[Report of immunoassay control surveys conducted in the past 30 years by the Subcommittee for Radioisotope in vitro Test, the Medical Science and Pharmaceutical Committee, and the Japan Radioisotope Association].

Immunoassay control surveys, were conducted by the Subcommittee for Radioisotope in vitro Test, the Medical Science and Pharmaceutical Committee, and the Japan Radioisotope Association, between 1978 to 2008. A total of 40 analytes for 26 hormones, 14 tumor markers and pharmaceutical drugs were investigated in participating facilities. In the first immunoassay control survey in 1978, samples were measured using only RI kits, however, non-RI kits increased gradually during the next 30 years. In the 30th immunoassay control survey, more than 90% samples were measured using non-RI kits. Coefficient variation (CV) of intra-kits has been decreasing yearly in all analytes for hormones as well as tumor markers. However, improvement of CV in inter-kits has not been seen in the past 30 years by a lack of international standards, although there has been continuous effort over the years for the standardization of immunoassay. Growth hormone (GH) deficiency has been diagnosed using various loading tests. However, the clinical diagnosis varies according to the GH kit used. Standardization for GH measurement has been possible by using recombinant GH as the standard among commercial GH kits. The diagnosis of subclinical Cushing's syndrome also varies according to the cortisol kits being used. Candidate reference measurement procedure and low level cortisol standards have been developed by the Biomedical Standard Section, of the National Metrology Institute of Japan. Standardization of measurement is necessary for improvement of immunoassay.

[Problems of cortisol assay: confusion in the diagnosis of preclinical Cushing's syndorme].

Cortisol assay is used for the diagnosis of hypothalamo-pituitary adrenal disorders. The Incidence of adrenal incidentaloma has been increasing with advances in imaging tools. The criteria for the diagnosis of preclinical Cushing's syndrome in Japan was made by the Nawata group supported by the Ministry of Health and Welfare in 1995. The presence of adrenal adenoma, a lack of overt signs of Cushing's syndrome and autonomic cortisol secretion are essential for the diagnosis of preclinical Cushing's syndrome. For the diagnosis of autonomy of cortisol secretion, cortisol should not be suppressed by either low dose dexamethasone (DEX) of 1 mg (cortisol > or =3 microg/dl) or high dose DEX of 8 mg (cortisol > or =1 microg/dl). We have reported that two doses of DEX suppression tests revealed a discrepancy in several cases of adrenal incidentaloma; therefore, we studied the cortisol values of DEX suppression tests in 47 cases with adrenal incidentaloma using four different cortisol kits (TFB, SPAC, TDX and TOSOH). Correlation between the kits was good; however, correlation coefficient in the low range (< or =5 microg/dl) among kits declined. In the inter assay, discrepant results of the cortisol level were seen in six cases after 1 mg of DEX and 18 cases after 8 mg of DEX. In the intra assay, discrepant results of cortisol after 1 mg of DEX and 8 mg of DEX were seen in 31 in TFB, 23 in SPAC, 24 in TDX and 25 in TOSOH. These results revealed that the clinical diagnosis varies according to the cortisol kit used. It is suggested that standardization of the cortisol assay is necessary for the accurate diagnosis of adrenal incidentaloma.

[Studies on the gonadal function in patients with anorexia nervosa using a highly sensitive radioimmunoassay kit for estradiol].

We measured serum estradiol (E2) using a highly sensitive radioimmunoassay kit in patients with anorexia nervosa (AN). It is possible to determine the ovarian function with hypogonadism in patients with AN whose levels of E2 were below 10 pg/ml. In patients with extremely low levels of BMI (less than 15 kg/m2), basal levels of E2, LH, FSH and IGF-I increased significantly with gain of body weight. Recovery of the hypothalamic-pituitary-ovarian function in AN patients were correlated with weight gain and nutritional status. The levels of IGF-I and E2 raised in advance of gonadotropins. Using highly sensitive assay of E2, we recognized the clinical usefulness for evaluation of the ovarian function in patients with AN in the course of treatment.

