atrial-natriuretic-factor and Carcinoma--Small-Cell

The term paraneoplastic syndrome refers to the ability of some tumors to produce signs and symptoms at a distance from the site of the primary tumor or its metastases. Paraneoplastic syndromes may develop before the diagnosis of carcinoma is made. Paraneoplastic syndromes associated with small cell lung cancer (SCLC) include endocrinologic abnormalities secondary to peptide hormone production, and neurologic sequelae due to autoantibody production. This article reviews the common paraneoplastic syndromes that may occur in patients with SCLC.

Topics: ACTH Syndrome, Ectopic; Atrial Natriuretic Factor; Carcinoma, Small Cell; Cerebellar Diseases; Encephalomyelitis; Humans; Inappropriate ADH Syndrome; Lambert-Eaton Myasthenic Syndrome; Lung Neoplasms; Paraneoplastic Syndromes; Retinal Diseases

Topics: Arginine Vasopressin; Atrial Natriuretic Factor; Carcinoma, Non-Small-Cell Lung; Carcinoma, Small Cell; Humans; Hyponatremia; Lung Neoplasms; Neoplasms

One-third of patients with lung cancer and hyponatremia have no evidence of ectopic arginine vasopressin (AVP) production and the cause of their hyponatremia is not conclusively established. We sought to distinguish patients with hyponatremia caused by elevated AVP versus those with ectopic atrial natriuretic peptide (ANP) via this detailed metabolic study.. We enrolled 24 patients recently diagnosed with lung cancer in a metabolic study in which patients were placed on sodium and fluid restriction for 4 days. Serum electrolytes, osmolality, urine electrolytes and osmolality, plasma AVP, ANP, aldosterone, urinary cyclic AMP and cyclic guanosine 3',5'-monophosphate were measured daily and tumor tissue was obtained to measure ectopic hormone production. We attempted to characterize the pathophysiology of hyponatremia caused by ectopic ANP production in patients with small cell lung cancer (SCLC) and to determine its effect on the aldosterone axis.. Seven of the nine patients with SCLC presented with hyponatremia and three had elevated ANP levels at presentation without elevation of AVP. All three patients who presented with hyponatremia and elevated ANP showed a decline in serum sodium following fluid restriction, whereas two patients with SCLC and elevated AVP had normalized serum sodium levels. The combination of hyponatremia and elevated ANP was associated with a persistent natriuresis and inappropriately low aldosterone levels despite sodium restriction, suggesting ANP suppression of the aldosterone axis.. Management of patients with hyponatremia and SCLC should be guided by the knowledge that some patients with SCLC have ectopic production of ANP as the cause of their hyponatremia.

Topics: Adult; Aged; Aldosterone; Arginine Vasopressin; Atrial Natriuretic Factor; Carcinoma, Non-Small-Cell Lung; Carcinoma, Small Cell; Cyclic AMP; Cyclic GMP; Female; Humans; Hyponatremia; Lung Neoplasms; Male; Middle Aged

Four cardiac hormones synthesized by the same gene, i.e. atrial natriuretic peptide, vessel dilator, long acting natriuretic peptide and kaliuretic peptide, and the kidney hormone urodilatin have anticancer effects in vitro.. These cardiac hormones and urodilatin were infused subcutaneously for 28 days with weekly fresh hormones since they lose biological effects at body temperature for more than a week at 0.3 nm kg(-1) body weight in athymic mice bearing human small-cell lung carcinomas.. Long acting natriuretic peptide, vessel dilator, kaliuretic peptide, atrial natriuretic peptide and urodilatin eliminated 86%, 71%, 57%, 43% (P < 0.001 for the cardiac hormones) and 25% (P < 0.05; urodilatin) of the human small-cell lung carcinomas. The treated small-cell lung carcinomas that were not cured grew rapidly, similar to the untreated controls, whose volume was 7 fold larger in 1 week, 18-fold increased in 2 weeks, 39-fold increased in 3 weeks, 63-fold increased in 1 month and 97-fold increased in volume in 6 weeks. One vessel dilator treated small-cell lung carcinoma animal developed a large tumour (8428 mm3 volume) on treatment and this tumour was eliminated with utilizing atrial natriuretic peptide and then long acting natriuretic peptide sequentially.. Four cardiac hormones eliminate up to 86% of human small-cell lung carcinomas in athymic mice. Urodilatin can also eliminate small-cell lung carcinomas but at a lower cure rate of 25%. Unresponsive lesions can be eliminated by utilizing different hormones synthesized by the atrial natriuretic peptide gene in a sequential manner.

