... No. 56, part I. Oxford, UK: Pergamon Press; 1989. 5. Cloutier R, Smith 5, Watson E, et al. Do... more ... No. 56, part I. Oxford, UK: Pergamon Press; 1989. 5. Cloutier R, Smith 5, Watson E, et al. Dose to the fetus from radionuclides in the bladder. Health Phys. 1973;25: 147—161. 6. Fenech M, Morley AA. Measurement of micronuclei in lymphocytes. Mutat Res. 1985:147:29—36. ...
Hyperthyroidism in elderly patients is not to be under-evaluated, since it is characterized in su... more Hyperthyroidism in elderly patients is not to be under-evaluated, since it is characterized in such age range by particular clinical and prognostic features. Based upon literature survey and their clinical experience, the authors discuss in the present paper clinical, diagnostic and therapeutic problems of hyperthyroidism in geriatric patients. Material and method: In the period between 1978-2003 out of 1804 patients surgically treated for thyroid disease (non neoplastic in 1470 pts.), 180 subjects presented hyperthyroidism (17%). 36 were in geriatric age-range (mean age 76 yr.; 29 females and 7 males). 26 presented a Multinodular Toxic Goiter (72.2%), whereas 9 patients complained of Plummer Adenoma (25%); only 1 patient showed Basedow disease (2.7%). Results: As far as ASA classification, there were 7 ASA I, 27 ASA II and 2 ASA III. Compression of digestive tract and/or respiratory airway represented a surgical indication in 15 patients (41.6%). 12 (33.4%) were operated due to predominant cardiac symptoms (tachycardia, atrial fibrillation). The remaining 9 patients (25%) were treated for the concomitance of atypical symptoms of hyperthyroidism. We performed 15 total thyroidectomy, 7 "near totally", 8 sub-total, 6 hemithyroidectomy in case of Plummer adenoma. Postoperative mortality was nihil; p.o. morbidity was 5.5% for medical conditions (pneumonia) and surgery-related (1 laryngeal recurrent paralysis and 1 hypoparathyroidism) in 5.5%. Post-operative follow-up, conducted at 6 and 12 months from the operation, showed regression of hyperthyroidism and regression or improvement of all clinical symptoms complained by the patient. Conclusion: Surgical treatment seems to be the only immediate and definitive cure for hyperthyroidism. Geriatric age does not seem to be a surgical contraindication.
Considerable, but as yet still controversial evidence indicates the presence, in mammalian tissue... more Considerable, but as yet still controversial evidence indicates the presence, in mammalian tissues of endogenous digitalis-like factors (EDLFs) which inhibit cell membrane Na+, K(+)-adenosine triphosphatase (Na+, K(+)-ATPase) and which may cross-react with anti-digitalis antibodies. The aim of this study was to evaluate the effect of antibodies against cardiac glycosides on Na+, K(+)-ATPase in human erythrocytes. For this purpose, we measured the effect of antibodies against two different cardiac glycosides (anti-ouabain rabbit antiserum and anti-digoxin Fab fragments) on the activity of the Na+, K(+)-ATPase, as measured by erythrocyte rubidium-86 (86Rb) uptake, in subjects who had never come into contact with exogenous cardiac glycosides, and compared these results with the effect of two control rabbit sera: a normal serum and an antiserum to a non-related antigen. Anti-ouabain rabbit antiserum and anti-digoxin Fab fragments induced a significantly greater percentage change in 86Rb uptake in the erythrocytes than the two control sera (ANOVA followed by multiple comparison by the Games-Howell test). The average percentage change was +11.8 +/- 16.3% (n = 19) (mean +/- SD) for anti-ouabain antiserum +10.8 +/- 15.6% (n = 23) for anti-digoxin Fab fragments, -1.68 +/- 11.2% (n = 11) for anti-rhGM-CSF antiserum, and -5.8 +/- 11.7 (n = 10) for normal control serum. In a subgroup of ten subjects in whom the 3 antisera were tested simultaneously, the stimulation of erythrocyte 86Rb uptake induced by the two antidigitalis antibodies correlated significantly (r = 0.906, p = 0.001, n = 10).(ABSTRACT TRUNCATED AT 250 WORDS)
