Primary aldosteronism with concurrent primary hyperparathyroidism: clinical case load in a single centre.

OBJECTIVE: Primary aldosteronism (PA) represents the main cause of endocrine secondary arterial hypertension in which aldosterone production is inappropriately elevated. Primary hyperparathyroidism (PHPT) is an endocrine disease characterized by hypercalcemia due to overproduction of parathyroid hormone (PTH). Although these two endocrine pathologies are secondary to hypertension in middle aged population, the occurrence of the PHPT in PA patients has rarely reported in the literature. The aim of the study was to describe some PA patients with concurrent PHPT, referred in a tertiary center of arterial hypertension. PATIENTS: We performed a retrospective study. In particular, the registry of 306 patients with PA seen in our center since 2004 was examined and revealed 8 patients (2.6%) with concurrent PHPT. CONCLUSIONS: There are several possible explanations for the association of these two endocrine disorders, including the combination was a random finding that PA inheres PHPT or vice versa.

Role of dopaminergic receptors in the human dura mater in the pathogenesis of headache.

AIMS: We hypothesize that dopaminergic receptors of dura mater may play a possible role in headache. MATERIALS AND METHODS: The dopaminergic receptors of cranial dura mater in man were studied by examining several dural zones (vascular, peri-vascular, inter-vascular) in different brain regions (basal, calvarial, tentorial, occipital, frontal, parietal, temporal). RESULTS: Our results demonstrate that dopaminergic receptors are present in human cranial dura mater and that these receptors show a specific morphological location. There are more dural dopaminergic receptors in the basal region than in the calvarial one. Moreover, these receptors are more abundant in the vascular and perivascular dural zone than in the intervascular one. CONCLUSIONS: The location of dopaminergic receptors in the dura mater may represent an important factor in the pathogenesis of headache. Further studies will be necessary in order to determine the role of dopaminergic system in this disease.

Catecholaminergic nerve fibers in bronchus-associated lymphoid tissue: age-related changes.

Age-related changes of the catecholaminergic nerve fibers of the trachea, bronchial smooth muscle, lung capillaries and bronchus-associated lymphoid tissue (BALT) were studied in male Wistar rats aged 3 months (young), 12 months (adult) and 24 months (old/aged). Catecholamine histo- and immuno-fluorescence techniques were used, associated with image analysis and high pressure liquid chromatography with electrochemical detection of nor-epinephrine (nor-adrenaline). In young rats, blue-green fluorescent nerve fibers supply the trachea-bronchial smooth muscle and tracheal and bronchial glands. These structures are innervated by a delicate network of nerve fibers, being rich in varicosities. Pulmonary capillaries are sparsely innervated. The highest nor-epinephrine concentration was found in the trachea and bronchi, followed by BALT. The density and the pattern of noradrenergic nerve fibers of the trachea-bronchial tree or of the pulmonary vessels were similar in young and adult rats. In aged rats, a loss of noradrenergic nerve fibers, involving primarily the supply to the smooth muscle of the trachea-bronchial tree, was observed. Fluorescence microscopic techniques demonstrated a higher sensitivity than nor-epinephrine assay in detecting changes of the sympathetic nerve supply of the trachea-bronchial tree, pulmonary vessels and BALT. The possible significance of reduced noradrenergic nerve supply of the trachea-bronchial-pulmonary tree in aged rats is discussed.

Cholinergic innervation of BALT (bronchus associated lymphoid tissue) in rat.

The presence and distribution of acetylcholinesterase (AChE) and cholineacetyl transferase activities (Chat) were examined in the bronchus-associated lymphoid tissue (BALT) of juvenile, adult and old rats. Histoenzymatic and immunochemical methods were used in association with quantitative analysis of images and statistical analysis of the data. Our results showed that both AChE and Chat activities were primarily confined to the BALT lymphoid cells. Only a low level of activity was observed in the sub-pleural parenchyma of the lung and in the wall of the bronchus. Moreover, both AChE and Chat activities in the BALT are specifically located in the lymphoid cells. Histoenzymatic staining and corresponding values of quantitative analysis of images confirmed morphological and immunochemical results. Finally, the intensity of histoenzymatic staining for AChE and of immunochemical staining for Chat in BALT of rats strongly decreases with age. On the basis of our results we hypothesize that both AChE and Chat activities may play an important role in BALT and both these enzymes undergo specific age-related changes.

