid arthritis syndrome who experienced severe migratory polyarthritis after the initiation of thiamazole therapy. The patient's ...symptoms promptly disappeared without any sequelae after the withdrawal of the drug. Antithyroid arthritis syndrome is poorly characterized, and the findings from our literature review indicate that this syndrome exhibits serological features that are distinct from those of antithyroid agent-induced vasculitis syndrome. The absence of autoantibodies, especially anti-neutrophil cytoplasmic antibodies, may help characterize and diagnose antithyroid arthritis syndrome. Furthermore, physicians' awareness of this syndrome is essential for its diagnosis in clinical practice.
Ghrelin, an endogenous ligand for the GH secretagogue receptor, was
isolated from rat stomach and is involved in a novel system for
regulating GH release. Although previous studies in rodents suggest
...that ghrelin is also involved in energy homeostasis and that ghrelin
secretion is influenced by feeding, little is known about plasma
ghrelin in humans. To address this issue, we studied plasma
ghrelin-like immunoreactivity levels and elucidated the source of
circulating ghrelin and the effects of feeding state on plasma
ghrelin-like immunoreactivity levels in humans. The plasma ghrelin-like
immunoreactivity concentration in normal humans measured by a specific
RIA was 166.0 ± 10.1 fmol/ml. Northern blot analysis of various
human tissues identified ghrelin mRNA found most abundantly in the
stomach and plasma ghrelin-like immunoreactivity levels in totally
gastrectomized patients were reduced to 35% of those in normal
controls. Plasma ghrelin-like immunoreactivity levels were increased by
31% after 12-h fasting and reduced by 22% immediately after
habitual feeding. In patients with anorexia nervosa, plasma
ghrelin-like immunoreactivity levels were markedly elevated compared
with those in normal controls (401.2 ± 58.4 vs.
192.8 ± 19.4 fmol/ml) and were negatively correlated with body
mass indexes. We conclude that the stomach is a major source of
circulating ghrelin and that plasma ghrelin-like immunoreactivity
levels reflect acute and chronic feeding states in humans.
Ghrelin, an endogenous ligand for growth hormone secretagogue (GHS) receptor originally isolated from the stomach, occurs in the hypothalamic arcuate nucleus and may play a role in energy ...homeostasis. Synthetic GHSs have activated the hypothalamic arcuate neurons containing neuropeptide Y (NPY), suggesting the involvement of NPY in some of ghrelin actions. This study was designed to elucidate the role of ghrelin in the regulation of food intake. A single intracerebroventricular (ICV) injection of ghrelin (5-5,000 ng/rat) caused a significant and dose-related increase in cumulative food intake in rats. Ghrelin (500 ng/rat) was also effective in growth hormone-deficient spontaneous dwarf rats. Hypothalamic NPY mRNA expression was increased in rats that received a single ICV injection of ghrelin (500 ng/rat) (approximately 160% of that in vehicle-treated groups, P < 0.05). The ghrelin's orexigenic effect was abolished dose-dependently by ICV co-injection of NPY Y1 receptor antagonist (10-30 microg/rat). The leptin-induced inhibition of food intake was reversed by ICV co-injection of ghrelin in a dose-dependent manner (5-500 ng/rat). Leptin reduced hypothalamic NPY mRNA expression by 35% (P < 0.05), which was abolished by ICV co-injection of ghrelin (500 ng/rat). This study provides evidence that ghrelin is an orexigenic peptide that antagonizes leptin action through the activation of hypothalamic NPY/Y1 receptor pathway.
Ghrelin is a recently identified endogenous ligand for the GH
secretagogue receptor and is involved in a novel system for regulating
GH release. However, little is known about its GH-releasing ...activity
and other endocrine effects in humans. To address this issue, we
studied the GH, ACTH, cortisol, PRL, LH, FSH, and TSH responses to
synthetic human ghrelin. In four normal male adults (28–37 yr), iv
ghrelin administration released GH in a dose-dependent manner and 0.2,
1.0, and 5.0 μg/kg ghrelin produced 43.3 ± 6.0, 81.5 ± 12.7, and
107.0 ± 10.7 ng/mL of the GH peak values at 30 min, respectively.
ACTH, cortisol, and PRL levels were also elevated after ghrelin
injection, while the lowest dose (0.2 μg/kg) resulted in only minimum
peak values of these hormones (22.8 ± 3.0 pg/mL, 9.4 ± 1.9 μg/dL,
and 4.6 ± 0.6 ng/mL, respectively). There were no significant changes
in LH, FSH, or TSH levels. This is the first study showing evidence
that ghrelin strongly stimulates GH release in humans.
Ghrelin is a novel hormone that possesses growth hormone (GH)-releasing, cardiovascular, and metabolic activities. Ghrelin is a unique acylated polypeptide, and the naked peptide, desacyl ghrelin, ...does not have the activity. This study examines plasma ghrelin concentrations in 41 patients with mild to severe renal diseases. Two kinds of radioimmunoassays were used: amino-terminal immunoreactivity represents ghrelin alone (N-IR), and carboxyl-terminal immunoreactivity corresponds to the sum of both ghrelin and desacyl ghrelin (C-IR). In all subjects, the plasma N-IR was much smaller than the C-IR, indicating that desacyl ghrelin predominates over ghrelin in the circulation. The plasma C-IR, but not N-IR, was significantly correlated with the serum creatinine level and was increased 2.8-fold in patients with end-stage renal disease compared with those in patients with normal renal function. The plasma GH concentration was significantly correlated with the plasma N-IR and the C-IR, as well as with the serum creatinine level. Bilateral nephrectomy in mice caused marked increase in the plasma C-IR without significant changes in the local C-IR and ghrelin mRNA level in the stomach, which is the main site of ghrelin production. These findings suggest that circulating ghrelin concentrations play a role in the regulation of blood GH concentrations and that the kidney is an important site for clearance and/or degradation of desacyl ghrelin. Furthermore, elevation of blood GH levels in renal failure seems to be caused by a mechanism other than alteration in the circulating ghrelin concentration.