In 28 blood samples from 21 patients undergoing 131I treatment after surgical thyroidectomy for c... more In 28 blood samples from 21 patients undergoing 131I treatment after surgical thyroidectomy for cancer, the micronucleus (MN) frequency observed in peripheral blood lymphocytes (MN-test on binucleated cells) had a weighted mean of 0.044 +/- 0.006 (SEM), which was significantly different (p < 0.001) from that observed in 93 healthy individuals (0.025 +/- 0.001). The MN frequency (F(MN)) of the patients correlated fairly well (R = 0.736) with the modified activity (Amod) calculated by the following equation: [formula: see text] where Ai is the 131I activity on a determined day, e the logarithm base, di the number of days that have passed between the determined day and the day when the blood was drawn, and k is a day coefficient, defined in this context as the "daily attenuation factor". The use of the value of 0.0003 for k allowed the following equation to be obtained: F(MN) = 7.9 x 10(-5) (+/- 1.4 x 10(-5)).Amod + 0.014 (R = 0.736) The MN frequency was used to estimate, by our DOSIME program, the dose (Gy) received at the individual level in the 131I treatment. In these subjects the calculated dose was well correlated with Amod by the relationship: DBio = 0.0009 (+/- 0.0002).Amod + 0.0675 (R = 0.755) 3-aminobenzamide (3AB), an inhibitor of the poly(ADP-ribose)polymerase enzyme involved in DNA repair, induced and increase in X-ray cytogenetic damage (MN yields), evaluated at the individual level using the 3AB-index (I-3AB). The index was obtained from the MN-yield count after x-irradiation with (MN + 3AB) and without (MN - 3AB) 3AB, using the following formula: I = 1-(MN - 3AB/MN + 3AB).(ABSTRACT TRUNCATED AT 250 WORDS)
Objective: The possibility to quantify in vivo the severity of the inflammatory process in the pa... more Objective: The possibility to quantify in vivo the severity of the inflammatory process in the pancreas of patients with recent onset insulin dependent diabetes mellitus (IDDM) could be of great relevance for follow-up studies involving immunotherapy. Scintigraphy with radiolabelled human polyclonal immunoglobulins (99mTc-HIG) is currently used for the diagnosis and follow-up of several acute and chronic inflammatory diseases. In this longitudinal study we have investigated to what extent 99mTc-HIG accumulate in the pancreas of patients with recent onset IDDM and in subjects at risk to develop IDDM. Methods: Combined computerised tomography and gamma camera imaging were used to measure the radioactivity in the pancreatic region, as the pancreas/bone radioactivity ratio (P/B). Patients with IDDM (n = 15) were investigated at the time of diagnosis and after 1 year. Five pre-diabetic ICA+ve subjects and 8 age and sex matched normal subjects were also investigated. Results: Eight out of 15 newly diagnosed IDDM patients and 2/5 ICA+ve subjects showed a significant accumulation of radiolabelled HIG in the pancreas (P/B higher than the upper 1st centile of normal subjects). One year after the diagnosis a significant accumulation of immunoglobulins was still detectable in the pancreas of IDDM patients positive who were positive at diagnosis. Conclusions: These results suggest that immunoglobulins home and bind to the pancreas of patients with recent onset IDDM and also in some ICA+ve individuals. This may reflect an increased vascular permeability of pancreatic capillaries as a consequence of the inflammatory process involving the islets. Thus, this technique may be useful for monitoring the efficacy of immune intervention at diagnosis.
