To identify patients with medullary thyroid carcinoma (MTC) at a potentially curable stage of the disease, serum concentrations of calcitonin (hCT) were determined in 14,000 patients (including 10,158 patients with thyroid nodules) referred to a thyroid outpatient clinic. Excluding patients in whom elevated basal hCT concentrations had already been known at the time of their referral, 507 patients with thyroid nodules presented basal concentrations of hCT of more than 10 pg/ml. Following stimulation by IV pentagastrin (0.5 microg/kg BW), hCT concentrations of more than 100 pg/ml were seen in 103 patients. This group included 32 new cases of MTC (29 patients with sporadic MTC and 3 new index cases of the familial form) and 43 patients with C cell hyperplasia (CCH). Among the 3,843 patients without thyroid nodules, 2 were found to harbor sporadic MTC while 4 had CCH. As compared to 1.1 cases of MTC per 1,000 patients with nodular thyroid diseases diagnosed in our institution before hCT screening was begun, 3.2 cases of MTC per 1,000 patients were identified when hCT was determined in all patients with thyroid nodules. The determination of hCT in all patients with thyroid nodular disease facilitates the timely diagnosis of MTC, thus providing the chance of curative surgery.

In a prospective study, plasma concentrations of human calcitonin (hCT) were determined in 1062 consecutive patients with thyroid nodular disease. Basal plasma hCT was above the normal range (Ͼ6 pg/mL) in 55 patients and was elevated up to more than 100 pg/mL (range, 127-5459) in 3 of these 55 patients. A pentagastrin-induced rise in hCT up to more than 100 pg/mL was observed in only 1 of 38 patients with a basal concentration of hCT between 5-10 pg/mL, but was found in 10 of 31 patients with basal hCT ranging from 10 -100 pg/mL. Histologically, 7 of the 14 patients with either basal or stimulated plasma concentrations of hCT above 100 pg/mL presented C cell hyperplasia, which in one case showed histological transition into a small (diameter, 3 mm) medullary thyroid carcinoma (MTC). Including this patient, MTC was found in 6 of the 12 patients. We conclude that the routine determination of hCT in all patients with thyroid nodular disease should be supplemented by pentagastrinstimulation when the basal hCT concentration exceeds 10 pg/mL. Patients with basal and/or stimulated plasma CT concentrations of more than 100 pg/mL should be operated on because they run a substantial risk to suffer either MTC or C cell hyperplasia, a potentially precancerous condition. This will increase the chance of a timely diagnosis of MTC and provide the chance of curative surgery. (J Clin Endocrinol Metab 82: 1589 -1593, 1997

In summary there is a substantial transcapillary insulin gradient in healthy human skeletal muscle under baseline and glucose-stimulated conditions. Our findings support the hypothesis of a saturable transcapillary insulin transport representing a partly rate-limiting step for insulin action.

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The prevalence of thyroid C-cell hyperplasia (CCH) was investigated prospectively in 57 patients with normal preoperative pentagastrin-stimulated plasma concentrations of calcitonin (hCT, range, 1-60 pg/mL; normal, 100 pg/mL) who subsequently underwent total thyroidectomy due to thyrotoxicosis (n = 18) or to nodular thyroid disease in the presence (n = 9) or absence (n = 30) of cytological follicular neoplasia. CCH was seen in 28 of 57 (49%) of all patients. CCH was more common in hyperthyroid (12/18 [66%]) than in euthyroid (16/39 [41%] patients. No age- or gender-related differences in the occurrence of CCH was seen. There was no histological evidence of medullary thyroid carcinoma (MTC) in any patient. CCH classified histologically as neoplastic was encountered in two instances. It was concluded that CCH may be expected in almost 50% of normocalcitonemic patients with various thyroid disorders. Although the potential clinical importance of this histological finding and specifically its neoplastic variety remains unknown, these results are in keeping with the assumption that pentagastrin-stimulated plasma concentrations of hCT within the normal range do not exclude the presence of CCH.