Michael Weissel

Do Iodine-Containing Contrast Media Induce Clinically Relevant Changes in Thyroid Function Parameters of Euthyroid Patients Within the First Week?

Little is known about the reaction of normal thyroid glands to the iodine load given by x-ray dyes. We have therefore investigated the short-term effects of high doses of iodine on thyroid parameters in euthyroid patients. We measured free triiodothyronine (FT3), free thyroxine (FT4), and thyrotropin (TSH) serum concentrations before and daily for 1 week after parenteral application of x-ray dyes (coronary angiography: n = 16; computed tomography [CT] of either thorax or abdomen: n = 6; iodine dose range from 300-1221 mg of iodine per kilogram). Inclusion criteria were as follows: normal FT4, normal TSH, negative thyroid antibodies, urinary iodine excretion below 30 microg/dL, no palpable goiter and no euthyroid sick syndrome. All but one patient reacted with a TSH increase. Mean TSH values increased significantly 3-5 days after the iodine load within the normal range. Four patients (18%) had a TSH increase above normal, the maximal observed value being 6.4 microU/mL. Basal TSH values of these four patients were above 2 microU/mL. The day peak TSH concentrations were reached varied from day 1 to day 7, the majority (32%) having the peak on day 3. Peak TSH was significantly correlated with basal TSH values (r = 0.794, p < 0.0001). FT4 and FT3 remained unchanged and there was no significant correlation between the dose of iodine and the TSH reaction. In conclusion, iodine-containing contrast media can induce transiently subclinical hypothyroidism even in euthyroid patients. The TSH reaction seems to depend on the preexisting state of thyroid function.

Differential expression of alphaB-crystallin and Hsp27-1 in anaplastic thyroid carcinomas because of tumor-specific alphaB-crystallin gene (CRYAB) silencing

Abstract Expression of the small heat shock protein alphaB-crystallin in differentiated thyroid tumors has been described recently. In this study, we investigated the molecular mechanisms that affect the expression of alphaB-crystallin in benign goiters (n = 7) and highly malignant anaplastic thyroid carcinomas (ATCs) (n = 3). AlphaB-crystallin expression was compared with that of Hsp27-1. Immunoblot and quantitative real-time (RT) polymerase chain reaction revealed marked downregulation of alphaB-crystallin in all the tested ATCs and the ATC-derived cell line C-643 . In contrast, considerable expression of Hsp27-1 in benign and malignant thyroid tissue was demonstrated. Immunofluorescence analysis revealed no relevant topological differences between benign and malignant thyrocytes in the cytoplasmic staining of both proteins. Consistent and marked downregulation of TFCP2L1 was identified as one of the main mechanisms contributing to CRYAB gene silencing in ATCs. In addition, CRYAB gene promoter methylation seems to occur in distinct ATCs. In silico analysis revealed that the differential expression of alphaB-crystallin and Hsp27-1 results from differences between the alphaB-crystallin and Hsp27-1 promoter fragments (712 bp upstream from the transcriptional start site). Biological activity of the analyzed promoter element is confirmed by its heat shock inducibility. In conclusion, we demonstrate downregulation of alphaB-crystallin expression in highly dedifferentiated ATCs because of a tumor-specific transcription factor pattern. The differential expression of alphaB-crystallin and Hsp27-1 indicates functional differences between both proteins.

Elevated blood markers 1 year before manifestation of malignant glioma

We detected distinct plasma concentration profiles of S100B, neuropeptide Y, and secretagogin in 3 of 191 patients enrolled in a previous study investigating brain-tissue-related markers in the blood of patients with atrial fibrillation. Intriguingly, 2 of these 3 patients, both of whom were without neurological symptoms at the time of blood sampling, were diagnosed with malignant glioma (MG) approximately 1 year later. To our knowledge, this is the first report indicating that distinct blood biomarker profiles may be detected long before clinical manifestation of MG.