What sedation to use during endoscopic procedure.

Many endoscopists sometimes prefer to perform endoscopies without anaesthetic support, using only benzodiazepines. Endogenous opioid peptides are believed to play an important role in the modulation of pain within the endogenous analgesic system. A group of 40 patients undergoing diagnostic and therapeutic Endoscopic Retrograde Cholangiography and Pancreatography (ERCP) was recruited. Patients were divided into 2 groups according to Visual Analog Scale: pain 1-5 (Group A) and pain 6-10 (Group B). The beta-endorphin baseline values were significantly different between patients of Group A and Group B. Our data show that patients with levels of beta-endorphin over 8 pmol/L were less sensitive to pain, so that they become candidates for a traditional utilization of the benzodiazepines. However in the patients with beta-end levels less of 8 pmol/L should be suitable an anaesthetic as propofol because strong pain might provoke neurohumoral reflexes, cardiovascular alterations, and even a heart attack.

ET-1 levels in cardioischemic patients undergoing atrial pacing.

Atrial pacing (AP) procedure was carried out in 11 cardioischemic patients to reproduce tachycardia-induced myocardial ischemia. Six control subjects underwent the same procedure until the maximum pacing rate was reached. During the procedure, endothelin-1 (ET-1) and plasma lactate levels were measured in the coronary sinus and in the aortic root. In all the patients, atrial pacing provoked electrocardiographic signs and metabolic evidence of myocardial ischemia and a significant decrease (p<0.001) in left ventricular ejection fraction. At AP-induced ischemia, coronary sinus (17.31 +/- 4.20 pg/mL) and arterial (9.60 +/- 3.31 pg/mL) ET-1 plasma levels were significantly different (p<0.001) in the patients. On the contrary, at maximum pacing rate, no significant difference (p=0.186) emerged between coronary sinus (9.72 +/- 1.09 pg/mL) and arterial (8.95 +/- 0.75 pg/mL) plasma ET-1 levels in the control group. These results suggest that, in cardioischemic patients, tachycardia can induce the coronary endothelium to release significant amounts of ET-1.

Met-enkephalin levels during PTCA-induced myocardial ischemia.

Met-enkephalin (Met-enk) has been demonstrated to modulate myocardial-ischemia mechanisms via the opioid receptors, but no studies are now available on Met-enk levels in the coronary circulation. In this experience Met-enk levels were evaluated in aortic root and in coronary sinus at baseline (T0), during PTCA induced transient ischemia (T1) and during reperfusion (T2). No significant differences were found at any time. Thus, it appears that there is no Met-enk extraction from the coronary circulation during provoked myocardial ischemia and no Met-enk release from the ischemic heart.

The role of met-enkephalin in silent myocardial ischemia in diabetic patients.

Met-enkephalin plasma levels were evaluated in 20 cardioischemic diabetic patients. All the patients had ECG ischemic signs. Ten patients with diabetic autonomic neuropathy, experienced no pain during myocarial ischemia. Met-enkephalin levels in the diabetic patients with silent myiocardial ischemia were significantly lower compared to those in the symptomatic patients. This demonstrates that the absence of myocardial ischemic pain in neuropathic diabetic patients is not accounted for by met-enkephalin action.

Increased plasma concentration of atrial natriuretic hormone in myotonic dystrophy.

Atrial natriuretic hormone (ANH) concentrations were measured in 16 patients affected with myotonic dystrophy (MyD) undergoing 24-hour Holter ECG and in 15 age-matched normal subjects. Although the MyD patients did not show overt left ventricular function impairment, their plasma ANH levels were found to be higher (183.76 +/- 113.25 pg/ml) compared to those of the control subjects (39.73 +/- 9.95 pg/ml, p < 0.001). Nine patients with arrhythmias and some echocardiographic alterations formed subgroup A. Seven patients without cardiac alterations formed subgroup B. No significant difference in ANH emerged between the two subgroups. This evidence suggests that high plasma ANH levels in MyD cannot always be related to overt or latent heart failure and to arrhythmias.

