Clinical presentation and management of patients with primary hyperparathyroidism in Italy.

PURPOSE: Evaluation of the phenotype of primary hyperparathyroidism (PHPT), adherence to International Guidelines for parathyroidectomy (PTx), and rate of surgical cure. METHOD: From January 2014-January 2016, we performed a prospective, multicenter study in patients with newly diagnosed PHPT. Biochemical and instrumental data were collected at baseline and during 1-year follow-up. RESULTS: Over the first year we enrolled 604 patients (age 61 ± 14 years), mostly women (83%), referred for further evaluation and treatment advice. Five hundred sixty-six patients had sporadic PHPT (93.7%, age 63 ± 13  years), the remaining 38 (6.3%, age 41 ± 17  years) had familial PHPT. The majority of patients (59%) were asymptomatic. Surgery was advised in 281 (46.5%). Follow-up data were available in 345 patients. Eighty-seven of 158 (55.1%) symptomatic patients underwent PTx. Sixty-five (53.7%) of 121 asymptomatic patients with at least one criterion for surgery underwent PTx and 56 (46.3%) were followed without surgery. Negative parathyroid imaging studies predicted a conservative approach [symptomatic PHPT: OR 18.0 (95% CI 4.2-81.0) P < 0.001; asymptomatic PHPT: OR 10.8, (95% CI 3.1-37.15) P < 0.001). PTx was also performed in 16 of 66 (25.7%) asymptomatic patients without surgical criteria. Young age, serum calcium concentration, 24 h urinary calcium, positive parathyroid imaging (either ultrasound or MIBI scan positive in 75% vs. 16.7%, P = 0.001) were predictors of parathyroid surgery. Almost all (94%) of patients were cured by PTx. CONCLUSIONS: Italian endocrinologists do not follow guidelines for the management of PHPT. Negative parathyroid imaging studies are strong predictors of a non-surgical approach. PTx is successful in almost all patients.

A simple ultrasound score for the identification of candidates to fine needle aspiration of thyroid nodules.

BACKGROUND: Cytological examination of fine needle aspirates (FNA) is the standard procedure for discriminating potentially malignant thyroid nodules to be referred to surgery. In a fraction of cases, ultrasound (US) examination could provide information theoretically sufficient to avoid FNA, when typical US features suggesting malignancies are lacking. AIM: The aim of this study was to construct a simple US score predicting malignant nodules so as to reduce the number of unnecessary FNA. SUBJECTS AND METHODS: In a series of 1632 consecutive patients undergoing US-guided FNA (1812 nodules), echostructure, echogenicity, margins, halo, microcalcification, and vascularization were assessed. RESULTS: At multivariate analysis, the following parameters showed a strong predictive value for positive cytology (Thy 4 and Thy 5, suspicious and diagnostic for malignancy, respectively, according to the Thyroid British Association): solid echostructure, irregular margins and hypoechogenicity [adjusted odd ratio (OR) 5.13 (1.58-16.66), 3.03 (1.70-5.39), 2.05 (1.17-3.57), respectively]. A 10-point Thyroid Risk Ultrasound Score (TRUS) was constructed on the basis of the adjusted OR. A TRUS≥6 identified malignant nodules with sensitivity and specificity of 73% and 65%, respectively. Among the patients with follicular lesions (Thy 3) and final diagnosis of carcinoma, about 65% had a TRUS≥6.0. CONCLUSIONS: The sensitivity of TRUS, although higher than that of other scores, could still be insufficient for the identification of patients who could avoid FNA in routine clinical practice, whereas its predictive value for Thy 3 lesions deserves further investigations.

The basal to total insulin ratio in outpatients with diabetes on basal-bolus regimen.

