Studies of Multiple Endocrine Neoplasia Type 2A Syndrome: Linkage Analyses and Comparison of Constitutional and Tumor Genotypes

Linkage analyses were carried out in nine Japanese kindreds with multiple endocrine neoplasia type 2A (MEN-2A) using polymorphic classical markers and DNA markers. We excluded close linkage of the MEN-2A gene (MEN2A) locus with Gm, JK, PGMl, and a DNA segment, D20S5, which is assigned to band 12 of the short arm of chromosome 20 (20p12.2). Assuming that MEN2A is recessive at the cellular level as in retinoblastoma (RB) and Wilms\u27 tumor (WT). comparison of constitutional and tumor genotypes may be useful in the search for the MEN2A locus. When DNA samples from 12 patients with medullary thyroid carcinoma (MTC) were compared with 15 polymorphic DNA markers including two assigned to chromosome 20, the results were negative. Both the negative linkage data and the failure to find loss of heterozygosity in MTC with chromosome 20 probes suggest that MEN2A may not be at 20p12.2, which was previously suggested as the site of an inherited chromosomal deletion in MEN-2A

Enzyme immunoassay for cortisol in serum using cortisol 21-amine

Cortisol 21-amine (21-amino-11β,17-dihydroxy-4-pregnene-3,20-dione) was prepared and an enzyme immunoassay for cortisol in serum was established using cortisol 21-amine conjugated with alkaline phosphatase. The minimal amount of cortisol detected was 1ng/tube and the measurable range was from 1 to 80 μg/d1, using 10 μ1 of serum sample. This enzyme immunoassay satisfied the standard criteria of dilution, accuracy and precision. The values correlated well with those obtained by radioimmunoassay. This enzyme Immunoassay is applicable to the routine determination of serum cortisol in any clinical laboratory. Cortisol 21-amine was found to be a useful derivative for preparing cortisol-enzyme conjugate in enzyme immunoassay

Multiple Endocrine Neoplasia Type 2 Syndromes in Japan

Through nationwide surveys, we collected and analyzed 242 patients of medullary thyroid carcinoma (MTC). Included were 40 patients with multiple endocrine neoplasia type 2A (MEN-2A), six patients with MEN-2B, and 36 patients with only MTC having a positive family history (82 total patients in the hereditary group). Ten-year survival rates were 81.5% for all cases, and 97.5% and 76.1% for the hereditary and the sporadic group, respectively. Epinephrine/norepinephrine ratio in the urine was found to be a good indicator of the adrenomedullary hyperfunction in patients with hereditary MTC. At least one patient in each family with hereditary MTC had overt pheochromocytoma or latent hyperfunction of adrenal medulla. Doubling times of plasma calcitonin levels correlated with life expectancy and recurrence rates. We carried out linkage analysis between the MEN-2 locus and several genetic markers in our MEN-2 families, but so far we have been unable to demonstrate or exclude a linkage