Nitin Trivedi

Downregulation of GLP-1 and GIP Receptor Expression by Hyperglycemia Possible Contribution to Impaired Incretin Effects in Diabetes

Stimulation of insulin secretion by the incretin hormones glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) has been found to be diminished in type 2 diabetes. We hypothesized that this impairment is due to a defect at the receptor level induced by the diabetic state, particularly hyperglycemia. Gene expression of incretin receptors, GLP-1R and GIPR, were significantly decreased in islets of 90% pancreatectomized (Px) hyperglycemic rats, with recovery when glucose levels were normalized by phlorizin. Perifused islets isolated from hyperglycemic Px rats showed reduced insulin responses to GLP-1 and GIP. To examine the acute effect of hyperglycemia on incretin receptor expression, a hyperglycemic clamp study was performed for 96 h with reduction of GLP-1 receptor expression but increase in GIP receptor expression. Similar findings were found when islets were cultured at high glucose concentrations for 48 h. The reduction of GLP-1 receptor expression by high glucose was prevented by dominant-negative protein kinase C (PKC)α overexpression, whereas GLP-1 receptor expression was reduced with wild-type PKCα overexpression. Taken together, GLP-1 and GIP receptor expression is decreased with chronic hyperglycemia, and this decrease likely contributes to the impaired incretin effects found in diabetes.

Successful Treatment of Thyroid Storm with Plasmapheresis in a Patient with Methimazole-Induced Agranulocytosis

OBJECTIVE To report a case of a patient with Graves disease presenting with agranulocytosis induced by methimazole, with subsequent thyroid storm and successful therapeutic use of plasmapheresis. METHODS The clinical features and laboratory findings in a patient with agranulocytosis and thyroid storm are presented, and the available literature on utilization of plasmapheresis in the setting of thyrotoxicosis is reviewed. RESULTS A 40-year-old Vietnamese woman with Graves disease was admitted with methimazole-induced agranulocytosis. Treatment with methimazole was discontinued, and therapy with antibiotics, granulocyte colony-stimulating factor, and ibuprofen was initiated. During hospitalization of the patient, her clinical status deteriorated, with development of pericarditis, thrombocytopenia, and thyroid storm. Treatment with plasmapheresis yielded near-euthyroidism in 3 days. Subsequently, she underwent successful total thyroidectomy. CONCLUSION Our case highlights the effectiveness of plasmapheresis when clinical situations prohibit the use of traditional treatment methods for thyrotoxicosis or thyroid storm (or both).

Challenges in the Management of Type 2 Diabetes Mellitus and Cardiovascular Risk Factors in Obese Subjects: What Is the Evidence and What Are the Myths?

The increasing worldwide prevalence of diabetes mellitus and obesity has projected concerns for increasing burden of cardiovascular morbidity and mortality. The dangers of obesity in adults and children have received more attention than ever in the recent years as more research data becomes available regarding the long-term health outcomes. Weight loss in obese and overweight subjects can be induced via intensive lifestyle modifications, medications, and/or bariatric surgery. These methods have been shown to confer overall health benefits; however, their effect on remission of preexisting diabetes mellitus and reduction in cardiovascular risk has been variable. Recent research data has offered a much better understanding of the pathophysiology and outcomes of these management strategies in obese patients. In this paper, the authors have summarized the results of major studies on remission of type 2 diabetes mellitus and reduction of cardiovascular events by weight loss induced by different methods. Furthermore, the paper aims to clarify various prevailing myths and practice patterns about obesity management among clinicians.

Tuberculosis of the Adrenal Gland: A Case Report and Review of the Literature of Infections of the Adrenal Gland

Infections of the adrenal glands remain an important cause of adrenal insufficiency, especially in the developing world. Indeed, when Thomas Addison first described the condition that now bears his name over 150 years ago, the vast majority of cases were attributable to tuberculosis. Here we describe a classic, but relatively uncommon, presentation in the United States of adrenal insufficiency followed by a review of the current literature pertaining to adrenal infections.

Glucagon-induced pheochromocytoma crisis.

OBJECTIVE To describe a previously asymptomatic woman who developed a glucagon-induced pheochromocytoma crisis during preparation for screening colonoscopy. METHODS We present the patients clinical features, laboratory and imaging findings, and outcome and review the related literature. RESULTS A 76-year-old woman received glucagon to inhibit intestinal motility before routine colonoscopy. She immediately developed severe hypertension, cardiac arrhythmia, and altered mental status. Her hospital course was complicated by encephalopathy and cardiac, respiratory, renal, and hepatic failure. Computed tomography of the abdomen showed a 6.5 × 4.8-cm mass in the left adrenal gland. Biochemical testing for pheochromocytoma revealed markedly elevated plasma catecholamines and metanephrines and urinary vanillylmandelic acid and metanephrine. She underwent a successful laparoscopic left adrenalectomy. Findings from histopathologic and immunohistochemical examination of the adrenal mass were diagnostic of pheochromocytoma. CONCLUSIONS Glucagon administration induced catecholamine release from an occult pheochromocytoma, which caused multiorgan injury. Health care providers using glucagon must consider this rare, but life-threatening, complication.

