AMP-activated protein kinase (AMPK) is an important cellular fuel sensor. Activation of AMPK requires phosphorylation at threonine (Thr)-172, which resides in the activation loop of the alpha1 and alpha2 subunits. Several AMPK upstream kinases are capable of phosphorylating AMPK at Thr-172, including LKB1 and CaMKKbeta. AMPK has been implicated in the regulation of physiological signals, such as inhibition of cholesterol, fatty acid, protein synthesis, and enhancement of glucose uptake and blood flow. AMPK activation also exhibits several salutary effects on vascular function and improves vascular abnormalities. AMPK is activated by numerous drugs and xenobiotics. Some of these are in clinical use for the treatment of type 2 diabetes (e.g., metformin and thiazolidinediones), hypertension (e.g., nifedipine and losartan), and impaired blood flow (e.g., aspirin, statins, and cilostazol). Plant-derived xenobiotics or nutraceuticals that were claimed to have health benefits in diabetes or cancer have been reported to activate AMPK. These include resveratrol from red wine, epigallocatechin gallate from green tea, capsaicin from peppers, berberine, which is a yellow dye of the genus berberis, genistein from soy bean, and ginsenoside from ginseng panax. AMPK is also modulated by numerous hormones and cytokines that regulate energy balance at the whole body level, including leptin, adiponectin, ghrelin, and even thyroid hormones. This work shows that the precise mechanisms of AMPK kinase and AMPK interaction.
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BACKGROUND It is important to differentiate Graves' disease from that of painless thyroiditis in patients with thyrotoxicosis. In this study, we evaluated the usefulness of total T3 to free T4 ratio in making a differential diagnosis between Graves' disease and painless thyroiditis. METHODS: We reviewed medical records of thyrotoxic patients, who had been diagnosed with Graves' disease or painless thyroiditis, from October 2009 to July 2011. We assessed clinical characteristics, serum levels of total T3, free T4, thyroid stimulating hormone, thyrotropin-binding inhibitory immunoglobulin, and findings of 99mTechnetium thyroid scan. We analyzed the total T3/free T4 ratios between Graves' disease and painless thyroiditis patients. RESULTS: A total of 76 untreated thyrotoxic patients "49 Graves' disease and 27 painless thyroiditis" were examined. The total T3, free T4 levels and the total T3/free T4 ratios were significantly higher in patients with Graves' disease than in those with painless thyroiditis (P < 0.001). In the total T3/free T4 ratio > 73, the possibility of Graves' disease was significantly higher than in painless thyroiditis (sensitivity, 75.5%; specificity, 70.3%). The sensitivity and specificity of the total T3/free T4 ratio in patients with free T4 < 3.6 ng/dL have been increased (sensitivity, 100%; specificity, 71.4%). CONCLUSION: The total T3/free T4 ratios was useful for making a differential diagnosis between Graves' disease and painless thyroiditis.
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BACKGROUND Bilirubin prevents oxidative modification of low density lipoprotein, and may protect vessels from atherosclerosis. Several studies showed an inverse relationship between serum bilirubin and coronary artery disease. However, there are some needs to clarify the relationship between serum bilirubin and carotid atherosclerosis in type 2 diabetes, especially. METHODS: A total of 346 type 2 diabetic patients, between 35 and 95 years of age (146 men and 200 women), were studied. Subjects with normal serum total bilirubin were divided into two groups, according to their serum total bilirubin levels (group I, total bilirubin > or = 1.0 mg/dL [n = 59]; group II, total bilirubin < or = 0.5 mg/dL [n = 76]). Carotid intima-media thickness (IMT) and plaque scores were measured by ultrasonography. Carotid atherosclerosis was defined by the presence of plaque or more than 1 mm of common carotid IMT. RESULTS: Carotid IMT was positively correlated with age, duration of diabetes and hypertension, high sensitive C-reactive protein (hs-CRP) and fibrinogen, but, it was negatively correlated with bilirubin, gamma glutaryltransferase, albumin, hemoglobin, cystatin C and estimated-glomerular filtration rate (GFR) in all subjects. After controlling for sex, age and levels of hemoglobin, direct bilirubin only was negatively correlated with carotid IMT (r = -0.151, P = 0.034). Low serum total bilirubin group had a lot of female, long duration of diabetes and hypertension, higher hs-CRP, platelet counts, serum creatinine, HbA1c and homeostasis model assessment-insulin resistance, lower albumin, hemoglobin, estimated-GFR and quantitative insulin sensitivity check index. Carotid IMT and plaque scores were significantly greater in low serum bilirubin group (0.785 +/- 0.210 mm vs. 0.678 +/- 0.146 mm, P < 0.01; 1.95 +/- 2.56 vs. 1.03 +/- 1.40, P < 0.05, respectively) than in the high serum bilirubin group. Multivariate logistic regression analysis showed that age, serum albumin and total bilirubin were independent associated factors for carotid atherosclerosis in type 2 diabetic women. CONCLUSION: Total bilirubin is inversely correlated with carotid atherosclerosis in type 2 diabetic patients, and it is an independent associated factor for carotid atherosclerosis in women.