European Journal of Nuclear Medicine and Molecular Imaging, May 13, 1998
Insulin-dependent type 1 diabetes (IDDM) is caused by the autoimmune destruction of insulin-produ... more Insulin-dependent type 1 diabetes (IDDM) is caused by the autoimmune destruction of insulin-producing beta cells. Approximately 10%-20% of patients may benefit from adjuvant immunotherapy upon diagnosis of the disease in order to protect residual beta-cell function. It has been suggested that this subgroup of patients differs from others by virtue of the presence of residual pancreatic inflammation and beta-cell function. In this study we have investigated to what extent technetium-99m-labelled human polyclonal immunoglobulins (99m Tc-HIG) accumulate in the pancreas of IDDM patients at the time of diagnosis and 1 year thereafter, with a view to ascertaining whether HIG scintigraphy is useful for the identification of IDDM patients with residual pancreatic inflammation. Patients with recent-onset IDDM (n=15) were investigated at the time of diagnosis and 1 year later, and ten age-and sex-matched normal subjects were also studied. Gamma camera imaging and target to background ratio, analysed blind by three independent readers, were used to quantify the radioactivity in the pancreatic region and findings were correlated with metabolic, immunological and clinical parameters. Seven out of 15 newly diagnosed IDDM patients showed a significant accumulation of radiolabelled HIG in the pancreas (pancreas/bone ratio higher than the mean +2SD of normal subjects). One year after diagnosis, pancreatic accumulation of HIG was still detectable in most IDDM patients who were positive at the time of diagnosis. Six out of seven patients with positive scintigraphy had a partial clinical remission. These results indicate that HIG scintigraphy at the time of onset of diabetes identifies a subset of patients with residual beta-cell function who may benefit from adjuvant immunotherapy.
Cancer Biotherapy and Radiopharmaceuticals, Apr 1, 2004
An early diagnosis of distant metastases or local recurrences of medullary thyroid carcinoma (MTC... more An early diagnosis of distant metastases or local recurrences of medullary thyroid carcinoma (MTC) can be achieved by several conventional radiological modalities (e.g., ultrasonography, computed tomography [CT], and magnetic resonance imaging [MRI] as well as by radioisotopic procedures, such as positron emission tomography (PET), scintigraphy with different types of radiopharmaceuticals, and radiolabeled receptor-ligands in particular. The aim of this study was to evaluate the clinical utility of 99mTc-EDDA/HYNIC-TOC, a new octreotide derivative, to detect recurrences of disease or distant metastases in MTC. Images obtained of 5 patients with high levels of serum calcitonin were compared to findings obtained with other diagnostic procedures: 111In-octreotide, 99mTc-DMSA-V, 18F-flouro-D-deoxyglucose-PET, and CT/MRI. 99mTc-EDDA/HYNIC-TOC was positive in all patients and showed 15 areas of pathological uptake in the cervical and mediastinal regions. 111In-octreotide was positive in 3 of 3 patients and showed 4 areas, compared to 8 of 99mTc-EDDA/HYNIC-TOC. 99mTc-V-DMSA was positive in 3 of 4 patients but showed 6 pathological areas, compared to 13 of 99mTc-EDDA/HYNIC-TOC. 18F-FDG-PET was positive in 5 of 5 patients but showed only 11 areas, compared to 15 of 99mTc-EDDA/HYNIC-TOC. The CT scan was positive in only 2 patients. In conclusion, 99mTc-EDDA/HYNIC-TOC detected more sites of pathological uptake than other modalities, showed better imaging properties than 111In-octreotide, and might be the radiopharmaceutical of choice for providing a rationale for radioisotopic therapy.
