Pheochromocytoma associated with pregnancy: unexpected favourable outcome in patients diagnosed after delivery.

OBJECTIVE: The objective of this study is to present the clinical findings and outcome of a large cohort of pregnant women with pheochromocytoma (PHEO) with the aim to contribute to the better recognition, detection and management of pregnancy-related PHEO in the population of pregnant patients with hypertension. METHODS: This is a longitudinal follow-up of a single cohort of 15 patients aged 19-40 years with PHEO associated with pregnancy. Urinary catecholamines and vanillylmandelic acid (VMA) were analysed. Ret proto-oncogene, SDHB and VHL mutations were determined in germline DNA from seven women using PCR followed by direct sequencing. RESULTS: During pregnancy, all women presented typical features of catecholamines excess. Nevertheless, biochemical diagnosis was performed only in four out of 15 cases during pregnancy and postpartum in the remaining 11. Paroxysmal hypertension was the predominant pattern. Urinary catecholamines and/or VMA were increased in all patients. Tumours were adrenal in 13 patients and extraadrenal in two. Mutations in the Ret proto-oncogene were found in four patients, in the VHL gene in one and in the SDHB gene in one. Antihypertensive treatment resulted in effective control of blood pressure and all women survived. In the group of women diagnosed postpartum, one foetus demised. Newborns from mothers receiving adequate treatment survived. One woman left the hospital after caesarean section but before PHEO surgery became pregnant again and this gestation ended with maternal-foetal dead. CONCLUSION: A high index of suspicion in all pregnant women presenting hypertension mainly paroxystic during any gestational phase and/or a history of familial PHEO are the keys to disclose this important diagnosis.

Involvement of dopamine signaling in the circadian modulation of interval timing.

Duration discrimination within the seconds-to-minutes range, known as interval timing, involves the interaction of cortico-striatal circuits via dopaminergic-glutamatergic pathways. Besides interval timing, most (if not all) organisms exhibit circadian rhythms in physiological, metabolic and behavioral functions with periods close to 24 h. We have previously reported that both circadian disruption and desynchronization impaired interval timing in mice. In this work we studied the involvement of dopamine (DA) signaling in the interaction between circadian and interval timing. We report that daily injections of levodopa improved timing performance in the peak-interval procedure in C57BL/6 mice with circadian disruptions, suggesting that a daily increase of DA is necessary for an accurate performance in the timing task. Moreover, striatal DA levels measured by reverse-phase high-pressure liquid chromatography indicated a daily rhythm under light/dark conditions. This daily variation was affected by inducing circadian disruption under constant light (LL). We also demonstrated a daily oscillation in tyrosine hydroxylase levels, DA turnover (3,4-dihydroxyphenylacetic acid/DA levels), and both mRNA and protein levels of the circadian component Period2 (Per2) in the striatum and substantia nigra, two brain areas relevant for interval timing. None of these oscillations persisted under LL conditions. We suggest that the lack of DA rhythmicity in the striatum under LL - probably regulated by Per2 - could be responsible for impaired performance in the timing task. Our findings add further support to the notion that circadian and interval timing share some common processes, interacting at the level of the dopaminergic system.

Enfermedad hereditaria en pacientes menores de 21 años con feocromocitoma "aparentemente" esporádico / Hereditary disease in patients younger than 21 years of age with ’apparently’ sporadic pheochromocytoma