OBJECTIVE: To evaluate the basal/total ratio of daily insulin dose (b/T) in outpatients with diabetes type 1 (DM1) and type 2 (DM2) on basal-bolus regimen, by investigating whether there is a relationship with HbA1c and episodes of hypoglycemia. METHODS: Multicentric, observational, cross-sectional study in Italy. Adult DM1 (n = 476) and DM2 (n = 541) outpatients, with eGFR >30 mL/min/1.73 m2, on a basal-bolus regimen for at least six months, were recruited from 31 Italian Diabetes services between March and September 2016. Clinicaltrials.govID: NCT03489031. RESULTS: Total daily insulin dose was significantly higher in DM2 patients (52.3 ± 22.5 vs. 46 ± 20.9 U/day), but this difference disappeared when insulin doses were normalized for body weight. The b/T ratio was lower than 0.50 in both groups: 0.46 ± 0.14 in DM1 and 0.43 ± 0.15 in DM2 patients (p = 0.0011). The b/T was significantly higher in the patients taking metformin in both groups, and significantly different according to the type of basal insulin (Degludec, 0.48 in DM1 and 0.44 in DM2; Glargine, 0.44 in DM1 and 0.43 in DM2; Detemir, 0.45 in DM1 and 0.39 in DM2). The b/T ratio was not correlated in either group to HbA1c or incidence of hypoglycemia (<40 mg/dL, or requiring caregiver intervention, in the last three months). In the multivariate analysis, metformin use and age were independent predictors of the b/T ratio in both DM1 and DM2 patients, while the type of basal insulin was an independent predictor only in DM1. CONCLUSION: The b/T ratio was independent of glycemic control and incidence of hypoglycemia.

Correction to: The basal to total insulin ratio in outpatients with diabetes on basal-bolus regimen.

[This corrects the article DOI: 10.1007/s40200-018-0358-2.].

Natriuretic hormone receptors and actions on bone endothelial cells.

[125I]Atrial natriuretic peptide (ANP) was used to identify ANP receptors on a clonal line of bovine bone endothelial (BBE) cells. Specific binding of [125I]ANP was saturable and of high affinity. Computer analysis of the equilibrium binding data indicated that the Scatchard plots are best fit by a straight line (Kd = 69.3 +/- 20.9 pM; binding capacity = 37.9 fmol/10(6) cells). The order of potency for competing with [125I]ANP binding was human ANP (hANP) > rat atriopeptin-1 (rAP-1) > porcine brain natriuretic peptide (pBNP) > porcine C-type natriuretic peptide. Affinity cross-linking studies indicated the presence of two major 130- and 70-kilodalton bands that specifically bound to hANP, rAP-1, pBNP, and porcine C-type natriuretic peptide. The binding of natriuretic peptides to BBE cells resulted in an increase in cGMP production and a significant decrease in Na+/K+/Cl- cotransport, without effects on cAMP intracellular accumulation. hANP, rAP-1, and pBNP at 100-nM concentrations, significantly inhibited PTH-induced cAMP production. Treatment with natriuretic hormones was also associated with an increase in 6-keto-prostaglandin F1 alpha levels in the culture medium of BBE cells and a higher cell growth rate. These studies demonstrate that bone endothelial cells bear receptors for natriuretic hormones associated with changes in PTH-induced cAMP production, prostaglandin production, and cell proliferation.

Endogenous dopamine (DA) and DA2 receptors: a mechanism limiting excessive sympathetic-adrenal discharge in humans.

We studied the effects of presynaptic dopamine (DA) 2 receptor blockade on the sympathetic-adrenal response to graded exercise in seven normal men. DA2 receptor blockade was achieved by means of domperidone (DMP) administration. The exercise consisted of progressive cycling activity, from 30-80% of the predetermined maximal oxygen consumption for each man. Systolic, diastolic, and mean arterial pressures; heart rate; and plasma norepinephrine (NE), epinephrine (E), PRL, glucose, lactate, FFA, sodium, potassium, cortisol, and PRA were measured at rest, during exercise, and during recovery after placebo or DMP administration. Graded exercise caused significant increases in systolic and mean arterial pressures and plasma NE, E, lactate, sodium, potassium, FFA, cortisol, and PRA. DMP administration before exercise caused a significant increase in plasma PRL (P = 0.0009), a greater increase in plasma NE at the end of the exercise (P = 0.002), and an overall increase in plasma E (P = 0.02) and FFA (P = 0.02) concentrations. These results strongly suggest that endogenous DA limits catecholamine release during sympathetic-adrenal stimulation by activating DA2 receptors.

Cardiovascular effects of parathyroid hormone: a study in healthy subjects and normotensive patients with mild primary hyperparathyroidism.

