Pheochromocytomas and paragangliomas (PHEOs) are rare neuroendocrine tumors. Clinical manifestations include different cardiovascular signs and symptoms, which are related to excessive secretion of catecholamines. Catecholamine-induced cardiomyopathy in PHEO (CICMPP) is a rare but dreaded complication of PHEO. Once patient is diagnosed with this condition, the prognosis is worse and a surgical risk is much higher than expected. This article focuses on how catecholamines affect the heart and the pathophysiologic mechanism of CICMPP. The cardiovascular responses to catecholamine depend mostly on which catecholamine is released as well as the amount of catecholamine that is released. The acute release of norepinephrine and epinephrine from PHEO increases heart rate, systemic vascular resistance, myocardial contractility, and reduces venous compliance. The excessive adrenergic stimulation by catecholamine results in severe vasoconstriction and coronary vasospasm, myocardial ischemia, and subsequently damage, and necrosis. Chronically elevated catecholamine levels lead to significant desensitization of cardiac β-adrenoceptors. The increased levels of the enzyme β-adrenoceptors kinase (βARK) in the heart seems to mediate these biochemical and physiological changes that are consistently correlated with attenuated responsiveness to catecholamine stimulation. Through these mechanisms different types of cardiomyopathy (CMP) can be formed. This review discusses extensively the 3 types of cardiomyopathies that can be present in a PHEO patient. It also provides the clinical presentation and diagnostic and therapeutic algorithm in managing patients with CICMPP.

It is proposed that the impaired counterregulatory response (CRR) to hypoglycemia in insulin deficient diabetes may be due to chronic brain insulin deficiency. To test this hypothesis, streptozotocin-diabetic Sprague-Dawley rats were infused with either insulin (3mU/day) or artificial cerebrospinal fluid (aCSF) bilaterally into the ventromedial hypothalamus (VMH) for 2 weeks and compared to nondiabetic rats. Rats underwent hyperinsulinemic (50 mU.kg-1.min-1) hypoglycemic (~45 mg/dl) clamps. Diabetic rats demonstrated an impaired CRR to hypoglycemia noted by an high glucose infusion rate (GIR) and blunted epinephrine and glucagon responses. The defective sympathoadrenal response was restored with chronic infusion of insulin into the VMH. Diabetic rats had decreased VMH Akt phosphorylation and decreased VMH glucose transporter 4 (GLUT4) content, which was also restored with chronic infusion of insulin into the VMH. Separate experiments in non-diabetic rats in which VMH GLUT4 translocation was inhibited with an infusion of indinavir was notable for an impaired CRR to hypoglycemia indicated by increased GIR and diminished epinephrine and glucagon responses. Results suggest that in this model of diabetes, VMH insulin deficiency impairs the sympathoadrenal response to hypoglycemia and chronic VMH insulin infusion is sufficient to normalize the sympathoadrenal response to hypoglycemia, via restoration of VMH GLUT4 expression.

Single injection of muscarinic cholinoceptor blocker atropine (1 mg/kg) to outbred male rats reduced β-adrenergic responsiveness of erythrocytes (by 2.2 times) and the content of epinephrine granules on erythrocytes (by 1.5 times), significantly increased HR and rigidity of the heart rhythm, and manifold decreased the power of all spectral components of heart rhythm variability. Stimulation of the central neurotransmitter systems increased β-adrenergic responsiveness of erythrocytes (by 15-26%), decreased the number of epinephrine granules on erythrocytes (by 25-40%), and increased HR and cardiac rhythm intensity. These changes were most pronounced after stimulation of the serotoninergic system. Administration of atropine against the background of activation of central neurotransmitter systems did not decrease β-adrenergic responsiveness of erythrocytes (this parameter remained at a stably high level and even increased during stimulation of the dopaminergic system), but decreased the number of epinephrine granules on erythrocytes, increased HR, and dramatically decreased the power of all components of heart rhythm variability spectrum. The response to atropine was maximum against the background of noradrenergic system activation and less pronounced during stimulation of the serotoninergic system. Thus, substances that are complementary to cholinergic receptors modulated adrenergic effect on the properties of red blood cells, which, in turn, can modulate the adrenergic influences on the heart rhythm via the humoral channel of regulation. Stimulation of central neurotransmitter systems that potentiates the growth of visceral adrenergic responsiveness weakens the cholinergic modulation of the adrenergic influences, especially with respect to erythrocyte responsiveness. Hence, changes in the neurotransmitter metabolism in the body can lead to coupled modulation of reception and reactivity to adrenergic- and choline-like regulatory factors at the level of erythrocyte membranes, which can be important for regulation of heart rhythm.

The monitoring of monoamines and their metabolites in CNS samples can be very valuable in pharmaceutical and biomedical research. A specific high performance liquid chromatography, coupled to a coulometric electrochemical detection method, for the assay of monoamines (dopamine, norepinephrine, epinephrine and serotonin) and their metabolites in rat brain tissue samples was developed. The chromatographic separation was achieved on a C8 reversed phase column with a mobile phase consisting of 0.1 M sodium formate buffer, 5 mM sodium 1-heptanesulfonate, 0.17 mM ethylenediaminetetraacetic acid disodium salt and 5% v/v acetonitrile (pH ±4.0). The detection was achieved through electrochemical detection, with a coulometric cell potential setting of +650 mV. The flow-rate was at 1 ml/min and the total run time was 50 min. The method was validated according to validation guidelines. The method was found to be linear (R2 > 0.99) over the analytical range (5 to 200 ng/ml) for all monoamines and their metabolites. All the other validation parameters were acceptable and within range. The method was applied to three rat brain areas (pre-frontal cortex, hippocampus and striatum), where the monoamines (except for epinephrine) and their metabolites were easily detected.

