Luigi Troncone

Abnormal Cardiac Adrenergic Nerve Function in Patients With Syndrome X Detected By [123I]Metaiodobenzylguanidine Myocardial Scintigraphy

BACKGROUND Previous studies have suggested that an abnormal cardiac adrenergic tone may have a pathophysiological role in syndrome X (effort angina, positive exercise testing, angiographically normal coronary arteries). METHODS AND RESULTS To evaluate cardiac adrenergic nerve function, we performed [123I]metaiodobenzylguanidine (MIBG) myocardial scintigraphy in 12 patients with syndrome X and 10 control subjects. Cardiac MIBG uptake was assessed by the heart/mediastinum (H/M) ratio and by an MIBG uptake defect score (higher values=lower uptake). In syndrome X patients, we also correlated MIBG scintigraphic findings with stress myocardial perfusion as assessed by 201Tl scintigraphy. An inferior MIBG defect was observed in only 1 control subject, whereas 9 patients (P<.01) showed MIBG defects. The heart was totally or almost totally invisible on MIBG images in 5 patients, and predominantly regional defects were observed in 4. The H/M ratio was lower (1.70+/-0.6 versus 2.2+/-0.3, P=.03) and MIBG uptake defect score higher (35+/-31 versus 4+/-2, P=.003) in syndrome X patients. Reversible stress thallium perfusion defects were found in 62% of patients with MIBG defects but in no patient with normal MIBG uptake. MIBG defects persisted unchanged in 7 patients at a 5+/-3-month follow-up study. CONCLUSIONS In this study, obvious defects in global and/or regional cardiac MIBG uptake, indicating an abnormal cardiac adrenergic nerve function, were detected in 75% of patients with syndrome X. These findings strongly support the cardiac origin of chest pain in syndrome X, although the mechanisms and the pathophysiological meaning of the abnormal cardiac MIBG uptake in these patients deserve further investigation.

Radio-guided surgery for lymph node recurrences of differentiated thyroid cancer

The objectives of this study were to assess the reliability of radioiodine (131I) and a gamma probe for radio-guided surgery (RGS) to detect and then radically dissect lymph node recurrences (LNRs) in 10 patients with differentiated thyroid cancer (DTC). The major inclusion criterion was the presence of an iodine-positive LNR after previous total thyroidectomy and at least two ineffective 131I treatments. The protocol was designed as follows. Day 0: all patients were hospitalized and received 3.7 GBq of 131I in the hypothyroid condition. Day 3: presurgery whole-body scan with a therapeutic dose (TxWBS). Day 5: neck surgery using a gamma probe (Navigator GPS, AutoSuture, Italy), recording the absolute counts and the lesion/background (L/B) counts ratio. Day 7: post-surgery TxWBS performed using the remaining radioactivity. The presurgery TxWBS was positive in all patients, and the post-surgery TxWBS showed a negative pattern in 7 of 10 patients, suggesting the efficacy of the surgical procedure in most of the patients. After RGS the mean decrease in the absolute counts and the L/B counts ratio were 77.6% (52.7% minimum, 94.6% maximum) and 77.4% (52.3% minimum, 94.8% maximum), respectively. After operation the surgeon judged the procedure to be decisive in two patients, favorable in six, and irrelevant in two. The final histologic examination showed the presence of 78 lymph node metastases (mean of 8 per patient). There were 33 neoplastic lesions found by both TxWBS and gamma probe evaluations; 41 were shown only by gamma probe, and 4 were negative by both TxWBS and gamma probe evaluations. This protocol permitted us to look for neoplastic foci with high sensitivity and specificity, and we were able to remove lymph node metastases resistant to radioiodine therapy at a single session. The protocol also allowed detection of some additional tumoral foci in sclerotic areas or behind vascular structures that are difficult to identify and were not seen at the presurgery TxWBS evaluation. However, because of the possible false-negative results, complete excision must be undertaken in high risk patients with a local recurrence to eradicate the largest number of lymph nodes, independent of the counts measured by the gamma probe.

