Do thyroid cancer patients with basal undetectable Tg measured by current immunoassays require rhTSH testing?

OBJECTIVE: To evaluate the predictive value of disease free status of basal thyroglobulin (Tg) in differentiated thyroid carcinoma (DTC). DESIGN: Basal and recombinant human TSH (rhTSH) stimulated Tg measured with a commercial immunoassay (Liaison DiaSorin, Italial), neck ultrasonography (US) and fine needle aspiration cytology if required were performed in DTC patients followed prospectively for 6.8 years in a university hospital. 92 consecutive DTC patients were included. 74 patients with basal and stimulated Tg <1.0 ng/ml and Tg antibodies and US negative were considered as disease-free and persistent/recurrent disease was detected in 18 patients. In 25/74 disease-free patients rhTSH test was repeated within one year. RESULTS: 63/92 patients had undetectable basal Tg (<0.5 ng/ml), with rhTSH-Tg <0.5 ng/ml in 52, in 6 rhTSH-Tg between 0.5 and 1 ng/ml, in 2 between 1-2 ng/ml (disease-free after 3 years of follow-up) and >2.0 ng/ml (mean 4.1±2.4 ng/ml) in another 3, with US lymphatic metastasis confirmed histologically. Disease-free state was predicted with a sensitivity (S) of 66.7% and specificity (Sp) of 75.7% for basal Tg-0.5 ng/ml, and S 100% and Sp 85.1% for stimulated Tg-0.92. rhTSH test and US were repeated within one year in 25 disease-free patients with Tg<1.0 ng/ml. No further elevation below 1 ng/ml was observed. CONCLUSIONS: Low risk patients with undetectable basal Tg measured with current commercially available immunoassays should be followed with at least one rhTSH stimulated Tg and neck US because of the insufficient predictive value for recurrence/persistent disease of basal Tg.

Polimorfismo G534A del gen 11Beta-hidroxiesteroide dehidrogenasa tipo-2 (11Beta-HSD2) y sensibilidad a la sal en la hipertensión arterial esencial / G534A polymorphisminthe11Beta-hydroxysteroid dehydrogenase type 2 gene (11Beta-HSD2) and salt-sensitivity in essential hypertension

Introducción. Los mineralocorticoides actúan regulando el transporte de sodio en la nefrona distal. Los tejidos sensibles a la aldosterona expresan tanto el receptor de mineralocorticoides (MR) como la enzima 11Beta-hidroxiesteroide dehidrogenasa tipo 2 (11Beta-HSD2). El MR puede ser activado tanto por aldosterona como por cortisol. La enzima 11Beta-HSD2 inactiva los glucocorticoides y evita así su capacidad de unirse de forma inespecífica al MR. Diversos estudios han asociado mutaciones en el gen 11Beta-HSD2 con el síndrome de exceso aparente de mineralocorticoides (AME), una forma monogénica de HTA sensible a la sal que cursa con alcalosis metabólica e hipopotasemia. También se han descrito polimorfismos en este gen en pacientes con HTA esencial. Todo ello sugiere que 11-Beta HSD2 sea un gen candidato en el desarrollo de HTA esencial y sensibilidad a sal. El objetivo de este trabajo ha sido investigar la relación entre un polimorfismo funcional (G534A) en el gen 11Beta-HSD2 y la sensibilidad a la sal en pacientes con HTA esencial. Material y métodos. Se estudiaron un total de 94 pacientes que fueron clasificados en sensibles a la sal --SS-- (SS, n=47) y resistentes a la sal --SR-- (SR, n=47) en función de su respuesta presora medida mediante monitorización ambulatoria de la presión arterial (MAPA), a un cambio en la ingesta de sal desde baja (20 mmol/d) a alta (260 mmol/d). La determinación de la variante alélica de 11-Beta HSD2 se realizó por reacción en cadena de la polimerasa (PCR) y posterior digestión enzimática con AluI. Resultados. La distribución de genotipos en los individuos SS fue: 45 GG y 2 GA+AA, mientras que para los SR fue: 40 GG y 7 GA+AA (p = 0,079). Al analizar la respuesta presora ( de PA sistólica de 24 h) a la sal se encontraron diferencias significativas entre los pacientes GA+AA (-0,63ñ 3,1 mmHg) en comparación a los pacientes GG (5,8ñ0,92 mmHg) (p=0,04).Discusión. Estos resultados sugieren que la variante G534A podría ser de utilidad como marcador genético de individuos hipertensos con diferente respuesta presora a la sal (AU)

The finding of a somaticdeletion in RET exon 15 clarified the sporadic nature of amedullary thyroid carcinoma suspected to be familial.