The Journal of Clinical Endocrinology and Metabolism, Mar 1, 2008
Context: Type 2 deiodinase (D2) converts T 4 in T 3 in several human tissues, including hypothala... more Context: Type 2 deiodinase (D2) converts T 4 in T 3 in several human tissues, including hypothalamus and pituitary, and, therefore, plays a pivotal role in the negative feedback regulation of TSH secretion. A common variant of the gene, threonine (Thr) 92 alanine (Ala), has been identified and associated with decreased D2 enzymatic activity. Objective: Our objective was to investigate whether this polymorphism predicts the T 4 dosage needed to obtain target TSH levels in thyroidectomized patients. Setting: Ambulatory patients were included in the study. Patients: A total of 191 consecutive thyroid cancer patients, previously treated by near total thyroidectomy and radioiodine ablation, were studied. They were on stable T 4 dose treatment aimed at obtaining either suppressed (supp) (n Ï 117, Ͻ 0.1 mU/liter) or near-supp (n Ï 74, Õ† 0.1 Ͻ 0.5 mU/liter) serum TSH levels. Main Outcome Measures: DNA genotyping for D2 Thr92Ala variant and evaluation of T 4 dose (g/kg) needed to obtain target TSH levels were determined. Results: Ala/Ala homozygous patients needed a higher T 4 dose as compared with patients carrying the Thr92 variant (X/Thr patients) according to a recessive genetic model (2.08 Ï® 0.43 vs. 1.90 Ï® 0.35 g/kg; P Ͻ 0.05). This difference was observable in the near-supp group (P Ï 0.002), but not in the supp group (P Ï 0.4). Conclusions: D2 Thr92Ala polymorphism seems to predict the need for higher T 4 intake in thyroidectomized patients. If this finding is confirmed in additional studies, it may predict the T 4 requirement to suppress TSH on the basis of the individual genetic background. (J Clin Endocrinol Metab 93: 910-913, 2008) T ype 2 deiodinase (D2), by catalyzing the intracellular conversion of L-T 4 to T 3 , plays a major role in thyroid hormone metabolism (1). D2 generates T 3 in several human tissues, including brown fat, brain, pituitary (thyrotroph cells), thyroid, and aortic smooth and skeletal muscle. T 3 concentration at both hypothalamic and pituitary level is the major determinant of the inhibitory control of TSH secretion; therefore, D2 activity plays a pivotal role in the negative feedback regulation of pituitary
We have recently reported that interleukin-2 (IL2) labelled with iodine-123 (1231) can be success... more We have recently reported that interleukin-2 (IL2) labelled with iodine-123 (1231) can be successfully used for the in vivo detection of areas of lymphocytic infiltration1. IL2 is a lymphocyte growth factor (M.W.:15.5kD) that binds to its specific receptor expressed on the surface membrane of activated T lymphocytes2. 1231 is a suitable isotope for in vivo studies and for protein labelling. However, it has some disadvantages such as the poor availability, the elevated cost and the low labelling efficiency.
Stunning is a phenomenon of reducing (131)I uptaking activity by residual or metastatic tissue du... more Stunning is a phenomenon of reducing (131)I uptaking activity by residual or metastatic tissue during the follow-up of patients after total thyroidectomy for differentiated thyroid carcinoma. It was observed at whole body scintigraphy performed after therapeutic dose, administered for remnant ablation, in patients who were previously given a (131)I dose for diagnostic purpose. This phenomenon could influence the efficacy of radioisotopic therapy, making it unsuccessful. Stunning was observed also in case of hyperthyroidism treated by fractionated doses of (131)I. After a careful revision of literature, Authors report their last 10 years-experience about very few cases of supposed stunning, observed in oncological and hyperthyroidal patients who underwent diagnostic scan and radioiodine therapy. In case of differentiated thyroid carcinoma, we recommended a careful selection of patients who will be given ablative therapy using very low diagnostic doses and administering further therapeutic dose in a short time. In case of hyperthyroidism treatment, it is confirmed the opportunity of a single therapeutic dose with TSH value within the normal range. Because it was found out a very small number of cases in our wide population, we conclude that stunning is not influent in clinical practice, above all if ''well-practice'' diagnostic-therapeutical procedures are strictly observed.
Malignant struma ovarii is a very rare disease and, therefore, there is neither common agreement ... more Malignant struma ovarii is a very rare disease and, therefore, there is neither common agreement on treatment regimens nor sufficient follow-up experience. We present a case of a 49-year-old woman with malignant struma ovarii of the follicular type, who received ablative radioiodine treatment after thyroidectomy and surgical removal of the primary tumour. During followup examinations an increasing thyroglobulin level was found, caused by a tumour relapse with suspected urinary bladder infiltration on CT and proven uptake of radioiodine on whole-body scanning with iodine-131. After administration of 6 GBq 131I, complete tumour regression was achieved with no evidence of a new relapse during a 30-month follow-up period. Correspondingly, repeated thyroglobulin measurements were all negative. This case demonstrates the benefit of combined surgical and radioiodine treatment of malignant struma ovarii for both monitoring and therapy of relapse or metastases; thus, the same therapeutic regimen as is employed in primary differentiated thyroid carcinoma may be recommended.
