Letter: Heterogeneity of calcitonin.
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Biomedical subjects
Publications and source records attributed to R H Snider.
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The influence of various agents on calcitonin release from human thyroid was studied in vitro. Under the condition of this investigation, calcium, magnesium and phosphate did not stimulate calcitonin release from short-term incubated slices of human thyroid. However, pentagastrin and USP glucagon were potent stimulators of calcitonin release. Theophylline and dibutyryl cyclic AMP were also potent stimuli. A highly purified preparation of pancreatic glucagon was without an effect. Those agents which stimulated calcitonin release were associated with augmented cyclic AMP accumulation. Although maximal discharge of calcitonin required the presence of calcium, out in vitro experiments raise the question as to whether a gastrointestinal hormone, rather than calcium, might not be the principal agent affecting calcitonin release.
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The lung-associated peptide calcitonin (CT) has been localized by immunocytochemical means to discrete pulmonary endocrine (PE) cells. A long-term cell culture of CT-staining PE cells has been established. The molecular configuration of immunoreactive (iCT) from PE cell extracts was determined by gel chromatography, revealing predominantly large molecular weight forms of iCT. The size distribution characteristics of PE Cell iCT were similar to those of intact hamster lung. In contrast, hamster thyroid extracts contain predominantly 4000 dalton iCT (presumed monomer) and apparent iCT fragments. The culture media of the PE cells were found to contain mainly 4000 dalton iCT. We conclude that although the predominant forms of iCT found within cultured PE cells are distinct from those found within thyroidal C-cells, both iCT producing cells release mainly the monomer into the media. Malignant human bronchial carcinoid cells store predominantly monomeric iCT while secreting large molecular weight forms of iCT. Since the PE cell is the putative precursor cell to neuroendocrine malignancies, the disparity noted in the processing of CT may have significant pathobiological implications.
Radioimmunoassay determinations of calcitonin from blood samples obtained by selective venous catheterization have demonstrated a large peripheral to thyroid vein gradient for this hormone in both normocalcemic and hypercalcemic persons. These fingings indicate that in fasting humans the thyroid gland maintains peripheral levels of calcitonin by actively secreting the hormone, and are consistent with the suggestion that the role of plasma calcitonin is of physiologic significance.
Hypothyroid patients with total or near-total thyroidectomy were found to have detectable immunoreactive calcitonin in the serum and urine. These findings suggest that human calcitonin may be secreted by extrathyroidal tissues.
A comparative study was made of the serum calcitonin levels of patients with hyperparathyroidism. The mean serum calcitonin of those with hyperparathyroidism did not differ significantly from normal persons (mean +/- SEM: 130 +/- 16 pg/ml vs 124 +/- 7 pg/ml, respectively.) Only 0.5% of patients with hyperparathyroidism had values exceeding the upper limits of normal. In contrast, the mean serum calcitonin of patients with hypercalcemia of nonparathyroid etiology was considerably higher than normal (354 +/- 75 pg/ml, p < 0.001)), and 41% exceeded the upper limits of normal. Calcium infusion induced less of an increase in serum calcitonin for patients with hyperparathyroidism than for normal persons. In addition, the diminished responsibility was also present postoperatively. These findings suggest that the prolonged hypercalcemia associated with hyperparathyroidism results in a decreased calcitonin reserve which may persist for unknown reasons. In the clinical evaluation of hypercalcemic patient, the finding of hypercalcitonemia is suggestive evidence against the diagnosis of hyperparathyroidism.
One of the principal causes of death from burns is inhalation injury. The pulmonary neuroendocrine cell contains and secretes immunoreactive calcitonin (iCT), and, under the influence of various irritative stimuli, can be induced to secrete iCT in excess. A prospective study of serum iCT levels in 41 patients with burns was undertaken. Mean serum iCT levels were four times normal values at the time of admission and reached 31 times normal values by 24 hours after injury. These levels did not correlate specifically with burn size. However, serum iCT had a very strong positive correlation with mortality, and in addition, was highest in patients who died early after injury compared with those who died late after injury. Patients who were clinically suspected to have pulmonary injury and who died had markedly higher levels of iCT than those who survived. In addition, serum iCT correlated positively with the need for mechanical ventilation and the amount of pulmonary shunting. Although other factors may also play a role in hypercalcitoninemia, serum iCT may be an important marker for the presence of inhalation injury, as well as a prognostic indicator.