Insulin Autoimmune Syndrome: a rare cause of postprandial hypoglycemia

Summary A 65-year-old obese Caucasian woman presented with symptomatic postprandial hypoglycemic episodes, resolution of symptoms with carbohydrate intake and significantly elevated anti-insulin antibody levels. She did not have any evidence for the use of oral antidiabetic medications, insulin, herbal substances, performing strenuous exercise or history of bariatric surgery. Fingerstick blood glucose readings revealed blood sugar of 35 mg/dL and 48 mg/dL, when she had these symptoms. Her medical history was significant for morbid obesity, hypothyroidism and gastro esophageal reflux disease. Her home medications included levothyroxine, propranolol and omeprazole. A blood sample obtained during the symptoms revealed the following: fingerstick blood sugar 38 mg/dL, venous blood glucose 60 mg/dL (normal (n): 70–99 mg/dL), serum insulin 202 IU/mL (n: <21), proinsulin 31.3 pmol/L (n: <28.9), C-peptide 8 ng/mL (n: 0.9–7), beta-hydroxybutyrate 0.12 mmol/L (n: 0.02–0.27) anti-insulin antibody >45.4 U/mL (n: <0.4). The result obtained while screening for serum sulfonylurea and meglitinides was negative. The repeated episodes of postprandial hypoglycemia associated with significantly elevated anti-insulin antibodies led to a diagnosis of insulin antibody syndrome (IAS). Significant improvement of hypoglycemic symptoms and lower anti-insulin antibody levels (33 U/mL) was noted on nutritional management during the following 6 months. Based on a report of pantoprazole-related IAS cases, her omeprazole was switched to a H2 receptor blocker. She reported only two episodes of hypoglycemia, and anti-insulin antibody levels were significantly lower at 10 U/mL after the following 12-month follow-up. Learning points: Initial assessment of the Whipple criteria is critical to establish the clinical diagnosis of hypoglycemia accurately. Blood sugar monitoring with fingerstick blood glucose method can provide important information during hypoglycemia workup. Autoimmune hypoglycemia is a rare cause of hypoglycemia, which can be diagnosed on high index of clinical suspicion and systematic evaluation.

Primary undifferentiated spindle-cell sarcoma of sella turcica: successful treatment with adjuvant temozolomide.

Sellar tumours in adults are most commonly pituitary adenomas. Primary spindle cell sarcoma of the sella turcica without a prior history of cranial radiation is extremely rare. We report a case of a large sellar mass with suprasellar and cavernous sinus extension in a geriatric male patient who presented with complete left oculomotor nerve palsy and panhypopituitarism. The patient underwent partial resection of the sellar mass through transcranial route. The pathology of the mass revealed a poorly differentiated spindle cell neoplasm most consistent with a sarcoma. Postoperatively, the size of the residual sellar mass decreased significantly following six cycles of external beam radiation in conjunction with temozolomide.

Transient thyrotoxicosis following minimally invasive radio-guided parathyroidectomy.

OBJECTIVE We report a case of thyrotoxicosis following minimally invasive parathyroidectomy. METHODS Case report with literature review. RESULTS A 70-year-old woman with primary hyperparathyroidism developed thyrotoxicosis 2 weeks following minimally invasive radio-guided parathyroidectomy. A diagnosis of postparathyroidectomy transient thyrotoxicosis (PTT) was made after excluding other causes of thyrotoxicosis. The patient reverted back to a euthyroid state in 4 weeks with conservative management. CONCLUSION PTT should be considered in the differential diagnosis in patients developing features of thyrotoxicosis following parathyroidectomy.

The silver man: a rare cosmetic complication of alternative medicine

A 58-year-old man with a medical history of schizoaffective disorder, delusional parasitosis and clostridium difficile colitis (CDC) was hospitalised for worsening diarrhoea, as a result of CDC exacerbation. His physical examination revealed normal vital signs and a bluish-grey pigmentation of the skin and nailbeds (figure 1). The patient firmly believed that he had Morgellons disease (a form of delusional parasitosis). In the past, he had seen several physicians including psychiatrists to seek treatment for his delusional parasitosis. The patient reported that he had been using oral silver colloidal …

Changes in diabetes-related complications in the United States.

n engl j med 371;3 nejm.org july 17, 2014 284 was most likely to have been infrequent. Finally, for the study to be methodologically rigorous, stratification of the patients according to the presence or absence of intraabdominal hypertension would have been mandatory at inclusion, with a risk of an underpowered subsequent analysis. We agree with Kimmoun et al. that our results are limited with regard to the vasopressors used; we used norepinephrine. Targeting a high mean blood pressure with the use of epinephrine or dopamine might have caused an increase in the incidence of adverse effects such as newonset arrhythmia1 or lactic acidosis.2 In contrast, one might speculate that infusing vasopressin to increase the mean blood pressure might have been associated with opposite findings: in patients with catecholamine-resistant vasodilatory shock, vasopressin significantly decreased the incidence of a new onset of atrial fibrillation,3 and a post hoc analysis of the Vasopressin and Septic Shock Trial showed a reduced progression to renal failure in vasopressin-treated patients at risk for kidney injury.4 Pierre Asfar, M.D., Ph.D.