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The incidence of thyroid carcinoma has been increasing worldwide. This is interpreted as an increase in the incidental detection of papillary thyroid microcarcinomas (PTMCs). However, mortality has not changed, suggesting overdiagnosis and overtreatment. Prospective clinical trials of active surveillance for low-risk PTMC (T1aN0M0) have been conducted in two Japanese institutions since the 1990s. Based on the favorable outcomes of these trials, active surveillance has been gradually adopted worldwide. A task force on the management of PTMC in adults organized by the Japan Thyroid Association therefore conducted a systematic review and has produced the present position paper based on the scientific evidence concerning active surveillance. This paper indicates evidence for the increased incidence of PTMC, favorable surgical outcomes for low-risk PTMC, recommended criteria for diagnosis using fine needle aspiration cytology, and evaluation of lymph node metastasis (LNM), extrathyroidal extension (ETE) and distant metastasis. Active surveillance has also been reported with a low incidence of disease progression and no subsequent recurrence or adverse events on survival if conversion surgery was performed at a slightly advanced stage. Active surveillance is a safe and valid strategy for PTMC, because it might preserve physical quality of life and reduce 10-year medical costs. However, some points should be noted when performing active surveillance. Immediate surgery is needed for PTMC showing high-risk features, such as clinical LNM, ETE or distant metastasis. Active surveillance should be performed under an appropriate medical team and should be continued for life.

It has been reported that mental retardation due to congenital hypothyroidism can be prevented by early detection and early adequate replacement therapy. We have developed a radioimmunoassay for TSH using the dried blood spot and have started screening for newborn congenital hypothyroidism using a part of sample of the inborn metabolic error screening. (1) The dried blood spot TSH of 61,000 newborn infants was assayed in the first half of our screening and that of 74,505 newborn infants was assayed in the latter half of our screening. As a result, although we were not able to detect any cases in the first screening, we were able to detect 9 cases of congenital hypothyroidism in the latter screening. From the results obtained through our investigation of the thyroid function of these 9 infants, we confirmed that mild hypothyroidism can be better detected by the screening of TSH. (2) As to the program of the screening, we chose from the latter half of our screening all the samples in which TSH concentrations contained above 3 percent of each assay and were remeasured on the next assay. (3) As we confirmed that the sensitivity of measurement was increased at very low concentrations, when the volume of antibodies, radioisotopes and eluates used for each assay were decreased, we measured TSH successfully using two 3 mm discs. (4) As we can perform very simple screening by the 3 mm disc method, we are changing the screening method from that with 10 mm disc to one with two 3 mm discs. We intend to extend our screening, and will make every effort to prevent mental retardation due to congenital hypothyroidism.

In order to perform neonatal mass-screening for 21-hydroxylase deficiency (21-OHD), two simplified radioimmunoassay (RIA) methods to estimate 17 alpha-hydroxyprogesterone (17-OHP) were devised, using discs 3 mm in diameter cut from filter paper impregnated with whole blood. One was a direct method to use assay buffer eluent as a sample, and the other was an extraction method to use diethyl ether extract. One disc in the direct method and one-fourth to four discs in the extraction method were used. We used [1, 2, 6, 7-3H(N)]-17-OHP as a tracer, anti-17-OHP-3-carboxymethyloxime-BSA serum as an antiserum and saturated ammonium sulfate to separate the bound from free 17-OHP. The specificity of the antiserum was nearly satisfactory, except for an unnegligible cross-reactivity with 17 alpha-hydroxypregnenolone (17-OH-delta 5P). Both methods were practically easy and rapid, and had satisfactory accuracy and precision. A significant correlation (p less than 0.005) was observed between "Disc-17-OHP" values by both methods and plasma 17-OHP concentrations measured by highly specific RIA, although the values obtained by the direct method were significantly higher (p less than 0.005) than plasma 17-OHP concentrations, which presumably resulted from the cross-reactivity of the antiserum with 17-OH-delta 5P-sulfate. "Disc-17-OHP" values of the untreated or poorly controlled patients with 21-OHD were extremely high compared with normal neonates and children. However, as most premature infants also showed high values, the possibility of giving false-positive results had to be considered.(ABSTRACT TRUNCATED AT 250 WORDS)

Specific antiserum for 17-hydroxyprogesterone (17-OH-P) was prepared by immunizing 7 alpha-(2-carboxyethylthio)-17-OH-P conjugated bovine serum albumin (BSA) in rabbits. Using this antiserum, 17-OH-P enzyme immunoassay for dried blood spots on filter paper was established. As a label, alkaline phosphatase was coupled covalently with 7 alpha-carboxy-methylthio-17-OH-P by carbodiimide method. B/F separation was carried out by the addition of anti-rabbit IgG goat antiserum. All specimens used were punched out with a paper puncher of 3mm diameter. The assay sensitivity was 2pg/tube, which was estimated by two standard deviation at zero concentrations of the calibration curve. Cross reactivities of this antibody were as follows: 11-deoxycortisol (8.21%), 17-OH-pregnenolone (3.33%), progesterone (1.67%), 11-deoxycorticosterone (0.31%), cortisol (0.16%), pregnenolone-3-sulfate Na salt (0.03%), dehydroepiandrosterone (DHEA) (less than 0.03%), 16 alpha-OH-DHEA (less than 0.03%), DHEA-3-glucuronide (less than 0.03%), DHEA-3-sulfate Na salt (less than 0.03%), pregnenolone (less than 0.02%). Intra- and inter-assay coefficient of variations were 4-14% and 9-18%, respectively. In normal babies, 17-OH-P concentrations measured directly (without sample extraction) were below 23pg/disk (n=204). The histogram of 17-OH-P level in normal babies obtained by the direct method was distributed lower than that obtained by the enzyme immunoassay system (range: 4-79pg/disk, n=268) which used antibody raised against 17-OH-P-3-O-carboxymethyloxime conjugated BSA (Enzaplate, Sapporo Diagnostic Laboratory).(ABSTRACT TRUNCATED AT 250 WORDS)

