Immunoradiometric Assay In Patients Research Articles

Growth-Differentiation Factor-15 for Risk Stratification in Patients With Stable and Unstable Coronary Heart Disease

Background— Growth-differentiation factor-15 (GDF-15) is a stress-responsive transforming growth factor-β-related cytokine that has emerged as a prognostic biomarker in acute coronary syndrome trial populations. Its predictive role in stable coronary heart disease (CHD) has never been assessed. Methods and Results— The circulating levels of GDF-15 were measured by immunoradiometric assay in patients with stable angina pectoris (n=1352) or acute coronary syndrome (n=877) who were followed up for a median of 3.6 years. Stable angina pectoris patients presenting with normal (<1200 ng/L), moderately elevated (1200 to 1800 ng/L), or markedly elevated (>1800 ng/L) GDF-15 levels had 3.6-year CHD mortality rates of 1.4%, 2.7%, and 15.0%, respectively ( P <0.001). By backward stepwise Cox-regression analysis, which adjusted for age and gender, clinical variables, the number of diseased vessels, renal function, the levels of C-reactive protein, cardiac troponin I, and N-terminal pro-B-type natriuretic peptide, GDF-15 remained an independent predictor of CHD mortality ( P <0.001). Addition of GDF-15 improved the prognostic accuracy of a clinical risk prediction model concerning CHD mortality (c-statistic, 0.84 versus 0.74; P =0.005). Analysis of the acute coronary syndrome part of the study population confirmed GDF-15 as an independent predictor of CHD mortality ( P <0.001). The circulating levels of GDF-15 did not predict the future risk of nonfatal myocardial infarction in patients with stable angina pectoris or acute coronary syndrome. Conclusion— This study identifies GDF-15 as a strong and independent predictor of CHD mortality across the broad spectrum of patients with stable and unstable CHD.

Redefining functional sensitivity of thyroglobulin assay on Immulite platform: implications in thyroid cancer management

Circulating thyroglobulin (Tg) measurement after thyrotropin stimulation is a pivotal tool in the management of patients affected by differentiated thyroid carcinoma. The Tg assay on Immulite platform has a declared functional sensitivity of 0.9 ng/mL and it is widely used in clinical practice and research on thyroid carcinoma. Recently, thyroglobulin measured during thyroxine treatment was found to be adequate for thyroid carcinoma follow-up if functional sensitivity at 0.2-0.3 ng/mL was reached by assay methods. Thus, the present study was then undertaken to evaluate the imprecision of Immulite Tg assay at very low concentrations. The detection limit was calculated on zero calibrator and Tg-free pooled sera replicates and was 0.14 and 0.16 ng/mL, respectively. Different serum pools with Tg concentrations ranging from 0.16 to 2.50 ng/mL were assayed according to the National Academy of Clinical Biochemistry guidelines to estimate functional sensitivity. By interpolating the imprecision profile with a coefficient of variation of 20%, the functional sensitivity was 0.36 ng/mL. The Immulite-Tg assay was directly compared with a high-sensitive immunoradiometric Tg assay in sera from 93 patients with thyroid carcinomas. No significant differences in sensitivity and specificity were observed by using the newly defined functional sensitivity. In conclusion, the Immulite Tg assay showed a lower functional sensitivity than expected and performed comparably to high-sensitive immunoradiometric assay in patients with thyroid carcinoma.

“Hook Effect” in Calcitonin Immunoradiometric Assay in Patients with Metastatic Medullary Thyroid Carcinoma: Case Report and Review of the Literature

Calcitonin is a well-established tumor marker for medullary thyroid carcinoma (MTC). Because surgery is the only effective treatment for patients with MTC, the postoperative level of serum calcitonin will dictate whether residual disease was left behind and whether reintervention is necessary. We describe here the case of a 41-yr-old man with metastatic MTC. Despite extensive disease in the neck as well as metastatic lesions in the liver, his serum calcitonin, measured with a commercial one-step immunoradiometric assay, was only minimally elevated (244 ng/liter). After serial dilutions, a nonlinear relationship became evident, suggesting the presence of a "hook effect." Treatment of the serum with heterophilic blocking reagent revealed no change. Calcitonin was then measured with a different immunoradiometric assay and revealed a much higher level. Similar discrepancies were found in different samples from various patients when analyzed with different calcitonin immunoassays. To our knowledge, this is the first reported case of a phenomenon such as the hook effect in a calcitonin immunoradiometric assay in patients with MTC. Being aware of this phenomenon is important, because a low calcitonin result could give false reassurance to both the patient and the clinician and could dramatically change the prognosis of the patient.

