tetragastrin and Carcinoma

Calcitonin gene-related peptide, originally found in rat medullary thyroid carcinoma cells, was measured by radioimmunoassay in plasma samples with added aprotinin from 17 normal volunteers and 21 patients with medullary thyroid carcinoma. The concentrations were below 75 pmol/l in all 17 normal subjects with a mean of 33 +/- 19 pmol/l plasma. In the patients, the plasma calcitonin gene-related peptide concentrations ranged from below 5 pmol/l to 236 pmol/l, although the mean (36 +/- 48 pmol/l) was not significantly different from the mean normal level. Increase in the plasma calcitonin gene-related peptide level was observed in 2 of 5 patients in response to infusion of 4.3 mg/kg of calcium for 10 minutes and in 3 of 5 patients in response to infusion of 4 micrograms/kg of tetragastrin for 5 minutes. These observations suggest that measurement of calcitonin gene-related peptide level may be helpful in determination of diseases in which the level of calcitonin is of less diagnostic value.

Topics: Adolescent; Adult; Apoproteins; Calcitonin; Calcitonin Gene-Related Peptide; Calcium; Carcinoma; Drug Stability; Female; Humans; Male; Middle Aged; Radioimmunoassay; Tetragastrin; Thyroid Neoplasms; Time Factors

Immunoreactive gastrin-releasing peptide (IR-GRP) was found to be present in medullary carcinoma of the thyroid (MCT) by use of a radioimmunoassay (RIA) specific for the carboxyl-terminal portion of GRP. Immunohistochemical studies revealed IR-GRP in the MCT tumor cells, indicating that the tumor cells produce IR-GRP. Immunoreactive GRP was also detected in macroscopically normal thyroid tissue of patients with multiple endocrine neoplasia type II (MEN II, or Sipple's syndrome) and in areas of C cell hyperplasia and micronodules in the thyroids of patients with MCT. When these tissue extracts were examined with a bombesin RIA that recognizes bombesin but not GRP, no IR-bombesin was detected, suggesting that the IR-GRP detected in these tissues is more similar to GRP than to bombesin. IR-GRP was also undetectable in normal thyroid tissues. Plasma IR-GRP was also undetectable in normal thyroid tissues. Plasma IR-GRP was elevated to 130 to 780 pg/mL (normal: undetectable, less than 62.5 pg/mL) in three patients with metastatic MCT, and both calcium and tetragastrin increased the plasma levels of IR-GRP. Sephadex G-50 gel filtration of the MCT extracts revealed two peaks, one coeluted with porcine GRP (1-27) and the other eluted just after its carboxyl-terminal (14-27) fragment. There was a significant correlation (P less than 0.01) between the concentration of IR-GRP and that of IR-calcitonin in MCT tumor tissue and in macroscopically normal portions of thyroid tissue from two patients with MEN II, although the concentration of IR-GRP was only about 0.1% of that of IR-calcitonin.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Bombesin; Calcitonin; Carcinoma; Chromatography, Gel; Gastrin-Releasing Peptide; Humans; Peptides; Radioimmunoassay; Tetragastrin; Thyroid Neoplasms

Medullary thyroid carcinomas (MCT) were obtained from patients with Sipple's syndrome or non-hereditary MCT. Cultures of enzymatically dissociated cells showed that MCT cells were mostly free-floating cells of epithelial characters. These MCT cells preserved the ability to secrete calcitonin for a long period of in vitro maintenance. However, the MCT cells under the usual culture conditions were filled with numerous cytoplasmic granules and appeared to be extremely fragile. When MCT cells were cultured in a low-calcium medium, such granules were not observed. In addition, MCT cells in the low-calcium medium increased the amount of calcitonin in response to added calcium and tetragastrin. Therefore, the culture of MCT cells in the low-calcium medium appeared to be useful for studies about the biochemical and physiological characters of human MCT cells in vitro.

Topics: Calcitonin; Calcium Chloride; Carcinoembryonic Antigen; Carcinoma; Culture Techniques; Humans; Tetragastrin; Thyroid Neoplasms