Seventy years of pheochromocytomas and paragangliomas in Argentina. The FRENAR database.

Pheochromocytomas and paragangliomas (PPGL) are neuroendocrine tumors characterized by the excessive production of catecholamines. This study aims to describe the clinical characteristics of PPGL cases in Argentina over recent decades. A multicenter retrospective cross-sectional analysis was carried out using a database comprising both pediatric and adult patients with confirmed PPGL diagnoses based on pathological reports. A cohort of 486 patients with PPGL was recruited. Women represent 58.4% of the patients, with a mean age of 38.3 years old at the time of diagnosis and 15.2% of the patients were under the age of 18. Hypertension, as well as classic signs and symptoms, were present in 80.9% of the patients. The adrenal incidentaloma, as a mode of presentation, increased in the last two decades rising from 3.9% (1953-2000) to 21.8% (2001-2022), p<0.001. Most tumors were located within the adrenal glands, accounting 83.0% of the cases, with bilateral occurrences noted in 20.0%. The median tumor size was 4.8cm. Local recurrence and metastases were observed in 10.9% and 12.2%. Out of 412 patients, 87.0% exhibited urinary excretion elevation of catecholamines and/or their metabolites. Furthermore, 148 patients, representing 30.4% of the study population, displayed a distinct genetic profile indicative of hereditary syndromes. The distribution of hereditary syndromes revealed that MEN2, VHL, and PGL4 constituted the most prevalent syndromes. This population-based study, spanning seven decades, offers valuable insights into the demographic and clinical characteristics of PPGL patients in Argentina.

Increased plasma atrial natriuretic factor in catecholamine-producing tumor patients.

The aim of this study was to evaluate plasma levels of ANF in patients with catecholamine-secreting tumors with and without hypertension and to relate ANF secretion to levels of plasma and urinary catecholamines and blood pressure. Twenty-one pheochromocytoma (15 with sustained, 6 with paroxysmal hypertension), 6 neuroblastoma (1 hypertensive) patients and 28 aged-matched controls were studied in basal conditions. Plasma and urinary norepinephrine (NE),epinephrine (E), dopamine (DA) and DOPA were determined by HPLC-ED and plasma ANF by RIA. Both neuroblastoma and pheochromocytoma patients had significantly higher plasma ANF levels than controls. Neuroblastomas showed higher ANF concentration than pheochromocytomas. No differences were found in plasma ANF between hypertensive and normotensive patients. Pheochromocytomas with ANF levels within the normal range had plasma and urinary NE and urinary DA and DOPA levels significantly higher than patients with high ANF. Plasma ANF levels were unrelated to systolic or diastolic blood pressure or heart rate. A negative correlation between plasma ANF and urinary DA was found only in the patients groups. In conclusion, plasma ANF was increased in pheochromocytoma and neuroblastoma patients. Our data suggest that the excessive catecholamine secretion is not responsible for the increased ANF secretion in these patients. The significance of the relationships among plasma ANF and urinary and plasma catecholamines requires further investigation.

The stress-induced reduction in monoamine oxidase (MAO) A activity is reversed by benzodiazepines: role of peripheral benzodiazepine receptors.

1. The effect of benzodiazepine pretreatment on the stress-induced decrease in MAO activity in rat tissues using footshock as stress model was investigated. 2. Animals were injected with vehicle, Lorazepam (1.25 mg/kg), or Clonazepam (0.5 mg/kg) 2 hr before or with PK 11195 (0.45 mg/kg) 2.5 hr before being subjected to one session of 10 inescapable footshocks or to a sham session. At the end of the session animals were sacrificed and MAO A and B activities in hearts and brains were determined. 3. Pretreatment of the animals with both Lorazepam and Clonazepam abolished the decrease induced by footshock in MAO A activity in brain. Pretreatment with Lorazepam but not with Clonazepam abolished the stress-induced decrease in MAO A in the heart. Pretreatment with PK 11195 before Lorazepam reversed its effects in the heart but not in the brain. Neither footshock nor any of the drugs used had any effect on heart and brain MAO B. 4. Our results suggest that in the heart but not in the brain, peripheral benzodiazepine receptors play a role in the regulation of MAO A activity under stress conditions.

Sympathetic adrenomedullary activity in cluster headache.

It is well known that autonomic phenomena, such as lacrimation, rhinorrhea, and Horner's syndrome, are associated with the pain attacks in episodic cluster headache. In order to elucidate the cause of these symptoms we studied plasma free and sulphoconjugated catecholamines in cluster headache patients during the pain attacks and in the following hours, as well as during the remission period. No change in these amine levels was found. We conclude that dysautonomic symptoms are not reflected in plasma catecholamine modification.

Changes in neutrophil met-enkephalin containing peptides in episodic cluster headache.