The aim of the study was to evaluate: 1) the cardiovascular function and the autonomic drive to the heart in patients affected by primary hyperparathyroidism (pHPT) with no evidence of renal and cardiovascular complications; 2) the cardiovascular effects of acute administration of PTH in normal subjects. In 14 patients affected by mild asymptomatic pHPT echocardiographic assessment of cardiovascular function and of the mechanic properties of the brachial and carotid artery, heart rate variability and the dispersion of QT interval were performed before and 6 months after successful surgery. Twenty age- and sex-matched healthy subjects were included in the study. Five healthy volunteers underwent a single blind, placebo-controlled, random order, cross-over study with infusion of PTH (hPTH 1-34, 200 U in saline over 5 min) or placebo. Echocardiographic assessment of cardiovascular function, heart rate variability, and QT interval were performed between 20 and 25 min after the start of the infusion and repeated after 15 min of tilting at 60 degrees. In pHPT patients the echocardiographic parameters were normal; left ventricular isovolumetric relaxation time was always in the normal range, but significantly shorter than in control subjects, suggesting an increased sympathetic stimulation. Arterial diameters and thickness, blood pressure, and QT interval were not significantly different with respect to normal subjects and were unchanged 6 months after surgery. pHPT patients lacked the circadian rhythm of the low frequency to high frequency ratio, suggesting an increased sympathetic drive to the heart at nighttime. In normal subjects there were no significant differences in basal echocardiographic measurements during PTH infusion with respect to placebo and in the hemodynamic response to tilt. These results suggest that cardiovascular function is substantially normal in normotensive pHPT patients with mild hypercalcemia. A modulation of the adrenergic control of circulation seems to be associated with hypercalcemia and/or chronic PTH excess, but its biological relevance needs further investigations.

Urinary endothelin-1 excretion is enhanced by low-dose infusion of brain natriuretic peptide in normal humans.

To evaluate the functional relationship between cardiac natriuretic peptides and endothelin-1 within the human kidney, we studied the effects exerted by infusion of brain natriuretic peptide on urinary endothelin-1 excretion. We studied twice in a single-blind manner five normal volunteers who received a constant infusion of 5% dextrose (250 mL/h) or human brain natriuretic peptide-32 at a dose of 4 pmol/kg per minute. Blood samples were drawn at intervals for measurement of hematocrit and concentrations of creatinine, electrolytes, brain natriuretic peptide, and endothelin-1. Urine was collected an intervals for measurement of flow rate and concentrations of creatinine, sodium, cGMP, and endothelin-1. Blood pressure and heart rate were measured every 15 minutes. Placebo administration did not change blood pressure, heart rate, or any of the other parameters measured in plasma and urine. As expected, brain natriuretic peptide infusion caused significant increases in its own plasma levels (basal versus peak levels [mean +/- SD], 1.45 +/- 0.20 versus 50.5 +/- 6.0 pmol/L, P < .01), in urinary cGMP (0.75 +/- 0.16 versus 1.92 +/- 0.81 fmol/min, P < .05), and in urinary sodium excretion (140.0 +/- 38.7 versus 624.2 +/- 181.6 mumol/min, P < .01). In addition, it caused an increase in urinary endothelin-1 excretion (4.32 +/- 2.11 versus 19.67 +/- 9.52 fmol/min, P < .05), without modifying plasma endothelin-1, blood pressure, heart rate, creatinine clearance, and urinary flow rate. Our data indicate that brain natriuretic peptide, at plasma levels comparable to those observed in patients with heart failure, causes a significant increase in urinary but not plasma endothelin-1, thus demonstrating a functional link between cardiac natriuretic peptides and renal release of endothelin-1.

Effects of different dopaminergic antagonists on bromocriptine-induced inhibition of norepinephrine release.