Topics: Animals; Antineoplastic Agents; Atrial Natriuretic Factor; Carcinoma, Small Cell; Humans; Lung Neoplasms; Mice; Mice, Nude; Neoplasm Metastasis; Peptide Fragments; Protein Precursors; Receptors, Atrial Natriuretic Factor

It is well documented in literature that a majority of small-cell lung cancers are associated with paraneoplastic phenomena. We report the case of a 63-year-old man diagnosed with small-cell lung carcinoma, in whom a severe hyponatremia and renal sodium loss with inappropriate antidiuresis were also found during a routine laboratory testing. Syndrome of inappropriate antidiuretic hormone secretion was first suspected in this patient, but another complex pathogenetic mechanism involving atrial natriuretic peptides could be associated, potentiating the deflation of the plasma sodium level. In our patient, the plasma-atrial natriuretic peptide base level, determined with a sensitive radioimmunoassay, was above the normal range (183 pg/mL; normal range, 50 pg/mL, +/- 10 pg/mL), and the antidiuretic hormone plasma level had an oscillatory pattern, varying between 5.5 pg/mL and 7 pg/mL (normal range, 0-4.7 pg/mL). We discuss the pathogenesis and clinical aspects of this association and the therapeutic options for these types of patients.

Topics: Arginine Vasopressin; Atrial Natriuretic Factor; Carcinoma, Small Cell; Humans; Hyponatremia; Inappropriate ADH Syndrome; Lung Neoplasms; Male; Middle Aged; Osmolar Concentration; Paraneoplastic Syndromes; Radiography; Radioimmunoassay; Sodium; Water-Electrolyte Imbalance

Four peptide hormones of a family of six hormones, i.e. atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), C-natriuretic peptide (CNP), long acting natriuretic peptide (LANP), vessel dilator and kaliuretic peptide, significantly decrease the number of adenocarcinoma cells in culture. The present investigation was designed to determine whether these peptide hormones' effects are specific to adenocarcinomas or whether they might decrease the number of cancer cells of a different type of cancer, i.e. small-cell lung cancer.. These six hormones were evaluated for their ability to decrease the number and/or proliferation of human small-cell lung cancer cells in culture for 24, 48, 72, and 96 h.. Within 24 h, vessel dilator, LANP, kaliuretic peptide, ANP and their intracellular mediator cyclic GMP, each at 1 microM, decreased the number of small-cell lung cancer cells by 63% (P < 0.001), 21% (P < 0.05), 30% (P < 0.05), 39% (P < 0.05), and 31% (P < 0.05), respectively. There was no proliferation in the 3 days following this decrease in cell number. These same hormones decreased DNA synthesis 68% to 82% (P < 0.001). Brain natriuretic peptide and CNP did not decrease the number of small-cell lung cancer cells or inhibit their DNA synthesis at 1 microM or 10 microM concentrations. Dose-response curves revealed that at 100 microM, the vessel dilator decreased 92% of the cancer cells in 24 h while BNP had no effect, but CNP caused a 39% decrease. Western blots revealed that the natriuretic peptide receptors A- and C- were present in these cancer cells.. Five peptide hormones significantly decrease the number of human small-cell lung cancer cells within 24 h and inhibit their proliferation for at least 96 h. Their mechanism of doing so involves inhibition of DNA synthesis mediated in part by cyclic GMP.

Topics: Adenocarcinoma; Atrial Natriuretic Factor; Blotting, Western; Carcinoma, Small Cell; Cell Proliferation; Humans; Lung Neoplasms; Natriuretic Peptide, Brain; Natriuretic Peptide, C-Type; Protein Precursors

Corin is a recently discovered pro-atrial natriuretic peptide (ANP) convertase that is abundantly expressed in the heart. ANP is a cardiac hormone but can be secreted ectopically by certain cancers including small cell lung cancer (SCLC). In this study, we examined the role of corin in ANP production by SCLC cells. Reverse transcription-PCR detected corin mRNA expression in all nine SCLC cell lines examined and ANP mRNA expression in seven of the nine cell lines. In contrast, arginine vasopressin mRNA was detected in only five of the nine SCLC cell lines studied. Corin-expressing SCLC cells were capable of converting recombinant human pro-ANP to biologically active ANP, as determined by Western analysis and a cyclic GMP assay. Transfection of small interfering RNA duplexes directed against the corin gene completely blocked the processing of pro-ANP in the SCLC cells. Our results show that corin functions as a pro-ANP convertase in SCLC cells. We also suggest that the expression of corin may contribute to the pathogenesis of the syndrome of inappropriate secretion of antidiuretic hormone associated with certain cancers.