Medullary thyroid carcinoma (MTC) occurs both sporadically and in the autosomal dominantly inherited multiple endocrine neoplasia (MEN) type 2 syndromes. The distinction between both is important for future clinical management. We report a family initially described as a familial MTC by pentagastrin stimulation test and clinical outcome, in which we found a 12 bp deletion within the catalytic domain of the protooncogene RET in the index case tumor alone. Linkage study suggests that it is a sporadic MTC. Therefore, in view of these results, in kindred with just one MTC case, borderline pentagastrin test values must be carefully assessed. In addition, this and other mutations can help us to understand some features about domains that play an important role in the normal function of this tyrosine kinase receptor and involved in MTC.

Screening of selected genomic areas potentially involved in thyroid neoplasms.

Loss of heterozygosity (LOH) studies have been used to identify sites harbouring tumour suppressor genes (TSGs) involved in tumour initiation or progression. To further elucidate the genetic mechanisms for follicular and papillary thyroid tumours development, we studied the frequency of LOH in 36 thyroid tumours (21 follicular thyroid adenomas (FAs) and 15 papillary thyroid carcinomas (PTCs)) on 10 specific genomic areas: 3p22, 3p25, 7q21, 7q31, 10q23, 10q25-26, 11q13, 11q23, 13q13 and 17p13.3-13.2 using 20 polymorphic markers. We have selected these areas for two reasons: (a) Even though LOH in thyroid neoplasms has been described in some of these areas, results are controversial, and (b) we have also studied areas described as involved in other epithelial or endocrine tumour types, but not studied up to now in thyroid neoplasms. Two areas showed a high percentage of LOH: 7q31 and 11q23. A 62% LOH was found at 7q31 in the FAs, suggesting, as other authors have proposed, that at least one TSG must be present in the vicinity of the c-met locus. The second area in frequency was at the 11q23 locus, with a 45% LOH in the FAs. This area was studied because it has been described as being involved in the development of epithelial and endocrine cancers. This locus had not been studied before in thyroid neoplasms. This result is interesting because the LOH11CR2A gene is localised at this locus. We suggest that this gene and/or an other TSG nearby may be involved in the progression to FA. In our study, a low percentage of LOH was found in the PTC samples, indicating that TSGs present in the areas we have studied are not significantly involved in their progression. Our data also suggest that TSGs located in areas where no LOH was detected (PTEN, MEN1, Cyclin D1, BRCA2 and RFC3) are not involved or do not have an important role in tumour progression.

[Increased adrenomedullin levels in hypertensive patients on maintenance hemodialysis]. / Niveles elevados de adrenomedulina en pacientes hipertensos en programa de hemodiálisis.

Hypertension is a frequent finding in uremic patients. The pathogenesis of this complication in uremia is complex and not fully elucidated. An imbalance between the vasoconstrictor and vasodilator systems may be involved in its pathogenesis. In this study we have evaluated the state of nitric oxide (NO) and adrenomedullin (ADM) in hemodialyzed patients, especially those with hypertension. We included a group of hypertensive hemodialyzed patients (n = 9) and a group of normotensive control patients (n = 10). We measured plasma renin activity, as well as plasma catecholamines, ADM, and nitrite/nitrate levels in basal conditions before starting the hemodialysis session. Plasma volume, as well as left ventricular ejection fraction were also measured. Hemodialysis patients showed plasma levels of nitrite/nitrates and ADM higher than the reference values in the normal population. We observed no differences in the plasma levels of nitrite/nitrates, but ADM levels were higher in hypertensive (278.2 +/- 15.5 pg/ml) patients than in normotensive patients (225 +/- 9.9 pg/ml) (p < 0.05). When considering all patients together, mean arterial pressure positively correlated with plasma ADM (r = 0.468, p < 0.05). Plasma volume and left ventricular ejection fraction were similar in the two groups of patients. In summary, plasma levels of nitrite/nitrates and ADM are increased in hemodialyzed patients, although only ADM levels were further increased in hypertensive patients. Our results do not suggest that a decreased production in the vasodilator factors evaluated is involved in the pathogenesis of hypertension in uremic patients.