... No. 56, part I. Oxford, UK: Pergamon Press; 1989. 5. Cloutier R, Smith 5, Watson E, et al. Do... more ... No. 56, part I. Oxford, UK: Pergamon Press; 1989. 5. Cloutier R, Smith 5, Watson E, et al. Dose to the fetus from radionuclides in the bladder. Health Phys. 1973;25: 147—161. 6. Fenech M, Morley AA. Measurement of micronuclei in lymphocytes. Mutat Res. 1985:147:29—36. ...
Hyperthyroidism in elderly patients is not to be under-evaluated, since it is characterized in su... more Hyperthyroidism in elderly patients is not to be under-evaluated, since it is characterized in such age range by particular clinical and prognostic features. Based upon literature survey and their clinical experience, the authors discuss in the present paper clinical, diagnostic and therapeutic problems of hyperthyroidism in geriatric patients. Material and method: In the period between 1978-2003 out of 1804 patients surgically treated for thyroid disease (non neoplastic in 1470 pts.), 180 subjects presented hyperthyroidism (17%). 36 were in geriatric age-range (mean age 76 yr.; 29 females and 7 males). 26 presented a Multinodular Toxic Goiter (72.2%), whereas 9 patients complained of Plummer Adenoma (25%); only 1 patient showed Basedow disease (2.7%). Results: As far as ASA classification, there were 7 ASA I, 27 ASA II and 2 ASA III. Compression of digestive tract and/or respiratory airway represented a surgical indication in 15 patients (41.6%). 12 (33.4%) were operated due to predominant cardiac symptoms (tachycardia, atrial fibrillation). The remaining 9 patients (25%) were treated for the concomitance of atypical symptoms of hyperthyroidism. We performed 15 total thyroidectomy, 7 "near totally", 8 sub-total, 6 hemithyroidectomy in case of Plummer adenoma. Postoperative mortality was nihil; p.o. morbidity was 5.5% for medical conditions (pneumonia) and surgery-related (1 laryngeal recurrent paralysis and 1 hypoparathyroidism) in 5.5%. Post-operative follow-up, conducted at 6 and 12 months from the operation, showed regression of hyperthyroidism and regression or improvement of all clinical symptoms complained by the patient. Conclusion: Surgical treatment seems to be the only immediate and definitive cure for hyperthyroidism. Geriatric age does not seem to be a surgical contraindication.
Considerable, but as yet still controversial evidence indicates the presence, in mammalian tissue... more Considerable, but as yet still controversial evidence indicates the presence, in mammalian tissues of endogenous digitalis-like factors (EDLFs) which inhibit cell membrane Na+, K(+)-adenosine triphosphatase (Na+, K(+)-ATPase) and which may cross-react with anti-digitalis antibodies. The aim of this study was to evaluate the effect of antibodies against cardiac glycosides on Na+, K(+)-ATPase in human erythrocytes. For this purpose, we measured the effect of antibodies against two different cardiac glycosides (anti-ouabain rabbit antiserum and anti-digoxin Fab fragments) on the activity of the Na+, K(+)-ATPase, as measured by erythrocyte rubidium-86 (86Rb) uptake, in subjects who had never come into contact with exogenous cardiac glycosides, and compared these results with the effect of two control rabbit sera: a normal serum and an antiserum to a non-related antigen. Anti-ouabain rabbit antiserum and anti-digoxin Fab fragments induced a significantly greater percentage change in 86Rb uptake in the erythrocytes than the two control sera (ANOVA followed by multiple comparison by the Games-Howell test). The average percentage change was +11.8 +/- 16.3% (n = 19) (mean +/- SD) for anti-ouabain antiserum +10.8 +/- 15.6% (n = 23) for anti-digoxin Fab fragments, -1.68 +/- 11.2% (n = 11) for anti-rhGM-CSF antiserum, and -5.8 +/- 11.7 (n = 10) for normal control serum. In a subgroup of ten subjects in whom the 3 antisera were tested simultaneously, the stimulation of erythrocyte 86Rb uptake induced by the two antidigitalis antibodies correlated significantly (r = 0.906, p = 0.001, n = 10).(ABSTRACT TRUNCATED AT 250 WORDS)
