leptin and Pheochromocytoma

Although catecholamine is a well-known classical hormone, its precise pathophysiological role remains obscure. Recently, growing evidence suggests that this hormone plays a causative role in several common diseases such as hypertension, diabetes, and dyslipidemia (metabolic syndrome). Thus, the discussion that follows will mainly focus on our data, including: 1) leptin as well Ang II subtype-2 receptor (AT2), assumed to be a key molecule for metabolic syndrome, much involved in regulating catecholamine synthesis and secretion. 2) Recent progress of pheochromocytoma (SDHX and Peptidergic Regulation). 3) Chromogranin A, as a possible marker for chronic sympatho-adrenal activities.

Topics: Adrenal Gland Neoplasms; Autonomic Nervous System Diseases; Biomarkers; Catecholamines; Chromogranin A; Chromogranins; Chronic Disease; Humans; Iron-Sulfur Proteins; Leptin; Membrane Proteins; Metabolic Syndrome; Mutation; Pheochromocytoma; Protein Subunits; Receptor, Angiotensin, Type 2; Succinate Dehydrogenase

Recent studies demonstrate major effects of adrenal medullary and catecholaminergic pathways on a wide variety of normal physiologic and regulatory events. Alterations in these pathways, involving changes in catecholamines or in proteins and peptides costored and coreleased with catecholamines, may lead to profound changes in autonomic, cardiovascular, neuroendocrine, metabolic, nociceptive, and immune function. These findings have important implications for a variety of human disease states. In addition, molecules associated with catecholaminergic function may provide novel diagnostic and therapeutic strategies for human disease and suggest specific genetic loci as important and fruitful targets for further genetic and pharmacogenetic studies.

Topics: Catecholamines; Chromaffin Cells; Chromogranin A; Chromogranins; Dopamine beta-Hydroxylase; Humans; Hypertension; Leptin; Mutation; Nervous System Diseases; Parkinson Disease; Pheochromocytoma

A 31-year-old woman was admitted to our hospital because of diabetic ketoacidosis (DKA). Ultrasound sonography revealed the existence of the left adrenal tumor and endocrinological examinations established a diagnosis of pheochromocytoma. She had been healthy and there was no evidence for gestational diabetes in her personal history. Characteristic features were not found in her tumor size and the catecholamine levels as compared with typical cases of pheochromocytoma. An overwhelming secretion of catecholamine might suppress insulin secretion, as evidenced by the improvement after the resection of the tumor. However, a significant insulin resistance continued after tumor resection. Obesity and the heterozygosity of beta3-adrenergic receptor gene (Try64Arg) might play a role in insulin resistance, which resulted in DKA at least in part. Literature survey revealed four cases of DKA in the patients with pheochromocytoma including ours, three of which were Japanese. Pancreatic capacity to secrete insulin has been reported to be less than Caucasians, which might be another reason for DKA. Thus, we speculate that both suppressed insulin secretion and insulin resistance deteriorated by obesity or other factor(s) such as abnormality in beta3 adrenergic receptor probably depress beta-cell function resulting in abnormal metabolic imbalance such as DKA.

Topics: Adrenal Gland Neoplasms; Adult; Diabetic Ketoacidosis; Female; Humans; Leptin; Pheochromocytoma

Obesity elevates the plasma level of leptin, which has been associated with hypertension. Our recent studies in mice demonstrated that leptin increases blood pressure by activating the carotid sinus nerve, which transmits the chemosensory input from carotid bodies (CBs) to the medullary centers, and that the effect of leptin is mediated via

Topics: Adrenal Gland Neoplasms; Animals; Epigenesis, Genetic; Gene Expression Regulation, Neoplastic; Leptin; Neoplasm Proteins; PC12 Cells; Pheochromocytoma; Rats; TRPM Cation Channels

To compare the mRNA, protein expression of long leptin receptor (Ob-Rb) in human adrenal tissues and tumors and observe the plasma level of leptin in primary aldosteronism (PA), cortisol-secreting tumors (CS) and pheochromocytomas (PHEO).. Total RNA and protein were extracted from 6 normal human adrenal glands, 10 CS, 20 PHEO; and 14 aldosterone-producing adenomas (APA) (RNA), 10 APA (protein); plasma samples were drawn from 20 controls, 15 PHEO, 29 PA and 11 CS.. The mRNA and protein of Ob-Rb were widely expressed in human adrenal glands and tumors. The mRNA (0.32±0.12) and protein (1.31±0.26) expressions of Ob-Rb were higher in normal human adrenal cortex (C) than all other tissues (P<0.05) while the mRNA expression of Ob-Rb in APA (0.15±0.10) was higher than CS (0.05±0.02) (P<0.05). The mRNA expression of Ob-Rb in APA was positively correlated with plasma supine aldosterone level (r=0.670, P=0.024). The mRNA expression of Ob-Rb in CS was positively correlated with 24-hour urinary free cortisol level (r=0.870, P=0.005). The plasma level of leptin was higher in CS than in non-CS groups (P=0.001).. Ob-Rb is widely expressed in adrenal tissues and tumors. There is a differential expression in various tissues. Further studies are warranted to understand the relationship between leptin and adrenal gland.