Niveles elevados de adrenomedulina en pacientes hipertensos en programa de hemodiálisis / Increased plasma adrenomedullin levels in patients with end-stage renal disease on maintenance hemodialysis: role of hypertension

Los pacientes urémicos presentan con frecuencia hipertensión arterial cuyo origen es multifactorial y no bien dilucidado. Un disbalance entre la actividad de los sistemas presores y vasodilatadores podría estar implicado en su patogenia. En este trabajo nos hemos propuesto valorar el estado del óxido nítrico (NO) y la adrenomedulina (ADM) en pacientes hemodializados con hipertensión arterial. Estudiamos un grupo de pacientes hemodializados hipertensos (n = 9) y un grupo de pacientes normotensos (n = 10) controles. A estos pacientes se les determinó la actividad renina plasmática (ARP), así como niveles plasmáticos de catecolaminas, ADM, nitritos/nitratos (para estimar la producción de NO) en condiciones basales, antes de iniciar la sesión de hemodiálisis. Los niveles plasmáticos cite catecolaminas y ARP eran similares en ambos grupos de pacientes. Los pacientes hemodializados en conjunto presentaban unos niveles de nitritos/nitratos y de ADM superiores a los valores de referencia en la población general. No se observaron diferencias significativas en los niveles de nitritos/n¡tira tos, pero los niveles de ADM eran superiores en los pacientes hipertensos (278,3 ñ 15,5 pg/ml) respecto a los normotensos (224,9 ñ 9,9 pglml) (p < 0;01). Considerando a todos los pacientes en conjunto observamos una correlación positiva entre niveles adrenomedulina y niveles de presión arterial diastólica (r = 0,51, p < 0,05) y media (r = 0,468, p = 0,05).En conclusión, los niveles de ADM y nitritoslnitratos están elevados en los pacientes en HD, aunque sólo los niveles de ADM eran superiores en los pacientes hipertensos. Nuestros resultados no sugieren que un descenso de la liberación de factores vasodilatadores estén implicados en la HTA del paciente urémico (AU)

Genetic and clinical characterisation of maturity-onset diabetes of the young in Spanish families.

OBJECTIVE: To investigate the frequencies of the major maturity-onset diabetes of the young (MODY) subtypes in a panel of Spanish families and to assess phenotypic differences in patients with the different subtypes of MODY. METHODS: Forty-eight subjects from twenty families with clinical diagnosis of MODY were studied. They underwent a standardised clinical examination and a 75-g oral glucose tolerance test (OGTT) was performed. Estimations of insulin sensitivity (%S) and insulin secretion capacity (%B) were calculated by the computer-solved homeostasis model assessment (HOMA). Mutations in the coding regions of hepatocyte nuclear factor (HNF)-4alpha/MODY1, glucokinase (GCK/MODY2) and HNF-1alpha/MODY3 genes were investigated by single strand comformation polymorphism and sequencing analysis. RESULTS: Mutations in the GCK and HNF-1alpha genes were observed in 5 (25%) and 7 (35%) families respectively. Novel mutations included R385X, M238fsdelT, V226fsdelTinsAA and S418-7del11 in the GCK gene, and S121fsdelC, V133M, R159Q and V259D in the HNF-1alpha gene. No MODY1 families were found. Subjects which were neither MODY2 nor MODY3 (MODY-X) had a higher fasting glucose than subjects in the other groups. Insulin secretion capacity was similar in the three groups and the insulin sensitivity was decreased in MODY-X subjects. Glucose levels were significantly higher and insulin levels significantly lower, throughout the OGTT, in MODY3 compared with MODY2 subjects. CONCLUSIONS: Mutations in the GCK/MODY2 and HNF-1alpha/MODY3 genes account for the majority of cases in a panel of Spanish MODY families, with MODY3 being the most frequent subtype. The relative frequencies and the clinical characteristics of these MODY subtypes are in agreement with data previously reported in other European populations. MODY-X patients seem to present a heterogeneous clinical profile.

Beta-adrenergic receptor density and function in left ventricular hypertrophy in young essential hypertensives.

