Highly purified preparations of human choriogonadotrophin (hCG), hCGα and hCGβ, including those preparations which are being distributed by the World Health Organization as International Standards, cross-reacted in a new radioimmunoassay with increased relative specificity for the β-core fragment of hCG. A major portion of the β-core immunoreactivity in the hCG and hCGα preparations eluted from Sephadex G-100 in a position (approximate apparent molecular size 15 000–18 000) corresponding to that of purified β-core fragment prepared from pregnancy urine. However, in the case of hCGβ-subunit preparations, virtually all of the β-core cross-reacting material eluted from Sephadex G-100 in the same fractions as the native hCGβ-subunit. Quantitatively, the cross-reacting β-core material accounts for less than 1% (w/w) of the total hCG or subunit immunoreactivity, as measured by conventional radioimmunoassays. The presence of the β-core fragments as discrete molecular components of the hCG and hCGα preparations should be borne in mind when these preparations are used to calibrate new radioimmunoassays for hCG-related molecules. J. Endocr. (1988) 117, 147–152

Highly purified preparations of human choriogonadotrophin (hCG), hCG alpha and hCG beta, including those preparations which are being distributed by the World Health Organization as International Standards, cross-reacted in a new radioimmunoassay with increased relative specificity for the beta-core fragment of hCG. A major portion of the beta-core immunoreactivity in the hCG and hCG alpha preparations eluted from Sephadex G-100 in a position (approximate apparent molecular size 15,000-18,000) corresponding to that of purified beta-core fragment prepared from pregnancy urine. However, in the case of hCG beta-subunit preparations, virtually all of the beta-core cross-reacting material eluted from Sephadex G-100 in the same fractions as the native hCG beta-subunit. Quantitatively, the cross-reacting beta-core material accounts for less than 1% (w/w) of the total hCG or subunit immunoreactivity, as measured by conventional radioimmunoassays. The presence of the beta-core fragments as discrete molecular components of the hCG and hCG alpha preparations should be borne in mind when these preparations are used to calibrate new radioimmunoassays for hCG-related molecules.

We intensively studied 30 women attempting pregnancy in order to lay groundwork for larger studies of early pregnancy loss. These women collected first morning urine specimens for up to 6 months after discontinuing use of birth control. Urine specimens were successfully collected for 98% of the woman-days in the study. Three assays for human chorionic gonadotropin (hCG) were performed on each urine specimen. An immunoradiometric assay (IRMA) specific to the carboxyterminal peptide of the hCG beta-chain proved to be more sensitive and more specific than two radioimmunoassays (RIAs). Using the IRMA, we found four cases in which hCG rose and fell over successive days, consistent with early pregnancy loss. For three of these four cases, the level of hCG was too low to be detectable with the RIAs. Among the control group of five women with tubal ligations, there was no detectable hCG above threshold with the IRMA. Thus, the enhanced sensitivity and specificity of the IRMA allows very early pregnancy losses to be identified that would otherwise be undetectable. Furthermore, its effectiveness with small quantities of first morning urine makes the IRMA a useful tool for epidemiologic studies.

We gave graded doses of levothyroxine sodium to 11 elderly hypothyroid subjects (mean age, 66.1 years). The daily levothyroxine sodium dose was initially 75 micrograms or less, and was increased by 25 micrograms every six weeks. Serum total thyroxine, total triiodothyronine, and basal thyrotropin levels were measured at the start of the study and at the end of each six-week dose period. A protirelin (thyrotropin-releasing hormone) test was performed when the thyrotropin level returned to normal. Mean daily levothyroxine sodium doses that normalized serum thyrotropin levels and protirelin test were 110 +/- 8 micrograms and 113 +/- 9 micrograms, respectively. Serial basal thyrotropin determinations during stepwise increments in levothyroxine dose indicated physiologic hormone replacement. As determined in our elderly patients, levothyroxine replacement dose was a third less than that formerly recommended.

A B S T R A C T We have observed low-molecular weight carboxyterminal fragments of the human choriogonadotropin (hCG) a-subunit in the urines of several women with choriocarcinoma, and we have characterized one fragment in detail. Its apparent molecular weight by gel chromatography on Sephadex G-100 was 14,200. The fragment was not adsorbed to concanavalin A-Sepharose, indicating that it lacked the asparagine-linked carbohydrate groups of intact hCG#. It was active in radioimmunoassays (RIA) using antisera either to the hCG# carboxyterminal peptide (CTP) or to the desialylated hCG# CTP (hCG# as-CTP), indicating the presence of not only the hCG# carboxyterminus but also desialylated O-serine-linked carbohydrate side chains on the fragment. It lacked luteinizing hormone/choriogonadotropin radioreceptor activity and hCG# conformational immunoreactivity (SB6 RIA). On Sephadex G-100 gel chromatography, the elution profiles of this fragment and the hCG# asCTP(115-145) prepared by trypsin digestion of ashCG were essentially indistinguishable (apparent molecular weights 14,200 and 14,000, respectively). The immunological characteristics of the fragment in both hCG# CTP and hCG# as-CTP RIA were indistinguishable from those of the hCG,6 as-CTP(115-145) glycopeptide. Carboxyterminal fragments of hCG# were evident in urine specimens obtained from 10 of 11 patients with choriocarcinoma but not in those ob

tection of hCG production is somewhat better than that achieved with the serumhCGRIA involvingantiserato the hCG/ subunit. The improved specificity and sensitivity of this assay, and the greater convenience of collecting samples of urine rather than blood, are clinically useful advantagesof this approachto assessinghCGproduction in humans.