Topics: Arginine Vasopressin; Atrial Natriuretic Factor; Carcinoma, Small Cell; Cell Line, Tumor; Humans; Lung Neoplasms; Protein Precursors; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; RNA, Small Interfering; Serine Endopeptidases; Transfection

Tumors and tumor cell lines from two patients with small cell lung carcinoma (SCLC) (one with and one without hyponatremia) were studied. Ectopic production and prohormone processing of atrial natriuretic peptide (ANP) were investigated to determine if a biologically active peptide was produced in a tumor cell line from a patient with hyponatremia and no evidence of arginine vasopressin (AVP) production.. Ribonuclease (RNase) protection assays were performed on mRNA isolated from tumors and tumor cell lines established from two SCLC patients, one with and one without hyponatremia. Cellular extracts and conditioned media were studied using reversed-phase high performance liquid chromatography (HPLC) to determine the immunoreactive form of ANP. Tumor cell line sonicates were studied for subcellular localization of enzymatic activity that cleaved pro-ANP peptide substrates.. RNase protection assays showed a 200-base pair protected fragment in the mRNA isolated from the tumor and tumor cell line from the patient with hyponatremia (Patient 4). HPLC characterization of the cellular extract and conditioned medium from the tumor and tumor cell line from Patient 4 demonstrated ANP immunoreactivity in the same fraction as ANP- (S99-Y126). The tumor cell line extract that localizes to a subcellular fraction enriched for lysosomes and secretory organelles contains a 60-kilodalton molecular weight protein with enzyme activity that hydrolyzes synthetic pro-ANP substrates and catalyzes the formation of ANP-(S99-Y126).. A tumor cell line from a patient with hyponatremia was able ectopically to produce, process, and secrete ANP in the same immunoreactive form as the biologically active molecule. Preliminary studies show that tumor cell line NCI-H1284 contains an enzyme that can cleave precursors at the same amino acid sequences needed to produce ANP-(S99-Y126) from pro-ANP.

Topics: Atrial Natriuretic Factor; Carcinoma, Small Cell; Chromatography, High Pressure Liquid; Humans; Hyponatremia; Lung Neoplasms; Male; Neoplasm Proteins; RNA, Messenger; Tumor Cells, Cultured

This study was undertaken to define the impact of arginine vasopressin (AVP) and atrial natriuretic peptide (ANP) on sodium homeostasis in patients with lung cancer. Patients had their serum and urine electrolytes and osmolality determined before and after a saline infusion of 500 ml. The plasma hormones, AVP, ANP, plasma renin activity (PRA), angiotensin II, and aldosterone were determined by radioimmunoassay every 15 min before, during and after the saline infusion. Fifty patients, 31 with small cell lung cancer and 19 with non-small cell lung cancer participated in this trial. All 11 patients (10 patients with small cell lung cancer and one patient with non-small cell lung cancer) who presented with hyponatremia had inappropriately elevated levels of AVP. Elevated plasma AVP levels were highly correlated with the presence of hyponatremia (p < 0.00001). Initial plasma ANP levels were not associated with hyponatremia (p = 0.73). Urinary sodium concentration increased during the saline infusion proportional to the initial plasma level of ANP (p = 0.0045). AVP appears to be elevated in nearly all patients with hyponatremia of malignancy. ANP plasma levels in patients with lung cancer are associated with the ability to excrete a sodium load but do not appear to downregulate renin, angiotensin II, and aldosterone production.

Topics: Adult; Aged; Aldosterone; Angiotensin II; Arginine Vasopressin; Atrial Natriuretic Factor; Carcinoma, Non-Small-Cell Lung; Carcinoma, Small Cell; Female; Homeostasis; Hormones, Ectopic; Humans; Hyponatremia; Immunohistochemistry; Lung Neoplasms; Male; Middle Aged; Prospective Studies; Radioimmunoassay; Renin; Sodium; Tumor Cells, Cultured

