Claudio Letizia

A new human chromogranin 'A' immunoradiometric assay for the diagnosis of neuroendocrine tumours

We investigated whether plasma chromogranin A (CgA), measured by a new immunoradiometric assay, may be a sensitive and specific marker of phaeochromocytoma and of other neuroendocrine tumours. This study involved 121 patients of whom 20 with phaeochromocytoma, 28 with other neuroendocrine tumours (19 gastroenteropancreatic tumors, 3 medullary thyroid and 6 small cell lung carcinomas), 25 with solid nonfunctioning adrenocortical tumours and 48 with essential hypertension. In addition, 130 normal subjects were taken as controls. Plasma catecholamines were measured by using high-performance liquid chromatography, and CgA by a two-site sandwich immunoradiometric assay involving monoclonal antibodies raised against the unprocessed central domain (145–245) of human CgA. Plasma CgA in controls (49.0 ± 3.1 ng ml–1, mean ± SE) and in essential hypertensives (50.8 ± 3.5 ng ml–1) was lower (P< 0.0001) than in adrenocortical tumours (91.8 ± 13.2 ng ml–1), in phaeochromocytomas (254 ± 49 ng ml–1) and in patients with other neuroendocrine tumours (469 ± 84 ng ml–1). Plasma CgA and catecholamines identified 13 and 18 out of 20 phaeochromocytomas with sensitivity of 65% and 90%, respectively. Combined measurement of both markers improved sensitivity up to 100%. In the other neuroendocrine tumours, CgA was abnormal in 23/28 cases (sensitivity 82%) and in 6 it was the only circulating marker of disease. In gastroenteropancreatic tumours, CgA measurement identified all cases (sensitivity 100%). Specificity of CgA in patients with essential hypertension was 98%. In conclusion, CgA determination showed high sensitivity in identifying gastroenteropancreatic tumours and, in association with catecholamines, in detecting patients with phaeochromocytoma. CgA sometimes appeared to be the only circulating marker of disease. Since the specificity of CgA proved to be excellent, this assay may be useful for diagnosis both of functioning and non-functioning neuroendocrine tumours.

The Medical and Endovascular Treatment of Atherosclerotic Renal Artery Stenosis (METRAS) study: rationale and study design.

It is unclear whether revascularization of renal artery stenosis (RAS) by means of percutaneous renal angioplasty and stenting (PTRAS) is advantageous over optimal medical therapy. Hence, we designed a randomized clinical trial based on an optimized patient selection strategy and hard experimental endpoints. Primary objective of this study is to determine whether PTRAS is superior or equivalent to optimal medical treatment for preserving glomerular filtration rate (GFR) in the ischemic kidney as assessed by 99mTcDTPA sequential renal scintiscan. Secondary objectives of this study are to establish whether the two treatments are equivalent in lowering blood pressure, preserving overall renal function and regressing target organ damage, preventing cardiovascular events and improving quality of life. The study is designed as a prospective multicentre randomized, un-blinded two-arm study. Eligible patients will have clinical and angio–CT evidence of RAS. Inclusion criteria is RAS affecting the main renal artery or its major branches either >70% or, if <70, with post-stenotic dilatation. Renal function will be assessed with 99mTc-DTPA renal scintigraphy. Patients will be randomized to either arms considering both resistance index value in the ischemic kidney and the presence of unilateral/bilateral stenosis. Primary experimental endpoint will be the GFR of the ischemic kidney, assessed as quantitative variable by 99TcDTPA, and the loss of ischemic kidney defined as a categorical variable.

PROSPECTIVE APPRAISAL ON THE PREVALENCE OF PRIMARY ALDOSTERONISM AND ITS SUTYPES IN HYPERTENSIVE PATIENTS PRESENTING WITH ATRIAL FLUTTER OR FIBRILLATION: PAPPHY STUDY

Objective: Excess aldosterone has been suggested to favour and/or cause atrial fibrillation (AF), particularly in the patients with arterial hypertension, but the relationship between AF and primary aldosteronism (PA) remains uncertain. Hence, we tested the hypothesis that AF is one of the presenting signs of unrecognized PA, and investigated the prevalence of PA and its subtypes in hypertensive patients presenting with lone AF. Design and method: Consecutive patients with an unambiguous diagnosis of arterial hypertension presenting with ECG-confirmed AF and no obvious causes of the arrhythmia were recruited and submitted to the screening and subtyping for PA according to the Endocrine Society PA current guidelines, including measurement of plasma renin activity and aldosterone levels after appropriate pharmacological preparation, and adrenal vein sampling (Funder J. JCEM 2016). The diagnosis of aldosterone-producing adenoma followed the four corner criteria, which imply cure of PA after adrenalectomy (Rossi GP. JACC 2006). Results: From 2015 to 2017, 296 patients (age 76 ± 12 years; 48/52 F/M, %) were recruited in three ESH centers of Excellence for arterial hypertension in Italy (Padua, Brescia and Rome). Fifty-five patients, who met the inclusion criteria and had no exclusion criteria, underwent the entire diagnostic work-up for PA. This allowed to ascertain that the overall prevalence of PA was 34.5%, 42% of the cases being accounted for by aldosterone-producing adenoma and the rest by bilateral forms. Conclusions: By providing compelling evidence for a high prevalence of PA in hypertensive patients presenting with the so-called “lone” AF, these results can lead to changing clinical practice in the management of these patients in that they indicate the need to carefully searching for PA and undertaking subtyping with the aim of pinpointing those who can be cured with unilateral laparoscopic adrenalectomy.