Background
The 99th percentile of cardiac troponin I level in the general population is accepted as the cut‐off for the diagnosis of acute myocardial infarction (AMI). However, it is not clear ...whether the cut‐offs derived in racially and geographically different populations are applicable in Japan.
Methods
Troponin I was determined using the Abbott ARCHITECT STAT high‐sensitive troponin I immunoassay in 698 apparently healthy individuals who visited the Japanese Red Cross Medical Center for a health checkup.
Results
The 99th percentile of the hsTnI in the overall population was 22.5 (95% confidence interval (CI), 16.8‐36.6) pg/mL, 17.7 (95% CI 12.0‐22.8) pg/mL for females and 30.6 (95% CI 17.1‐53.4) pg/mL for males. The median of the hsTnI in the overall population was 3.2 (95% CI, 3.0‐3.3) pg/mL, 2.6 (95% CI 2.4‐2.8) pg/mL for females and 4.0 (95% CI 3.8‐4.3) pg/mL for males. The age and gender had a significant influence on these values. The troponin I level also showed significant associations with the body mass index (BMI), the gamma glutamyl transferase (GGT), lactate dehydrogenase (LDH), estimated glomerular filtration rate (eGFR), and cardiac abnormalities by electrocardiography (ECG) but not with the high‐sensitive C‐reactive protein (hsCRP) level.
Conclusions
The 99th percentiles of the troponin I measured in the general population in Japan were comparable as the ones derived in the US, Germany, and Singapore. The troponin I level was dependent on the gender, age, BMI, and cardiac abnormalities found by ECG but not by the hsCRP level.
Ghrelin, a 28-amino acid acylated peptide, displays strong GH-releasing activity in concert with GHRH. The fatty acid modification of ghrelin is essential for the actions, and des-acyl ghrelin, which ...lacks the modification, has been assumed to be devoid of biological effects. Some recent reports, however, indicate that des-acyl ghrelin has effects on cell proliferation and survival. In the present study, we generated two lines of transgenic mice bearing the preproghrelin gene under the control of chicken β-actin promoter. Transgenic mice overexpressed des-acyl ghrelin in a wide variety of tissues, and plasma des-acyl ghrelin levels reached 10- and 44-fold of those in control mice. They exhibited lower body weights and shorter nose-to-anus lengths, compared with control mice. The serum GH levels tended to be lower, and the serum IGF-I levels were significantly lower in both male and female transgenic mice than control mice. The responses of GH to administered GHRH were normal, whereas those to administered ghrelin were reduced, especially in female transgenic mice, compared with control mice. These data suggest that overexpressed des-acyl ghrelin may modulate the GH-IGF-I axis and result in small phenotype in transgenic mice.
Ghrelin is a novel growth hormone-releasing peptide with a unique acylated structure. Here we reveal that prepro-ghrelin gene is expressed in the mouse kidney and glomerulus. We also show by ...reverse-phase high performance liquid chromatography coupled with radioimmunoassay that the mouse kidney does produce ghrelin. The ghrelin immunoreactivity in the mouse kidney is 6.79±0.48 fmol/mg (
n=5), which is much more abundant than that in the mouse plasma of 0.339±0.029 fmol/μl (
n=6). Furthermore, prepro-ghrelin gene is expressed in cultured rat mesangial cells, fibroblast-like NRK-49F cells and mouse podocytes, but not in rat epithelial cell-like NRK-52E cells. Ghrelin receptor gene is also expressed in the rat kidney. These findings demonstrate that the kidney, glomerulus and renal cells express prepro-ghrelin gene and ghrelin is produced locally in the kidney, and suggest the endocrine and/or paracrine roles of ghrelin in the kidney.
Ghrelin is an acylated peptide, whose lipid modification is essential for its biological activities. Previous studies demonstrated that it strongly stimulates GH release and has a potent orexigenic ...action. Meanwhile, there is enough evidence showing that feeding states influence plasma ghrelin levels. Fasting stimulates ghrelin secretion, and feeding reduces plasma ghrelin levels. In this study we examined the regulation of plasma ghrelin by fasting in genetically obese animals considering its molecular forms. Plasma levels of active form of ghrelin as well as those of total ghrelin were reduced in ob/ob and db/db mice compared with those in their control mice. Zucker fatty (fa/fa) rats also showed lower plasma ghrelin levels by fasting than the control rats. Insulin-induced hypoglycemia, however, stimulated ghrelin secretion in the fasted fatty rats. Moreover, glucose injection was revealed to reduce plasma ghrelin levels in rats. The effect of the severity of obesity on secretory regulation of ghrelin was also studied. Older fatty rats showed low plasma ghrelin levels even after 48-h fasting. These data suggest that the short-term secretory regulation of total ghrelin and the active form of ghrelin is delayed in obese animals and that blood glucose levels may be involved in the delayed regulation.
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