INTRODUCCION: Los feocromocitomas son tumores productores de catecolaminas, que durante mucho tiempo fueron considerados esporádicos. Actualmente, se sabe que pueden ser familiares, como parte de neoplasia endocrina múltiple tipo 2 A o B, causada por mutaciones en el protooncogen RET (Rearregement during Transfection), enfermedad de Von Hippel Lindau (VHL) causada por mutaciones en el gen supresor VHL, neurofibromatosis tipo 1 o síndromes de paraganglioma familiar (PGL) 1, 3 y 4, causados por mutaciones en las subunidades D, C o B de la succinato deshidrogenada (SDHD, SDHC, SDHB).OBJETIVO: Evaluar la presencia de alteraciones en los genes susceptibles de enfermedad hereditaria en pacientes con diagnóstico bioquímico y anatomopatológico de feocromocitoma.METODOS: Se analizó a 69 pacientes <21 años. Para el estudio de biología molecular se realizó la extracción de ADN de sangre periférica, la amplificación por PCR, el screening por SSCP (single strand conformation polymorfism) y la confirmación por secuenciación y/o digestión enzimática. Se realizó la evaluación clínica, la medición de las catecolaminas urinarias, la localización y el tratamiento del tumor.RESULTADOS: Tuvieron fenotipo sindrómico o fueron familiares 14/69 pacientes. Tuvieron feocromocitoma aparentemente esporádico 55/69. En 33/55 pacientes se realizaron los estudios de biología molecular. Se identificaron mutaciones en 22/33 (67%): 17 en VHL (52%) y 5 en SDHB (15%). No se encontraron mutaciones en el RET ni en SDHD. En cuanto a la localización del tumor, en los pacientes con VHL predominó la bilateralidad (11/17) y en los esporádicos la mayoría fue unilateral (7/11). El porcentaje de tumores extraadrenales y malignos fue mucho mayor entre los pacientes con mutaciones del gen de SDHB (3/4).CONCLUSIONES: Es importante realizar el estudio genético en pacientes jóvenes con feocromocitoma aparentemente esporádico, dado que existe una alta prevalencia de mutaciones, entre las que predomina la del gen de VHL

INTRODUCTION: Pheochromocytomas are catecholamine secreting tumors, which have been traditionally considered sporadic. Nowadays, familial pheochromocytomas are found to be more common due to their association with multiple endocrine neoplasia type 2A or B caused by mutations of the RET gene, von Hippel-Lindau disease (VHL) caused by mutations of the suppressor gen VHL, neufibromatosis type 1, and familial paraganlioma (PGL) 1, 3 and 4 syndromes caused by mutations of the gene coding for D, B and C subunits of succinate dehydrogenase (SDHD, SDHB and SDHC).OBJECTIVE: To evaluate the presence of mutations in any of the susceptible genes in patients with biochemical and anatomopathological diagnosis of pheochromocytoma.METHODS: The studies were performed in 69 patients younger than 21 years of age. They included clinical examination, measurement of urinary catecholamines, localization of the tumor and treatment. Molecular biology analyses were carried out in DNA from peripheral blood, PCR (polymerase chain reaction), amplification, (SSCP) single strand conformation polymorfism screening, and confirmed by sequencing and/or enzymatic digestion.RESULTS: 14/69 patients were relatives or had clinical features of familial disease. 55/69 had apparently sporadic pheochromocytoma. In 33/55 patients molecular biology analyses were carried out. 22/33 (67%) presented germ-line mutations: 11/22 (52%) had VHL mutation and 5/22 (15%) SDHB mutations. Neither SDHD nor RET mutations were found. Regarding the localization of the tumores, 11 patients with VHL presented bilateral tumors, and 7/11 patients with sporadic tumors showed unilateral pheochromocytoma. Extra-adenal and malignant tumors were much more frequend among patients with SDHB gene mutations (3/4).CONCLUSIONS: The high prevalence of mutations, mainly in the VHL gene, highlights the importance of performing genetic studies in young patients with apparently sporadic pheochromocytoma.

Enfermedad hereditaria en pacientes menores de 21 años con feocromocitoma "aparentemente" esporádico / Hereditary disease in patients younger than 21 years of age with apparently sporadic pheochromocytoma

