Vitamin D-neutralizing CYP24A1 expression, oncogenic mutation states and histological findings of human papillary thyroid cancer.

OBJECTIVE: The aims of the present study were to examine gene and protein expression of the vitamin D-inactivating 24-hyroxylase (CYP24A1) and the activating 1-alpha-hydroxylase (CYP27B1) enzyme in human papillary thyroid cancer (PTC), furthermore, to investigate the association between CYP24A1 expression and numerous clinical, histological parameters and somatic oncogene mutation status of thyroid tumor tissues. MATERIALS AND METHODS: Gene expression analysis was carried out in 100 Hungarian thyroid samples, both normal and papillary tumor tissue sections of the same patient. The specific mRNA to the selected genes was analyzed by TaqMan probe-based quantitative real-time RT-PCR. The somatic oncogene mutation states of BRAF, NRAS, HRAS and KRAS were also tested. RESULTS: CYP24A1 mRNA expression was markedly increased in 52 cases (52%) of the examined papillary cancers compared with that of normal thyroid tissue. There was a tendency toward difference in the distribution of high-level CYP24A1 in the PTC accompanied with somatic oncogene mutation. Positive correlation was seen between increased CYP24A1 expression rate and a group of variables reflecting tumor malignity (mainly vascular invasion, lymph node metastasis, tumor size, hypothyreosis) by principal components analysis. No significant alteration was seen in CYP27B1 gene expression between neoplastic and normal tissues. CONCLUSIONS: A definite alteration was seen in vitamin D3-inactivating CYP24A1 gene activity in PTC compared to their normal tissues on a relatively large patient population. Our findings raise the possibility that CYP24A1 may also directly be involved in thyroid carcinogenesis.

Long term efficacy of radioiodine treatment in hyperthyroidism.

OBJECTIVES: Radioiodine is the mainstay of the treatment of thyroid hyperfunction. However, it is difficult to apply the appropriate amount of radioidone to achieve optimal efficacy with the least possible adverse effects. Results of the investigation on the efficacy of a relatively new protocol for radioiodine treatment of hyperthyroidism are reported. DESIGN: A retrospective evaluation of data from 326 patients with a mean average follow-up of 5.7 (1.0-11.7) years was performed. 64% of these patients suffered from Graves' disease and 36% had uni- or multinodular toxic goitre. RESULTS: In Graves' disease, the recurrence rate was 5% 1 year after the treatment, and that remained the same after 5 years. In toxic goitre, these rates were 6 and 7%, respectively. After 5 years 70% of the patients with autonomous adenomas were euthyroid, while 78% of the Graves patients developed hypothyroidism and 17% showed euthyroid state. A relationship between the lack of normalisation of thyroid-stimulating hormone levels after radioiodine treatment and the increased recurrence of late hyperthyroidism has also been established in patients with Graves's disease. CONCLUSION: Compared to the available data published in the literature, the success rate of the treatment is fairly high confirming the effectiveness of our protocol.

Exhaled breath condensate pH standardised for CO2 partial pressure.

Exhaled breath condensate (EBC) pH is considered to reflect the acid-base balance of the airways. Current pH measurements do not take into account the effect of CO2. The aim of the present study was to determine the effect of condensate CO2 partial pressure on pH and to provide a more precise mode of EBC pH determination. Condensate pH and CO2 partial pressure were measured in parallel from 12 healthy volunteers and 12 asthmatics using a blood gas analyser in neat, argon de-aerated and CO2-loaded samples. The regression analysis was used to test the relationship between pH and CO2, and to calculate the pH at a CO2 level of 5.33 kPa (physiological alveolar CO2 partial pressure). Reproducibility of different pH readings was compared using the Bland-Altman test. Condensate CO2 concentration was variable both in neat and argon de-aerated samples. There was a close negative logarithmic relationship between CO2 and pH. Calculation of pH at a CO2 level of 5.33 kPa provided reproducibility approximately six times as good as that of the currently used measurements. Condensate CO2 partial pressure influences pH measurements. Determination of pH at a standard CO2 level provides the most reproducible condensate pH values to date.