Plasma Concentration of Brain Natriuretic Peptide as an Indicator of Cardiac Ventricular Function in Patients on Hemodialysis

The plasma concentration of human brain natriuretic peptide (BNP) was measured by immunoradiometric assay in patients on maintenance hemodialysis (HD) to assess the possible relationship between the plasma levels of this peptide and cardiac ventricular function, as judged by M-mode echocardiography. The plasma BNP levels in the pre-HD state were significantly higher (688.5 ± 154.5 pg/ml) than those of healthy subjects (<40 pg/ml). In addition, the plasma BNP levels were slightly decreased during HD (post-HD, 617.3 ± 157.1 pg/ml). There was no correlation between the plasma levels of BNP and body weight changes during HD. The mean plasma BNP level was significantly higher in the group of patients with a low left ventricular ejection fraction (EF < 60%) than in the group with a normal EF. In the patients as a whole, there was an inverse correlation between plasma BNP levels and EF. Moreover, a positive correlation was found between plasma BNP levels and left ventricular mass index (r = 0.57, p < 0.05). These results suggest that plasma BNP levels increase in response to chronic stimulation in accordance with increased cardiac load, and that they may be a possible indicator of reduced ventricular function in HD patients.

Analysis of serum CYFR21-1 by immunoradiometric assay in patients with non-small cell lung cancer: Guo HB, Klingmuller D, Bidlingmaier F. Department of Clinical Biochemistry, Bengbu Medical College, Bengbu 233003. Chin J Clin Oncol 1996;23:236–239

Analysis of serum CYFR21-1 by immunoradiometric assay in patients with non-small cell lung cancer: Guo HB, Klingmuller D, Bidlingmaier F. Department of Clinical Biochemistry, Bengbu Medical College, Bengbu 233003. Chin J Clin Oncol 1996;23:236–239

Bone alkaline phosphatase measured with a new immunoradiometric assay in patients with metabolic bone diseases.

We have investigated the clinical utility of a new quantitative two-site radioimmunometric assay specific for bone alkaline phosphatase (B-ALP) in 219 healthy control subjects and in 264 patients with various metabolic bone diseases. B-ALP was compared with total alkaline phosphatase (T-ALP) and with osteocalcin (BGP). B-ALP increased linearly with age in both sexes. In postmenopausal normal women B-ALP increased by 82% compared with premenopausal normal women, whereas the differences between pre- and postmenopausal women for T-ALP and BGP were 18% and 30% respectively. As assessed by Z-score, the highest values of B-ALP were found in patients with Paget's disease of bone, bone metastases or hyperparathyroidism and in patients on maintenance haemodialysis. In osteoporotic patients, B-ALP< but not T-ALP, showed a slight but significant (P < 0.05) difference compared with normal women. On the basis of bone turnover, osteoporotic patients were divided into two groups: high turnover and low turnover; B-ALP, like BGP, was significantly (P < 0.01) higher in patients with high turnover. In conclusion, B-ALP, measured by this new method, can be considered a sensitive marker of bone turnover and could be especially useful in identifying women at risk of developing osteoporosis.

High prolactin levels may be missed by immunoradiometric assay in patients with macroprolactinomas.

