Clinical implication of elevated CA 19-9 level and the relationship with glucose control state in patients with type 2 diabetes.

The aim is to investigate whether there is a difference in CA 19-9 levels between diabetes and healthy subjects except malignancies and associated factors with CA 19-9 in diabetes. We performed a retrospective analysis in 146 type 2 diabetes and 154 healthy subjects who visited our medical institution from 2005 to 2009. We compared the CA 19-9 in each group, and analyzed clinical and biochemical variables in diabetes. The average value of CA 19-9 in diabetes was higher than that of healthy subjects significantly (14.1 vs 8.1 U/mL, p < 0.01). CA 19-9 had a positive correlation with HbA1c (r = 0.22), fasting plasma glucose (r = 0.24), and C-reactive protein (r = 0.38) in diabetes (p < 0.05). 48 type 2 diabetes who showed decreased CA 19-9 during follow-up of 1.8 ± 1.0 years were also improved in glucose control state. The proportion of insulin use for glucose control was significantly higher in the group of CA 19-9 ≥ 37 U/mL (75.0 %) as compared with the group of CA 19-9 < 37 U/mL (34.0 %). CA 19-9 was significantly higher in the patients with diabetic peripheral neuropathy (DPN) as compared with those without DPN (p = 0.02). However, after excluding the influences from glycemic control state, significant difference was not observed. Our results indicate not only that CA 19-9 is influenced by glycemic control state but also can be elevated irrespective of any malignancy in diabetes. Therefore, CA 19-9 should be interpreted carefully in diabetic patients when CA 19-9 is used as the tool for malignancy screening.

Subacute thyroiditis presenting as acute psychosis: a case report and literature review.

We describe herein an unusual case of subacute thyroiditis presenting as acute psychosis. An 18-year-old male presented at the emergency department due to abnormal behavior, psychomotor agitation, sexual hyperactivity, and a paranoid mental state. Laboratory findings included an erythrocyte sedimentation rate of 36 mm/hr (normal range, 0 to 9), free T4 of 100.0 pmol/L (normal range, 11.5 to 22.7), and thyroid stimulating hormone of 0.018 mU/L (normal range, 0.35 to 5.5). A technetium-99m pertechnetate scan revealed homogeneously reduced activity in the thyroid gland. These results were compatible with subacute thyroiditis, and symptomatic conservative management was initiated. The patient's behavioral abnormalities and painful neck swelling gradually resolved and his thyroid function steadily recovered. Although a primary psychotic disorder should be strongly considered in the differential diagnosis, patients with an abrupt and unusual onset of psychotic symptoms should be screened for thyroid abnormalities. Furthermore, transient thyroiditis should be considered a possible underlying etiology, along with primary hyperthyroidism.

Type B insulin-resistance syndrome presenting as autoimmune hypoglycemia, associated with systemic lupus erythematosus and interstitial lung disease.

We describe an unusual case of systemic lupus erythematosus with pulmonary manifestations presenting as hypoglycemia due to anti-insulin receptor antibodies. A 38-year-old female suffered an episode of unconsciousness and was admitted to hospital where her blood glucose was found to be 18 mg/dL. During the hypoglycemic episode, her serum insulin level was inappropriately high (2,207.1 pmol/L; normal range, 18 to 173) and C-peptide level was elevated (1.7 nmol/L; normal range, 0.37 to 1.47). Further blood tests revealed the presence of antinuclear antibodies, anti-double-stranded DNA antibodies, and anti-Ro/SSA, anti-La/SSB, anti-ribonucleoprotein, and anti-insulin receptor antibodies. A computed tomography scan of the abdomen, aimed at tumor localization, such as an insulinoma, instead revealed ground-glass opacities in both lower lungs, and no abnormal finding in the abdomen. For a definitive diagnosis of the lung lesion, video-associated thoracoscopic surgery was performed and histopathological findings showed a pattern of fibrotic non-specific interstitial pneumonia.

The protective effects of DA-9801 (Dioscorea extract) on the peripheral nerves in streptozotocin-induced diabetic rats.

