Omega L. Silva

Calcitonin in extrathyroidal tissues of man.

Prior studies have demonstrated detectable immunoreactive calcitonin in the serum and urine of totally thyroidectomized humans, suggesting that the hormone may be secreted by extrathyroidal tissues. Accordingly, a study of the immunoreactive calcitonin content of human tissues was undertaken, utilizing autopsy material from 23 patients. Significant amounts of calcitonin were found in many extrathyroidal tissues, ranging up to 40 ng/g wet weight. The hormone was detectable with two antibodies having different region specificities for calcitonin. Gel filtration and subsequent radioimmunoassay demonstrated that extrathyroidal tissue has calcitonin fractions of the same molecular size and charge characteristics as do the serum and thyroid. The finding of large amounts of extrathyroidal calcitonin may explain why thyroidectomy in man is not accompanied by marked changes in calcium metabolism.

Calcitonin in thyroidectomized patients.

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.

Immunoreactive calcitonin in cerebrospinal fluid of man.

We have detected immunoreactive calcitonin (iCT) in the cerebrospinal fluid (CSF) of normal individuals. Using an antibody with midportion recognition, the mean +/- S.D. of the cerebrospinal iCT in 27 normal subjects was 28 +/- 14 pg/ml. The mean serum iCT was 89 +/- 68 pg/ml, the CSF/serum distribution ratio being 0.31. There were no significant correlations between CSF iCT or serum iCT and the calcium, magnesium, phosphate, sodium, potassium or chloride in the CSF or serum. Although there was a trend for serum iCT values to be related to CSF iCT values, it did not attain statistical significance. The demonstration that the CSF contains iCT may have important physiologic implications, and its measurement offers a useful parameter to study its effects on calcium metabolism and/or other aspects of brain function.

Calcitonin Levels in Chronic Renal Disease

High levels of serum calcitonin were found in patients with chronic renal failure. Serum calcitonin correlated directly with the phosphate to total calcium ratio; calcitonin levels correlated inversely with serum calcium in those patients on dialysis and directly with serum calcium in nondialysis patients. All patients had elevated serum gastrin. The high levels of serum calcitonin usually decreased following successful kidney transplantation. The pathophysiology of this hypercalcitonemia and its relationship to renal osteodystrophy and the disordered calcium metabolism of uremia remains to be elucidated.

Urine calcitonin as a test for medullary thyroid cancer: a new screening procedure.

Although the radioimmunoassay of serum calcitonin (CT) has facilitated the diagnosis of medullary thyroid cancer (MTC) one may encounter patients whose basal serum levels of CT are normal or nearly normal. In such cases clinicians have utilized intravenous stimulation tests such as calcium or penta-gastrin to obtain a diagnostic increase in serum CT. We have reported finding immunorcactive CT in the urine of man and have found it to be a useful technique for the diagnosis and study of patients at risk for MTC or other hypercalcitonemic diseases. Using basal urine CT alone we were able to separate 73% of patients at risk for MTC into clearly normal or abnormal groups. For the remaining 27% a stimulation test with subsequent determination of urine CT was required. The radioimmunoassay of urine CT is a simple, reliable, accurate test for the screening diagnosis of MTC. A protocol for the screening workup of a patient at risk for MTC is given.

Limited calcitonin reserve in hyperparathyroidism

A comparative study was made of the serum calcitonin levels of patients with hyperparathyroidism and those with hypercalcemia of etiologies other than 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 responsivity 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.

Calcitonin levels in thyroid-vein blood of man.

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 findings 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.

A comparison of the urinary metabolites of L-histidine-C14 in schizophrenic and normal subjects

Analysis of the urinary metabolites of uniformly radioactive L-histidine was done on a group of adult male schizophrenics and a group of normal males. Uniformly radioactive L-histidine-C14 was administered orally to twelve schizophrenics and eleven normal control subjects, and radioactive urinary metabolites were separated by ion-exchange chromatography and measured by isotope dilution techniques. No significant difference was found between the normal and schizophrenic groups in the fraction of radioactivity excreted, the amount of Cl4 lost after concentration of the urine, the urinary hydantoin propionic acid-F, histidine-C14, and l-methylhistidine-C14 or the combined value for the free and conjugated imidazoleacetic acid-C14. No evidence was found for the presence of any qualitatively different radioactive metabolites in the schizophrenic groups, nor did any subject in either group lack any of the known major histidine products. Acknowledgement The authors are grateful to Dr. M. KIES and Dr. S. KETY for their helpful criticism throughout the course of this study. We are further indebted to Dr. S. GREENHOUSE for assistance in the statistical analysis of the data.