A sympathetic overactivity has been reported in the early stages of essential hypertension and has been involved in the pathogenesis of left ventricular hypertrophy (LVH) in essential hypertension. The state of beta2-adrenergic receptors as related to the presence of this complication was investigated in a group of 15 essential hypertensive patients and compared to 10 normotensive control subjects. Left ventricular mass index was determined by bidimensional echocardiography. Plasma catecholamine levels were measured by a radioenzymatic assay. beta2-adrenoceptor density was measured in intact lymphocytes by radioligand binding assay, using the hydrophilic ligand CGP 12177. beta2- adrenoceptor function was assessed by measuring intracellular cAMP levels in isoproterenol-stimulated lymphocytes. Left ventricular mass index (P < 0.05), body mass index (P < 0.01), plasma noradrenaline levels (P < 0.05) and beta2-adrenoceptor density (P < 0.05) were higher in hypertensives than in controls. Left ventricular mass index correlated with body mass index both in normotensives and hypertensives, as well as with plasma noradrenaline levels only in normotensives. Left ventricular mass index also showed a positive correlation with mean arterial pressure and an inverse relationship with beta2-adrenoceptor density and response only in hypertensive patients. In conclusion, left ventricular hypertrophy in young essential hypertensives is associated to a reduced beta2-adrenoceptor density and function, probably as a compensating mechanism of the hypertrophied myocardiocyte secondary to the increased sympathetic outflow. Journal of Human Hypertension (2000) 14, 17-21.

Increased plasma adrenomedullin levels in hemodialysis patients with sustained hypotension.

BACKGROUND: Sustained hypotension in end-stage renal disease patients is characterized, despite an overactivation of the sympathetic and renin-angiotensin systems, by decreased vascular resistance and a blunted vascular response to pressor stimuli. An increased production of one or more vasodilator substances might play a role in the reduced vascular resistance and response to pressor stimuli in these patients. We evaluated the possible role of an increased production of nitric oxide and/or adrenomedullin (ADM) in the pathophysiology of chronic hypotension in hemodialysis (HD) patients. METHODS: Three groups of hypotensive (N = 9), normotensive (N = 10), and hypertensive (N = 9) HD patients were included in the study. Plasma renin activity (PRA) and plasma levels of catecholamines, ADM, nitrite/nitrate (an estimator of nitric oxide production), tumor necrosis factor (TNF), and interleukin-1beta (IL-1beta) were measured. Plasma volume and left ventricular ejection fraction (LVEF) were also evaluated. RESULTS: Plasma levels of nitrite/nitrate and ADM were elevated in HD patients with respect to the reference values in normal subjects. Plasma ADM levels, but not nitrite/nitrate levels, were higher in hypotensive (368.1 +/- 25.4 pg/mL) than normotensive (225 +/- 9.9 pg/mL) and hypertensive HD patients (278.2 +/- 15.5 pg/mL, P < 0.01). When considering hypotensive and normotensive patients together, the mean blood pressure inversely correlated with time on HD (r = -0. 53, P < 0.05) and plasma ADM levels (r = -0.78, P < 0.01). CONCLUSIONS: Plasma ADM and nitrite/nitrate levels are increased in HD patients, but only ADM levels were higher in hypotensive than in normotensive and hypertensive HD patients. The higher plasma levels of this peptide in hypotensive patients and its inverse correlation with mean arterial pressure suggest that ADM may be involved in the pathophysiology of chronic hypotension in HD patients.

Novel point mutation in exon 10 of the RET proto-oncogene in a family with medullary thyroid carcinoma.

Medullary thyroid carcinoma (MTC) may occur sporadically or as part of the autosomal dominant multiple endocrine neoplasia type 2 (MEN 2). Three hereditary forms of MEN 2 have been identified: MEN 2A, MEN 2B, and familial MTC (FMTC). Missense germ-line mutations in the RET proto-oncogene have been identified as cause of these endocrine diseases. Mutations are found in exons 10 and 11 in MEN 2A and FMTC families and in a small number of families in exons 13, 14, and 15. Although a strong correlation between codon mutations and phenotypes has been described, not all the expected cystein codon mutations have been found. Therefore, the more mutations are found, the better it is possible to establish phenotype-genotype correlations. We report on a novel RET mutation at codon 611 in a family with MTC without other clinical manifestations and of rather benign course.

Autonomic nervous system and adrenergic receptors in chronic hypotensive haemodialysis patients.

