Background: Knowledge about the population's iodine status is important, because it allows adjustment of iodine supply and prevention of iodine deficiency. The validity and comparability of iodine-related population studies can be improved by standardization, which was one of the goals of the EUthyroid project. The aim of this study was to establish the first standardized map of iodine status in Europe by using standardized urinary iodine concentration (UIC) data. Materials and Methods: We established a gold-standard laboratory in Helsinki measuring UIC by inductively coupled plasma mass spectrometry. A total of 40 studies from 23 European countries provided 75 urine samples covering the whole range of concentrations. Conversion formulas for UIC derived from the gold-standard values were established by linear regression models and were used to postharmonize the studies by standardizing the UIC data of the individual studies. Results: In comparison with the EUthyroid gold-standard, mean UIC measurements were higher in 11 laboratories and lower in 10 laboratories. The mean differences ranged from −36.6% to 49.5%. Of the 40 postharmonized studies providing data for the standardization, 16 were conducted in schoolchildren, 13 in adults, and 11 in pregnant women. Median standardized UIC was <100 μg/L in 1 out of 16 (6.3%) studies in schoolchildren, while in adults 7 out of 13 (53.8%) studies had a median standardized UIC <100 μg/L. Seven out of 11 (63.6%) studies in pregnant women revealed a median UIC <150 μg/L. Conclusions: We demonstrate that iodine deficiency is still present in Europe, using standardized data from a large number of studies. Adults and pregnant women, particularly, are at risk for iodine deficiency, which calls for action. For instance, a more uniform European legislation on iodine fortification is warranted to ensure that noniodized salt is replaced by iodized salt more often. In addition, further efforts should be put on harmonizing iodine-related studies and iodine measurements to improve the validity and comparability of results.

This work discusses the clinical performance of chromogranin A (CGA), a commonly measured marker in neuroendocrine neoplasms, for the diagnosis of pheochromocytoma/paraganglioma (PPGL). Plasma CGA (cut-off value 150 µg/L) was determined by an immunoradiometric assay. Free metanephrine (cut-off value 100 ng/L) and normetanephrine (cut-off value 170 ng/L) were determined by radioimmunoassay. Blood samples were collected from PPGL patients preoperatively, one week, six months, one year and two years after adrenal gland surgery. The control patients not diagnosed with PPGL suffered from adrenal problems or from MEN2 and thyroid carcinoma. The clinical sensitivity in the PPGL group of patients (n = 71) based on CGA is 90% and is below the clinical sensitivity determined by metanephrines (97%). The clinical specificity based on all plasma CGA values after surgery (n = 98) is 99% and is the same for metanephrines assays. The clinical specificity of CGA in the control group (n = 85) was 92% or 99% using metanephrines tests. We can conclude that plasma CGA can serve as an appropriate complement to metanephrines assays in laboratory diagnosis of PPGL patients. CGA is elevated in PPGLs, as well as in other neuroendocrine or non-neuroendocrine neoplasia and under clinical conditions increasing adrenergic activity.

Iodine is essential in the biosynthesis of thyroid hormones that affect metabolic processes in the organism from the prenatal state to the elderly. The immediate indicator of iodine intake is the concentration of iodine in urine, but the indicator of iodine intake in the longer term of several months is thyroglobulin (Tg). Tg negatively correlated with increasing intake of iodine in population that do not suffer from thyroid disease, while a more than adequate to excessive iodine intake leads to an increase in Tg. The dependence of Tg on iodine can be described by a U-shaped curve. Thyroglobulin in serum is elevated in thyroid disease mainly in hyperthyroidism (diagnosis E05 of WHO ICD-10 codes) and in goiter (diagnosis E04 of WHO ICD-10 codes). Tg values decrease below 20 µg/l after effective treatment of patients with thyroid disease. Thyroglobulin may thus be an indicator of thyroid stabilization and the success of the thyroid gland treatment.