INTRODUCCION: Los feocromocitomas son tumores productores de catecolaminas, que durante mucho tiempo fueron considerados esporádicos. Actualmente, se sabe que pueden ser familiares, como parte de neoplasia endocrina múltiple tipo 2 A o B, causada por mutaciones en el protooncogen RET (Rearregement during Transfection), enfermedad de Von Hippel Lindau (VHL) causada por mutaciones en el gen supresor VHL, neurofibromatosis tipo 1 o síndromes de paraganglioma familiar (PGL) 1, 3 y 4, causados por mutaciones en las subunidades D, C o B de la succinato deshidrogenada (SDHD, SDHC, SDHB).OBJETIVO: Evaluar la presencia de alteraciones en los genes susceptibles de enfermedad hereditaria en pacientes con diagnóstico bioquímico y anatomopatológico de feocromocitoma.METODOS: Se analizó a 69 pacientes <21 años. Para el estudio de biología molecular se realizó la extracción de ADN de sangre periférica, la amplificación por PCR, el screening por SSCP (single strand conformation polymorfism) y la confirmación por secuenciación y/o digestión enzimática. Se realizó la evaluación clínica, la medición de las catecolaminas urinarias, la localización y el tratamiento del tumor.RESULTADOS: Tuvieron fenotipo sindrómico o fueron familiares 14/69 pacientes. Tuvieron feocromocitoma aparentemente esporádico 55/69. En 33/55 pacientes se realizaron los estudios de biología molecular. Se identificaron mutaciones en 22/33 (67%): 17 en VHL (52%) y 5 en SDHB (15%). No se encontraron mutaciones en el RET ni en SDHD. En cuanto a la localización del tumor, en los pacientes con VHL predominó la bilateralidad (11/17) y en los esporádicos la mayoría fue unilateral (7/11). El porcentaje de tumores extraadrenales y malignos fue mucho mayor entre los pacientes con mutaciones del gen de SDHB (3/4).CONCLUSIONES: Es importante realizar el estudio genético en pacientes jóvenes con feocromocitoma aparentemente esporádico, dado que existe una alta prevalencia de mutaciones, entre las que predomina la del gen de VHL

INTRODUCTION: Pheochromocytomas are catecholamine secreting tumors, which have been traditionally considered sporadic. Nowadays, familial pheochromocytomas are found to be more common due to their association with multiple endocrine neoplasia type 2A or B caused by mutations of the RET gene, von Hippel-Lindau disease (VHL) caused by mutations of the suppressor gen VHL, neufibromatosis type 1, and familial paraganlioma (PGL) 1, 3 and 4 syndromes caused by mutations of the gene coding for D, B and C subunits of succinate dehydrogenase (SDHD, SDHB and SDHC).OBJECTIVE: To evaluate the presence of mutations in any of the susceptible genes in patients with biochemical and anatomopathological diagnosis of pheochromocytoma.METHODS: The studies were performed in 69 patients younger than 21 years of age. They included clinical examination, measurement of urinary catecholamines, localization of the tumor and treatment. Molecular biology analyses were carried out in DNA from peripheral blood, PCR (polymerase chain reaction), amplification, (SSCP) single strand conformation polymorfism screening, and confirmed by sequencing and/or enzymatic digestion.RESULTS: 14/69 patients were relatives or had clinical features of familial disease. 55/69 had apparently sporadic pheochromocytoma. In 33/55 patients molecular biology analyses were carried out. 22/33 (67%) presented germ-line mutations: 11/22 (52%) had VHL mutation and 5/22 (15%) SDHB mutations. Neither SDHD nor RET mutations were found. Regarding the localization of the tumores, 11 patients with VHL presented bilateral tumors, and 7/11 patients with sporadic tumors showed unilateral pheochromocytoma. Extra-adenal and malignant tumors were much more frequend among patients with SDHB gene mutations (3/4).CONCLUSIONS: The high prevalence of mutations, mainly in the VHL gene, highlights the importance of performing genetic studies in young patients with apparently sporadic pheochromocytoma.

Actividad del sistema dopaminérgico renal en ratas con distinto contenido de sodio en la dieta / Activity of the renal dopaminergic system in rats

La dopamina (DA) renal modula la excreción de sodio y agua y la presión arterial por medio de receptores D1 (D1R) y D2 y es degradada por las enzimas monoamino-oxidasa (MAO) y catecol-O-metiltransferasa (COMT). Nuestro propósito es estudiar el patrón de excreción urinaria de DA (UDAV) y la actividad de MAO y COMT durante el consumo de dietas con distinto contenido de sodio.(AU)

Actividad del sistema dopaminérgico renal en ratas con distinto contenido de sodio en la dieta / Activity of the renal dopaminergic system in rats

La dopamina (DA) renal modula la excreción de sodio y agua y la presión arterial por medio de receptores D1 (D1R) y D2 y es degradada por las enzimas monoamino-oxidasa (MAO) y catecol-O-metiltransferasa (COMT). Nuestro propósito es estudiar el patrón de excreción urinaria de DA (UDAV) y la actividad de MAO y COMT durante el consumo de dietas con distinto contenido de sodio.

Patterns of renal dopamine release to regulate diuresis and natriuresis during volume expansion. Role of renal monoamine-oxidase.

