G. De Toma

99mTc-interleukin-2 scintigraphy for the in vivo imaging of vulnerable atherosclerotic plaques

PurposeSeveral histopathological studies have demonstrated that vulnerable plaques are enriched in inflammatory cells. The aims of this study were: (1a) to test the ability of 99mTc-labelled interleukin-2 (99mTc-IL2) to bind to IL2R-positive (IL2R+) cells in carotid plaques and (1b) to correlate the plaque uptake of 99mTc-IL2, measured in vivo, with the number of IL2R+ cells within the plaque, measured ex vivo by histology (transversal study, TS), and (2) to evaluate changes in 99mTc-IL2 uptake in plaques, before and after treatment with a statin or a hypocholesterolaemic diet (longitudinal study, LS).MethodsUltrasound scan was performed for plaque characterisation and localisation. Fourteen patients (16 plaques) eligible for endoarterectomy were recruited for the TS and underwent 99mTc-IL2 scintigraphy before surgery. Nine patients (13 plaques) were recruited for the LS; these patients received atorvastatin or a standard hypocholesterolaemic diet and 99mTc-IL2 scintigraphy was performed before and after 3 months of treatment.ResultsThe degree of 99mTc-IL2 uptake was expressed as the plaque/background (T/B) ratio. In patients from TS, T/B ratios correlated with the percentage of IL2R+ cells at histology (r=0.707; p=0.002) and the number of IL2R+ cells at flow cytometry (r=0.711; p=0.006). No correlations were observed between ultrasound scores and either scintigraphic or histological findings. In patients from the LS, the mean 99mTc-IL2 uptake decreased in statin-treated patients (1.75±0.50 vs 2.16±0.44; p=0.012), while it was unchanged in the patients on the hypocholesterolaemic diet (2.33±0.45 vs 2.34±0.5).Conclusion99mTc-IL2 accumulates in vulnerable carotid plaques; this accumulation is correlated with the amount of IL2R+ cells and is influenced by lipid-lowering treatment with a statin.

High plasma endothelin-1 levels in hypertensive patients with low-renin essential hypertension.

Endothelin-1 (ET-1) is a potent vasoconstrictor peptide derived from endothelial cells and may be important in the control of systemic blood pressure (BP) and local blood flow. Immunoreactive ET-1 plasma levels may be normal or elevated in human arterial hypertension, although the exact pathophysiological role of ET-1 remains to be established. The aim of our study was to determine the relationship between the components of the renin-angiotensin-aldosterone system and plasma ET-1 levels in patients with low, normal or high-renin essential hypertension. The study groups included 13 patients with low-renin essential hypertension (average age 43.5 ± 16.2 years), 16 patients with normal-renin essential hypertension (46.5 ± 13.4 years), 11 patients with high-renin essential hypertension (40.7 ± 13.8 years) and 12 healthy subjects (43.1 ± 11.4 years). Our results demonstrated that the mean ET-1 values of all patients with essential hypertension were 10.4 ± 3.4 pg/ml; there was not a statistical correlation between plasma renin activity (PRA) and the ET-1 levels of hypertensives; instead there was a statistically significant correlation between plasma ET-1 and plasma aldosterone (PA) (r = 0.393; P < 0.026). in particular mean plasma et-1 values in patients with low-renin essential hypertension (12.6 ± 2.1 pg/ml) were significantly higher (anova = 0.000, P < 0.05) than those of normotensive subjects (7.7 ± 1.7 pg/ml), patients with normal-renin essential hypertension (8.5 ± 2.8 pg/ml), and patients with high-renin essential hypertension (9.9 ± 3.8 pg/ml), respectively. there was a statistical correlation between pa and et-1 levels in patients with low-renin essential hypertension (r = 0.619, P < 0.024). Our study demonstrated that there was an increase of circulating ET-1 levels in patients with low-renin essential hypertension and ET-1 plasma levels correlated with PA. The results suggest that ET-1 may play an important role in this particular form of human essential hypertension.

Circulating levels of adrenomedullin in patients with Addison's disease before and after corticosteroid treatment

A novel hypotensive peptide, adrenomedullin (AM), had recently been isolated, purifed and its encoding gene sequenced from a human phaeochromocytoma. In humans AM circulates in physiological levels and possesses a distinct vasodilatatory activity. The purpose of this study was to examine the behaviour of AM levels in primary adrenal failure.

