[Nuclear medicine of the thyroid and parathyroid glands].

Nuclear medicine plays an important role in the diagnosis and treatment of thyroid and parathyroid disorders. Basic nuclear medicine in the diagnosis of thyroid and parathyroid disorders and our clinical study on 131I treatment for differentiated thyroid cancer are described. Characteristics of thyroid, parathyroid, tumor scans and typical bone scintigrams in hyperparathyroidism are presented. Combined 99mTc-MIBI/99mTc-HSA-D SPECT imaging clearly demonstrated localization of ectopic parathyroid adenoma. Very interesting uncommon three cases of thyroid cancer are presented. 99mTcO4- thyroid scan in the first patient demonstrated intense tracer uptake in the lymph node metastasis from papillary microcancer. Post-therapy 131I scan following total thyroidectomy visualized multiple pulmonary metastases. The second patient with metastatic follicular cancer developed thyrotoxicosis with high TSH receptor antibodies. Post-therapy 131I total body scan in the third patient with papillary cancer demonstrated large skull metastasis. Cardiac blood pool and large blood vessel visualization was also clearly seen at this time.

[Seven cases of brain metastasis from papillary thyroid carcinoma].

Brain metastases from differentiated thyroid carcinoma are extremely rare and carry a poor prognosis. We describe here clinical details of 7 cases of brain metastases from papillary thyroid carcinoma. Of 153 patients with metastases from differentiated thyroid carcinoma (papillary in 123, follicular in 30) treated at our institution between 1981 and 1999, 7 patients (4.6%) had brain metastases. Histologically, the primary tumor was papillary carcinoma in all 7 cases. Four were males and 3 were females. The median age at first diagnosis of distant metastases was 63 yr (range, 47-76 yr). Of these patients, one had brain metastases only and six had metastases to the lungs as well. Five of these patients were treated with 131I. Three of these 5 patients had marked uptake in the metastases (131I positive) on post-therapy 131I scans and another 2 patients had no significant activity (131I negative) in both pulmonary and brain metastatic lesions. One of 3 patients with 131I positive lesions had intense activity in the brain tumor, but no uptake in multiple pulmonary metastatic tumors. In a patient with 131I positive brain metastases, the tumors progressed rapidly after 131I therapy. In another one patient, acute hemorrhage of the tumor occurred four days after 131I therapy, requiring surgical removal. Loner case of 131I negative 2 patients was treated with radiosurgery (gamma-knife) and complete reduction in tumor volume was observed. On the other hand, one of 2 patients receiving no 131I therapy had radiosurgery (x-knife) and remaining one received conventional external radiation and chemotherapy for small solitary brain and pulmonary metastatic tumors. These therapeutic interventions were useful in both cases. The mean length of survival after the development of brain metastases in the five patients who died of the disease was 30 months. One patient treated with x-knife has been alive at 21 months and another one who has 131I uptake in the brain tumor without uptake in lung lesions has been alive 15 months after diagnosis of brain metastasis. These results indicate that it is important to detect brain metastasis by imaging techniques and Tg measurements and give treatment as early as possible since the brain is the third most common distant metastatic site and the prognosis is poor.

Thyroxine (T4) metabolism in an athyreotic patient who had taken a large amount of T4 at one time.

As we had an opportunity to take blood samples from a totally thyroidectomized patient who had attempted suicide by taking 2,000 microg of Levothyroxine (L-T4), the serum levels of thyroid hormones were sequentially measured to investigate the metabolism of circulating thyroid hormones in an athyreotic human. The serum concentrations of most thyroid hormones reached a peak on the second day, but the serum T3 level showed a peak one day later. The maximum concentrations of T4 (315 microg/l), FT4 (48.8 ng/l) and rT3 (0.80 microg/l) were very high, while the peak T3 level (1.92 microg/l) did not exceed the upper limit of the normal range. The serum T4 and rT3 levels returned to their normal range 13-17 days after the suicide attempt. The TSH level was suppressed rapidly and reached its nadir (0.044 mU/l) on the 6th day. During this period, the T1/2 and MCR of serum T4 were 10.4 days and 0.64 l/day, respectively, which values were almost equivalent to those observed during 15 days after discontinuation of the maintenance L-T4 therapy. In summary, the oral intake of a large amount of L-T4 at one time does not induce a proportional increase in the T3 level in an athyreotic person. The MCR of serum T4 is decreased and the T1/2 of serum T4 is prolonged, probably due to the lack of intrathyroidal deiodination. These findings support the conclusion that the D1 activity in the thyroid is one of the major determinants in the metabolic clearance of serum T4.