Diuretic and natriuretic effects of renal dopamine (DA) are well established. However, in volume expansion the pattern of renal DA release into urine (UDAV) and the role of enzymes involved in DA synthesis/degradation have not yet been defined. The objective was to determine the pattern of UDAV during volume expansion and to characterize the involvement of monoamine-oxidase (MAO) and aromatic amino-acid decarboxylase (AADC) in this response. In this study male Wistar rats were expanded with NaCl 0.9% at a rate of 5% BWt per hour. At the beginning of expansion three groups received a single drug injection as follows: C (vehicle, Control), IMAO (MAO inhibitor Pargyline, 20 mg/kg BWt, i.v.) and BNZ (AADC inhibitor Benserazide, 25 mg/kg BWt, i.v.). Results revealed that in C rats UDAV (ng/30 min/100g BWt) increased in the first 30 min expansion from 11.5 +/- 1.20 to 21.8 +/- 3.10 (p < 0.05) and decreased thereafter. IMAO showed a similar pattern but significantly higher than C at 30 min expansion (32.5 +/- 2.20, p < 0.05). IMAO greatly reduced MAO activity from 8.29 +/- 0.35 to 1.1 +/- 0.03 nmol/mg tissue/hour and significantly increased diuresis and natriuresis over controls. BNZ abolished the early UDAV peak to 3.2+/-0.72 (p < 0.01) and though, UDAV increased over C after 60 min expansion, natriuresis and diuresis were diminished by BNZ treatment. Results indicate that an increment in renal DA release into urine occurs early in expansion and in a peak-shaped way. In this response MAO plays a predominant role.

Patterns of renal dopamine release to regulate diuresis and natriuresis during volume expansion: Role of renal monoamine-oxidase / Perfiles de secreción de dopamina renal en la expansión de volumen para regular diuresis y natriuresis: Rol de la monoaminoxidasa renal

Diuretic and natriuretic effects of renal dopamine (DA) are well established. However, in volume expansion the pattern of renal DA release into urine (U DA V) and the role of enzymes involved in DA synthesis/degradation have not yet been defined. The objective was to determine the pattern of U DA V during volume expansion and to characterize the involvement of monoamine-oxidase (MAO) and aromatic amino-acid decarboxylase (AADC) in this response. In this study male Wistar rats were expanded with NaCl 0.9% at a rate of 5% BWt per hour. At the beginning of expansion three groups received a single drug injection as follows: C (vehicle, Control), IMAO (MAO inhibitor Pargyline, 20 mg/kg BWt, i.v.) and BNZ (AADC inhibitor Benserazide, 25 mg/kg BWt, i.v.). Results revealed that in C rats U DA V (ng/30 min/100g BWt) increased in the first 30 min expansion from 11.5 ± 1.20 to 21.8 ± 3.10 (p < 0.05) and decreased thereafter. IMAO showed a similar pattern but significantly higher than C at 30 min expansion (32.5 ± 2.20, p < 0.05). IMAO greatly reduced MAO activity from 8.29 ± 0.35 to 1.1 ± 0.03 nmol/mg tissue/hour and significantly increased diuresis and natriuresis over controls. BNZ abolished the early U DA V peak to 3.2±0.72 (p < 0.01) and though, U DA V increased over C after 60 min expansion, natriuresis and diuresis were diminished by BNZ treatment. Results indicate that an increment in renal DA release into urine occurs early in expansion and in a peak-shaped way. In this response MAO plays a predominant role.

La dopamina (DA) intrarrenal ejerce efectos diuréticos y natriuréticos. Sin embargo, en los estado de expansión de volumen aún no está bien definido el patrón de liberación de dopamina renal hacia la orina y si cumplen un rol las enzimas involucradas en la síntesis o degradación de la amina. El objetivo del presente trabajo fue determinar el patrón de excreción urinaria de DA (U DA V) durante la expansión de volumen, caracterizando la participación de las enzimas monoaminooxidasa (MAO) y decarboxilasa de aminoácidos aromáticos (AADC) en esta respuesta. Para ello ratas Wistar macho fueron expandidas de volumen con NaCl 0.9% al 5% del peso corporal por hora durante dos horas y divididas en tres grupos, los que al comienzo de la expansión recibieron: C (vehículo, Control), IMAO (Pargilina, inhibidor de MAO, 20 mg/kg PC, i.v.) y BNZ (Benserazida, inhibidor de AADC, 25 mg/kg PC, i.v.). Se observó que en C la U DA V (ng/30min/100gPC) aumentó durante los primeros 30 minutos de expansión de 11.5 ± 1.20 a 21.8 ± 3.10 (p < 0.05), disminuyendo posteriormente. IMAO mostró un patrón de liberación similar pero significativamente mayor que C a los 30 min de expansión (32.5 ± 2.20, p < 0.05). En este grupo la actividad de MAO disminuyó de 8.29 ± 0.35 a 1.1 ± 0.03 nmol/mg tejido/hora y aumentaron la diuresis y natriuresis por sobre los controles. En BNZ, el pico de U DA V observado a los 30 min de la expansión disminuyó a 3.2 ± 0.72 (p < 0.01), aunque luego de 60 minutos fue mayor que en C. BNZ disminuyó tanto la diuresis como la natriuresis. Podemos concluir que al comienzo de la expansión de volumen se produce un pico de excreción de dopamina renal hacia la orina. La enzima MAO juega un rol fundamental en esta respuesta.