Large amounts of antigen may produce falsely low values in immunoradiometric assays due to the so-called high dose, hook effect. The study was designed to identify the clinical and biochemical features of patients with pituitary macroadenomas in whom a high dose PRL hook effect was documented. The clinical and biochemical features of four patients with the high dose PRL hook effect were compared with those of 54 patients with pituitary non-functioning adenomas and 11 with macroprolactinomas who underwent transsphenoidal microsurgery between 1989 and 1994. The presence of the high dose PRL hook effect was confirmed by an increase in the initial PRL concentration when the immunoradiometric assay was processed after dilutions of the serum. This phenomenon was observed in 5.8% (4/69) of patients with pituitary macroadenomas. Undiluted median (range) PRL levels were 9140 (1530-83850), 1530 (162-3210) and 2110 mU/l (1470-45,000) in patients with macroprolactinoma, non-functioning macroadenoma and the hook effect, respectively. In patients with the hook effect, the median PRL levels increased to 384,720 (317,520-950,000) mU/l when the assay was performed after serum dilution. The proportion of males was 9.9% (1/11) in the macroprolactinoma group, 46.3% (25/54) in the non-functioning macroadenoma group and 100% (4/4) in patients with the hook effect. Patients with prolactinoma and non-functioning adenoma had mean tumour sizes of 20 +/- 9 and 27 +/- 11 mm (SD), respectively, while in the hook effect group it was 51 +/- 10 mm. This study suggests that the high dose PRL hook effect is observed particularly in patients with very large tumours. The immunoradiometric PRL assay must be performed with serum dilution in order to overcome the high dose PRL hook effect in all new patients with pituitary macroadenomas who may have a prolactinoma.

Serum levels of bone alkaline phosphatase measured with a new immunoradiometric assay in patients with metabolic bone diseases

Serum levels of bone alkaline phosphatase measured with a new immunoradiometric assay in patients with metabolic bone diseases

Assessment of the serum levels of bone alkaline phosphatase with a new immunoradiometric assay in patients with metabolic bone disease

Assessment of the serum levels of bone alkaline phosphatase with a new immunoradiometric assay in patients with metabolic bone disease

Assessment of the serum levels of bone alkaline phosphatase with a new immunoradiometric assay in patients with metabolic bone disease.

We measured serum bone alkaline phosphatase (B-ALP) with a new immunoradiometric assay (IRMA) in a large sample of healthy controls comprising 173 women and 180 men, 20-88 yr of age, and in patients with metabolic bone disease. Using serum samples from patients with liver disease and patients with Paget's disease with elevated total alkaline phosphatase (T-ALP) as a source of, respectively, liver and bone isoenzymes, we determined a liver cross-reactivity of the IRMA of 16% that was confirmed by electrophoresis of the circulating alkaline phosphatase isoenzymes. The IRMA was linear for serial sample dilutions, the recovery ranged from 89-110%, and the intra- and interassay variations were below 7% and 9%, respectively. B-ALP increased linearly with age in both sexes, and the mean B-ALP serum levels were not significantly different for women and men (11.3 +/- 4.8 ng/mL for women; 11.0 +/- 4.0 ng/mL for men). The increase in B-ALP after the menopause was significantly higher than that in T-ALP (+77% vs. +24%; P < 0.001). When the values of postmenopausal women were expressed as the SD from the mean of premenopausal women, the mean Z scores were 2.2 +/- 1.8 for B-ALP and 0.9 +/- 1.3 for T-ALP (P < 0.001 between the two). Serum B-ALP was increased from control values in patients with Paget's disease (n = 57; mean, 171.8 +/- 135.6 ng/mL; P < 0.001), in patients with primary hyperparathyroidism (n = 18; mean, 17.2 +/- 5.9 ng/mL; P < 0.001), and in patients with chronic renal failure on hemodialysis (n = 83; mean, 36.6 +/- 35.7 ng/mL; P < 0.001). In patients with Paget's disease, B-ALP was highly correlated with T-ALP (r2 = 0.94; P < 0.001), and the decrease in its serum level was larger than that in T-ALP after treatment with the bisphosphonate pamidronate (-58% vs. -43%; P < 0.03). In patients with various liver diseases, B-ALP was slightly increased, but stayed within the normal range (mean +/- 2 SD) until T-ALP did not exceed 4.5 mu katal/L. We conclude that this new IRMA for B-ALP is reliable, has a low cross-reactivity with the liver isoenzyme, and appears to be more sensitive than T-ALP for the clinical investigation of patients with osteoporosis and other metabolic bone diseases.