[The progress and methodologic problems of in vitro radioassay].

The history of development of in vitro radioassays is reviewed. The basic principles and clinical uses of saturation analysis, competitive radioassay and immunoradiometric assay are described. The more rapid, sensitive, specific and accurate assays are required at all times. However, it is well known that autoantibodies or heterophilic antibodies in serum interfere with radioassay and cause false results. Here I present the technical problems of the assay in the presence of such interfering substances which need to be resolved and also discussed the discrepancy between bioactivity and immunoreactivity in the assay.

Compartmental analysis of asialoglycoprotein receptor scintigraphy for quantitative measurement of liver function: a multicentre study.

A multicentre study on multicompartmental analysis of hepatic scintigraphy using technetium-99m labelled galactosyl serum albumin (GSA), which binds to the asialoglycoprotein receptor, was carried out at seven institutions in Japan. Seventy-four patients with liver disease received 3 mg (185 MBq) of 99mTc-GSA by intravenous injection. Sequential scanning was performed 30 min after injection to obtain anterior images of the heart and liver, followed by single-photon emission tomography (SPET). The indices included in this analysis were hepatic blood flow (Q) and maximal receptor binding rate (Rmax), which showed a good correlation with semiquantitative ratio indices for 99mTc-GSA, namely the retention rate in blood (HH15) and the hepatic uptake rate (LHL15). Q and Rmax also showed a significant correlation with other measures of hepatic function. When patients were grouped according to the severity of chronic liver damage (hepatocellular functional damage), Q was reduced in the moderate and severe groups, while Rmax was reduced in proportion to the functional stage. Both parameters showed no inter-institution difference using analysis of co-variance with the functional stage as a co-variant. With regard to the hepatic uptake rate, anterior planar images and SPET images gave similar results for Q and Rmax. Acquisition times of 15 or 30 min provided the same results. The multicompartmental model analysis permitted comparable results to be obtained at institutions using different gamma cameras, and is therefore considered a universally applicable method. These results indicate that Q and Rmax are useful general indices for evaluating the functional reserve capacity of the liver.

[Study of serum thrombomodulin(TM) levels in patients with hyper- or hypo- thyroidism].

We studies a relationship between the serum levels of thrombomodulin(TM) and the thyroid functions. Serum TM levels were measured in 48 patients with Graves' disease, 17 patients with primary hypothyroidism, 7 patients with subacute thyroiditis, 5 patients with painless thyroiditis and 2 patients with systematic Refetoff syndrome. These patients did not have malignant tumor, kidney failure, or blood vessel injury. Control sera were obtained from 42 healthy subjects. Serum levels of TM in patients with untreated Graves' disease were significantly higher(p < 0.001) compared with those in controls. Serum levels of TM in patients with hypothyroidism were not significantly changed as compared with those of controls. There were a positive correlation between the serum levels of TM and FT3 as well as FT4. Serial determinations of the serum levels of TM and thyroid function(FT3, FT4 and TH) in patients with Graves' disease during treatment showed that both the serum levels of TM and thyroid hormones (FT3 and FT4) lowered progressively during treatment. After normalization of serum FT3 and FT4, the serum TM levels returned to normal. However, the serum levels of TM in patients with destructive thyroiditis and Refetoff syndrome were normal in spite of high serum levels of thyroid hormones. These data suggest that an increase in serum levels of TM is not the direct result of thyroid hormones themselves but is the result of the prolonged hypermetabolic state induced by their peripheral activities. Thyroid hormones may stimulate the synthesis or metabolism of TM on the surface of vascular endothelial cells in the patients with Graves' disease.