Hyponatremia in patients with small cell lung cancer (SCLC) is a common clinical problem usually attributed to tumor secretion of arginine vasopressin (AVP). It recently was shown that some SCLC cell lines produce atrial natriuretic peptide (ANP). The purpose of this investigation was to determine the frequency and clinical consequences of secretion of ANP by SCLC and the relative contribution of ANP and AVP to the hyponatremia associated with this disease.. Levels of ANP and AVP were measured in 23 SCLC cell lines and 23 other human tumor cell lines. Also, ANP and AVP levels were determined in plasma samples from 69 patients with active small cell carcinomas.. Of the 23 SCLC lines, 16 (70%) had elevated ANP levels. Only two (8.7%) had elevated AVP levels, and these two also had elevated ANP levels. One of the ANP-producing cell lines was derived from a hyponatremic patient with no other apparent explanation for a low sodium level. However, the four cell lines with the highest levels of ANP were derived from patients who were not hyponatremic. Two other human tumor lines also produced ANP. Of the 69 patients with SCLC, 21 (30.4%) had elevated ANP levels, whereas 4 (6%) had elevated AVP levels. Fifteen of these patients were hyponatremic during their clinical course (21.7%). Of the eight patients who were hyponatremic when samples were collected, two had elevated ANP levels, and only one had elevated AVP levels. Six patients (8.7%) had symptoms of postural hypotension, possibly attributable in some cases of tumor secretion of ANP.. The majority of SCLC lines produce ANP, and a minority produce AVP. Secretion of ANP may result in hyponatremia and/or postural hypotension. However, secretion of either or both of these peptides does not account for all cases of hyponatremia in patients with SCLC and does not necessarily cause clinical manifestations.

Topics: Adenocarcinoma; Arginine Vasopressin; Atrial Natriuretic Factor; Carcinoma, Non-Small-Cell Lung; Carcinoma, Small Cell; Female; Humans; Hyponatremia; Hypotension, Orthostatic; Lung Neoplasms; Male; Sodium; Tumor Cells, Cultured

Although atrial distension is widely accepted as the primary stimulus for atrial natriuretic peptide (ANP) release, a number of agonists are also known to induce its secretion. The mechanisms underlying these processes are not well understood. Studies of this nature are hampered by the inherent difficulty in culturing homogeneous populations of cardiac myocytes in sufficient quantities to perform molecular investigations. For this reason, we have examined the possibility of using other cell types as a model of ANP release. It has been reported that a number of tumor samples from small cell lung cancer (SCLC) patients express the ANP gene. Characterization of a large number of cell lines derived from SCLC tumor samples indicated that two of these cell lines, OS-A and SHP-77, secrete ANP at rates of approximately 10(-20) g.cell-1.min-1. This is a sufficient quantity to facilitate secretion studies using a perifusion system. We have demonstrated that ANP is released through regulated secretory pathways, as the Ca2+ ionophore A-23187, arginine vasopressin (AVP), and the sodium ionophore, monensin, were capable of modifying secretion rates. High-pressure liquid chromatography (HPLC) analysis indicated that the primary secretory product is ANP-(99-126), the circulating form of this hormone. Intracellularly, both ANP-(99-126) and ANP-(1-126) were present, suggesting the synthesis and appropriate cleavage of pro-ANP-(1-126). Because both of these cell lines have doubling times in the range of 3-5 days, they could serve as a rapidly proliferating and easily maintainable supply of homogeneous tissue for release studies.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Arginine Vasopressin; Atrial Natriuretic Factor; Calcimycin; Carcinoma, Small Cell; Chromatography, High Pressure Liquid; Humans; Molecular Structure; Time Factors; Tumor Cells, Cultured

Peptide hormone synthesis in neuroendocrine tumors is a well-recognized phenomenon. However, production in neuroendocrine tumors of atrial natriuretic polypeptide (ANP), a newly discovered peptide hormone from the heart, has not been studied extensively.. The presence of immunoreactive human ANP (IR-hANP) in neuroendocrine tumors was determined using a specific human ANP radioimmunoassay. Neuroendocrine tumors examined included 9 small cell carcinomas of the uterus, 28 small cell carcinomas of the lung, 20 carcinoid tumors, 54 pancreatic endocrine tumors, 17 neuroblastic tumors, 14 pheochromocytomas, and 14 medullary carcinomas of the thyroid. Twenty atrial tissues also were examined as the control. Molecular size of IR-hANP in the extracts of atrial and tumor tissues was determined by gel chromatography.. IR-hANP was detected in the extracts of small cell carcinoma of the uterus, small cell carcinoma of the lung, and carcinoid tumor, with concentrations ranging from 3.1 to 210 ng/g wet weight tissue. No IR-hANP was detected in the extracts of pancreatic endocrine tumor, neuroblastic tumor, pheochromocytoma, and medullary carcinoma of the thyroid. The frequency of production of IR-hANP in neuroendocrine tumors was highest in small cell carcinoma of the uterus (44%), followed by small cell carcinoma of the lung (18%) and carcinoid tumor (15%). IR-hANP present in the extracts of small cell carcinomas of the uterus had molecular size heterogeneity, with three fragments in addition to alpha-, beta- and gamma-human ANP.. These results indicate that IR-hANP is produced by neuroendocrine tumors and that the molecular size of IR-hANP in tumor tissues is different from that in atrial tissues.