Tianeptine influence on plasmatic catecholamine levels and anxiety index in rats under variable chronic stress after early maternal separation.

The aim of this work was to determine the effect of chronic treatment with 5 mg/kg of tianeptine in male adult Wistar rats separated from the mother as neonates and submitted to variable chronic stress, plasma catecholamines, and anxiety. The plus maze test was performed in order to calculate the anxiety index and catecholamine levels were determined by high-pressure liquid chromatography. Both stress and maternal separation elevated catecholamine levels without affecting anxiety. In the maternally separated stress group, tianeptine decreased epinephrine. Anxiety was reduced in the maternally separated unstressed tianeptine group. Also, all groups showed a tendency to lower anxiety index.

Maternal separation and lesion of adtn alters anxiety and adrenal activity in male rats.

The present study investigated the effect of early maternal separation on anxiety and hypophyso-adrenal system activity to anterodorsal thalamic nuclei (ADTN) lesion in male rats as adults in order to compare this with previous results with female rats. During the first 3 weeks of life, male rats were isolated 4.5 hr daily and tested as adults. Thirty days after ADTN lesion we found that adrenocorticotropic hormone (ACTH) plasma levels were affected neither by maternal separation nor by ADTN lesion. Plasma corticosterone (CORT) concentration was increased with lesion of the ADTN in maternally separated rats. A significant increase in plasma catecholamine concentration was induced by early maternal separation. In ADTN-lesioned rats, plasma norepinephrine (NE) concentration was significantly lower than in the respective sham-lesioned groups. In terms of anxiety, there were no significant effects of early experience. However, the ADTN lesion tended to decrease anxiety-related behavior.

Amitriptyline treatment under chronic stress conditions: effect on circulating catecholamines and anxiety in early maternally separated rats.

The aim of this work was to determine the effect of amitriptyline (AMI) on peripheral outcomes such as plasma epinephrine (E) and norepinephrine (NE) concentration and anxiety-like behavior displayed in the plus maze test in adult male Wistar rats under variable chronic stress and daily oral administration of AMI (5 mg/kg). Animals were previously isolated from the mother for 4.5 hr every day for the first 3 weeks of life. Administration of the antidepressant AMI reduced anxiety-like behavior in animals submitted only to chronic stress but not in early maternally separated (MS) subjects or in animals subjected to the two types of stresses.

Plasma melatonin pattern in chronic and episodic headaches: evaluation during sleep and waking.

To look for a relationship between pineal function in chronic migraine (CM), cluster headache (CH) (during active and remission periods), chronic tension-type headache (CTTH) patients and controls during NREM sleep, REM sleep and waking, we performed serial sampling of plasma melatonin in the different sleep stages during the first half of the night, in order to avoid chronobiological interferences. Plasma melatonin levels did not show a normal curve either in the CTTH or in the CM patients and no significant differences between these groups were found in any of the sleep stages studied. Plasma melatonin values of CH patients during the cluster period showed an abnormal pattern. The curve showed a pathological lack of peaks during the active period, melatonin levels remaining within normal daytime range throughout the study. A trend to normalization of the curve during the remission period was observed. On the basis of these different melatonin secretion patterns, it might be hypothesized that the involvement of the hypothalamus in chronic-type headaches differs from that displayed in episodic forms.

Possible autocrine enkephalin regulation of catecholamine release in human pheochromocytoma cells.