Long-term clinical course of two cases of lymphocytic adenohypophysitis.

In two patients with lymphocytic adenohypophysitis, images of the pituitary gland were serially observed by MRI. In both cases, the pituitary gland had swollen during the late stage of the first pregnancy. In case 1, MRI findings were representative of lymphocytic adenohypophysitis. After delivery, plasma levels of PRL, ACTH and cortisol decreased markedly. The height of the pituitary gland gradually decreased from 22 mm (14 days after delivery) to 13 mm (73 days) and became rapidly smaller (4.9 mm, 115 days) following administration of massive doses of hydrocortisone for the treatment of acute adrenal insufficiency induced by painless thyroiditis. Six years later, the height was 2.5 mm. Low plasma levels of PRL and cortisol persisted. Diabetes insipidus did not develop. In case 2, MRI revealed a pituitary mass accompanied by a cystic change. Lymphocytic adenohypophysitis was confirmed by histological examination. Because pituitary function tests indicated that ACTH, PRL, GH and TSH were of low levels, hydrocortisone and L-thyroxine were orally administered. No diabetes insipidus was demonstrated. MRI disclosed that the height of the pituitary gland was 23 mm (17 days after delivery) but decreased to 17 and 5.5 mm after 44 and 128 days, respectively. Four years later immediately after the second delivery, it was 1 mm, and the patient was diagnosed as having empty sella. Long-term observation of lymphocytic adenohypophysitis demonstrated that the pituitary gland was markedly atrophied, leading to empty sella. It is believed that some of the classic cases of Sheehan's syndrome associated with empty sella may include lymphocytic adenohypophysitis.

Prognostic value of iodine-123 labelled BMIPP fatty acid analogue imaging in patients with myocardial infarction.

This study was undertaken to evaluate the prognostic value of iodine-123 labelled 15-iodophenyl-3-R,S-methyl pentadecanoic acid (BMIPP) imaging in patients with myocardial infarction. BMIPP is an iodinated methyl branched fatty acid analogue which is trapped in the myocardium with little washout, thereby reflecting fatty acid utilization in the myocardium. We previously reported that in patients with myocardial infarction, regions are often observed where reduced BMIPP uptake is seen relative to thallium-201 perfusion at rest. However, the clinical significance of such discordant BMIPP uptake remains unknown. Fifty consecutive patients with chronic myocardial infarction referred for stress thallium scan and coronary arteriography underwent BMIPP imaging at rest. Each patient was in a stable condition at the time of the radionuclide study. Follow-up was performed at a mean interval of 23 months to investigate the prognostic implications of the radionuclide studies. Nine patients had cardiac events during the follow-up period. Univariate analysis showed that the number of discordant BMIPP versus 201TL uptake segments was the best predictor of future cardiac events (P=0.0245), followed by the presence of discordant BMIPP uptake (P=0.0388) and the number of 201TL redistribution segments (P=0.0444). When all the clinical and radionuclide variables were analysed by Cox regression analysis, the presence of discordant BMIPP uptake was the best, and an independent, predictor of future cardiac events (chi 2=8.5) followed by the number of coronary stenoses on angiography (chi 2=3.9). These preliminary data suggest that decreased BMIPP uptake relative to 201TL is a valuable predictor of future cardiac events in patients with myocardial infarction. Areas with such discordant BMIPP uptake may contain jeopardized myocardium where fatty acid utilization has been severely suppressed relative to myocardial perfusion.

Immunoglobulin G can cross-react with glucagon antisera and cause a spuriously high plasma immunoreactive glucagon level.