We have previously demonstrated an increase in plasma met-enkephalin levels during the pain attacks in episodic cluster headache. The present study was undertaken in order to clarify the source of the plasma met-enkephalin increase. Recent evidence has shown that peripheral blood polymorphonuclear cells contain peptides derived from the proenkephalin A system, which can be released by specific stimuli. We studied neutrophil met-enkephalin containing peptides (NMECP) in 27 episodic cluster headache patients: 24 in a cluster period (6 of them during a pain attack), and 3 in the remission period. Neutrophil met-enkephalin containing peptide levels (after sequential enzymatic digestion with trypsin and carboxypeptidase B) were determined by radioimmunoassay with specific antiserum. Neutrophil peptide concentration (pmol/mg prot) was lower (p less than 0.01) in patients during the pain attack (14.4 +/- 0.36) than after their pain had subsided (36.7 +/- 0.31) and lower than in the remission period patients (35.8 +/- 0.4). We conclude that neutrophil met-enkephalin containing peptides decrease during pain in episodic cluster headache, and that they may be involved in the concomitant plasma met-enkephalin increase.

Increase in plasma methionine-enkephalin levels during the pain attack in episodic cluster headache.

Since high levels of endogenous opioids (endorphins, enkephalins) were found in brain areas classically related to nociception, their peripheral levels in humans were studied in different pain syndromes yielding contradictory results. This study was undertaken to assess changes in plasma methionine-enkephalin (met-enkephalin) levels in patients with episodic cluster headache associated with the pain period. Twenty-nine patients, 24 in the cluster period (6 of them during an attack) and 3 in the remission period were studied. Two other patients were subjected to a longitudinal follow-up. Plasma met-enkephalin levels were determined by radioimmunoassay (RIA) with specific antibody. Plasma peptide concentration (pmol/ml) was higher (p less than 0.001) in patients during the pain attack (3.97 +/- 1.18) than in controls (0.25 +/- 0.03). When measured 4 and 48 h after the pain attack lower levels were found (0.46 +/- 0.06) which decreased to control values after 24 h. These results may suggest involvement of peripheral enkephalins in pain modulation in patients with episodic cluster headache.

Free and conjugated plasma catecholamines in pheochromocytoma patients with and without sustained hypertension.

Ten pheochromocytoma patients, five with paroxysmal hypertension (Group 1), five with sustained hypertension (Group 2) and 15 normals were studied to determine the relationship between differential secretion of the catecholamines (CA) or differences in their sulphoconjugation and the hypertension patterns in these patients. Group 1 patients were studied in the normotensive period. A consistent finding in this study is that permanent hypertensive patients showed the highest free and conjugated norepinephrine (NE) levels while paroxysmal patients studied during the normotensive period showed the highest conjugated epinephrine (E) levels. Although no significant difference was found in levels of free plasma epinephrine in the Group 1 patients, in the ratio of total plasma E/NE, E was clearly predominant. No significant differences could be found in the degree of the per cent conjugation of individual catecholamines between both groups of patients. Group 1 showed a higher (P less than 0.05) E and a lower dopamine (DA) per cent conjugation than controls. In conclusion, although the dominant type of CA secreted seems to be the main factor in determining the hypertension pattern, sulphoconjugation ability may also play an important role.

Sympathetic nervous system response to graded exercise: effect of beta-blockade.

This study compares the sympathetic nervous system response to graded exercise in normotensive and essential hypertensive subjects with and without beta-adrenergic blockade. Blood pressure (BP), heart rate, and plasma norepinephrine (NE), epinephrine (E), and dopamine (DA) were measured just before starting the exercise (Pre-Ex), in the submaximal exercise (Sub-max),and after 8 minutes rest (Post-Ex). On placebo, Sub-max induced in both normotensives and hypertensives a similar increase in NE and E plasma levels. Plasma DA remained unchanged. Propranolol in controls and propranolol or mepindolol in hypertensives didn't modify significantly: 1) Pre-Ex plasma levels of E, NE, and DA; 2) response at Sub-max in controls; 3) plasma E and DA in hypertensive patients. In hypertensives on beta-blockade, submaximal exercise elicited a greater increase in plasma NE. Values for plasma NE in patients on propranolol were 1135 +/- 229 pg/ml higher than those obtained in the same patients on placebo (p less than 0.001). On mepindolol, the plasma NE increment was higher than that on placebo (p less than 0.05), but lower than that on propranolol (p less than 0.01). In controls, propranolol did not significantly modify BP at Pre-Ex or its response to exercise, whereas systolic and diastolic BP were significantly lower at Pre-Ex, Sub-max, and Post-Ex in hypertensives. On beta-blockade, heart rate decrease in Pre-Ex, Sub-max, and Post-Ex were not different in controls and hypertensives. The differences found on beta blockade would indicate that the effects of beta blockers are not identical in normotensive and hypertensive subjects.