AIMS: Pheochromocytomas are catecholamine-secreting tumors that also synthesize and secrete several neuropeptides, including opioids. A negative regulation of catecholamine secretion by opioids has been postulated in chromaffin cells. However, results obtained so far are contradictory when referred to human pheochromocytomas. The aim of this study was to define the role of locally produced enkephalins on catecholamine release in human pheochromocytoma cells. MAIN METHODS: Cells obtained from eleven human pheochromocytomas of different genetic origins were cultured for 5 days. Cultures were maintained under basal condition or under enkephalin, dexamethasone and naloxone alone or in combination with enkephalin or dexamethasone-stimulated conditions. Catecholamine and enkephalin levels in the culture medium were measured by HPLC-ED and RIA respectively. KEY FINDINGS: Enkephalin induced a decrease in norepinephrine levels in all tumor cultures. Dexamethasone treatment, which increased enkephalin levels, also decreased catecholamine levels. On the other hand, the addition of naloxone to the cultures reverted to normal the inhibitory action exerted by enkephalin and dexamethasone treatments. SIGNIFICANCE: These results suggest the existence of an autocrine negative regulatory loop exerted by enkephalin on norepinephrine release in human pheochromocytoma cells.

Some components of the cardiac ß-adrenergic system are altered in the chronic indeterminate form of experimental Trypanosoma cruzi infection.

The chronic indeterminate form of Trypanosoma cruzi infection could be the key to knowing which patients will develop chagasic myocardiopathy. Infected mice present a period in which cardiac functional and structural alterations are different from those described for acute or chronic phases. We studied some components of the cardiac ß-adrenergic system in mouse hearts infected with T. cruzi Tulahuen strain or SGO-Z12 isolate during the chronic indeterminate phase of infection. We determined: (i) the primary messenger (epinephrine and norepinephrine) levels in plasma by reverse-phase-HPLC; (ii) the cardiac ß-adrenergic receptors' (ß-AR) density and affinity by binding with tritiated dihidroalprenolol and by immunofluorescence; (iii) the cardiac concentration of the second messenger (cAMP) (by ELISA) given its importance for the phosphorylation of the proteins involved in cardiac contraction; (iv) the cardiac contractility and functional studies of the ß-ARs as a response to the ligand binding to the receptor; and (v) the left ventricular ejection fraction as a measure of in vivo cardiac function. Plasma catecholamines levels remained similar to those found in uninfected controls. The ß-ARs' affinity decreased in both infected groups compared with the uninfected group (P<0.05) while the receptors' density increased only in the SGO-Z12 group (P<0.01). Cyclic AMP levels were higher in both infected groups (P<0.01) relative to controls, and were higher in SGO-Z12-infected mice compared with those infected with the Tulahuen strain. However, the basal contractile force remained unchanged and the response to catecholamines only increased in the Tulahuen group (P<0.05). The left ventricular ejection fraction, on the other hand, was diminished in SGO-Z12-infected mice. Heterogeneity between T. cruzi strains determine, in the chronic indeterminate form, alterations in the signaling pathways of the ß-adrenergic system at different levels: (i) between catecholamines and the ß(1)-receptors; (ii) between the receptors' activation and the adenylyl-cyclase activation; and/or (iii) between cAMP and the contractile response.

Characteristics of pheochromocytoma in a 4- to 20-year-old population.

Hypertension in children and adolescents has become a major health problem recently recognized, and in a significant number of patients it is due to an endocrine tumor. The aim of this study was to establish the characteristics of pheochromocytoma in a population of 58 patients between 4 and 20 years of age studied at our Center. They represented a 23% of the total population of 255 pheochromocytoma patients studied. In the younger group (under 20 years of age), there was a marked predominance of severe sustained hypertension (93%), only 7% presented paroxysmal hypertension and none of them was normotensive. The youngsters studied showed a higher incidence of bilateral adrenal pheochromocytoma (34%) and extra-adrenal pheochromocytoma (22%). Malignancy was found in 12% of these patients. In addition, the incidence of familial pheochromocytoma was elevated in these patients (39%). Surprisingly, in contrast with the adult population where the most frequent familial pheochromocytomas were multiple endocrine neoplasia (MEN) type 2A (15%), the younger population showed a higher predominance of von Hippel-Lindau (VHL) (28%) and lower incidence of MEN 2A, MEN 2B, neurofibromatosis (NF), and succinate dehydrogenase subunit B (SDHB). In the VHL group, only two patients belonging to one family, showed the R167W mutation, while the others showed novel mutations in conserved amino acids. It may be speculated that the high incidence of VHL in youngsters may account for the biochemical and clinical features they usually present.