We had a patient with asymptomatic hyper-immunoreactive glucagonemia and with no evidence of pancreatic tumor detected by radiological examinations. The glucagon level was not decreased by the administration of glucose or somatosatin analogue (SMS 201-995). Gel filtration studies revealed that most glucagon immunoreactivity was eluted at the position of 150,000 daltons [big plasma glucagon (BPG)]. Binding studies with 125I-glucagon showed that glucagon autoantibody was negative. Acid treatment of plasma and reduction of immunoglobulin G (IgG) did not result in a shift of BPG to normal glucagon (3485 daltons). Glucagon immunoreactivity determined with anti-glucagon antiserum OAL 123 (C-terminal specific antiserum used in the present radioimmunoassay kit) did not dilute out in parallel to normal glucagon (3485 daltons), and the plasma glucagon level was normal with Unger's 30K (anther C-terminal specific antiserum) and OAL 196 (N-terminal specific antiserum). The patient's IgG dose-dependently reduced the binding of 125I-glucagon to anti-glucagon antiserum OAL-123. Glucagon degrading activity (GDA) was negative in the patient's plasma. These results suggest that the patient's IgG cross-reacted with the present anti-glucagon antiserum OAL 123, and caused a spuriously high plasma immunoreactive glucagon level.

[Three thyroid patients showing fluctuation of thyroid hormone autoantibody titers during long-term treatment].

Development and fluctuation of thyroid hormone autoantibody (THAA) titers were observed during long-term treatment of thyroid diseases in three patients. The presence of THAA was noticed by spuriously high serum free thyroid hormone levels measured with an analog tracer RIA (Amerlex-M FT3, FT4) in all three patients. Amerlex-M FT3 or FT4 levels gradually decreased to appropriate values for the clinical status according to the decreasing titers of THAA. Free thyroid hormone levels with radiolabeled antibody radioassay (Amerlex-MAB FT3, FT4) were not affected by the THAA and always reflected actual thyroid function. Case 1 was a 46-year-old man with untreated primary hypothyroidism. Auti-T4 autoantibody was detected in his serum. The 125I-T4 analog binding to the autoantibody (125I-T4 analog binding ratio) gradually declined after L-T4 therapy and finally almost disappeared two years and four months later. Amerlex-MAB FT4 level rose to the normal range two months after T4 therapy, but TSH level remained slightly elevated (5.4-13 microU/ml) for five months during T4 therapy. The 125I-T4 analog binding ratio and anti-Tg autoantibody (TgAb) titer were inversely correlated. Case 2 was a 72-year-old woman had received desiccated thyroid for a long time. Sequential changes of 125I-T4 analog binding ratio were very similar to those of TgAb titer. Case 3 was a 74-year-old woman with Graves' disease. She had been treated with methimazole (MMI) and desiccated thyroid for three years and five months. Ten months after stopping both drugs, anti-T3 autoantibody was detected. The 125I-T3 analog binding ratio was transiently elevated and gradually declined to reference range for four years during L-T4 therapy. 125I-T3 analog binding ratio and TgAb titer changed in a similar way. These results suggest that desiccated thyroid hormone therapy and TgAb formation are related to the development of THAA and that L-T4 therapy reduces the THAA titer.

[Clinical studies using measurement of N-telopeptides of type 1 collagen (NTx) in patients with bone metastasis--comparison with bone scintigraphy and other metabolic bone markers].

Urinary metabolites of N-telopeptide of type 1 collagen cross-links (NTx) are known as a bone resorption marker. We performed a multi-center trial of NTx measurement in evaluation of bone metastasis. In total, 251 patients with or without bone metastasis from various malignancies were studied. Comparing with other bone markers such as urinary total deoxypyridinoline, osteocalcin, and bone specific alkaline phosphatase, NTx was the most sensitive one to detect bone metastasis and its levels correlated well with the extensiveness of bone metastasis. Measurement of NTx will be useful to determine to order bone scan in patients with malignancy and to monitor the clinical course in patients with bone metastasis.

[Adenosine triphosphate loading thallium-201 myocardial scintigraphy: optimal dose and diagnostic accuracy].

Adenosine triphosphate (ATP) is an alternative to dipyridamole or adenosine in thallium-201 myocardial scintigraphy. However, the optimal dose of ATP has not been determined. A Doppler guide wire study showed the coronary flow velocity at a dose of 0.15 mg/kg of ATP was equal or higher than that at 0.14 mg/kg of adenosine or 0.56 mg/kg of dipyridamole. ATP was given intravenously to 67 patients with coronary artery disease at 0.15 mg/kg/min for 6 min. Thallium-201 was injected at 3 min, followed by immediate and delayed (3 hrs) tomographic imaging. There was no serious side effect during examination, although chest pain (26%), dyspnea (17%), and flushing (33%) were common. The sensitivity and specificity to detect coronary artery disease were 98 and 100%, respectively. The sensitivity to detect left anterior descending artery, left circumflex artery, and right coronary artery lesions was 94, 59 and 77%, respectively. ATP loading thallium-201 scintigraphy provides an accurate diagnosis of coronary artery disease. The optimal dose of ATP is 0.15 mg/kg/min for 6 min.