[Fecal elastase-1 test: clinical evaluation of a new noninvasive pancreatic function test].

UNLABELLED: We evaluated clinical significance of fecal elastase-1(FE-1) in patients with pancreatic diseases and pancreatic dysfunction, in comparison with other tubeless test and secretin test. PATIENTS AND METHODS: FE-1 was determined in healthy controls(n = 131), chronic pancreatitis(CP) (n = 52), acute pancreatitis(AP) (n = 14), pancreatic cyst(Pcyst) (n = 20), pancreatic cancer(Pca) (n = 12), post pancreatic surgery(post P) (n = 28), biliary diseases(B) (n = 6), and gastro-duodenal ulcer(G) (n = 6). Fecal chymotrypsin(FCT) and BT-PABA test were performed in those patients digestive diseases. Secretin test collecting duodenal juice through a duodenal tube was performed in only 65 patients described above. RESULTS: FE-1 was 1504 +/- 100 micrograms/g(M +/- SE) in healthy controls. Using a cut off of 200 micrograms/g, 94.6% for healthy controls had FE-1 above this limit. FE-1 was 517 +/- 106 micrograms/g in CP, 1802 +/- 437 micrograms/g in AP, 525 +/- 109 micrograms/g in Pcyst, 528 +/- 126 micrograms/g in Pca, 135 +/- 36 micrograms/g in post P, 1435 +/- 506 micrograms/g in B, and 1115 +/- 325 micrograms/g in G, respectively. Sensitivity in the diagnosis of CP was 51.9%, 46.2% and 54.8% for FE-1, FCT, and BT-PABA test, respectively. Specificity of FE-1 and FCT was 81.3% and 78.7%, while that of BT-PABA test was 44.4%. Significant correlation was observed between FE-1 and secretory data including juice volume, maximum HCO3- concentration, and amylase output obtained form secretin test. In diagnosis of severe pancreatic dysfunction classified based on secretin test, the sensitivity was 86.7% for FE-1, 66.7% for FCT, and 66.7% for BT-PABA test. The specificity was also 70.0%, 80.0%, and 54.3%, for FE-1, FCT, and BT-PABA test, respectively. CONCLUSION: These results indicate that FE-1 may be recommended as a new, noninvasive tubeless test of pancreatic function.

The diagnostic standard of preclinical Cushing's syndrome: evaluation of the dexamethasone suppression test using various cortisol kits.

Incidental discovery of an adrenal mass, the so-called adrenal incidentaloma, has been increasing due to the advances in non-invasive diagnostic imaging tools. The criteria of diagnosis for preclinical Cushing's syndrome (preCS) in Japan were made by Nawata et al. supported by the Ministry of Health and Welfare in 1995. The results of suppression of cortisol by dexamethasone (DEX) (plasma cortisol above 3 microg/dl after 1 mg of DEX and above 1 microg/dl after 8 mg of DEX) are essential for the diagnosis of preCS due to an adrenal adenoma. However, plasma cortisol levels after the two doses of DEX suppression tests were found to be discrepant and repeated DEX suppression tests sometimes yielded different results. Therefore, we examined the cortisol values of DEX suppression tests in patients with preCS using four different cortisol assay kits: Amerlex cortisol kit (AMA), SPAC-S cortisol kit (SPA), ADVIA-Centaur cortisol assay (ADV) and ECLusys 2010 cortisol assay (ECL). The diagnosis for preCS was done using the AMA kit. Correlation between the kits was good. However, cortisol levels measured by SPA, ADV and ECL were lower than those measured by AMA. In the 1 mg DEX test, the cortisol levels measured with the SPA, ADV and ECL kits were suppressed in 2 patients with preCS. With 8 mg of DEX, cortisol levels measured with the SPA and ADV kits were suppressed in 2 patients with preCS. The diagnosis of preCS is decided by the cortisol kit used, but the cortisol levels differ among the kits. It is suggested that the lack of the standardization of cortisol measurement is one of the causes of confusion in the diagnosis of preCS.