Topics: Adrenal Cortex; Adrenal Gland Neoplasms; Case-Control Studies; Humans; Leptin; Pheochromocytoma; Receptors, Leptin

The aim of our study was to evaluate the influence of surgical removal of pheochromocytoma on the endocrine function of adipose tissue and subclinical inflammation as measured by circulating C-reactive protein (CRP) levels. Eighteen patients with newly diagnosed pheochromocytoma were included into study. Anthropometric measures, biochemical parameters, serum CRP, leptin, adiponectin and resistin levels were measured at the time of diagnosis and six months after surgical removal of pheochromocytoma. Surgical removal of pheochromocytoma significantly increased body weight, decreased both systolic and diastolic blood pressure, fasting blood glucose and glycated hemoglobin levels. Serum CRP levels were decreased by 50 % six months after surgical removal of pheochromocytoma (0.49+/-0.12 vs. 0.23+/-0.05 mg/l, p<0.05) despite a significant increase in body weight. Serum leptin, adiponectin and resistin levels were not affected by the surgery. We conclude that increased body weight in patients after surgical removal of pheochromocytoma is accompanied by an attenuation of subclinical inflammation probably due to catecholamine normalization. We failed to demonstrate an involvement of the changes in circulating leptin, adiponectin or resistin levels in this process.

Topics: Adiponectin; Adipose Tissue; Adrenal Gland Neoplasms; Adrenalectomy; Adult; Biomarkers; Blood Pressure; C-Reactive Protein; Down-Regulation; Female; Humans; Inflammation; Leptin; Male; Middle Aged; Pheochromocytoma; Resistin; Treatment Outcome; Weight Gain

The relationship between plasma leptin and catecholamine concentrations during chronic and acute catecholamine excess is studied. Patients with phaeochromocytoma, divided according to gender, were examined under basal conditions (n = 18) and at selected time-points during surgical removal of the tumour (n = 12). Appropriate controls were used (n = 23) for the basal study. Plasma leptin was determined by radioimmunoassay (RIA) and plasma noradrenaline (NA) and adrenaline (A) by high-performance liquid chromatography (HPLC). Statistical evaluation employed Student's t-test, Wicoxon test and Spearman's correlation coefficient. Gender-related differences in plasma leptin in normal subjects was confirmed, and these were maintained in the patients. Phaeochromocytoma patients had normal plasma leptin levels in the basal state and decreased levels following the massive catecholamine surge provoked by surgery. Plasma leptin concentration did not correlate with plasma NA or A in either group studied. In the patients with phaeochromocytoma, acute but not chronic catecholamine excess affected plasma leptin, suggesting a role for sympathetic activity in modulating leptin release.

Topics: Adrenal Gland Neoplasms; Adult; Epinephrine; Female; Humans; Leptin; Male; Middle Aged; Neoplasm Proteins; Norepinephrine; Pheochromocytoma

Leptin, a hormone mainly secreted from adipose tissue, communicates a metabolic signal to the adrenal gland. Ob-Receptor (Ob-R) expression was reported in rat, mice and human adrenal glands. This study intended to investigate possible differences in the Ob-R expression and distribution of Ob-R protein in human adrenal tumors as compared to normal adrenal tissue. Proliferative effects of leptin were analyzed in the human adrenocortical carcinoma cell line (NCI-H295). The full length Ob-R mRNA and the isoforms B219.1 and B219.3 could be demonstrated by RT-PCR in all adrenal tumors (n=8), the tumor cell line (NCI-H295) and normal tissue. In contrast the Ob-R isoform B219.2 was absent in the carcinoma cell line and in most of the adrenal tumors (n=5), whereas it was present in normal adrenals. The Ob-R protein could be demonstrated in benign and malignant adrenocortical tumors. Pheochromocytomas showed only a weak immunostaining with the human Ob-R antibody. Human leptin did not affect the proliferation or variability of adrenal tumor cells as demonstrated by [3H]-thymidine assay and WST-1 test. In conclusion, although functional leptin receptors are expressed in human adrenal tumors, leptin does not regulate tumor cell proliferation.

Topics: Adenoma; Adrenal Cortex Neoplasms; Adrenal Gland Neoplasms; Adrenal Glands; Adult; Carrier Proteins; Cell Division; Cell Survival; Gene Expression; Humans; Immunohistochemistry; Leptin; Middle Aged; Pheochromocytoma; Proteins; Receptors, Cell Surface; Receptors, Leptin; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Tumor Cells, Cultured

Leptin is a major regulator of body weight and energy balance and is subject to a variety of regulatory inputs. From several previous studies, catecholamines have been suggested to exert an inhibitory influence on leptin production in animals. In the present study, we analyzed leptin levels in relation to catecholamine hypersecretion in 27 human pheochromocytoma patients. A 10-fold increase in circulating norepinephrine (P < .0001) did not result in suppression of plasma leptin in the patients compared with normal controls (median and interquartile range, 4.3 ng/mL [2.4 to 6.8] v 2.2 ng/mL [1.9 to 3.0] in men and 18.6 [12.3 to 27.0] v 11.4 [10.1 to 15.9] in women). Correlation analysis indicated a significant association of leptin with epinephrine in normal subjects (r = -.81, P < .0001), but not in pheochromocytoma patients. Leptin was not related to norepinephrine in either group. In conclusion, our data suggest that a chronic elevation of catecholamines does not cause suppression of leptin secretion in patients with pheochromocytoma. This lack of effect may be attributable to the development of tolerance of adipose tissue leptin production to catecholamines.

Topics: Adrenal Gland Neoplasms; Adult; Body Mass Index; Body Weight; Epinephrine; Female; Humans; Leptin; Male; Middle Aged; Norepinephrine; Pheochromocytoma; Proteins; Reference Values

Topics: Adrenal Gland Neoplasms; Aged; Humans; Leptin; Male; Pheochromocytoma; Proteins