BACKGROUND: The pathophysiology of chronic hypotension (CH) in uraemia is not elucidated. The possible role of autonomic nervous system dysfunction and adrenoceptor alterations in the pathophysiology of CH in uraemia was evaluated in this study. METHODS: Seventeen hypotensive haemodialysis (HD) patients, 17 normotensive HD patients, and 17 control subjects were studied. We evaluated the integrity of the baroreflex arc (Valsalva manoeuvre), the parasympathetic efferent pathway ('deep-breathing test') and the sympathetic efferent pathway ('hand-grip test'). We also evaluated platelet alpha 2-adrenoceptor and lymphocyte beta 2-adrenoceptor densities (radioligand binding assay), and beta 2-adrenoceptor response (intracellular cAMP generation after isoproterenol stimulation in lymphocytes). RESULTS: Responses to the Valsalva manoeuvre and the deep-breathing test were altered in all HD patients (P < 0.05). Valvalva ratio was lower in hypotensive patients than in normotensive patients (P < 0.01), whereas the pressor response to the hand-grip test was reduced only in hypotensive HD patients (P < 0.01). In haemodialysed patients, basal mean blood pressure (MBP) correlated with MBP increases during the hand-grip exercise (r = 0.59, P < 0.01). Plasma catecholamine levels were elevated in both groups of patients (P < 0.025). Plasma adrenaline levels were higher in hypotensive HD patients than in normotensive patients (P < 0.05). alpha 2- and beta 2-adrenoceptor densities and beta 2-adrenoceptor response were reduced in hypotensive patients (P < 0.05 vs normotensive patients). MBP correlated with alpha 2-adrenoceptor (r = 0.46, P < 0.01) and beta 2-adrenoceptor (r = 0.43, P < 0.025) densities in HD patients. CONCLUSIONS: Normotensive haemodialysed patients have increased plasma catecholamine levels with preserved alpha 2- and beta 2-adrenoceptor numbers, as well as beta 2-adrenoceptor responses. In hypotensive patients, plasma adrenaline levels were even higher; the increased plasma catecholamine levels induced an alpha 2- and beta 2-adrenoceptor downregulation. This downregulation may play a role in the reduced cardiovascular responses to adrenergic stimuli reported in hypotensive HD patients.

Rapid screening method for detecting mutations in the 21-hydroxylase gene.

Impaired synthesis of adrenal steroid hormones because of steroid 21-hydroxylase deficiency is one of the most common inborn errors of metabolism. To expedite molecular diagnosis in families with 21-hydroxylase deficiency, we have designed a rapid strategy to determine nine of the most common mutations in the 21-hydroxylase gene. According to the mutation to be detected, we apply either of two simple strategies: digestion with adequate restriction enzyme or use of the amplification-created restriction site (ACRS) approach and subsequent restriction analysis. Both procedures are rapid and, being nonradioactive, are safer to perform; moreover determination of zygosity in the analyzed mutations requires only one tube per mutation.

Vasoactive hormones in uraemic patients with chronic hypotension.

BACKGROUND: We evaluated the possible role of an imbalance between vasoconstrictor and vasodilator hormones in the pathophysiology of chronic hypotension in uraemia. METHODS: Fourteen hypotensive haemodialysed patients, 14 normotensive haemodialysed patients, and 17 control subjects were included in this study. Plasma renin activity (PRA) and plasma levels of catecholamines, angiotensin II (AII), atrial natriuretic peptide (ANP), and arginine vasopressin (AVP) were measured. RESULTS: The mean time on haemodialysis (HD) was longer in hypotensive patients than in normotensive patients (P < 0.01). Catecholamine levels were higher in the whole group of HD patients than in controls (P < 0.01). Catecholamine levels were higher in hypotensive patients than in normotensive patients, but the differences reached significance only for adrenaline (P < 0.05). PRA and plasma AII levels were higher in hypotensive patients than in the other two groups (P < 0.05), while no differences were observed between normotensive patients and controls. Plasma ANP and AVP levels were higher in HD patients than in controls (P < 0.01), but there were no differences between hypotensive and normotensive patients. In HD patients, mean blood pressure inversely correlated with PRA (r = -0.59, P < 0.01) and plasma AII levels (r = -0.80, P < 0.01). CONCLUSIONS: Our results indicate that in HD patients with chronic hypotension there is an activation of the sympathetic and the renin-angiotensin systems. This activation is probably secondary in an attempt to compensate the vascular resistance to pressor stimuli reported in these patients.

Genetic analysis of seven Mediterranean families with multiple endocrine neoplasia type 2A.