Spontaneous growth hormone (GH) secretion by unstimulated human lymphocytes and the effects of GH-releasing hormone and somatostatin.

We investigated in five normal subjects whether the secretion of GH from lymphocytes would occur spontaneously without mitogens and be regulated by GHRH and somatostatin as in the endocrine system. Peripheral blood mononuclear cells were isolated from heparinized blood by the standard Ficoll-Hypaque gradient centrifugation method, and incubated for up to 7 days with or without GHRH, somatostatin analog (SMS 201-995), cycloheximide, or actinomycin D. GH levels in the lyophilized samples were measured by a highly sensitive enzyme immunoassay. GH concentration in culture medium (5 x 10(5) cells/mL) time dependently increased in all subjects, reaching 0.47 +/- 0.18 ng/L at day 7. A protein synthesis inhibitor (cycloheximide) and RNA synthesis inhibitor (actinomycin D) completely blocked GH secretion from lymphocytes. Immunoreactive GH secreted by unstimulated human lymphocytes was similar to pituitary GH in terms of antigenicity and molecular weight. Physiological concentrations of GHRH (10(-10)-10(-8) mol/L) and SMS 201-995 (10(-8)-10(-6) mol/L) had no effects on the spontaneous secretion of GH from human lymphocytes. These results indicate that GH is spontaneously synthesized de novo and secreted from unstimulated human lymphocytes, and that the regulation of GH in the immune system differs from that in the endocrine system.

Insulinoma with normal plasma insulin concentrations and insulin/glucose ratios during hypoglycemic episodes.

A patient with insulinoma had frequent hypoglycemic episodes with normal plasma insulin levels and insulin/glucose ratios. When immunoreactive insulin (IRI) concentrations in this patient were compared among plasma samples with the same C-peptide immunoreactivity (CPR) levels, the concentrations were significantly lower than in control patients with insulinoma and equal to or lower than those of normal subjects. In hepatic venous samples, CPR levels were significantly higher and the IRI/CPR molar ratios were lower than those in a control subject. These results may indicate that normoinsulinemia in this patient could be explained by increased hepatic extraction of insulin.

[Detection of neural crest tumors by 123I-MIBG scintigraphy].

From January 1993 to January 1994, scintigraphy with 123I-MIBG and/or 131I-MIBG were performed in 22 patients and their scintigraphic usefulness was evaluated. Iodine-123 MIBG and 131I-MIBG scintigrams were obtained 24 hours after injection of 222 MBq of 123I-MIBG and 48 hours after injection of 20 MBq of 131I-MIBG, respectively. In two patients with pheochromocytoma, the 123I-MIBG and 131I-MIBG scans were performed and both images were compared. In a patient with single intraadrenal pheochromocytoma, the lesion not detected with 131I-MIBG was clearly visualized with 123I-MIBG. In the other patient with multiple metastatic pheochromocytoma, much more lesions were distinctly demonstrated on the 123I-MIBG images than on the 131I-MIBG images. All of the lesions were detected with 123I-MIBG in a patient with pheochromocytoma, 3 patients with neuroblastoma and a patient with medullary thyroid cancer. Most of the normal adrenal glands (86%) were visualized on the 123I-MIBG scintigrams, in 7 patients without neural crest tumor and adrenal diseases, while 131I-MIBG scintigraphy failed to visualize normal adrenal glands in 2 hypertensive patients. The main reason for the superiority of 123I-MIBG to 131I-MIBG is considered to be as follows: 1) higher specific activity of 123I-MIBG. 2) the larger amount of 123I-MIBG used. 3) gamma ray energy of 123I is ideal for gamma camera. In conclusion, 123I-MIBG appears to be a more suitable imaging agent than 131I-MIBG in depicting neural crest tumors.