Plasma atrial natriuretic hormone in hyperthyroidism.

In 22 hyperthyroid patients, atrial natriuretic hormone (ANH) levels (71.91 +/- 21.03 pg/ml), measured during a 3-h-Holter, were found to be significantly higher (p < 0.001) than those in 20 age-matched normal subjects (37.22 +/- 8.73 pg/ml). We have demonstrated that the presence of tachiarrhythmias does not influence ANH release. The positive and significant correlation of FT3 with both ANH and heart rate confirms the hypothesis of a direct action of thyroid hormones on ANH release.

Coronary sinus plasma beta endorphin levels in cardioischemic patients undergoing PTCA.

Plasma beta-endorphin levels were studied in the coronary sinus of 8 patients undergoing percutaneous transluminal coronary angioplasty (PTCA). All the patients had ECG ischemic signs and pain during the inflation of the balloon. No significant changes in plasma beta-endorphin levels were observed during PTCA-induced ischemia. Baseline coronary sinus plasma beta-endorphin levels were found to be elevated when compared with peripheral ones which would suggest an accumulation of beta-endorphin in the ischemic heart.

ET-1 plasma levels during cold stress test in sclerodermic patients.

Endothelial cell injury in blood vessels of small arteries and capillaries is considered the primary event in the pathogenesis of systemic sclerosis (SSc). Because endothelin-1 (ET-1) is mainly released in the site of endothelial cell damage, thereby inducing a potent vasoconstriction, it was our intention to study ET-1 release in a group of SSc patients during a cold pressor test (CPT). Twelve SSc patients and a control group of 10 healthy subjects underwent CPT. Blood samples for ET-1 assay were collected at 90 and 180 seconds of exposure to cold stress. Heart rate and blood pressure were recorded at the same intervals. A capillaroscopic examination was performed in both groups before and after CPT. We observed significantly higher levels of plasma ET-1 in SSc patients compared with those of the control group at baseline (P=0.007) and at 90 (P=0.006) and 180 seconds (P=0.03) of CPT. During the test, the capillaroscopic examination showed a dramatic worsening of the vascular picture that was parallel to the increase in ET-1 plasma levels. This suggests that higher ET-1 plasma levels can have a part in the acute vascular reactivity of SSc patients undergoing CPT.

Plasma met-enkephalin levels in diabetic patients: influence of autonomic neuropathy.

The presence of opioid peptides within pancreatic islets in several animal species and in humans suggests that these peptides could play a role in pancreatic endocrine secretion, influencing glucose metabolism. We measured plasma met-enkephalin (met-Enk) levels in eight neuropathic (four with insulin-dependent diabetes mellitus [IDDM] and four with non-insulin-dependent diabetes mellitus [NIDDM]) and eight nonneuropathic (four IDDM and four NIDDM) diabetic patients to study met-Enk secretion in diabetic patients with asymptomatic autonomic neuropathy. Plasma met-Enk levels were significantly lower in neuropathic compared with nonneuropathic patients both in the IDDM group (28.7 +/- 4.8 v 61.6 +/- 4.1 pg/mL, P < .0025) and in the NIDDM group (26.5 +/- 3.6 v 44.3 +/- 4.6 pg/mL, P < .0125). This study suggests that the presence of neuropathy in diabetic patients, even if asymptomatic, is associated with a significant decrease of plasma met-Enk levels, thus contributing to a worsening of metabolic control under stress conditions.

Beta-endorphin in silent duodenal ulcer.