OBJECTIVE: Genetic analysis is now essential for the accurate screening of families with multiple endocrine neoplasia type 2 (MEN2). We present the genetic analyses by both haplotype and direct RET proto-oncogene mutation analysis in seven Mediterranean MEN 2A families and have compared these results with biochemical screening tests and pathological examinations. DESIGN: Total DNA was extracted from leucocytes. Linkage analysis was performed using five RFLP systems from three loci that flank the MEN2A locus (FNRB, RBP3, D10S15). RET proto-oncogene analysis was carried out by automatic DNA sequencing and adequate digestion of PCR amplified products for exons 10 and 11. Screening for medullary thyroid carcinoma or C-cell hyperplasia was performed by the pentagastrin provocation test. Adrenal medullary function was assessed by measurements of 24-hour urinary excretion of catecholamines and their metabolites. Serum calcium and phosphate measurements were the initial screen for hyperparathyroidism. Serum PTH was determined only if hyperparathyroidism was suggested by the former determinations. PATIENT: Genetic study was performed in 59 individuals (39 at risk) from seven kindreds of Mediterranean origin with MEN 2A. RESULTS: Diagnosis by linkage analysis was not possible in 30% of individuals at risk, but RET proto-oncogene analysis identified all these individuals. Mutations of the RET proto-oncogene were detected in exon 10 (codon 618) in one MEN 2A kindred and in exon 11 (codon 634) in the others. The results of direct analysis were concordant with linkage studies in each case. Three individuals from different MEN 2A kindreds, who were subsequently shown not to be gene carriers, had false positive pentagastrin stimulation tests. CONCLUSION: Biochemical tests can be replaced by direct DNA mutation analysis as the first line screening test in order to identify gene carriers of MEN 2A.

Discriminative value of biochemical markers of bone turnover in assessing the activity of Paget's disease.

Clinical biochemical markers of bone turnover are usually increased in Paget's disease. However, the analysis of "new" markers, such as serum bone alkaline phosphatase (BAP), carboxy-terminal propeptide of type I procollagen (PICP), tartrate-resistant acid phosphatase (TRAP), telopeptide carboxy-terminal propeptide of type I collagen (ICTP), and urinary pyridinoline (PYR) and deoxipyridinoline (D-PYR), may improve the diagnostic efficacy and the evaluation of Paget's disease compared with conventional markers, such as serum total alkaline phosphatase (TAP) and urinary hydroxyproline (HYP). To evaluate the diagnostic accuracy and the changes of biochemical markers of bone turnover according to Paget's disease activity, we measured the levels of all these markers in three groups of pagetic patients classified according to their serum TAP activity: G-I, patients with serum TAP lower than 250 U/l (upper limit) (n = 15); G-II, patients with serum TAP between 251 and 500 U/l (n = 18); and G-III, patients with serum TAP greater than 501 U/l (n = 26). Serum TAP and BAP showed the highest diagnostic accuracy among the markers of bone formation with a sensitivity of 78% and 84%, respectively, when the specificity was 100%. Urinary PYR was the most sensitive marker of bone resorption. Also, urinary PYR showed the highest proportion of increased values in pagetic patients (73%) compared with urinary HYP (64%), urinary D-PYR (60%), serum ICTP (41%), or serum TRAP (39%). In pagetic patients with normal serum TAP activity (G-I), serum BAP concentration was increased in 60% of patients, and urinary PYR was increased in 40% of patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Arginine vasopressin infusion increases plasma levels of atrial natriuretic factor in humans.

Seven normal subjects underwent sequential 20-min infusion of arginine vasopressin (AVP) at 0.5 and 2 ng/(kg.min) and a complete right-side heart hemodynamic evaluation during the study to analyze the effect of this hormone on atrial natriuretic factor (ANF) secretion in humans and to elucidate whether this effect was primary or secondary to the hemodynamic or hormonal changes induced by AVP. Plasma ANF levels increased at the end of the first (P less than 0.05) and second (P less than 0.01) infusion periods. No significant changes in mean arterial, pulmonary artery, right and left atrial pressures were recorded during the study. Cardiac output (P less than 0.05) and heart rate (P less than 0.05) decreased, while total vascular resistances (P less than 0.05) increased with respect to basal values in both infusion periods. Plasma renin activity decreased (P less than 0.01) at the end of the infusion, while plasma aldosterone, epinephrine and norepinephrine showed no significant changes. We conclude that arginine vasopressin increases plasma ANF levels in humans and that this effect cannot be ascribed to hemodynamic or hormonal changes induced by this hormone, suggesting a direct effect of vasopressin on the atrial myocyte.