Ectopic prolactinoma on MRI.

OBJECTIVE: We present two patients with ectopic prolactinoma in the sphenoid sinus who were examined by MRI. MATERIALS AND METHODS: Endocrinological evaluations including spontaneous and drug-induced secretion of prolactin (PRL) and MRI features of two patients with ectopic prolactinoma were studied. RESULTS: Both patients had elevated serum PRL levels, and the endocrinological evaluations were similar to those in ectopic prolactinoma. Magnetic resonance of the head revealed a mass occupying the sphenoid sinus with partially empty sella in Case 1 and with normal pituitary gland in Case 2. Ectopic PRL secretion was confirmed by immunocytochemical examination of the ectopic tumor. Case 1 was treated with bromocriptine, leading to marked decrease in serum PRL levels and reduction of tumor size. Transsphenoidal surgery was performed in Case 2, resulting in normalization of serum PRL levels. CONCLUSION: It is necessary to consider ectopic prolactinoma for the differential diagnosis of the sphenoid sinus tumors.

Correlation of the antibody titers with serum prolactin levels and their clinical course in patients with anti-prolactin autoantibody.

Patients with anti-prolactin (PRL) autoantibody were surveyed among 208 patients with hyperprolactinemia (PRL > or = 30 micrograms/l) and 228 subjects with normal PRL levels, and the relationship of the antibody titers with serum PRL levels and their clinical course were studied. Diagnosis of possessing the anti-PRL autoantibody was based on the polyethylene glycol method, displacement of the binding of [125I]PRL with the serum by unlabeled PRL and the binding of PRL to protein G, the affinity gel for immunoglobulin G. Prolactin was measured by an immunoradiometric assay that we found was not affected by the anti-PRL autoantibody. A significantly high frequency of anti-PRL autoantibody in patients with idiopathic hyperprolactinemia (16%) and a positive correlation between titers of the autoantibody and serum PRL levels (r = 0.74, p < 0.01) may indicate that the anti-PRL autoantibody itself is another cause of hyperprolactinemia, probably owing to the delayed clearance of PRL. Most patients with anti-PRL autoantibody lacked the clinical symptoms of hyperprolactinemia, such as amenorrhea and galactorrhea, and spontaneous pregnancy occurred despite the marked hyperprolactinemic state, indicating that the biological activity of PRL was attenuated by the autoantibody. In addition, PRL levels and the titers of anti-PRL autoantibody were not changed significantly during the observation period of up to 5 years without any medical intervention. These results suggest that the anti-PRL autoantibody itself is one of the causes of hyperprolactinemia and that medical intervention is unnecessary for this type of hyperprolactinemia.

Effects of anti-prolactin autoantibodies on serum prolactin measurements.

The influence of anti-PRL autoantibodies on PRL measurements determined by immunoassays was investigated in 10 patients with anti-PRL autoantibodies. Four different immunoassay systems (two double-antibody radioimmunoassays (RIAs), a single-antibody RIA and an immunoradiometric assay (IRMA)) were examined. Total and free PRL were extracted from sera by precipitating gamma-globulin with polyethylene glycol with and without acidification, respectively. PRL values determined by direct measurement were compared with total PRL values. The proportion of free to total PRL levels determined by each immunoassay in sera with anti-PRL autoantibodies was significantly lower than in control sera. Values obtained by direct measurement of PRL (a routine assay procedure) in control sera were similar to total PRL values, whereas in sera with anti-PRL (a routine assay procedure) in control sera were similar to total PRL values, whereas in sera with anti-PRL autoantibodies the values varied from one immunoassay to the other. In sera with anti-PRL autoantibodies, double-antibody RIA 1, RIA 2 and single-antibody RIA 3 yielded values lower for PRL than for total PRL (52 +/- 15% in RIA 1, 40 +/- 8.8% in RIA 2, 40 +/- 14% in RIA 3), while PRL levels determined by IRMA were not significantly different (112 +/- 14%). Immunoglobulin G purified from serum with anti-PRL autoantibodies dose-dependently decreased the recovery of PRL assayed by the double-antibody technique, while it did not affect that by IRMA. These data suggest that the presence of anti-PRL autoantibodies gives variable results depending on the immunoassays used.(ABSTRACT TRUNCATED AT 250 WORDS)

[Measurement of serum free thyroxine concentrations using anti-T4 monoclonal antibody].