Angioedema is a self-limiting edema of the subcutaneous or submucosal tissues due to localised increase of microvascular permeability whose mediator may be histamine or bradykinin. Patients present to emergency department when angioedema involves oral cavity and larynx (life-threatening conditions) or gut (mimicking an acute abdomen). After initial evaluation of consciousness and vital signs to manage breathing and to support circulation if necessary, a simple approach can be applied for a correct diagnosis and treatment. Forms of edema such as anasarca, myxedema, superior vena cava syndrome and acute dermatitis should be ruled out. Then, effort should be done to differentiate histaminergic from non-histaminergic angioedema. Concomitant urticaria and pruritus suggest a histaminergic origin. Exposure to allergens and drugs (mainly ACE inhibitors and non steroidal anti-inflammatory drugs) should be investigated as well as a family history of similar symptoms. Allergic histaminergic angioedema has a rapid course (minutes) whereas non histaminergic angioedema is slower (hours). Since frequently the intervention needs to be immediate, the initial diagnosis is only clinical. However, laboratory tests can be subsequently confirmatory. Allergic angioedema is sensitive to standard therapies such as epinephrine, glucocorticoids and antihistamines whereas non histaminergic angioedema is often resistant to these drugs. Therapeutic options for angioedema due C1-inhibitor deficiencies are C1-inhibitor concentrates, icatibant and ecallantide. If these drugs are not available, fresh frozen plasma can be considered. All these medications have been used also in ACE inhibitor-induced angioedema with variable results thus they are not currently recommended whereas experts agree on the discontinuation of the causative drug.

Objective: To summarize the clinical characteristics of silent paraganglioma. Methods: A total of 247 pheochromocytoma cases in Peking University First Hospital between January 1993 and December 2015 were analyzed retrospectively.The cases were divided into two groups according to whether they had hypertension: non-silent group (193 cases) and silent group (53 cases), then the clinical characteristics between the groups were compared, and the clinical features of silent pheochromocytoma were reviewed. Results: There were 53 silent pheochromocytoma cases in this study, which accounted for 21.5% (53/247), and imaging was the main way to find the tumor. Forty-one in 53 cases (77.4%) located in adrenal gland, in which 31 cases (75.6%) were benign and 2.3-8.0 cm in diameter, while 10 cases (24.4%) were malignant and 3.5-12.0 cm in diameter. Twelve in 53 cases (22.6%) located in extra-adrenal tissue, in which 4 cases were benign and 2.0-5.5 cm in diameter, while 8 cases were malignant and 5.0-10.5 cm in diameter. With the tumor diameter increased, the malignant rate increased: 1 in 8 cases in diameter<3 cm, 2 in 12 cases in diameter 3-5 cm, 15 in 33 cases in diameter>5 cm were malignant. There was no significant difference in age, sex, tumor location, benign or malignant rate between the two groups (all P>0.05). Compared with the non-silent group, the proportion of tumor size≥5 cm in silent group was significantly higher (62.3% vs 45.9%, P=0.034), and the incidence of hyperglycemia and the concentrations of norepinephrine and epinephrine were lower (all P<0.05) in silent group.Misdiagnosis was common in silent group, and up to 35.8% (19/53) had not been diagnosed correctly before operation. Twenty-one in 53 (39.6%) silent pheochromocytoma cases occured severe intra-operative blood pressure fluctuation. Conclusions: Silent pheochromocytoma was not uncommon and imaging was the main way to find it. The tumor size was always big and misdiagnosis was common, especially extra-adrenal tumors. Therefore, regardless of the adrenal or extra-adrenal tumors, especially in diameter>3.0 cm but with normal blood pressure, the possibility of silent pheochromocytoma should be considered. In order to reduce misdiagnosis and intra-operative blood pressure fluctuations, preoperative diagnosis and preparation, as well as intra-operative monitoring should be fully made.

Epistaxis is a common emergency encountered by primary care physicians. Up to 60% of the general population experience epistaxis, and 6% seek medical attention for it. More than 90% of cases arise from the anterior nasal circulation, and most treatments can be easily performed in the outpatient setting. Evaluation of a patient presenting with epistaxis should begin with assessment of vital signs, mental status, and airway patency. When examining the nose, a nasal speculum and a good light source, such as a headlamp, can be useful. Compressive therapy is the first step to controlling anterior epistaxis. Oxymetazoline nasal spray or application of cotton soaked in oxymetazoline or epinephrine 1: 1,000 may be useful adjuncts to compressive therapy. Directive nasal cautery, most commonly using silver nitrate, can be used to control localized continued bleeding or prominent vessels that are the suspected bleeding source. Finally, topical therapy and nasal packing can be used if other methods are unsuccessful. Compared with anterior epistaxis, posterior epistaxis is more likely to require hospitalization and twice as likely to need nasal packing. Posterior nasal packing is often associated with pain and a risk of aspiration if it is dislodged. After stabilization, patients with posterior packing often require referral to otolaryngology or the emergency department for definitive treatments.