In 28 blood samples from 21 patients undergoing 131I treatment after surgical thyroidectomy for c... more In 28 blood samples from 21 patients undergoing 131I treatment after surgical thyroidectomy for cancer, the micronucleus (MN) frequency observed in peripheral blood lymphocytes (MN-test on binucleated cells) had a weighted mean of 0.044 +/- 0.006 (SEM), which was significantly different (p < 0.001) from that observed in 93 healthy individuals (0.025 +/- 0.001). The MN frequency (F(MN)) of the patients correlated fairly well (R = 0.736) with the modified activity (Amod) calculated by the following equation: [formula: see text] where Ai is the 131I activity on a determined day, e the logarithm base, di the number of days that have passed between the determined day and the day when the blood was drawn, and k is a day coefficient, defined in this context as the "daily attenuation factor". The use of the value of 0.0003 for k allowed the following equation to be obtained: F(MN) = 7.9 x 10(-5) (+/- 1.4 x 10(-5)).Amod + 0.014 (R = 0.736) The MN frequency was used to estimate, by our DOSIME program, the dose (Gy) received at the individual level in the 131I treatment. In these subjects the calculated dose was well correlated with Amod by the relationship: DBio = 0.0009 (+/- 0.0002).Amod + 0.0675 (R = 0.755) 3-aminobenzamide (3AB), an inhibitor of the poly(ADP-ribose)polymerase enzyme involved in DNA repair, induced and increase in X-ray cytogenetic damage (MN yields), evaluated at the individual level using the 3AB-index (I-3AB). The index was obtained from the MN-yield count after x-irradiation with (MN + 3AB) and without (MN - 3AB) 3AB, using the following formula: I = 1-(MN - 3AB/MN + 3AB).(ABSTRACT TRUNCATED AT 250 WORDS)
Objective: The possibility to quantify in vivo the severity of the inflammatory process in the pa... more Objective: The possibility to quantify in vivo the severity of the inflammatory process in the pancreas of patients with recent onset insulin dependent diabetes mellitus (IDDM) could be of great relevance for follow-up studies involving immunotherapy. Scintigraphy with radiolabelled human polyclonal immunoglobulins (99mTc-HIG) is currently used for the diagnosis and follow-up of several acute and chronic inflammatory diseases. In this longitudinal study we have investigated to what extent 99mTc-HIG accumulate in the pancreas of patients with recent onset IDDM and in subjects at risk to develop IDDM. Methods: Combined computerised tomography and gamma camera imaging were used to measure the radioactivity in the pancreatic region, as the pancreas/bone radioactivity ratio (P/B). Patients with IDDM (n = 15) were investigated at the time of diagnosis and after 1 year. Five pre-diabetic ICA+ve subjects and 8 age and sex matched normal subjects were also investigated. Results: Eight out of 15 newly diagnosed IDDM patients and 2/5 ICA+ve subjects showed a significant accumulation of radiolabelled HIG in the pancreas (P/B higher than the upper 1st centile of normal subjects). One year after the diagnosis a significant accumulation of immunoglobulins was still detectable in the pancreas of IDDM patients positive who were positive at diagnosis. Conclusions: These results suggest that immunoglobulins home and bind to the pancreas of patients with recent onset IDDM and also in some ICA+ve individuals. This may reflect an increased vascular permeability of pancreatic capillaries as a consequence of the inflammatory process involving the islets. Thus, this technique may be useful for monitoring the efficacy of immune intervention at diagnosis.