Brain natriuretic peptide correlates with the extent of atrial fibrillation-associated silent brain lesions.

OBJECTIVE Identification of plasma markers indicative for atrial fibrillation-associated silent brain lesions. DESIGN AND METHODS 1. Comparative determination of the plasma concentrations of secretagogin, S100B, neuropeptide Y, brain fatty acid binding protein, matrix metalloprotease 9, brain natriuretic peptide, and of D-Dimer in 222 patients with atrial fibrillation and 28 controls by immunoassays. 2. Correlation of the biochemical marker plasma concentration with the extent of silent white matter brain lesions, as determined by the Fazekas score and N-acetylaspartate-spectroscopy. RESULTS 1. Plasma concentrations of brain natriuretic peptide, of neuropeptide Y, and of matrix metalloprotease 9 were significantly higher (all with a p<0.05) in patients suffering from atrial fibrillation than in control subjects. 2. Brain natriuretic peptide correlated significantly with the Fazekas score (R=0.41; p<0.005). 3. Brain natriuretic peptide plasma concentrations were significantly higher in patients with a pathological N-acetylaspartate magnetic resonance-spectrometry (p<0.05). CONCLUSION Brain natriuretic peptide plasma concentrations correlate with the extent of atrial fibrillation-associated silent brain lesions.

Myocardial glucose uptake and breakdown during adenosine-induced vasodilation.

SummaryIn isolated K+ (16.2 mM)-arrested cat hearts perfused at constant pressure adenosine infusions (0.8 μmoles · min−1 · 100 g−1 for 10 min) caused an increase in myocardial14C-glucose uptake and release of14CO2+H14CO−3 and14C-lactate simultaneously with a rise in coronary flow. The ratio of the release of14CO2+H14CO−3 to that of14C-lactate and the specific activity of lactate in the effluate were not altered. In K+-arrested hearts perfused with constant volume neither glucose uptake nor glucose breakdown were influenced by 0.8 or 100 μmoles · min−1 · 100 g−1 adenosine with 0.1–5 mM glucose in the perfusion medium. It is concluded that adenosine does not affect directly the myocardial glucose carrier system, aerobic or anaerobic glucose breakdown or glycogenolysis, but enhances glucose uptake secondarily by increasing coronary flow. This interpretation is substantiated by the finding that mechanically produced increases in perfusion volume caused similar increases in myocardial glucose uptake as were observed with comparable adenosine-induced coronary flow increments.

A newly identified RET proto-oncogene polymorphism is found in a high number of endocrine tumor patients

Multiple RET proto-oncogene transcripts, due to genomic variations and alternate splicing, have been described. To investigate endocrine tumor tissue characteristic RET proto-oncogene expression, we performed quantitative RT-PCR, Northern blot and Southern blot analyses of benign and malignant endocrine-derived tissues. We newly describe RET proto-oncogene expression in carcinoid-, gastrinoma- and insulinoma-derived tissue samples. In addition, the presence of a 3′-terminally truncated RET proto-oncogene mRNA variant in benign and malignant thyroid neoplasias, as well as in a pheochromocytoma, an ovarian carcinoma and a medullary thyroid carcinoma, is demonstrated. Southern blot analysis revealed no evidence of gross RET proto-oncogene rearrangements or deletions. As the underlying cause for a bi-allelic TaqI restriction fragment length polymorphism (RFLP), a C (allele 1)/T (allele 2) transition within intron 19, was characterized. This polymorphism is close to a recently described polyadenylation site and lies within a binding site for the nucleic acid binding protein Pbx-1. Screening of healthy subjects and of patients suffering from various endocrine malignancies revealed exclusively allele 1 homozygous and allele 1/allele 2 heterozygous genotypes. Heterozygous genotypes were found in a significantly higher percentage in samples derived from endocrine tumor patients when compared with those from healthy control subjects. Homozygosity for allele 2 was found exclusively in somatic DNA derived from endocrine tumors with high malignant potential. Analysis of DNA derived from varying regions within individual anaplastic thyroid carcinomas revealed an allele 1/allele 2 switch of the RFLP banding pattern, indicating loss of heterozygosity at the RET proto-oncogene locus. In conclusion, our data demonstrate presence of a 5′-terminal RET proto-oncogene transcript in endocrine tissues and reveal a bi-allelic RET proto-oncogene polymorphism. A heterozygous genotype for this polymorphism is found in a considerable number of endocrine tumor patients.