A new one-step radiolabeled antibody radioassay for measuring free T4 (FT4) in serum (Amerlex-MAB FT4) was evaluated in comparison with an analog tracer RIA of FT4 (Amerlex-M FT4). In this new method, 125I-labeled anti-T4 monoclonal antibody which has cross-reactivity with T3 is used as a tracer. When incubated with serum sample, the tracer binds to FT4 and the remaining tracer binds to a T3 coated particle (Amerlex MAB). The radioactivity bound to Amerlex MAB is measured. Counts of 125I bound to the T3 coated particle were inversely proportional to sample FT4 concentrations. The assay procedure is as follows. Fifty microliter of patient's serum or standard FT4, 500 microliters of Amerlex MAB and tracer is incubated at 37 degrees C for 30 minutes and centrifuged. Then the radioactivity of Amerlex MAB is measured using an autowell gamma counter. The intra-and interassay coefficients of variation were 1.6-2.7% and 2.6-8.0%, respectively. Although Amerlex-M FT4 values were significantly increased by adding human albumin to the serum, Amerlex-MAB FT4 values were not effected by the change of albumin concentrations. In nonthyroidal illness patients, Amerlex-MAB FT4 values were not affected by the concentrations of albumin, TBG and NEFA. The euthyroid central 95% reference range for FT4 determined by Amerlex-MAB FT4 was 0.99 to 1.54 ng/dl. The FT4 levels correlated well with the metabolic status. Although Amerlex-M FT4 values were spuriously increased in patients with anti-T4 autoantibodies, Amerlex-MAB FT4 values were not affected by the autoantibodies. Amerlex-MAB FT4 values of normal pregnant women were slightly lower in the second and third trimesters than in the first trimester. These lower FT4 concentrations in late pregnancy were considered likely not to be artefact by low serum albumin or high serum TBG but to be a physiological event. Amerlex-MAB FT4 values correlated well with FT4 indices and inversely correlated with TSH levels. A significant correlation (n = 401, r = 0.86, p = 0.0001) was observed between Amerlex-MAB FT4 and Amerlex-M FT4 values in various thyroid conditions without antithyroid autoantibodies. In summary, this new assay for FT4 is simple, rapid and reproducible. The measurement is useful for the evaluation of physiological thyroid function and helpful in the management of patients with thyroid diseases.

[Phase 3 clinical study of 99mTc-MAG3 injectable, a dynamic renal imaging agent--comparison with 123I-OIH and 99mTc-DTPA].

A Phase 3 clinical study of 99mTc-mercaptoacetyl glycylglycylglycine (99mTc-MAG3) injectable was performed in 506 patients with renal and/or urinary disorders. The scintigraphic findings and renogram patterns of 99mTc-MAG3 were similar to those of 123I-OIH, and Tmax and T1/2 of the 99mTc-MAG3 renogram correlated with those of 123I-OIH (r = 0.62 and r = 0.74, respectively). The clinical efficacy of 99mTc-MAG3, evaluated by the investigators in the same patients, was superior to the efficacy of 123I-OIH and 99mTc-DTPA in 93 of 150 patients (62.0%) and 68 of 151 patients (45%), respectively. The image quality and the reliability of the scintigraphic findings with 99mTc-MAG3 were superior to those with 123I-OIH and 99mTc-DTPA, which reflect the more abundant photons of 99mTc-MAG3 than those of 123I-OIH and higher renal extraction of 99mTc-MAG3 than those of 99mTc-DTPA, respectively. Neither adverse reactions nor abnormal laboratory findings due to 99mTc-MAG3 administration were observed. These results suggest that 99mTc-MAG3 injectable is safe and a useful radiopharmaceutical for diagnosis of renal and urinary disorders.