European Journal of Nuclear Medicine and Molecular Imaging, May 13, 1998
Insulin-dependent type 1 diabetes (IDDM) is caused by the autoimmune destruction of insulin-produ... more Insulin-dependent type 1 diabetes (IDDM) is caused by the autoimmune destruction of insulin-producing beta cells. Approximately 10%-20% of patients may benefit from adjuvant immunotherapy upon diagnosis of the disease in order to protect residual beta-cell function. It has been suggested that this subgroup of patients differs from others by virtue of the presence of residual pancreatic inflammation and beta-cell function. In this study we have investigated to what extent technetium-99m-labelled human polyclonal immunoglobulins (99m Tc-HIG) accumulate in the pancreas of IDDM patients at the time of diagnosis and 1 year thereafter, with a view to ascertaining whether HIG scintigraphy is useful for the identification of IDDM patients with residual pancreatic inflammation. Patients with recent-onset IDDM (n=15) were investigated at the time of diagnosis and 1 year later, and ten age-and sex-matched normal subjects were also studied. Gamma camera imaging and target to background ratio, analysed blind by three independent readers, were used to quantify the radioactivity in the pancreatic region and findings were correlated with metabolic, immunological and clinical parameters. Seven out of 15 newly diagnosed IDDM patients showed a significant accumulation of radiolabelled HIG in the pancreas (pancreas/bone ratio higher than the mean +2SD of normal subjects). One year after diagnosis, pancreatic accumulation of HIG was still detectable in most IDDM patients who were positive at the time of diagnosis. Six out of seven patients with positive scintigraphy had a partial clinical remission. These results indicate that HIG scintigraphy at the time of onset of diabetes identifies a subset of patients with residual beta-cell function who may benefit from adjuvant immunotherapy.
Cancer Biotherapy and Radiopharmaceuticals, Apr 1, 2004
An early diagnosis of distant metastases or local recurrences of medullary thyroid carcinoma (MTC... more An early diagnosis of distant metastases or local recurrences of medullary thyroid carcinoma (MTC) can be achieved by several conventional radiological modalities (e.g., ultrasonography, computed tomography [CT], and magnetic resonance imaging [MRI] as well as by radioisotopic procedures, such as positron emission tomography (PET), scintigraphy with different types of radiopharmaceuticals, and radiolabeled receptor-ligands in particular. The aim of this study was to evaluate the clinical utility of 99mTc-EDDA/HYNIC-TOC, a new octreotide derivative, to detect recurrences of disease or distant metastases in MTC. Images obtained of 5 patients with high levels of serum calcitonin were compared to findings obtained with other diagnostic procedures: 111In-octreotide, 99mTc-DMSA-V, 18F-flouro-D-deoxyglucose-PET, and CT/MRI. 99mTc-EDDA/HYNIC-TOC was positive in all patients and showed 15 areas of pathological uptake in the cervical and mediastinal regions. 111In-octreotide was positive in 3 of 3 patients and showed 4 areas, compared to 8 of 99mTc-EDDA/HYNIC-TOC. 99mTc-V-DMSA was positive in 3 of 4 patients but showed 6 pathological areas, compared to 13 of 99mTc-EDDA/HYNIC-TOC. 18F-FDG-PET was positive in 5 of 5 patients but showed only 11 areas, compared to 15 of 99mTc-EDDA/HYNIC-TOC. The CT scan was positive in only 2 patients. In conclusion, 99mTc-EDDA/HYNIC-TOC detected more sites of pathological uptake than other modalities, showed better imaging properties than 111In-octreotide, and might be the radiopharmaceutical of choice for providing a rationale for radioisotopic therapy.