It has been reported that DA-9801, an extract mixture of Dioscorea japonica Thunb and Dioscorea nipponica Makino, produces a neurotrophic activity. Therefore, this study was conducted to examine the neuroprotective effects of DA-9801 in streptozotocin-induced diabetic rats. The experimental rats were divided into six groups: the control group, Group I (non-diabetic rats treated with DA-9801), Group II (diabetic, non-treated rats) and Groups III, IV, and V (diabetic rats treated with DA-9801 at doses of 10, 50 or 100 mg/kg/d). Following a 16-wk course of oral treatment with DA-9801, functional parameters (von Frey filament test, hot plate test), biochemical parameters (nerve growth factor (NGF), tumor necrosis factor (TNF)-α, interleukin (IL)-6) were measured. An immunohistochemical staining was done to assess the neuroprotective effects of DA-9081 in the skin, sciatic nerve, gastric mucosa and renal cortex. In Week 8, pain was evoked by either tactile or thermal stimuli, whose threshold was significantly higher in Group III, IV and V than Group II. Western blot analysis showed a more significant increase in NGF and decrease in TNF-α and IL-6 in Group III, IV and V than in Group II (p<0.05). Moreover, following the treatment with DA-9801, a loss of intraepidermal nerve fibers (IENFs) was inhibited to a significant level in the skin, myelinated axonal fibers of the sciatic nerve and small nerve fibers innervating the gastric mucosa or renal cortex (p<0.05). Our results demonstrated that DA-9801 is a beneficial agent that protects the peripheral nerves in diabetic rats.

Mainly adrenal gland involving NK/T-cell nasal type lymphoma diagnosed with delay due to mimicking adrenal hemorrhage.

A 29-yr-old man, presented with abdominal pain and fever, had an initial computed tomography (CT) scan revealing low attenuation of both adrenal glands. The initial concern was for tuberculous adrenalitis or autoimmune adrenalitis combined with adrenal hemorrhage. The patient started empirical anti-tuberculous medication, but there was no improvement. Enlargement of cervical lymph nodes were developed after that and excisional biopsy of cervical lymph nodes was performed. Pathological finding of excised lymph nodes was compatible to NK/T-cell lymphoma. The patient died due to the progression of the disease even after undergoing therapeutic trials including chemotherapy. Lymphoma mainly involving adrenal gland in the early stage of the disease is rare and the vast majority of cases that have been reported were of B-cell origin. From this case it is suggested that extra-nodal NK/T-cell lymphoma should be considered as a cause of bilateral adrenal masses although it is rare.

Neuroprotective effect of the glucagon-like peptide-1 receptor agonist, synthetic exendin-4, in streptozotocin-induced diabetic rats.

BACKGROUND AND PURPOSE: Glucagon-like peptide-1 (GLP-1) receptors are widely expressed in neural tissues and diminish neuronal degeneration or induce neuronal differentiation. The aim of this study was to investigate the effect of the GLP-1 pathway on peripheral nerves in streptozotocin-induced diabetic rats. EXPERIMENTAL APPROACH: Diabetic and nondiabetic rats were treated with the GLP-1 receptor agonist, synthetic exendin-4 (i.p., 1 nmol·kg(-1)·day(-1)) or placebo for 24 weeks, and current perception threshold values, cAMP levels and nerve fibre size in the sciatic nerve were measured. We also investigated GLP-1 receptor expression, quantitative changes in PGP9.5-positive intraepidermal nerve fibres and cleaved caspase 3-stained Schwann cells by immunohistochemistry. KEY RESULTS: GLP-1 receptor expression was detected in the sciatic nerve and skin. After exendin-4 treatment, the increase seen in current perception threshold values at 2000 and 250 Hz in diabetic rats was reduced. Also, the decrease in myelinated fibre size or axon/fibre area ratio in the sciatic nerve and the loss of intraepidermal nerve fibre in the skin of diabetic rats were ameliorated. These responses were closely associated with the attenuation of Schwann cell apoptosis and improvement in the cAMP level in exendin-4-treated diabetic rats, compared with placebo-treated animals. CONCLUSION AND IMPLICATIONS: Synthetic exendin-4 may prevent peripheral nerve degeneration induced by diabetes in an animal model, supporting the hypothesis that GLP-1 may be useful in peripheral neuropathy. The neuroprotection is probably attributable to GLP-1 receptor activation, antiapoptotic effects and restoration of cAMP content.

Effect of rimonabant, the cannabinoid CB1 receptor antagonist, on peripheral nerve in streptozotocin-induced diabetic rat.