In this study we evaluated the effects of placebo or acute bromocriptine (BC) administration (2.5 mg orally) on plasma catecholamines, systolic and diastolic blood pressure (BP), heart rate, and plasma PRL in six normal subjects [group I, mean age 33.2 +/- 5.4 (SD) yr] in the supine as well as upright position. BC induced a significant decrease in plasma norepinephrine in the supine [167.7 +/- 16.8 (SEM) vs. 101.9 +/- 33.7 pg/ml, P less than 0.005] and upright positions [397.3 +/- 27.7 vs. 211.3 +/- 26.7 pg/ml, P less than 0.005], a decrease in systolic and diastolic BP and a decrease in plasma PRL (P less than 0.01). After standing, epinephrine levels increased significantly (53.6 +/- 11.8 vs. 226.4 +/- 71.0 pg/ml, P less than 0.05). The study was repeated in a second group of seven normal subjects (mean age, 32.3 +/- 12.9 yr) after placebo or metoclopramide (20 mg orally) plus BC. In this group metoclopramide, a central and peripheral antidopaminergic agent, counteracted the BC-induced effects found in group I, both in the basal and stimulated conditions. Plasma PRL increased significantly (P less than 0.025). Finally, to assess the effect of peripheral dopaminergic blockade on BC-induced changes in sympathetic outflow, we repeated the study in seven normal subjects (group III, mean age, 30.1 +/- 5.0 yr) after placebo or domperidone (20 mg orally) plus BC. Domperidone blocked the effects of BC on norepinephrine and BP in the supine position. On standing there was a significant decrease in systolic (P less than 0.05) and diastolic (P less than 0.05) BP and an increase in epinephrine levels (58.9 +/- 12.2 vs. 109.8 +/- 24.6 pg/ml, P less than 0.05) was still observed. Plasma PRL increased significantly (P less than 0.025). The results of this study suggest that the inhibition of sympathetic outflow induced by BC is peripherally mediated. As peripheral dopamine receptor blockade did not counteract all the effects after BC during standing, dopaminergic modulation of central reflex sympathetic activation is suggested.

Naloxone administration does not affect gonadotropin secretion in agonadal men either basally or during testosterone treatment.

Naloxone administration has no effect on plasma gonadotropin levels of agonadal men. The present study was designed to evaluate whether testosterone replacement therapy could restore LH responsiveness to naloxone in such men. We measured plasma LH and FSH levels at 15-min intervals during naloxone infusion (8 mg in 1 min followed by 12 mg in 3 h) and for the following 3 h in a group of agonadal men both before and after at least 2 months of three different schedules of testosterone replacement therapy: 1) testosterone undecanoate, 40 mg three times a day by mouth; 2) testosterone enanthate 200 mg im every 2 weeks; and 3) testosterone enanthate 100 mg im once a week. Mean plasma gonadotropin levels as well as LH pulse frequency did not vary during naloxone infusion vs. placebo either basally or during each testosterone regimen. These results suggest that long term testosterone therapy does not affect the altered opioid modulation of gonadotropin secretion which is present in agonadal men.

Systemic hemodynamics and renal function during brain natriuretic peptide infusion in patients with essential hypertension.

We assessed the cardiovascular and renal effects of human brain natriuretic peptide (BNP) infused at a dose inducing an increase in plasma BNP to pathophysiologic levels, in eight hypertensive patients in a randomized, placebo-controlled, cross-over study. Left ventricular performance, cardiac output (echocardiography), heart rate, arterial pressure, glomerular filtration rate (GFR; creatinine clearance), sodium excretion, intrarenal sodium handling (lithium clearance method), and urine flow rate were measured in the infusion and postinfusion periods (1 h each), together with plasma BNP and the urinary excretion rate of cGMP. Plasma BNP levels increased from 2.90 +/- 0.74 to 36.43 +/- 5.51 pmol/L (P < .01) at the end of the infusion and were still elevated at the end of the postinfusion period (7.03 +/- 1.41 pmol/L, P < .05). The urinary excretion of cGMP was also significantly higher during BNP infusion. Left ventricular performance, cardiac output, arterial pressure, and peripheral vascular resistance were not affected by BNP. Peptide infusion induced a significant increase in GFR (placebo, 115 +/- 24; BNP, 147 +/- 19 mL/min), sodium excretion (placebo, 129 +/- 40; BNP, 243 +/- 60 mumol/min), and urine flow rate. All these effects were observed also in the postinfusion period. The natriuretic effect of BNP was attributable to both an increase in filtered sodium load and a reduction of distal sodium reabsorption. These results suggest that BNP may contribute to maintain renal function and sodium excretion in patients with essential hypertension.