Unusual false-positive radioiodine whole-body scans in patients with differentiated thyroid carcinoma.

Radioiodine whole-body imaging is the most accurate method in the diagnosis of metastases from differentiated thyroid cancer. However, false-positive images rarely occur. The authors report unusual cases of thymic hyperplasia and post-traumatic skull changes mimicking mediastinal, skull, or cerebral metastases. Nonthyroidal causes were diagnosed by other radionuclide studies (bone and brain scintigraphy) and CT scans. Follow-up and undetectable thyroglobulin levels helped confirm the benign cause.

Thyroid carcinoma mimicking a toxic adenoma

A young woman with a thyroid papillary carcinoma behaving as an autonomously hyperfunctioning nodule is described. Only 17 similar patients have been seen in the past 25 years. It is emphasized that hyperthyroidism does not exclude malignant disease in hot nodules. This possibility suggests that all thyroid nodules, either cold or hot, require careful management. Therefore, in “at risk” cases, surgery could be the most useful treatment.

Optimal use of the 131-I-metaiodobenzylguanidine and cisplatin combination in advanced neuroblastoma

Neuroblastoma (NB), a childhood radiosensitive tumor, is very aggressive and malignant; in its disseminated form, despite very intensive chemotherapy, prognosis continues to be dismal. Owing to its capacity to concentrate in NB lesions, large doses of 131-I-MIBG, have given very encouraging therapeutic results in patients resistant to conventional therapy as well as at diagnosis.We recently reported the first attempt in combination therapy (CO-TH) using 131-I-MIBG and cisplatin. This new form of CO-TH appears very effective in obtaining a rapid and excellent response in relapsed patients.In this report, we describe the results of further experience with CO-TH in disseminated NB. We have attempted to verify to what extent interaction between the effects of the two agents may produce therapeutic benefit, and we have sought the optimization of CO-TH use.Three stage IV NB patients were treated with CO-TH. The following treatment schedule, was planned: day 1, cisplatin 50 mg/m2 i.v. over 6 h; day 2, 131-I-MIBG 100—130 mCi at high specific activity (- 1.1 Gbq/mg) i.v. over 6 h followed, a week later, by the same treatment combination.The therapeutic results were encouraging. However, hematological toxicity continued to represent a major limiting factor. In view of the overall effectiveness of CO-TH, at the price of lasting hematological toxicity, it may be indicated as a consolidationregimen some time before conditioning chemotherapy for autologous bone marrow transplantation.

Growth hormone response to propranolol and l-dopa in obese subjects

Oral administration of propranolol and L-dopa produced a marked increase in plasma growth hormone values in 12 obese subjects who had failed to respond to L-dopa alone. GH values after propranolol and L-dopa in obese subjects were not significantly different from those of normal subjects after L-dopa at 60, 90, and 120 min. Association of propranolol and L-dopa appears to be a simple means of investigating GH response in obese subjects.

Solitary liver metastasis from Hürthle cell thyroid cancer: A Case Report and review of the literature

Metastasis to the liver from thyroid cancer is a rare event with a reported frequency of 0.5%. Metastatic liver involvement from differentiated thyroid cancer (DTC) is nearly always multiple or diffuse and usually found along with other distant metastases (lung, bone and brain). The authors describe a patient with a solitary liver metastasis from Hürthle cell thyroid cancer, which appeared during long-term follow-up. The lesion was diagnosed by progressive increase of thyroglobulin in the serum and imaged with I-131 whole body scan, ultrasonography, magnetic resonance imaging (MRI) and F-18 fluoro-deoxyglucose positron emission tomography (FDG-PET) scan. For patients with a Tg level above some arbitrary limit, the administration of a large dose (3.7–5.5 GBq; 100–150 mCi) of I-131, in order to obtain a highly sensitive Tx whole body scan (WBS), remains the best diagnostic strategy. However, on very rare occasions, physiological enteric radioactivity can hide possible abdominal lesions and further indepth studies, such as FDG-PET scans, are sometimes necessary.