Plasma Endothelin-1 Levels in Patients with Aldosterone-Producing Adenoma and Pheochromocytoma

The aim of the study was to evaluate possible changes of plasma endothelin-1 levels (ET-1) in patients with hypertension secondary to primary aldosteronism and pheochromocytoma. We enrolled in the study: 12 patients affected by aldosterone-producing adenoma (5 M and 7 W; mean age 42.1 +/- 17.2 years); 8 patients with pheochromocytoma (5 M, 3 W; mean age 36.2 +/- 17.1 years); 15 patients with essential hypertension (9 M, 6 W; mean age 48.5 +/- 10 years). We also enrolled a normal control group (8 M, 12 W; mean age 34.2 +/- 11 years). The mean plasma ET-1 concentrations in patients with pheochromocytoma were significantly higher (23.9 +/- 5.2 pg/ml) than those in normal subjects (7.3 +/- 1.9 pg/ml), in patients with primary aldosteronism (12.1 +/- 3.8 pg/ml) and in patients with essential hypertension (9.2 +/- 3 pg/ml); p < 0.001, respectively. The present investigation demonstrates that in human adrenal hypertension patients with pheochromocytoma have increased circulating ET-1 levels respect to patients with aldosterone-producing adenoma.

Growth Factor Receptors Gene Expression and Akt Phosphorylation in Benign Human Thyroid Nodules are Unaffected by Chronic Thyrotropin Suppression

Levothyroxine (L-T4)-based suppression of thyrotropin (TSH) secretion is widely used to prevent the growth of benign thyroid nodules, although the effectiveness of this approach has been demonstrated only in a subset of patients. In this study, we analyzed the in vivo effects of L-T4-mediated TSH suppression on elements of insulin/IGF-1-dependent growth-regulating pathways in tissues from patients with benign thyroid nodules. Nodular and non-nodular tissue specimens were collected from 63 patients undergoing thyroidectomy. 32 had received preoperative TSH suppressive therapy with TSH levels consistently below 0.5 mU/l (L-T4 group). TSH suppression had not been used in the other 31, and their TSH levels were normal (0.8-4 mU/l (control group). Quantitative RT-PCR was used to measure mRNA levels for TSH receptor, IGF1, IGF-1 receptor, insulin receptor, insulin receptor substrate 1 in nodular and non-nodular tissues from the 2 groups. Akt and phosphorylated Akt protein levels were detected by Western blot. Mean levels of mRNA for all genes tested were similar in the 2 groups, in both nodular and non-nodular tissues. The 2 groups were also similar in terms of phosphorylated Akt protein levels (measured by densitometric scan in 10 randomly selected nodules from each group). This is the first demonstration based on the study of human thyroid tissues that TSH suppression does not affect the expression of components of the insulin/IGF-1-dependent signaling pathways regulating thyrocyte growth. This may explain the lack of effectiveness of TSH-suppressive therapy in a substantial percentage of benign thyroid nodules.

False-positive diagnosis of adrenal pheochromocytoma on iodine-123-MIBG scan

I-123 metaiodobenzylguanidine (I-123 MIBG) scintigraphy is known for its high specificity in detecting pheochromocytoma and other tumors of neural crest origin. In this rare case report, we describe a definite adrenocortical adenoma that demonstrated false-positive uptake at I-123 MIBG scintigraphy and a remarkable accumulation of 75-SE-6-beta-selenomethyl-norcholesterol.

Adrenomedullin Levels are High in Primary Aldosteronism due to Adenoma and Decline after Surgical Cure

The aim of the study was to evaluate the possible changes in plasma adrenomedullin (AM) levels in patients with primary aldosteronism before and after surgical resection. The study included 13 patients affected by aldosterone-producing adenoma (9 women, 4 men; mean age 36.2+/-14.2 years) and 20 healthy control subjects (7 women, 13 M; mean age 31.8+/-12.4 years). Unilateral adrenalectomy was performed in all patients and adrenal mass consisted of a benign adrenal cortical adenoma. The mean plasma AM concentrations in patients with primary aldosteronism (36.2+/-19.3 pg/ml) were significantly (p < 0.0001) higher than those of normal subjects (13.2+/-6.2 pg/ml). In these patients the plasma AM levels significantly (p < 0.0001) reduced after surgical removal of the tumours (14.9+/-7.6 pg/ml). In all patients with aldosterone-producing adenoma, tumour diameter correlated with the plasma AM concentrations (r=0.631; p < 0.021). In conclusion, the present investigation shows that in primary aldosteronism due to adrenal adenoma plasma AM levels are higher at the moment of diagnosis and decline after successful adrenal operation.