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BACKGROUND In approach to an adrenal incidentaloma, early exclusion of pheochromocytoma is clinically important, due to the risk of catecholamine crisis. The aims of this study are to investigate the characteristics of incidentally detected pheochromocytomas, compared with that of the other adrenal incidentalomas, and to compare these characteristics with those of symptomatic pheochromocytomas. METHODS: In this retrospective study, we reviewed the medical records of 198 patients with adrenal incidentaloma from 2001 to 2010. We analyzed the clinical, laboratory and radiological data of pheochromocytomas, in comparison with those of the other adrenal incidentalomas. We also compared the characteristics of these incidentally detected pheochromocytomas with the medical records of 28 pathologically proven pheochromocytomas, diagnosed based on typical symptoms. RESULTS: Among the 198 patients with adrenal incidentaloma, nineteen patients were diagnosed with pheochromocytoma. Pheochromocytomas showed larger size and higher Hounsfield unit at precontrast computed tomography (CT) than did non-pheochromocytomas. All pheochromocytomas were larger than 2.0 cm, and the Hounsfield units were 19 or higher in precontrast CT. When both criteria of size > 2.0 cm and Hounsfield unit > 19 were met, the sensitivity and specificity for the diagnosis of pheochromocytoma were 100% and 79.3%, respectively. Compared with patients with pheochromocytoma, diagnosed based on typical symptoms, patients with incidentally detected pheochromocytoma were older, presented less often with hypertension, and showed lower levels of 24-hour urine metanephrine. CONCLUSION: Adrenal incidentaloma with < 2.0 cm in size or < or = 19 Hounsfield units in precontrast CT imaging was less likely to be a pheochromocytoma. Patients with incidentally discovered pheochromocytoma showed lower catecholamine metabolites, compared with those patients with symptomatic pheochromocytoma.
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A 53-year-old woman was presented with several 0.3-0.6 cm-sized nodules within the right lobe of the thyroid. Histologic sections of the thyroid demonstrated multiple papillary microcarcinomas in the background of lymphocytic thyroiditis, with a small focus of Langerhans cell histiocytosis (LCH). Small LCH nodules were also found in the draining cervical lymph nodes. Although the association of LCH with papillary thyroid carcinoma in the thyroid has been reported, their co-existence with LCH in the draining lymph nodes is very rare.
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Hyperthyroidism is diagnosed when a patient is presented with typical symptoms, such as weight loss, palpitation, and hand tremor. However, early diagnosis is difficult in elders, because they have no typical symptoms, but only cardiovascular or muscular symptoms. In hyperthyroidism, there are often with neurologic changes, leading to various neurologic symptoms. Generalized or focal seizures are rarely reported in thyrotoxicosis and thyrotoxic crisis. Further, cases of hyperthyroidism presented as generalized seizure attack are extremely rare. We report a case of hyperthyroidism. A patient is presented at the hospital with mental change, as well as generalized seizure, who was finally diagnosed to have Graves' disease. A 56-year-old male was admitted to the hospital because of mental change with generalized seizure attack. Initial neurologic evaluations, including a brain magnetic resonance imaging and electroencephalogram proved to be normal. But, thyroid function test showed abnormal results. We diagnosed him as Graves' disease and prescribed anti-thyroid drug. Thereafter, there has been no recurrence of neurologic symptoms for 12 months.