[The effects of the acute administration of atrial natriuretic peptide on the mechanisms regulating diuresis and natriuresis in the essential hypertension patient]. / Effetti della somministrazione acuta di peptide atriale natriuretico su alcuni meccanismi di regolazione della diuresi e della natriuresi nell'iperteso essenziale.

The authors investigated the role of atrial natriuretic peptide (alpha-hANP 99-126) in essential hypertension by evaluating some hemodynamic and renal effects of acute peptide infusion (1 micrograms/kg for 1 min + 50 ng/kg for the following 20 min) in fourteen subjects: eight mild to moderate, untreated, essential hypertensives (EH) and six normotensive (N) controls, during 2 hour-clearance periods, the 1st after ANP infusion, the 2nd during placebo (PL) administration. The double-blind study was carried out after the patients had rested and fasted overnight. It showed no significant changes in heart rate (HR); instead, compared with placebo, mean blood pressure (MBP) decreased significantly in both groups, beginning from the 3rd min after ANP infusion was begun (N: PL = 87.04 +/- 1.7 mmHg, ANP = 80.9 +/- 3.7 mmHg, p less than 0.0001; EH: PL = 102.6 +/- 3.2 mmHg, ANP = 97.7 +/- 5.9 mmHg, p less than 0.01). Among the urinary parameters we considered, cyclic GMP (cGMP) increased after ANP infusion in all subjects (N: PL = 129.1 +/- 56.3 pmol/mL, ANP = 199.2 +/- 85.4 pmol/mL; EH: PL = 106.55 +/- 56.2 pmol/mL, ANP = 220.03 +/- 92.7 pmol/mL, p less than 0.05); diuresis showed a prompt and significant increase in EH (N: PL = 837 +/- 368 mL, ANP = 1066 +/- 340 mL; EH: PL = 713 +/- 286 mL, ANP = 1043 +/- 280 mL, p less than 0.005), and so did natriuresis (N: PL = 23 +/- 14.3 mEq/L, ANP = 33 +/- 14.6 mEq/L; EH: PL = 25.6 +/- 8.9 mEq/L, ANP = 41.9 +/- 13.8 mEq/L, p less than 0.01); urinary potassium excretion was significantly reduced in EH (N: PL = 18.7 +/- 12.9 mEq/L, ANP = 14.2 +/- 6.9 mEq/L; EH: PL = 16.5 +/- 7.9 mEq/L, ANP = 10.7 +/- 4.8 mEq/L, p less than 0.005), while no changes were noted in glomerular filtration rate (GFR), estimated as creatinine clearance, urinary magnesium, albumin and aldosterone excretion. To investigate other potential mechanisms involved in renal effects of ANP, the urinary excretion of both prostaglandins 6-cheto PGF1-alpha and thromboxane B2 (TXB2), and dopamine were studied. The results showed only a significant decrease of dopamine urinary excretion in EH after ANP administration (N: PL = 50.4 +/- 28.7 micrograms/L, ANP = 45.0 +/- 29.7 micrograms/L; EH: PL = 47.3 +/- 21.5 micrograms/L, ANP = 27.1 +/- 12.7 micrograms/mL, p less than 0.01).(ABSTRACT TRUNCATED AT 400 WORDS)

Circulating BRAFV600E in the diagnosis and follow-up of differentiated papillary thyroid carcinoma.

CONTEXT: Cell-free nucleic acids circulating in plasma are considered a promising noninvasive tool for cancer monitoring. BRAF(V600E) mutation in cell-free DNA (cfDNA) could represent an appropriate marker for papillary thyroid carcinoma (PTC). OBJECTIVE: Our aim is to investigate the role of BRAF(V600E)-mutated allele in cfDNA as a marker for the diagnosis and follow-up of PTC. STUDY DESIGN: BRAF(V600E) allele was detected and quantified by an allele-specific real-time quantitative PCR assay in plasma from 103 patients affected by nodular goiter. As control populations, we enrolled 49 healthy subjects and 16 patients with non-nodular thyroid diseases. RESULTS: The percentage of circulating BRAF(V600E) was significantly different between patients and controls and throughout different cytological categories of ultrasound-assisted fine-needle aspiration. Patients with a histopathological diagnosis of PTC showed a higher percentage of circulating BRAF(V600E) (P = .035) compared to those with benign histology. In 19 patients, a second blood draw, taken 3-6 months after surgery, showed a lower percentage of BRAF(V600E) in cfDNA than the presurgical sample (P < .001). The diagnostic performance of circulating BRAF(V600E) was assessed by receiver operating characteristic curve analysis resulting in an area under the curve of 0.797. A cutoff value was chosen corresponding to maximum specificity (65%) and sensitivity (80%). On this basis, we evaluated the predictive value of BRAF(V600E) in Thy 3 patients with a resulting positive predictive value of 33% and a negative predictive value of 80%. CONCLUSIONS: The results of the present study provide encouraging data supporting the possibility to take advantage of circulating BRAF(V600E) in the management of PTC.