Recurrent laryngeal nerve palsy and substernal goiter. An Italian multicenter study

The aim of this retrospective multicenter study was to verify whether the substernal goiter and the type of surgical access could be risk factors for recurrent laryngeal nerve palsy during total thyroidectomy. Between 1999-2008, 14,993 patients underwent total thyroidectomy. Patients were divided into three groups: group A (control; n=14.200, 94.7%), cervical goiters treated through collar incision; group B (n=743, 5.0%) substernal goiters treated by cervical approach; group C (n=50, 0.3%) in which a manubriotomy was performed. Transient and permanent unilateral palsy occurred significantly more frequently in B+C vs. A (P≤.001) and in B vs. A (P≤.001). Transient bilateral palsy was significantly more frequent in B+C vs. A (P≤.043) and in C vs. A (P≤.016). Permanent bilateral palsy was significantly more frequent in B+C vs. A (P≤.041), and in B vs. A (P≤.037). Extension of the goiter into the mediastinum was associated to increased risk of recurrent nerve palsy during total thyroidectomy.

Cushing's syndrome patient who exhibited congestive heart failure.

Cushing’s Syndrome (CS) may sometimes lead to dilated cardiomiopathy, even though this condition can be partially or completely reversed after treatment. In this article we report the case of a 28-yr-old woman with CS secondary to adrenal adenoma who exhibited congestive heart failure as an initial symptom. Two weeks before being admitted to our hospital, the patient started complaining of shortness of breath, orthopnea, paroxysmal nocturnal dyspnea and generalized edema. A physical examination did not reveal signs of hypercortisolism. Chest auscultation revealed bilateral diffused crepitation; blood pressure was 180/120 mmHg with heart rate of 90 beats/min. A chest X-ray showed a cardiac shade enlargement due to congestive heart failure. Transthoracic echocardiography demonstrated a dilatated left ventricle and an impaired left ventricular systolic function. The patient’s urinary cortisol excretion was elevated and circadian rhythm of cortisol was absent. ACTH level was low. In addition, plasma cortisol failed to decrease after administration of dexamethasone. An abdominal magnetic resonance imaging scan showed a 7-cm right adrenal mass. The patient was administered oxygen, spironolactone, ACE-inhibitor and the signs and symptoms of heart failure gradually improved. A laparoscopic right adrenalectomy was performed and pathological examination of the gland showed a benign adrenocortical adenoma. After the adrenalectomy the patient was started on hydrocortisone therapy and 5 months later the wall thickness of the left ventricle was within normal range and the patient’s blood pressure was 130/80 mmHg. In conclusion we report the case of heart failure as the main clinical symptom in CS secondary to adrenal adenoma.

Epicardial Fat Thickness and Primary Aldosteronism.

Primary aldosteronism (PA) is associated with increased cardiovascular risk and left ventricle (LV) changes. Given its peculiar biomolecular and anatomic properties, excessive epicardial fat, the heart-specific visceral fat depot, can affect LV morphology. Whether epicardial fat can be associated with aldosterone and LV mass (LVM) in patients with PA is unknown. We performed ultrasound measurement of the epicardial fat thickness (EAT) in 79 consecutive newly diagnosed patients with PA, 59 affected by bilateral adrenal hyperplasia (IHA), 20 aldosterone-producing adenoma (APA), and 30 patients with essential hypertension (low renin hypertension) (EH). The 3 groups did not differ by age, sex distribution, body mass index (BMI), waist circumference (WC), or blood pressure values. EAT showed a trend of increase in both APA and IHA groups when compared to patients with EH (8.3±1.8 vs. 7.9±1.3 vs. 7.8±2 mm, respectively). EAT was significantly correlated with indexed LVM in the IHA group (r=0.35, p<005), better than BMI or WC were. Interestingly, EAT was highly associated with plasma aldosterone concentrations (PAC) and PAC/plasma renin activity (PRA) (PAC/PRA) in the APA group (p=0.58, p=0.37, p<0.01, for both), whereas BMI and WC were not. EAT was also correlated with PRA in the IHA group (p=-0.28, p<0.05). Our study indicates a novel and interesting interaction of EAT with PA, independent of obesity, abdominal fat and blood pressure control. EAT can locally affect LVM, at least in patients with IHA. Further studies in larger population will be required to confirm these findings.