Basal Calcitonin Research Articles

Provocative agents and the diagnosis of medullary carcinoma of the thyroid gland.

Twenty-six patients with known or suspected medullary thyroid carcinoma (MTC) and 21 normal control subjects were tested intravenously on four separate days with calcium gluconate (CG), 2 mg Ca(++)/kg/1 min.; pentagastrin (P), 0.5 ug/kg/ 5 sec.; calcium chloride (CC), 3 mg Ca(++)/kg/10 min.; and a combination of calcium gluconate and pentagastrin (CG + P). Calcitonin (CT) levels were determined by radioimmunoassay on plasma collected before and immediately following each test infusion. In none of the 21 control subjects was there a clear increase in CT above 200 pg/ml following any of the four provocative tests. Conversely, in all 26 patients with known or suspected MTC, plasma CT levels were markedly increased (>300 pg/ml) following the combined infusion of CG + P. The peak CT response was greater with CG + P than with a) CG alone (22 of 24 patients, p < 0.002), b) P alone (25 of 26 patients, p < 0.002), or c) CC alone (17 of 17 patients, p < 0.002). Of 12 MTC patients with undetectable basal calcitonin levels, all had peak responses greater than 300 pg/ml following CG + P, whereas such responses occurred less often following CG alone (8 of 12) or P alone (8 of 12). The results demonstrate that the combined administration of pentagastrin and calcium gluconate constitutes a more effective and reliable stimulus for CT secretion from MTC cells than the use of either agent alone, and appears the most useful single screening test for the detection of occult MTC.

FAMILIAL MEDULLARY THYROID CARCINOMA

Medullary thyroid carcinoma (M.C.T.) is a tumour of the calcitonin-secreting cells of the thyroid gland; it affects both lobes, has a variable malignant potential, and is often familial. Despite the availability of diagnostic plasma-calcitonin immunoassays, the condition is rarely considered in the initial assessment of a patient with a thyroid mass so that the tumour is often disseminated by the time it is diagnosed, inadequate surgery is performed, and family members are not investigated. We studied 22 members of a family with M.C.T. and gave alcohol to provoke calcitonin secretion. 3 (excluding the index case) had raised basal calcitonin levels and the diagnosis of M.C.T. was confirmed at operation; their calcitonin levels became undetectable after total thyroidectomy. 3 others had detectable levels after alcohol stimulation and are being re-screened at regular intervals.

286 STUDIES OF PLASMA CALCITONIN IN HYPOITUITARISM AND HYPOTHYROIDISM

The secretion of calcitonin (CT) was studied in 17 children, 10 with hypopituitarism and 7 with agoitrous hypothyroidism. Plasma CT levels were measured by radioimmunoassay in the basal state and following infusion of pentagastrin (0.5 μg/kg) and 10 minute infusions of calcium (2.3 mg/kg Ca++ as CaCl2). Of the 10 children who have hypopituitarism, 5 were studied before and after one year of human growth hormone (HGH) therapy and 5 were studied before treatment only. Basal and peak response CT levels were essentially unchanged by HGH. In the patients with hypopituitarism, CT levels increased from 41.9 ± 5.1 pg/ml to a peak of 67.4 ± 10 pg/ml after pentagastrin and from 38.8 ± 5.2 pg/ml to a peak of 107 ± 14.9 pg/ml after calcium infusion. In the cretins, CT levels increased from 33.8 ± 6.5 pg/ml to 35.8 ± 7 pg/ml following pentagastrin and from 31.4 ± 5.9 pg/ml to 40 ± 4.9 pg/ml following calcium. Although basal levels of CT seemed to be lower in cretins, these values could not be rigorously validated. The patients with hypopituitarism had greater CT responses than the cretins, especially to calcium infusion. These studies suggest that children with hypopituitarism have a greater CT response to calcium infusion than do normal adults and that CT secretion is abnormal in patients with athyreotic cretinism.

Somatostatin inhibits the pentagastrin-induced release of serum calcitonin in medullary carcinoma of the thyroid.

The effect of somatostatin on the secretion of calcitonin was studied in four patients with medullary carcinoma of the thyroid (MCT). The basal serum calcitonin level was markedly elevated in all cases. A bolus injection (100 microgram) of somatostatin followed by an intravenous infusion (5 microgram/min) for 60 min suppressed the basal calcitonin level in three of the four patients by 24-42%, while it had no inhibitory effect in one case. In another experiment, the pentagastrin-stimulated (6 microgram/kg s.c.) calcitonin release was partially blocked by a simultaneous i.v. injection of somatostatin (200 microgram) in all four patients studied. These experiments add human calcitonin to the list of hormones whose release in inhibited by somatostatin.