Naloxone administration does not affect gonadotrophin secretion in male patients with isolated hypogonadotrophic hypogonadism.

We evaluated the gonadotrophin response to acute naloxone administration (10 mg iv) in 4 male patients with isolated hypogonadotrophic hypogonadism (age range 18.5-26 years) before and after pituitary priming with daily infusions of GnRH (25 micrograms/h for 4 h) for 4 days. A blunted gonadotrophin response to acute GnRH administration (100 micrograms iv) and a lack of response to naloxone was observed before pituitary priming. After repeated infusions of GnRH, pituitary gonadotrophin responsiveness to GnRH was restored, whilst naloxone still did not affect gonadotrophin levels. Our data suggest that in male isolated hypogonadotrophic hypogonadism 1) the lack of pituitary response to naloxone is not due to pituitary hyporesponsiveness to GnRH; 2) endogenous opioids do not exert any inhibitory influence on GnRH secreting neurons and thus are not involved in the pathogenesis of this disease.

Does endogenous dopamine modulate human sympathetic activity through DA2 receptors?

The effects of placebo and DA2 antidopaminergic agents on basal and stimulated catecholamine (CA) plasma levels in humans have been evaluated by administration either of domperidone or metoclopramide to separate groups of subjects. The latter group was subjected domperidone to sympathetic stimulation by handgrip coldpressor tests, and standing. Pharmacological DA2 receptor blockade, either peripheral by or central and peripheral by metoclopramide, did not modify plasma CA whilst resting or during acute sympathetic stimulation. It is concluded that endogenous dopamine does not seem to play a significant role in modulating NE release in man, at least not under the physiological conditions examined.

Effects of thyroid replacement therapy on catecholamine plasma levels.

Plasma catecholamines (CA), total and free thyroid hormones (T4, FT4, T3, FT3) and thyrotropin (TSH) were measured before and during therapy in seven normotensive women with primary hypothyroidism lasting for more than 6 months. Twelve normal women matched for age were used as controls. In hypothyroid patients plasma norepinephrine (NE) was found increased in supine and upright position and plasma epinephrine (E) unchanged. After 30-60 days of therapy with dry thyroid extract, NE, T3, and FT3 levels were found in the normal range while T4 and FT4 levels, although raised, were still significantly lower than those of controls. These results seem to demonstrate that low doses of replacement therapy can restore NE levels to normal and therefore suggest that severe hypothyroidism alone is able to affect the sympathetic function.

Usefulness of basal catecholamine plasma levels and clonidine suppression test in the diagnosis of pheochromocytoma.

In the present paper we report our experience on the utility of basal plasma catecholamine (CA) measurement and of the clonidine-suppression test in the diagnosis of pheochromocytoma. Basal noradrenaline (NA) and adrenaline (A) were assayed in plasma samples of 27 subjects affected by pheochromocytoma. When compared to basal values obtained in hypertensive patients without pheochromocytoma, one or both the CA resulted pathologically elevated in all patients except one. The response to the clonidine-suppression test was evaluated in 41 hypertensive patients suspected of having a pheochromocytoma measuring plasma NA and A in basal conditions and 2 and 3 h after oral administration of 300 micrograms clonidine. Extensive laboratory and instrumental findings confirmed the presence of pheochromocytoma only in 12 patients. Among the other 29 patients basal plasma CA resulted higher than normal in 4 patients. In patients without pheochromocytoma clonidine induced a significant fall in both NA and A plasma levels. The decrease in NA was observed in each patient. The 12 patients with pheochromocytoma showed a pathological elevation of one or both the CA. In this group clonidine did not significantly suppress plasma CA. The individual responses were extremely variable. Our data confirm the validity of plasma CA measurement as a diagnostic tool for the diagnosis of pheochromocytoma. The results of the clonidine-suppression test were generally confirmatory of the basal CA plasma values but in the 4 hypertensive patients without pheochromocytoma who showed basal plasma CA higher than normal clonidine resulted a useful tool in excluding the presence of pheochromocytoma.