Changes in the cardiac beta-adrenergic system provoked by different T. cruzi strains.

BACKGROUND: It has been demonstrated that the beta-adrenergic signal transduction system is altered somewhere along its pathway in Trypanosoma cruzi infected hearts and we think that these alterations would differ according to the infection phase and the parasite strain. Their study would be important for the understanding of the disease's pathophysiology. METHODS: In the present work we studied important components of this system in mice hearts infected with T. cruzi, Tulahuen strain and with SGO-Z12 isolate, obtained from a patient of an endemic area, in the acute phase of the infection, determining: the plasma catecholamines levels, the beta-receptors density and affinity as well as their function, the cardiac concentration of cAMP and the cardiac contractility as the physiologic response to the initial stimulus. RESULTS: Plasma catecholamines levels were diminished in both infected groups when compared to the uninfected one (P < 0.01). The receptor's affinity was also diminished (P < 0.05) while their density was augmented only in the SGO-Z12 infected one (P < 0.01). The cAMP levels were higher in both infected groups (P < 0.01), the basal contractile force however increased only in the Tulahuen infected one (P < 0.01) while the response to catecholamines remained unchanged. The hearts infected with the SGO Z12 isolate presented an inferior response to epinephrine (P < 0.05) than the ventricles infected with the Tulahuen strain. CONCLUSIONS: This model represents an important approach to understand the biochemical, physiological and molecular changes in the cardiac beta-adrenergic signalling that clearly begin in the acute phase of Chagas' disease and reveal a clear differentiation in the alterations produced by different parasite strains.

Familial isolated pheochromocytoma presenting a new mutation in the von Hippel-Lindau gene.

We report a novel germ-line point mutation in the von Hippel-Lindau (vhl) gene in a family with childhood occurrence of isolated pheochromocytoma. Two members of this family (the father and his son) were affected. The son had bilateral adrenal pheochromocytoma and the father had one adrenal and one extra-adrenal localization. Both patients presented cardiac arrest while exposed to surgical stress and severe hypoglycemia was registered in the son. The outcome was uneventful. A DNA sequence analysis of vhl tumor suppressor gene revealed the L163R mutation. This new mutation may be specifically associated with the von Hippel-Lindau type 2C disease phenotype. Whether this mutation is linked to the metabolic alterations developed by these patients remains to be determined.

Normal sympathetic nervous system response in reflex sympathetic dystrophy.

We evaluated sympathetic nervous system activity by sympathetic skin response (SSR) recording and we further investigated sympathetic and opioid outflow indirectly in patients with features of reflex sympathetic dystrophy by measuring concentrations of plasma catecholamines (CAs) and their metabolites and plasma metenkephalin (ME), before and after corticoid treatment. Six patients were studied. Basal SSR latencies, morphologies and amplitudes were normal in five patients. In one woman, latency and amplitude were also normal but the morphology was disturbed. Basal plasma ME, CA and metabolite levels were similar in the affected and non-affected limbs and a significant increase in plasma ME concentrations was observed in both affected and non-affected limbs after two weeks of steroid treatment. Altogether these results point to an adaptive supersensitivity rather than a sympathetic hyperactivity in this syndrome; also, they indicate that the therapeutic effect of steroids adds, to their known anti-inflammatory action, a stimulatory action on the endogenous opioid system.

La cinética del sistema renina-angiotensina en distintos tipos de hipertensión arterial / The kinetic of the renin-angiotensin system in different types of arterial hypertension