The Journal of Clinical Endocrinology and Metabolism, Mar 1, 2008
Context: Type 2 deiodinase (D2) converts T 4 in T 3 in several human tissues, including hypothala... more Context: Type 2 deiodinase (D2) converts T 4 in T 3 in several human tissues, including hypothalamus and pituitary, and, therefore, plays a pivotal role in the negative feedback regulation of TSH secretion. A common variant of the gene, threonine (Thr) 92 alanine (Ala), has been identified and associated with decreased D2 enzymatic activity. Objective: Our objective was to investigate whether this polymorphism predicts the T 4 dosage needed to obtain target TSH levels in thyroidectomized patients. Setting: Ambulatory patients were included in the study. Patients: A total of 191 consecutive thyroid cancer patients, previously treated by near total thyroidectomy and radioiodine ablation, were studied. They were on stable T 4 dose treatment aimed at obtaining either suppressed (supp) (n Ï 117, Ͻ 0.1 mU/liter) or near-supp (n Ï 74, Õ† 0.1 Ͻ 0.5 mU/liter) serum TSH levels. Main Outcome Measures: DNA genotyping for D2 Thr92Ala variant and evaluation of T 4 dose (g/kg) needed to obtain target TSH levels were determined. Results: Ala/Ala homozygous patients needed a higher T 4 dose as compared with patients carrying the Thr92 variant (X/Thr patients) according to a recessive genetic model (2.08 Ï® 0.43 vs. 1.90 Ï® 0.35 g/kg; P Ͻ 0.05). This difference was observable in the near-supp group (P Ï 0.002), but not in the supp group (P Ï 0.4). Conclusions: D2 Thr92Ala polymorphism seems to predict the need for higher T 4 intake in thyroidectomized patients. If this finding is confirmed in additional studies, it may predict the T 4 requirement to suppress TSH on the basis of the individual genetic background. (J Clin Endocrinol Metab 93: 910-913, 2008) T ype 2 deiodinase (D2), by catalyzing the intracellular conversion of L-T 4 to T 3 , plays a major role in thyroid hormone metabolism (1). D2 generates T 3 in several human tissues, including brown fat, brain, pituitary (thyrotroph cells), thyroid, and aortic smooth and skeletal muscle. T 3 concentration at both hypothalamic and pituitary level is the major determinant of the inhibitory control of TSH secretion; therefore, D2 activity plays a pivotal role in the negative feedback regulation of pituitary
We have recently reported that interleukin-2 (IL2) labelled with iodine-123 (1231) can be success... more We have recently reported that interleukin-2 (IL2) labelled with iodine-123 (1231) can be successfully used for the in vivo detection of areas of lymphocytic infiltration1. IL2 is a lymphocyte growth factor (M.W.:15.5kD) that binds to its specific receptor expressed on the surface membrane of activated T lymphocytes2. 1231 is a suitable isotope for in vivo studies and for protein labelling. However, it has some disadvantages such as the poor availability, the elevated cost and the low labelling efficiency.
Stunning is a phenomenon of reducing (131)I uptaking activity by residual or metastatic tissue du... more Stunning is a phenomenon of reducing (131)I uptaking activity by residual or metastatic tissue during the follow-up of patients after total thyroidectomy for differentiated thyroid carcinoma. It was observed at whole body scintigraphy performed after therapeutic dose, administered for remnant ablation, in patients who were previously given a (131)I dose for diagnostic purpose. This phenomenon could influence the efficacy of radioisotopic therapy, making it unsuccessful. Stunning was observed also in case of hyperthyroidism treated by fractionated doses of (131)I. After a careful revision of literature, Authors report their last 10 years-experience about very few cases of supposed stunning, observed in oncological and hyperthyroidal patients who underwent diagnostic scan and radioiodine therapy. In case of differentiated thyroid carcinoma, we recommended a careful selection of patients who will be given ablative therapy using very low diagnostic doses and administering further therapeutic dose in a short time. In case of hyperthyroidism treatment, it is confirmed the opportunity of a single therapeutic dose with TSH value within the normal range. Because it was found out a very small number of cases in our wide population, we conclude that stunning is not influent in clinical practice, above all if ''well-practice'' diagnostic-therapeutical procedures are strictly observed.
Malignant struma ovarii is a very rare disease and, therefore, there is neither common agreement ... more Malignant struma ovarii is a very rare disease and, therefore, there is neither common agreement on treatment regimens nor sufficient follow-up experience. We present a case of a 49-year-old woman with malignant struma ovarii of the follicular type, who received ablative radioiodine treatment after thyroidectomy and surgical removal of the primary tumour. During followup examinations an increasing thyroglobulin level was found, caused by a tumour relapse with suspected urinary bladder infiltration on CT and proven uptake of radioiodine on whole-body scanning with iodine-131. After administration of 6 GBq 131I, complete tumour regression was achieved with no evidence of a new relapse during a 30-month follow-up period. Correspondingly, repeated thyroglobulin measurements were all negative. This case demonstrates the benefit of combined surgical and radioiodine treatment of malignant struma ovarii for both monitoring and therapy of relapse or metastases; thus, the same therapeutic regimen as is employed in primary differentiated thyroid carcinoma may be recommended.
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