Naloxone administration does not affect gonadotropin secretion in patients with Klinefelter's syndrome.

Plasma LH and FSH were measured every 20 min in a group of patients with Klinefelter's syndrome before and after placebo or naloxone administration (8 mg iv as a bolus followed by an infusion of 4 mg/h for 4 h) both in baseline conditions (N = 6) and during treatment with testosterone enanthate (200 mg im every two weeks; N = 4). The mean LH areas measured during saline infusion in baseline conditions (7888 +/- 758 IU/l per min mean +/- SEM) and during testosterone treatment (5042 +/- 2039 IU/l per min) were not significantly different from those measured during naloxone infusion (baseline 8317 +/- 818 IU/l per min; during testosterone treatment 5395 +/- 2007 IU/l per min). Similar results were obtained for FSH. These data suggest that in patients with Klinefelter's syndrome, the opioidergic inhibition of gonadotropin release is lacking and is not restored by testosterone replacement therapy.

Effects of repeated atrial natriuretic peptide bolus injections in cirrhotic patients with refractory ascites.

The renal and hormonal effects of repeated atrial natriuretic peptide (ANP) boli (1 microgram/kg of body weight) were studied in eight cirrhotic patients with refractory ascites. Under basal conditions the patients showed a striking activation of the renin-angiotensin-aldosterone system (plasma renin activity 19.3 +/- 3.0 ng/ml.h, plasma aldosterone concentration 3.87 +/- 0.58 ng/ml) and a tenfold elevation in plasma ANP levels compared to healthy subjects (131.7, range 47.0-288.6, vs. 9.8, range 5.0-15.0, fmol/ml, p less than 0.001). The first ANP injection was followed by a remarkable increase in plasma ANP levels and by a slight increase in urinary cyclic guanosine-monophosphate excretion (from 1050.8 +/- 454.8 to 1446.6 +/- 822.2 pmol/min). A significant reduction of mean blood pressure (MBP) occurred 5 min after the first injection (from 86.7 +/- 7.2 to 79.9 +/- 5.8 mmHg, p less than 0.05), but values gradually returned to the baseline after 30 min. Heart rate (HR) increased 10 min after the first bolus injection (from 83.75 +/- 4.7 to 88.1 +/- 4.6 beats/min) and reached baseline values after 30 min. Similar behaviour of MBP and HR was observed after the second, third and fourth bolus injections. Urinary sodium excretion, urinary flow, glomerular filtration rate, plasma renin activity, and plasma aldosterone concentration did not show any significant modification during ANP administration, nor did these parameters change in the following 12-h recovery period.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of naloxone on catecholamine plasma levels in adult men. A dose-response study.

To evaluate a possible role for endogenous opiates in modulating sympathetic-adrenal function in humans, we measured plasma epinephrine and norepinephrine (radioenzymatic method), blood pressure and heart rate in 8 normal men (aged 24-33 years) before and after placebo or different doses (0.4, 4.8, 10 mg) of naloxone. In 6 subjects plasma insulin and glucagon levels were also measured by radioimmunoassay after placebo and 10 mg naloxone. Naloxone had no significant effect upon blood pressure, heart rate, plasma insulin, glucagon or norepinephrine. Placebo, 0.4 and 4.8 mg naloxone caused no significant change in peripheral levels of epinephrine while 10 mg produced an increase in epinephrine concentrations 15 min after iv injection (186 +/- 23 vs 99 +/- 9 pmol/l, P less than 0.01). Since naloxone did not modify plasma levels of insulin and glucagon, an indirect effect of naloxone on adrenal medullary secretion seems to be excluded. These results are in agreement with in vitro experimental data obtained in animals and suggest that endogenous opiates also have a role in modulating adrenal medullary secretion in man.