The function of chromogranin A (CGA) is reviewed, and the radioimmunometric determination of plasma CGA was evaluated as a marker of pheochromocytoma using a comparison of pheochromocytoma patients immediately before surgery (group P, n=25, 635+/-451 ng/ml) with other groups of patients, i.e. pheochromocytoma patients approximately 1 year after removal of tumor (group PP, n=13, 69+/-33 ng/ml), medullary thyroid carcinoma patients (group M, n= 22, 106+/-59 ng/ml), congenital adrenal hyperplasy patients (n=33, 65+/-40 ng/ml), and controls (n=31, 66+/-29 ng/ml). A CGA level above cut off value 130 ng/ml was found in 24 of 25 patients in group P, 1 (relapse) of 13 patients in group PP, and 4 of 22 patients in group M. In the group P we found a significant association between the size of the tumors removed and plasma CGA concentrations (p=0.0016), and also a significant (p=0.0016) relationship between plasma CGA concentrations and PASS score rating the malignity of pheochromocytoma. We can conclude that plasma CGA concentration as determined by radioimmunometric assay (which is simple without the necessity of special laboratory equipment) is an effective marker of pheochromocytoma with association to malignity and tumor mass.

The Czech Republic is an iodine-deficient area. Insufficient iodine intake was reduced by enriching cooking salt with iodine in the range 20–34mgI/kg. An important indicator for tracking changes in iodine nutrition over time is accurate information about urinary iodine concentrations in the population. In this paper we describe and characterize our method used for the determination of iodine in biological material, which is based on alkaline ashing of urine specimens preceding Sandell-Kolthoff reaction using brucine as a colorimetric marker. The losses of radioiodine added during sample preparation have not exceeded 0.001%. The detection limit is 2.6μgI/L and the limit of quantification is 11.7μgI/L, with intra-assay precision of 4% and inter-assay precision of 4.9%. During the period 1994–2002, the urinary iodine concentration was determined in 29,612 samples in the Institute of Endocrinology. The mean basal urinary iodine concentrations±SD were 115±69μgI/L. Of the samples, 0.7% were in severe (200μgI/L) subsets of iodine nutrition. A statistically significant (p<0.00001) difference was found between mean male (127μgI/L) and female (112μgI/L) urinary iodine, and an inversely proportional trend also exists in the age-related data.

This work discusses the clinical performance of chromogranin A, free metanephrine and normetanephrine determination in plasma using a radioimmunoanalytical methods for the diagnosis of pheochromocytoma and paraganglioma. Blood samples were collected from 55 patients (46 pheochromocytomas, 9 paragangliomas). A sampling of biological materials was performed preoperatively and about one week, six months and one year after adrenal gland surgery. The comparative group without a diagnosis of pheochromocytoma/paraganglioma consisted of 36 pheochromocytoma/paraganglioma patients more than 4 months after adrenal gland surgery, and of 87 patients, 16 of them with multiple endocrine neoplasia, 9 with medullary and 5 with parafolicullar carcinoma of the thyroid gland. The rest were patients with various adrenal gland disorders. Chromogranin A, metanephrine and normetanephrine were determined in the EDTA-plasma using a radioimmunoassay kits Cisbio Bioassays, France and IBL International GmbH, Germany. Clinical sensitivity was 96 % for the combination of metanephrine and normetanephrine, and 93 % for chromogranin A. Clinical specificity was 100 % for the combination metanephrine and normetanephrine, and 96 % for chromogranin A. Falsely elevated levels of chromogranin A were observed in 1 patient with chronic renal insufficiency and 9 analyses were influenced by the administration of proton pump inhibitors. These results were excluded of CGA specificity. Both the combination of plasma free metanephrine, normetanephrine and chromogranin A as determined by radioimmunoassays, which are simple without the necessity of special laboratory material, are effective markers of pheochromocytoma or paraganglioma. Chromogranin A exerts association to malignity and all markers are associated with tumor mass.