Se estudió la cinética del sistema renina - angiotensina en 51 enfermos con hipertensión arterial (2 enfermos con aldosternismo primario, 31 pacientes con hipertensión arterial esencial y 18 con hipertensión arterial secundaria a enfermedad renal parenquimatosa. Como control se estudiaron 31 sujetos normales. Se midieron los valores basales de actividad plasmática de la renina (APR) y los niveles de la APR después de la administración de 40 mg de furosemida, ev y después de una dosis presora de angiotensina II, ev. Además se estudiaron los niveles del sustrato de la renina y la velocidad de reacción entre la renina y el sustrato. En algunos de los enfermos los estudios se repitieron después de tratar a los enfermos durante un mes con furosemida (160-240 mg,d), propranolol (160-240 mg,d) o con terbuclomida (48 mg,d). El 23 por ciento de los pacientes con hipertensión esencial presentó niveles bajos, el 45 por ciento niveles normales y el 32 por ciento niveles altos de APR. Mientras que los pacientes con hipertensión arterial secundaria a enfermedad renal parenquimatosa presentaron en un 16 por ciento niveles bajos, en un 39 por ciento niveles normales y en un 45 por ciento niveles altos de APR. Hubo una excelente correlación entre los niveles de APR y la respuesta presora a la infusión de angiotensina II en los 2 grupos de pacientes. La velocidad de reacción de renina sustrato fue más alta en los pacientes con hipertensión secundaria a enfermedad renal que en los enfermos con hipertensión esencial en los cuales la velocidad de reacción fue similar a la observada en sujetos normales. La administración de furosemida aumentó, mientras que la administración de angiotensina inhibió la APR en los sujetos normales. Los pacientes con hipertensión arterial secundaria a enfermedad renal parenquimatosa no modificaron los niveles de APR en respuesta ambos estímulos, mientras que en los pacientes con hipertensión arterial los resultados fueron variables. La administración de lasix, propranolol y terbuclomida disminuyó los niveles de la presión diastólica en todos los enfermos estudiados, a pesar de que, la administración de Lasix aumentó los niveles de renina, el propranolol los disminuyó y la terbuclomida no los modificó. Estos últimos fármacos disminuyeron la velocidad de reacción enzimática en los pacientes con hipertensión arterial secundaria a enfermedad renal y no la modificaron en los enfermos con hipertensión esencial. (AU)

La cinética del sistema renina-angiotensina en distintos tipos de hipertensión arterial / The kinetic of the renin-angiotensin system in different types of arterial hypertension

Se estudió la cinética del sistema renina - angiotensina en 51 enfermos con hipertensión arterial (2 enfermos con aldosternismo primario, 31 pacientes con hipertensión arterial esencial y 18 con hipertensión arterial secundaria a enfermedad renal parenquimatosa. Como control se estudiaron 31 sujetos normales. Se midieron los valores basales de actividad plasmática de la renina (APR) y los niveles de la APR después de la administración de 40 mg de furosemida, ev y después de una dosis presora de angiotensina II, ev. Además se estudiaron los niveles del sustrato de la renina y la velocidad de reacción entre la renina y el sustrato. En algunos de los enfermos los estudios se repitieron después de tratar a los enfermos durante un mes con furosemida (160-240 mg,d), propranolol (160-240 mg,d) o con terbuclomida (48 mg,d). El 23 por ciento de los pacientes con hipertensión esencial presentó niveles bajos, el 45 por ciento niveles normales y el 32 por ciento niveles altos de APR. Mientras que los pacientes con hipertensión arterial secundaria a enfermedad renal parenquimatosa presentaron en un 16 por ciento niveles bajos, en un 39 por ciento niveles normales y en un 45 por ciento niveles altos de APR. Hubo una excelente correlación entre los niveles de APR y la respuesta presora a la infusión de angiotensina II en los 2 grupos de pacientes. La velocidad de reacción de renina sustrato fue más alta en los pacientes con hipertensión secundaria a enfermedad renal que en los enfermos con hipertensión esencial en los cuales la velocidad de reacción fue similar a la observada en sujetos normales. La administración de furosemida aumentó, mientras que la administración de angiotensina inhibió la APR en los sujetos normales. Los pacientes con hipertensión arterial secundaria a enfermedad renal parenquimatosa no modificaron los niveles de APR en respuesta ambos estímulos, mientras que en los pacientes con hipertensión arterial los resultados fueron variables. La administración de lasix, propranolol y terbuclomida disminuyó los niveles de la presión diastólica en todos los enfermos estudiados, a pesar de que, la administración de Lasix aumentó los niveles de renina, el propranolol los disminuyó y la terbuclomida no los modificó. Estos últimos fármacos disminuyeron la velocidad de reacción enzimática en los pacientes con hipertensión arterial secundaria a enfermedad renal y no la modificaron en los enfermos con hipertensión esencial.