RAISED CIRCULATING PLASMA LEVELS OF ATRIAL NATRIURETIC PEPTIDE IN ADOLESCENT AND ADULT PATIENTS WITH CYSTIC FIBROSIS AND PULMONARY ARTERY HYPERTENSION

Since pulmonary artery hypertension (PH) complicates advanced stages of cystic fibrosis (CF), we wondered whether plasma concentrations of h-ANP would be increased in adult patients with CF. Furthermore, if only the right ventricle is faced with an increased afterload in these patients, the increased h-ANP plasma levels should stem primarily from the right atrium. To test this hypothesis we studied 12 adult patients with CF in a clinically stable condition using right heart catheterization. Mean pressures were measured in the right atrium (Pra) and pulmonary artery (Ppa), pulmonary capillary wedge (PCWP) position, and blood were drawn from the pulmonary artery and from a peripheral vein to determine h-ANP. Plasma levels in the pulmonary artery were significantly higher than in a peripheral vein (54.3±6.0 pg/ml vs. 32.2±4.4 pg/ml; p<0.001). Four of the 12 patients had PH (Ppa, 25.8±2.9 mmHg) whereas 8 patients exhibited normal pulmonary artery pressures (Ppa, 15.9±0.7 mmHg). Patients with PH had higher Pra (4.2±0.4 mmHg) than patients with CF without PH (1.9±0.7 mmHg; p < 0.05). Plasma h-ANP concentrations were significantly higher in patients with CF with PH (70±10.4 pg/ml in the pulmonary artery; 42.6±4 pg/ml in a peripheral vein) than in patients with normal pulmonary artery pressure (43±3.3 pg/ml in the pulmonary artery; p<0.01; 24.7±5.6 pg/ml in a peripheral vein; p<0.05).Although our results are derived from a small group of patients with CF, we conclude from our results that in patients with CF PH may cause increased h-ANP secretion. The right atrium seems to be a major source.

Effect of L-Thyroxine on Bone Mass

To the Editors: In their recent article, Stall and colleagues (1) conclude that thyroxine-treated women with low serum thyrotropin levels lose bone mineral from the spine more rapidly than do women...

Cor pulmonale in cystic fibrosis.

Introduction In cystic fibrosis (CF) precapillary injury is the main pathology leading to pulmonary heart disease according to the WHO definition of cor pulmonalel. Interference with efficient intrapulmonary gas exchange due to bronchial wall and parenchymal damage will lead to an increase ofpulmonary artery pressure or pulmonary vascular resistance early in the course of the disease both at rest and during exercise, without clinical signs ofright sided cardiac failure. The ensuing right ventricular hypertrophy has no clinical correlates and overt clinical signs are rare and appear late in the course of CF. Cor pulmonale as a complication of CF was reported as early as 19512. Whereas autopsy material showed cardiac involvement in about 70% of children dying from CF, only 15% of patients with CF older than 25 years showed clinical right heart failure3. Other centres have reported right ventricular failure in 46% of CF patients from the age of 15 years onwards for at least two weeks before death4. With the improved life expectancy ofCF, pulmonary heart disease will gain greater importance. It should be stressed that the synonymous term cor pulmonale does not necessarily stand for right heart failure. Advances in the management of heart disease in chronic obstructive pulmonary disease (COPD) have been made56 which may bear direct relevance to future treatment of CF. In addition, drug-mediated pulmonary artery dilatation by vasoactive substances has gained acceptance and should be explored for use in CF7.