The prognostic value of baseline (18)F-FDG PET/CT in steroid-naïve large-vessel vasculitis: introduction of volume-based parameters.

PURPOSE: The aim of this study was to analyse if the result of a baseline (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT scan, in large-vessel vasculitis (LVV) patients, is able to predict the course of the disease, not only in terms of presence/absence of final complications but also in terms of favourable/complicated progress (response to steroid therapy, time to steroid suspension, relapses, etc.). METHODS: A total of 46 consecutive patients, who underwent (18)F-FDG PET/CT between May 2010 and March 2013 for fever of unknown origin (FUO) or suspected vasculitis (before starting corticosteroid therapy), were enrolled. The diagnosis of LVV was confirmed in 17 patients. Considering follow-up results, positive LVV patients were divided into two groups, one characterized by favourable (nine) and the other by complicated progress (eight), on the basis of presence/absence of vascular complications, presence/absence of at least another positive PET/CT during follow-up and impossibility to comply with the tapering schedule of the steroid due to biochemical/symptomatic relapse. Vessel uptake in subjects of the two groups was compared in terms of intensity and extension. To evaluate the extent of active disease, we introduced two volume-based parameters: "volume of increased uptake" (VIU) and "total lesion glycolysis" (TLG). The threshold used to calculate VIU on vessel walls was obtained by the "vessel to liver" ratio by means of receiver-operating characteristic analysis and was set at 0.92 × liver maximum standardized uptake value in each patient. RESULTS: Measures of tracer uptake intensity were significantly higher in patients with complicated progress compared to those with a favourable one (p < 0.05). Measures of disease extension were even more significant and TLG emerged as the best parameter to separate the two groups of patients (p = 0.01). CONCLUSION: This pilot study shows that, in LVV patients, the combined evaluation of the intensity and the extension of FDG vessel uptake at diagnosis can predict the clinical course of the disease, separating patients with favourable or complicated progress.

Role of adrenal gland scintigraphy in patients with subclinical hypercortisolism and incidentally discovered adrenal mass.

BACKGROUND: The role of adrenal scintigraphy (AS) in the diagnosis of subclinical hypercortisolism (SH) in adrenal incidentaloma (AI) is debated. AIM: To evaluate the possible role of AS in identifying SH in AI patients. SUBJECTS AND METHODS: In the retrospective phase (2000-2004), 102 AI patients [71 females (F)/31 males (M)] referred to our center were reevaluated for SH. In the prospective phase (2005-2006), 42 patients (32F/10M) with suspected SH were evaluated performing AS and biochemical assessment of cortisol secretion. We report data of the prospective phase of the study. In these patients AS was performed at baseline; the difference between the uptake of the affected and the controlateral gland [mean Delta uptake (MDeltau)] was calculated. Cortisol secretion was evaluated in 3 different occasions. Patients were considered affected with SH if they presented at least twice 2 of the following criteria: urinary free cortisol >193 nmol/l, cortisol after 1 mg dexamethasone suppression test >83 nmol/l, ACTH levels <2.2 pmol/l. RESULTS: MDeltau was higher in patients with SH (no.=27, 5/22 M/F) than in patients without SH (83.7+/-12.5 vs 54.7+/-24.1%, p<0.001), and directly correlated with UFC (beta=0.387, p=0.015) and was predictive of SH (odds ratio 1.12, 95% confidence interval 1.03-1.22, p=0.009) regardless of age, body mass index, and diameter of the mass. A 75% MDeltau cut-off has 86.7% specificity and 81.5% sensitivity in diagnosing SH. CONCLUSIONS: AS is not recommended as screening test in AI patients, but it can be useful to exclude the presence of a subtle cortisol excess in patients with unclear biochemical diagnosis of SH.

Possible involvement of endogenous opiates in the tolerance to the anorectic effect of fenfluramine.

Repeated administration of fenfluramine leads to a rapid and progressive loss of its effectiveness in reducing food intake. The animals tolerant to the anorectic effect of fenfluramine had markedly low basal hypothalamic serotonin (5-HT) levels. In this brain area the levels of [Met5]enkephalin-like immunoreactive material were, on the contrary, significantly higher in fenfluramine-tolerant animals than in controls. In tolerant animals the drug failed to further decrease 5-HT concentrations unless it was given at doses also reducing food intake. On the other hand, in acute experiments, morphine pretreatment potentiated and naloxone antagonized fenfluramine-induced depletion of striatal and hypothalamic 5-HT stores. In addition, when given to fenfluramine-tolerant rats, morphine restored the efficacy of the anorectic agent. After morphine pretreatment, fenfluramine depleted 5-HT and reduced food intake in tolerant animals. These findings, while further substantiating the importance of 5-HT in mediating fenfluramine anorexia, also suggest that endogenous opiates may play an important role in the processes through which tolerance to this drug develops. Fenfluramine reduces food intake by releasing 5-HT and tolerance to its anorectic effect would be a consequence of an inability to further release 5-HT. However, because release of 5-HT by fenfluramine seems to be modulated by opiates, repeated administration of fenfluramine might alter such modulatory mechanisms and tolerance to the effects of the drug would develop.

Interactions between serotonergic and enkephalinergic neurons in rat striatum and hypothalamus.

We report evidence for an interaction between serotonergic and enkephalinergic neurons in rat striatum and hypothalamus. The administration of drugs such as p-chlorophenylalanine (PCPA), 5,6-dihydroxytryptamine (5,6-DHT) and fenfluramine that lower the striatal and hypothalamic serotonin (5-HT) content caused an increase in Met-enkephalin-like immunoreactive material (ME-IR) in these brain areas. Moreover, chronic treatment with PCPA induced an increase in the number of striatal [3H][D]Ala2,Met5]enkephalinamide binding sites. These observations suggest that serotonergic neurons modulate the functional activity of enkephalinergic neurons in the rat striatum and hypothalamus. The significance of this interaction is discussed.