OBJECTIVE: To investigate whether duodenal ulcer patients with painful active peptic ulcer and those with silent active ulceration have different plasma beta-endorphin levels. PATIENTS: Forty-five patients (28 men and 17 women), aged 38-50 years, with at least a 5-year history of duodenal ulceration. Twenty-two patients had painful symptoms, while 23 had silent active duodenal ulcer. METHODS: Beta-endorphin plasma levels (pmol/l) were measured during an acute episode of duodenal ulcer, before and after antisecretory therapy with omeprazole. In three patients we measured the concentration of beta-endorphin in gastric juice before and after pentagastric (6 micrograms/kg subcutaneous) stimulation. RESULTS: The basal values of beta-endorphin in both patients with asymptomatic and those with symptomatic duodenal ulcer showed no difference before or after 30 days of antisecretory treatment. Plasma beta-endorphin levels (median values in the normal range < 12 pmol/l) were significantly higher (Student's t-test, P < 0.005) in the asymptomatic than in symptomatic patients, both before (9.07 +/- 4.8 versus 5.6 +/- 2.5 pmol/l) and after (8.7 +/- 4.1 versus 5.7 +/- 2.4 pmol/l) omeprazole treatment. The highest levels of beta-endorphin were found in four patients with a negative history for any pain symptom (visual analogue scale score 0). CONCLUSIONS: Our data suggest that the opioid system, particularly beta-endorphin, is involved in the perception of pain in duodenal ulcer disease, which explains the silent clinical characteristics of some peptic ulcers. In addition, the concentration of beta-endorphin found in gastric juice indicates a possible peripheral effect of this opiate.

Plasma opioid levels during extracorporeal gallstone lithotripsy.

Plasma levels of beta-endorphin (beta-EP), met-enkephalin (met-ENK), ACTH, cortisol, and prolactin were measured in 20 patients who underwent extracorporeal gallstone lithotripsy (ESWL) before the treatment, at 500 shock waves (SW) (15-20 min), at 1000 SW (40-50 min), and 10 min after the end of ESWL. According to the Visual Analog Scale, nine patients had no pain, seven patients had pain from level 1 to 5, and four patients had pain from 5 to 10. No complications were observed. Plasma beta-EP values increased during the treatment, both in patients without pain and in those with pain. Only in the former group was the increase significant (baseline values (pmol/L): no pain = 4.04 +/- 1.3; pain 1-5 = 3.6 +/- 1.06; pain 5-10 = 2.9 +/- 0.5. Peak values: no pain = 6.6 +/- 1.2 (p < 0.005); pain 1-5 = 4.6 +/- 2.5; pain 5-10 = 4.5 +/- 2.2). Moreover, a negative correlation between beta-EP levels and individual pain scores during ESWL has been observed (CC = -0.64, p < 0.003). Plasma met-ENK levels reached the peak at 1000 SW and declined 10 min after the end of the treatment, although they were always higher than basal values (baseline values (pg/ml): no pain = 45 +/- 12; pain 1-5 = 38 +/- 10; pain 5-10 = 48 +/- 8. Peak values: no pain = 112 +/- 42 (p < 0.005), pain 1-5 = 114 +/- 48 (p < 0.005), pain 5-10 = 85 +/- 10 (p < 0.005). This behavior has been the same, regardless of the presence or absence of pain. We conclude that during ESWL, a rise of beta-EP and met-ENK occurs, and the increase of the former can be responsible for induction of analgesia because of its inverse correlation with pain intensity.

Plasma met-enkephalin in type I diabetes.

Physiological and pathological evidence suggests that opioid peptides may play a role in glucose homeostasis. We measured plasma levels of beta-endorphin (beta-END) and met-enkephalin (met-ENK) in 22 type I diabetic patients and 15 healthy women (control group). No differences were observed in plasma beta-END levels, whereas plasma met-ENK levels were significantly higher (Student's t test, P less than .005) in diabetics than in controls before (68 +/- 3 pg/mL v 32 +/- 7 pg/mL) and 1 hour after, a standard meal and administration of insulin therapy (81 +/- 9 pg/mL v 32 +/- 7 pg/mL). This is the first report of met-ENK levels in insulin-dependent diabetes mellitus (IDDM), and an impaired feedback of insulin/met-ENK is suggested.

High levels of circulating met-enkephalin in pregnant and menstruating type 1 diabetic women.

Plasma met-enkephalin (MET-ENK) levels are increased in type 1 diabetic women and in pregnant diabetic women in comparison with normal women. Plasma MET-ENK levels further increase in the peripartum period both in diabetic and non-diabetic females, probably due to the analgesic and behavioural properties of the opioid system.