The aim of this study is to investigate the effect of rimonabant, which has antiatherosclerotic and antiinflammatory properties, on peripheral neuropathy in a diabetic rat. Diabetic rat models were induced by treatment with streptozotocin and then either normal or diabetic rats were treated with an oral dose of 10mg/kg/day rimonabant or placebo for 24 weeks. We quantified the densities of intraepidermal (PGP9.5+) nerve fiber and total skin (RECA-1+) capillary length. We also measured the current perception threshold, as defined by the intensity of sine-wave stimulus, skin blood flow after treadmill running and TNF-alpha level in spinal cord tissue or plasma. After 24 weeks, rimonabant reduced the body weight and food intake in both diabetic and normal rats, but it had no effect on blood sugar levels. In addition, rimonabant treatment significantly improved the decreased intraepidermal nerve fiber density (5.53+/-0.12 vs. 4.36+/-0.27/mm, P<0.05) and alleviated the increased current perception threshold in rimonabant-treated versus control diabetic rats. These responses were closely associated with the attenuation of skin capillary loss (1.98+/-0.07 vs. 1.67+/-0.10 mm/mm(2), P<0.05), increase in skin blood flow (14.93+/-1.08 vs. 12.07+/-0.87 TPU, P<0.05) and reduction in TNF-alpha level in tissue (70.10+/-4.99 vs. 91.18+/-3.34 pg/mg, P<0.05) in rimonabant-treated diabetic rats compared with placebo. These findings suggest that rimonabant can be beneficial for treatment of diabetic peripheral neuropathy, possibly due to its potential role in micro- and macrovessel protection and its anti-inflammatory properties.

Effect of cartilage oligomeric matrix protein angiopoietin-1 on peripheral nerves in db/db diabetic mice.

BACKGROUND: Vascular and inflammatory processes have been reported to be factors in the pathogenesis of diabetic neuropathy. Angiopoietin-1 (Ang1) plays essential roles in regulating vascular growth, development, maturation, permeability, and inflammation. OBJECTIVE: The aim of this study was to investigate the effect of cartilage oligomeric matrix protein (COMP)-Ang1, which is a soluble, stable, potent Ang1 variant, on peripheral nerves in db/db diabetic mice. METHODS: The db/db diabetic mice were randomized into 2 groups based on their weight and glucose level and treated with recombinant adenovirus (Ade), expressing either COMP-Ang1 or the ß-galactosidase gene (LacZ) (control), for 8 weeks. Immunohistochemistry was performed using a polyclonal antibody of antiprotein gene product and a secondary antibody. Intraepidermal nerve fiber density (IENFD) was quantified as nerve fiber abundance per unit length of epidermis (IENF/mm). In addition, the total capillary length (TCL) per unit length of epidermis was summed (mm/mm(2)). All slides were coded and the capillary length and the number of nerve fibers were calculated by a blinded observer. RESULTS: Ten diabetic db/db mice (mean [SD] weight, 38.7 [1.95] g) were randomized to receive Ade-COMP-Ang1 or Ade-LacZ. IENFD was significantly greater in the Ade-COMP-Ang1 group compared with the Ade-LacZ group (mean [SD] 8.95 [3.30] vs 3.57 [0.73]/mm; P < 0.05). TCL was also significantly greater in the Ade-COMP-Ang1 group (2.79 [0.99] vs 2.04 [0.58] mm/mm(2); P < 0.05). Compared with baseline, fasting blood glucose concentration after 8 weeks of treatment decreased significantly more in the Ade-COMP-Ang1 group than in the Ade-LacZ group (489 [45] to 361 [81] vs 495 [48] to 521 [70] mg/dL; P < 0.05). CONCLUSIONS: These results suggest that Ade-COMP-Ang1 might have had proliferative effects on peripheral nerve and cutaneous capillaries in this small animal study. Further investigation of the metabolic effect, target site, and related mediator of COMP-Ang1 is needed.

A case of a ruptured pheochromocytoma with an intratumoral aneurysm managed by coil embolization.

Although the spontaneous rupture of adrenal pheochromocytoma is rare, it can be lethal because it can induce serious changes in the circulation. We describe a 32 year old man with bilateral pheochromocyroma presenting as abdominal pain. In the emergency room, an abdominal MRI showed an aneurysmal vessel in the right adrenal mass and accompanying hemorrhage around the tumor capsule. The bleeding site was found by transfemoral abdominal angiography. Coil embolization was done in the bleeding vessels, specifically branches of the right adrenal artery. The hemorrhage was successfully controlled and vital signs of the patient were restored. Following emergency care, biochemical and imaging studies showed compatible findings of a bilateral adrenal pheochromocytoma. Postoperative histologic findings confirmed these observations. A ruptured pheochromocytoma should be considered as a cause of acute abdomen in cases of a concomitant adrenal mass. Intratumoral aneurysmal bleeding may be a cause of ruptured tumor, and careful angiographic intervention will help to ensure safe control of bleeding in such an emergency situation, even in cases of bilateral tumor.