Kenneth E. W. Melvin

C-Cell Hyperplasia Preceding Medullary Thyroid Carcinoma

Abstract Two sisters at risk for hereditary medullary carcinoma and having small but progressive increases of serum calcitonin in response to calcium infusion underwent thyroidectomy. The thyroid g...

Immunoassay of Human Calcitonin

Abstract A radioimmunoassay using 131I-labeled synthetic human calcitonin and antiserum to human calcitonin revealed normal basal levels of the peptide in serum of 0.02 to 0.4 ng per milliliter. Calcium infusion produced a twofold to threefold rise in serum calcitonin in most control subjects. Chronic hypercalcemia was not regularly associated with elevated serum calcitonin, and calcitonin levels were normal in six patients with chronic hypocalcemia. In medullary carcinoma of the thyroid gland basal serum calcitonin was 1 to 540 ng per milliliter. Calcitonin levels correlated with the extent of disease. In patients with medullary carcinoma, serum calcitonin responses to calcium and glucagon infusions tended to be greater than in control subjects. Results of family studies suggest that the immunoassay may prove useful in the early diagnosis of this tumor among high-risk persons. We conclude that calcitonin normally circulates in human serum, that its concentration may not always correlate directly with ser...

Early Diagnosis of Medullary Carcinoma of the Thyroid Gland by Means of Calcitonin Assay

Abstract Medullary thyroid carcinoma was predicted correctly by means of radioimmunoassay of serum and urine calcitonin in 11 members of one family. An increased concentration of calcitonin in seru...

Natural history of familial medullary thyroid carcinoma: effect of a program for early diagnosis.

To detect familial medullary thyroid carcinoma in a premetastatic stage, we administered tests provocative of calcitonin secretion (infusion of calcium or pentagastrin or both) each year for seven years to members of a pedigree now numbering 107. Since 1970, 21 patients converted from normal to abnormal secretory responses (two separate tests in which calcitonin levels exceeded 0.58 ng per milliliter). Twenty of 21 glands removed showed C-cell hyperplasia, and eight of the 20 also showed foci of carcinoma. As compared to the 12 patients with tumors detected during the first year of screening, all of whom had bilateral carcinoma (seven of 12 with local metastases), later carcinomas were smaller (mean diameter of 0.2 vs. 0.8 cm), were unilateral (in all but two cases) and occurred in younger patients (mean age of 14.9 vs. 36.4 years), and none had detectable metastases.

Medullary carcinoma of the thyroid gland. Studies of thyrocalcitonin in plasma and tumor extracts.

Abstract In two patients with medullary carcinoma of the thyroid gland tumor extracts contained 1000 to 2000 times more hypocalcemic activity than normal human thyroid tissue. Activity was detected by bioassay in plasma of both patients. One had severe hypocalcemia and hypophosphatemia. Hypocalcemic activity rose in response to calcium infusion and closely paralleled changes in plasma calcium. Several lines of evidence supported the conclusion that the hypocalcemic material in tumors and plasma was thyrocalcitonin. Parallel log dose-response lines were obtained in bioassays of tumor extracts, plasma and porcine thyrocalcitonin. The hypocalcemic activity was lost during incubation with purified thyrocalcitonin-inactivating factor and hydrogen peroxide. Like authentic thyrocalcitonin, the activity did not sediment in the ultracentrifuge. Net synthesis of thyrocalcitonin was shown by culture of tumor cells in vitro. Human tumor thyrocalcitonin did not cross-react significantly in the radioimmunoassay for por...

Surgical approach to early familial medullary carcinoma of the thyroid gland

Abstract The application of a radioimmunoassay for human calcitonin to a high risk family group has predicted the diagnosis of medullary carcinoma of the thyroid in twelve persons. With the calcium infusion test, elevated levels of calcitonin have been measured in the serum and urine in these patients with medullary carcinoma. In eleven, the tumors were clinically occult. In all twelve patients the tumors were found to be bilateral, and in six patients the lymph nodes contained metastases in the periglandular and paratracheal areas. On the basis of these findings, total thyroidectomy, removal of the inferior parathyroid glands, and limited neck dissection of the central zone of the neck was carried out. Postoperative studies have shown an abnormal serum calcitonin response to calcium infusion in two patients consistent with persistent disease. Venous catheterization studies with calcitonin analysis for localization of the residual tumor are projected for these patients. Four of the twelve patients with thyroid tumors were also found to have pheochromocytomas. These tumors in three were removed prior to the thyroid surgery. An additional pheochromocytoma was found and removed in one member of the family without evidence of medullary carcinoma. Ten of those having thyroidectomy also showed parathyroid hyperplasia. Four had a history of renal calculi. It is anticipated that new cases of thyroid carcinoma will become evident as the children and young adults at risk are repeatedly tested, and hopefully these will become detectable still earlier. The effectiveness of this approach in altering the ultimate outcome or course of the disease needs to be demonstrated by long term follow-up study.

Histaminase and Medullary Thyroid Carcinoma

The recognition of circulating gene products of tumor cells, and the development of sensitive methods for their detection in the serum of affected patients, is a potentially rewarding approach to t...