Potential use of iodine-123 metaiodobenzylguanidine radioaerosol as a marker of pulmonary neuroadrenergic function

Iodine-123 metaiodobenzylguanidine (123IMIBG) radioaerosol is of potential use in the investigation of the neuroadrenergic function of the lungs; however, before the method can be successfully employed the following issues need to be clarified: (1) Does the nebulization affect the radiochemical purity of123IMIBG? (2) Is the pulmonary distribution of inhaled123IMIBG homogeneous in normal subjects? (3) Does the pulmonary clearance of inhaled123I-MIBG reflect the functional status of the neuroadrenergic system of the lungs? In this study we performed: (1) a chromatographic study of nebulized123I-MIBG; (2) a quantitative evaluation of the lung distribution of123I-MIBG radioaerosol in normal subjects as compared with that of technetium-99m diethylene triamine penta-acetic acid (99mTc-DTPA) and (3) an assessment of123I-MIBG lung clearance both under control conditions and after pharmacologically induced beta-blockade, again compared with99mTc-DTPA. For these purposes, eight normal subjects were divided randomly into an “MIBG group” and a “DTPA group” (four subjects each) and submitted to three scintigraphic studies each: a baseline study, and studies after the administration of a low (80 mg) and a high (160 mg) dose of propranolol. Radiochemical purity of nebulized123IMIBG ranged between 97.18% and 98.70%. The lung distribution of123I-MIBG, as judged by the aerosol penetration index, was identical to that of99mTc-DTPA under all study conditions. The123I-MIBG clearance rate was slower than that of99mTc-DTPA under baseline conditions (135±32 min vs 69±27 min,P<0.01) and increased significantly after propranolol administrations, while the99mTc-DTPA clearance did not change. The following conclusions were drawn: (1) the nebulization does not affect the radiochemical purity of123I-MIBG; (2) the lung distribution of123I-MIBG is homogeneous in normal subjects; (3) the pulmonary clearance of123IMIBG reflects the functional status of the neuroadrenergic system of the lungs. Thus this scintigraphic method is suitable for research and perhaps for future clinical use.

131I-metaiodobenzylguanidine in the treatment of neuroblastoma at diagnosis

Radioactive metaiodobenzylguanidine (131I-MIBG) is taken up specifically by neuroblastoma cells and appears to represent a new treatment modality in patients with advanced neuroblastoma. Taking into account the fact that all patients so far treated were heavily pretreated and resistant to chemotherapy, the results obtained appear encouraging. In order to explore further the potential role of this new drug in untreated patients, we treated with 131I-MIBG a child with stage III neuroblastoma at diagnosis. We observed the complete disappearance of a large abdominal tumor mass after a relatively low dosage of 131I-MIBG, with minimal hematologic toxicity. No further treatment was given and, at present, the patient is alive with no evidence of disease 18 months from diagnosis. This child represents, to our knowledge, the only case of neuroblastoma thus far treated at diagnosis and the excellent response obtained suggests the need for further investigations of this therapy in untreated patients.

Scintigraphic localization of a disseminated malignant pheochromocytoma with the use of 131I-meta-iodobenzylguanidine

Preliminary clinical studies with 131I-meta-iodobenzylguanidine, a newly synthesized radiopharmaceutical and guanethidine analog capable of imaging the adrenal medulla, have led to the identification of a case of disseminated malignant pheochromocytoma with the localization of brain and bone metastases. The result is of particular interest as the symptomatology in this case appeared rather equivocal and various investigations had led to a completely different diagnosis. This new scintigraphic technique has proved to be safe, specific and noninvasive, and it may have a clinical application as a complementary or alternative technique to conventional diagnostic tests.