We examined the method of radioimmunoassay of the Disc T4 (dried blood spot T4) for the purpose of mass screening of neonatal hypothyroidism and tried the parallel assay of T4 and TSH in dried blood spotted on filter paper at the fifth day of life, and we compared the results. By changing the volumes of T4 antibody and T4 antigen solutions, it is possible to measure thyroxine using two discs 3mm in diameter. Disc T4 values obtained in 45 unknown samples by this method were in good correlation with serum T4 values of the same subjects (Y = 0.97X + 0.06). The coefficients of variation were 5.6 to 18.9% in the range of 5.3 to 10.7 micrograms/100ml of Disc T4 (within assay), and 7.9 to 20.8% in the range of 2.4 to 10.3 micrograms/100ml of Disc T4 (between assay). We measured both Disc T4 and Disc TSH of 26,067 newborn infants born between June 1978 and May 1979. Out of 26,067 measurements, four cases of primary hypothyroidism, fourteen cases of TBG deficiency and two cases of transient hypothyroidism were discovered. Out of the four cases of primary hypothyroidism, three showed low Disc T4 (1.3 to 4.0 micrograms/100ml) and high Disc TSH (200 to 240 micromicrons/ml), one showed normal Disc T4 (7.1 micrograms/100ml) and high Disc TSH (30 micromicrons/ml). It was thought the last case might be mild hypothyroidism. In 14 cases of TBG deficiency, Disc T4 was not detectable to 3.4 micrograms/100ml while Disc TSH was within the normal range. In two cases of transient hypothyroidism, Disc T4 measurements showed normal range (6.5, 10.6 micrograms/100ml), and Disc TSH showed high values (41, 120 micromicrons/ml). Therefore, Disc TSH was more sensitive and showed less false positive cases than did Disc T4 for screening hypothyroidism. Although no secondary hypothyroidism existed in the 26,067 measurements, it continues to be important to measure Disc T4 for the discovery of secondary or tertiary hypothyroidism.

It is reasonable to presume that the metabolism of the steroid hormones in the liver may play an important role in elucidating their physiologic significance. Although there are many methods by which the intrahepatic metabolism of the steroid hormones can be evaluated, little has been reported on a method to elucidate simultaneously such dynamic factors as metabolic rate, quantities passing through the liver, structural change, conjugation and the like. In this paper, comparative studies on the methods for the investigation of steroid hormone metabolism in the liver were carried out. These include batch incubation, dialysis, continuous flow perfusion, portal vein injection and the "tissue column method" which was newly designed in order to search for the dynamic factors described above in a simple system, simultaneously. In the "tissue column method" studied here, cell suspension of the rabbit liver mixed with Sephadex G 75 gel (4:1 in volume) was packed at the height of 4 cm in a glass column (internal diameter; 1.5 cm). After an isotopically labelled steroid was placed on the tissue column, this column was perfused with oxygenated extracellular fluid (pH 7.4), keeping the perfusion system at 37 degrees C. The perfusion was continued for 60 min. and the perfusate was collected in 5 fractions. Flow rate was kept at 2 ml/min. When the perfusion was stopped, the cells were rapidly homogenized. The concentrations of the radioactivity in each perfusate, and in the final cells were measured. The amount of entry into the liver cells were calculated. The compounds in the perfusate and in the cells were separated by alumina column chromatography for analyzing the metabolites. Based on these experiments, the following conclusions were drawn; 1) Usual methods with liver slices and homogenates can clarify only the metabolic pathway. 2) To examine the amount of entry of steroids into the liver, portal vein injection as well as the "tissue column method" are preferable to the methods of dialysis and batch incubation. It seemed probable that the entry of steroids into the liver might not be explained simply on the basis of passive transfusion. 3) Incubation of slices and homogenate are of great advantage in studying the metabolic transformation in a specific organ. However, portal vein injection as well as the "tissue column method" are much more preferable to investigate the conjugation of steroids in the liver. 4) Continuous flow perfusion reported by Elrio Gurpide is suitable to examine the metabolism and the entry of steroids in a specific organ, but it is disadvantageous for investigating the conjugation of steroids because of its low production rate of conjugated steroids. 5) The portal injection method is intricate, troublesome and expensive, but this method provides a situation similar to in vivo circumstances...