A 30-year-old man was admitted to our hospital because of fatigue, palpitation and severe weakness of both legs. The admission laboratory findings revealed thyrotoxicosis, and 131I thyroid scintigraphic imaging revealed a low radioactive iodine uptake. He was treated for painless thyroiditis for about 4 months. However, thyrotoxic state had continued and radioactive iodine uptake was markedly increased in the follow up scan. Painless thyroiditis often relapses, but rarely develops into Graves' disease. This is a rare case in which painless thyroiditis was followed by Graves' disease.
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CATCH 22 is a medical acronym for cardiac defects, abnormal faces, thymic hypoplasia, cleft palate, and hypocalcemia, and a variable deletion on chromosome 22. It includes DiGeorge syndrome, conotruncal anomaly face syndrome, and velo-cardio-facial syndrome. It has a prevalence estimated at 1:3,000-1:6,000. Most deletions occur at de novo, but autosomal dominant inheritance is observed in 6-10% of cases. Hormonal disorders are common in patients with CATCH22 syndrome. While hypoparathyroidism was the predominant endocrine disturbance that has been documented in the DiGeorge syndrome, other hormonal defects, such as growth hormone deficiency, hypothyroidism, and hyperthyroidism have been occurred in patients with CATCH22 syndrome. The spectrum of parathyroid gland dysfunction in this syndrome ranges from severe neonatal hypocalcemia to normal parathyroid function. Most patients are usually diagnosed in young age, but a few patients with mild abnormality are presented later in life. We report a case of CATCH22 syndrome with normal parathyroid hormone and calcium level in an adult. The diagnosis of CATCH22 syndrome was confirmed by fluorescence in situ hybridization analysis.
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A 65-year-old man with diabetes mellitus was presented with left visual aura, followed by a versive seizure, each lasting approximately 3 minutes. Neurological examination showed an intermittent left homonymous hemianopsia. Brain magnetic resonance imaging (MRI) showed right occipital lobe lesion, with cytotoxic edema. Blood glucose was 593 mg/dL and serum osmolarity was 309 mOsm/kg. The seizures were controlled by normalization of blood sugar and short-term anticonvulsant, and the lesions were resolved in a follow-up MRI. We report a case of visual seizures associated with non-ketotic hyperglycemia.
A pheochromocytoma is a neuroectodermal tumor that originates from the chromaffin cells of the sympathetic system. It has typical symptoms or signs, such as periodic attacks of paroxysmal hypertension, palpitation, headache, and sweating, related to an increased catecholamine secretion. Types of catecholamine secreted from tumors are usually norepinephrine and epinerphrine. There are a few reports of dopamine-secreting pheochromocytoma with absence of other catecholamines secretion. Here, we report the case of a 59-year-old man with dopamine-secreting pheochromocytoma, with no typical symptoms or signs.
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The natural history of primary hyperparathyroidism, due to parathyroid adenoma, is unknown. Furthermore, spontaneous resolution of parathyroid necrosis or hemorrhage is rare and usually asymptomatic. Here, we report a case of parathyroid apoplexy of primary hyperparathyroidism, presenting as auditory hallucinations, accompanied with hypocalcemia. A 39-year-old man who was incidentally diagnosed with primary hyperparathyroidism, and waiting surgery for parathyroidectomy presented to psychiatric service with auditory hallucinations. He developed tetany, while taking psychiatric drugs. On a follow-up investigation, his serum calcium level fell from 11.8 to 5.8 mg/dL. His intact parathyroid hormone level also decreased from 1,017 pg/mL to 71.1 pg/mL. The parathyroid apoplexy was confirmed after a surgical removal of the infarcted adenoma. The auditory hallucinations disappeared, and serum calcium level was returned to within the normal range.
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