Topics: Atrial Natriuretic Factor; Carcinoid Tumor; Carcinoma, Small Cell; Female; Humans; Lung Neoplasms; Neuroendocrine Tumors; Pancreatic Neoplasms; Pheochromocytoma; Radioimmunoassay; Thyroid Neoplasms; Uterine Neoplasms

Patients with lung cancer (n = 263) were studied to determine the relationship among ectopic production of atrial natriuretic factors (ANF) and arginine vasopressin (AVP), serum sodium, and patient outcome. Of 133, 21 (16%) patients with small cell lung cancer (SCLC) had hyponatremia (serum sodium, < 130 mmol/liter), compared to none of 130 (0%) patients with non-small cell lung cancer (P < 0.0001). Patients with extensive-stage SCLC and hyponatremia had shorter survival than patients with extensive stage SCLC and normal serum sodium values (P = 0.012). Of the 11 hyponatremic patients with SCLC and tumor cell lines available for study, 9 produced ANF mRNA, 7 of 11 produced AVP mRNA, and 5 of 11 produced both ANF mRNA and AVP mRNA. All 11 cell lines produced either ANF mRNA and ANF peptide or AVP mRNA and AVP peptide, or both. The quantity of AVP peptide in the tumor cell lines was more closely associated with hyponatremia in the patients (P = 0.0026, r2 = 0.28) than was the production of ANF peptide (P = 0.066, r2 = 0.12), although neither association was strong. All tumor cell lines studied from SCLC patients with hyponatremia produce ANF and/or AVP mRNA and peptides.

Topics: Arginine Vasopressin; Atrial Natriuretic Factor; Carcinoma, Non-Small-Cell Lung; Carcinoma, Small Cell; Humans; Hyponatremia; Inappropriate ADH Syndrome; Lung Neoplasms; Prognosis; Radioimmunoassay; Ribonucleases; RNA, Messenger; Sodium; Tumor Cells, Cultured

We describe a patient who presented with the syndrome of inappropriate antidiuretic hormone secretion (SIADH) 2 months before clinical evidence of bronchogenic malignancy. Because of the potential for the ectopic production of atrial natriuretic peptide (ANP) to mimic SIADH, both hormones were measured in this hyponatremic patient to seek a possible marker of tumor activity. A hypertonic saline infusion at presentation revealed excessive osmotically decoupled secretion of arginine vasopressin but a normal ANP response.

Topics: Aged; Arginine Vasopressin; Atrial Natriuretic Factor; Carcinoma, Small Cell; Humans; Inappropriate ADH Syndrome; Lung Neoplasms; Male; Saline Solution, Hypertonic

Small cell lung cancer cell (SCLC) lines, NCI-H82, NCI-H660, and NCI-H1284, and HeLa cells were analyzed for the presence of atrial natriuretic peptide (ANP) receptors. In these SCLC cell lines and HeLa cells, ANP A receptor mRNA was identified by Southern blot analyses of polymerase chain reaction products and RNase protection assays using poly(A)(+)-selected RNA. Saturable binding assays revealed that HeLa cells had 2000 to 5000 high affinity atrial natriuretic peptide receptors per cell with a dissociation constant of 140 pM. In the SCLC cell lines, the binding was saturable but too low to accurately estimate the number of binding sites. After addition of human ANP, radioimmunoassays revealed accumulation of cyclic GMP in SCLC cells as well as HeLa cells in a dose-dependent fashion. The half-maximal stimulation concentration of cyclic GMP accumulation in HeLa and these SCLC cell lines was approximately 2 nM. Tetrazolyl blue assays and tritiated thymidine incorporation did not show any remarkable growth inhibition or growth stimulation of SCLC cell lines after addition of human ANP up to 3.3 microM, more than 1000-fold greater than the half-maximal stimulation concentration of cyclic GMP accumulation. Our results indicate that human SCLC cells express functional ANP receptors but ANP addition produced no detectable change in their growth pattern.