Radioimmunoassay for human calcitonin employing synthetic calcitonin M: its clinical application.

A sensitive and reliable radioimmunoassay for human calcitonin was described and applied to preliminary clinical studies. 125I-labelled synthetic human calcitonin M was purified by gel filtration with Sephadex G-25 and G-100. A nonequilibrium incubation system was applied at the final volume of incubation mixture of 500 mul, in which pooled plasma from normal subjects or hormone free serum was used as carrier protein at 20% incubation mixture. Dextran T 40 coated charcoal, resuspended in 1% bovine serum albumin buffer, was used for the separation of free from bound tracer. This showed the least nonspecific adsorption of tracer to charcoal. The assay was sensitive to 0.1 ng per milliliter of plasma. Recovery of synthetic human calcitonin added to plasma was found to be 101% (S. D., +/- 8). Diluted plasma from a patient with medullary thyroid carcinoma showed a dilution curve parallel to standards. Basal calcitonin levels were less than 0.3 ng/ml in normal subjects. Relatively high values were found in patients with chronic renal failure and in patients with malignant tumors. Extremely elevated values were found in patients with medullary thyroid carcinoma. Provocative calcium infusion tests were also performed.

A radioimmunoassay for ovine calcitonin: an evaluation of calcitonin secretion during gestation, lactation and foetal life.

SUMMARY A radioimmunoassay capable of measuring ovine calcitonin in unextracted ovine plasma has been developed. Guinea-pig antisera to partially purified porcine calcitonin were highly specific for calcitonin and were capable of detecting 5 pg porcine calcitonin. One of these antisera cross-reacted significantly with pure ovine calcitonin and with foetal ovine plasma. The mean basal calcitonin secretion rate for the left thyroid lobe found in sheep foetuses 10 days before term was 3·36 ng/min/kg body weight. An infusion of calcium into the foetus was followed by an increase in the calcitonin secretion rate. The mean fasting calcitonin concentration in samples from the jugular vein of five pregnant ewes 10 days before term was 5·28 ng/ml. An infusion of calcium into the mother induced a sevenfold increase in plasma calcitonin concentration whereas the calcitonin concentration was unchanged in the foetal thyroid venous plasma. At parturition the plasma calcitonin concentration fell in the mother (1·85 ng/ml), and a sharp increase was observed during lactation (11·60 ng/ml). In the lamb from birth to 6 weeks post partum the calcitonin concentration was very high (8·10–10·40 ng/ml).

A short calcium infusion in the diagnosis of medullary thyroid carcinoma.

A brief calcium infusion has been utilized as a provocative test for calcitonin secretion in patients with medullary thyroid carcinoma. One hundred and fifty mg calcium was infused over 5–10 min and plasma samples collected at intervals up to 1 hr for calcitonin measurements. Seven infusions in 4 patients with medullary tumor produced a significant increase of plasma calcitonin over basal concentrations. In one patient with normal (nondiagnostic) basal calcitonin, the calcium infusion produced a diagnostic increase in hormone concentration. The infusions were well tolerated and the plasma calcium increase was less than one milligram. Our results suggest that this short calcium infusion, with calcitonin measurements made before and 10–30 min after the beginning of infusion provides a reliable, convenient, and safe provocative procedure for calcitonin secretion in medullary thyroid carcinoma suspects.

Radioimmunoassay of Calcitonin in Human Plasma

Abstract A sensitive, specific radioimmunoassay of calcitonin is described, suitable for measuring the hormone in peripheral plasma of normal man. With this assay we have demonstrated that calcitonin is detectable under ba sal conditions and the concentrations respond to induced and spontaneous hypercalcemia and induced hypocalcemia. The mean value for basal calcitonin of normal men was 182 pg/ml (range 63-450); patients with hypercalcemia of various etiologies had a statistically significant higher mean value of 510 pg/ml (range 110-2700). In calcium-infusion studies, concentrations of both total calcium and ionic calcium correlated well with plasma calcitonin (0.77 and 0.84, respectively). These findings strongly suggest that calcitonin is of physiologic importance in man.