Topics: Atrial Natriuretic Factor; Base Sequence; Blotting, Southern; Carcinoma, Small Cell; Cell Division; Cyclic GMP; HeLa Cells; Humans; Iodine Radioisotopes; Lung Neoplasms; Molecular Sequence Data; Polymerase Chain Reaction; Radioimmunoassay; Receptors, Atrial Natriuretic Factor; Ribonucleases; RNA, Messenger; Stimulation, Chemical; Tetrazolium Salts; Thiazoles; Thymidine; Tritium; Tumor Cells, Cultured

One autopsy case with small cell lung cancer and the syndrome of inappropriate antidiuretic hormone secretion (SIADH) is reported. Both plasma atrial natriuretic peptide (ANP) and arginine vasopressin (AVP) levels were high, and the presence of significantly high levels of ANP and AVP in tumor tissue was confirmed by gel chromatography and radioimmunoassay techniques. To the best of the authors' knowledge, this is the first case in which ectopic ANP production and its secretion into blood (leading to SIADH) were proved.

Topics: Aged; Arginine Vasopressin; Atrial Natriuretic Factor; Carcinoma, Small Cell; Electrolytes; Female; Humans; Inappropriate ADH Syndrome; Lung Neoplasms; Paraneoplastic Endocrine Syndromes

Hyponatremia in patients with small cell lung cancer can be caused by tumor production of arginine vasopressin (AVP) and result in the syndrome of inappropriate antidiuretic hormone. In evaluating the expression of AVP mRNA from tumor and tumor cell line specimens from five patients with small cell lung cancer and hyponatremia (presumed to have the syndrome of inappropriate antidiuretic hormone), we found that the tumors and tumor cell lines from two of these five patients expressed AVP mRNA. The RNA samples from the three patients with undetectable AVP mRNA expressed abundant atrial natriuretic factor (ANF) mRNA. Analysis of specimens from three patients with small cell lung cancer and normal serum sodium levels revealed no detectable AVP mRNA expression, and samples from only one of these three patients' specimens expressed detectable ANF mRNA. The AVP and ANF peptide levels in lysate preparations of the tumor cell lines from four of these patients were tested by radioimmunoassay and confirmed the gene expression data. These studies demonstrate ectopic production of ANF mRNA in small cell lung cancer specimens from patients with this cancer and the syndrome of inappropriate antidiuretic hormone. These findings will be of particular interest if future studies demonstrate that ectopic ANF production can cause sodium abnormalities in patients with small cell lung cancer.

Topics: Aged; Arginine Vasopressin; Atrial Natriuretic Factor; Blotting, Northern; Carcinoma, Small Cell; Gene Expression Regulation, Neoplastic; Hormones, Ectopic; Humans; Hyponatremia; Lung Neoplasms; Middle Aged; Radioimmunoassay; RNA, Messenger; RNA, Neoplasm; Single-Strand Specific DNA and RNA Endonucleases; Tumor Cells, Cultured

Topics: Arginine Vasopressin; Atrial Natriuretic Factor; Carcinoma, Small Cell; Hormones, Ectopic; Humans; Lung Neoplasms; Neurophysins; Oxytocin; Paraneoplastic Endocrine Syndromes; Protein Precursors; Vasopressins

A 62-year-old man with small cell carcinoma (oat cell type) of the lung who had hyponatremia and renal sodium loss with inappropriate antidiuresis is reported. Plasma levels of arginine vasopressin (AVP) were not elevated inappropriately. Plasma levels of atrial natriuretic peptide (ANP), however, were high, and increased after water loading and hypertonic saline infusion. The renin-aldosterone axis was normal, as were adrenal, thyroid, and renal functions. Water restriction to 500 to 700 ml/d resulted in a rise in serum sodium. Analysis of the tumor tissue failed to demonstrate the presence of AVP or ANP. The findings (1) suggest that hyponatremia and renal sodium loss with inappropriate antidiuresis observed in the patient is due to an antidiuretic substance distinct from AVP, and (2) point to the possibility that hypersecretion of ANP may play a role in the pathophysiology.

Topics: Arginine Vasopressin; Atrial Natriuretic Factor; Carcinoma, Small Cell; Humans; Hyponatremia; Inappropriate ADH Syndrome; Lung Neoplasms; Male; Middle Aged; Saline Solution, Hypertonic; Water