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.

Cardiometabolic risk and educational level in adult patients with type 1 diabetes.

A low educational level and a poor socioeconomic status could be associated with increased risk for chronic diseases. The aim of the study was to evaluate the relationship between the educational level and cardiometabolic risk in adult patients with type 1 diabetes (n = 437; age: 38.0 +/- 10.4 years, duration of diabetes: 19.2 +/- 11.1 years; x +/- SD). Educational levels were classified as low [primary school, n = 56 (12.8%)], middle [high school, n = 251 (57.4%)] or high [university, n = 130 (29.7%)]. The prevalence rate of the metabolic syndrome proved to be higher in patients with low versus high educational levels (ATP-III criteria: 42.9 vs. 21.5%, P = 0.0006). Antihypertensive treatment and cardiovascular diseases were more prevalent in patients with low versus high educational level (46.4 vs. 26.2%, P = 0.01; 12.5 vs. 2.3%, P = 0.02; respectively). Overall glycemic control was worse in patients with low versus high educational level (HbA(lc): 8.8 +/- 1.6 vs. 7.9 +/- 1.4%; P = 0.0006). Patients with low versus high educational level differed significantly regarding smoking habits (smokers: 28.6 vs. 11.6%; P = 0.01) and regular physical activity (5.4 vs. 33.1%; P = 0.0001). Higher prevalence rate of certain cardiometabolic risk factors was associated with low educational level in middle-aged type 1 diabetic patients with relatively long duration of diabetes; therefore, these patients should have priority when preventing cardiovascular complications.

Effect of treatment of hypothyroidism on the plasma concentrations of neuroactive steroids and homocysteine.

Autoimmune thyroiditis with hypothyroidism is frequently accompanied by symptoms of psychiatric disorders and atherogenic changes in lipid metabolism. Recent studies suggest that some neuroactive steroids and homocysteine are involved in the pathophysiology of both disorders. Homocysteine metabolism may be affected by some steroids. We were interested if the treatment of hypothyroidism would affect the above factors. We studied plasma concentrations of allopregnanolone, pregnenolone sulfate, dehydroepiandosterone and its sulfate, progesterone, estradiol and homocysteine in 14 patients (12 women, 2 men) during the 3-month treatment with levothyroxine. Steroids and thyroid function were monitored by measuring thyrotropin, free triiodothyronine, free thyroxine and levels of thyroid antimicrosomal antibodies and antibodies to thyroglobulin. We have found that with the restoration of the thyrotropin level, free triiodothyronine, free thyroxine and homocysteine levels decreased, but the levels of steroids were not significantly altered. Steroid concentrations correlated negatively with the level of thyroid antimicrosomal antibodies.

[Epidemiological profile of thyroid volume and disorders in Slovakia]. / Epidemiologický profil objemu stítnej zl'azy a tyreopatií na Slovensku.

UNLABELLED: After 45 years of successful iodine prophylaxis a total of 6324 subject aged 7 to 70 years from East (72.0%), Central (16.2%) and West Slovakia (11.8%) were examined. The thyroid volume (ThV) by ultrasound was examined in a total of 6045 subjects. Serum level of thyrotropin (TSH) was estimated in 1919 (30.3%) and anti-thyroperoxidase antibodies (anti-TPO) in 2589 (40.9%) subjects. Iodine was estimated in 1983 (31.3%) spot urine samples. The median and 75th percentile of ThV were increasing (respectively) from 3.9 and 5.2 ml (10 yr), 8.2 and 10.2 ml (17 yr), 12.4 and 16.3 ml (31-40 yr) up to 14.1 and 19.9 ml (61-70 yr). The frequency of ultrasound hypoechogenicity as an early sign of autoimmune thyroiditis increased from 3.9% (28/709; 10 yr), 16.3% (66/403; 21-40 yr) and 30.3% (205/665; 41-60 yr) up to 51.0% (48/94; 61-70 yr). Positive anti-TPO level as an other sign of autoimmune thyroiditis was found in 1.6% (11/683; 7-13 yr), 7.3% (47/644; 17-30 yr) and 20.4% (257/1262; 31-70 yr). In the adults 19.0% (268/1409) positive anti-TPO were found. Among 1367 adults 6.2% (N = 85) of TSH levels were higher than 4.0 mU/l and 7.5% (N = 103) were lower than 0.2 mU/l. Among 1504 adults a total of 93 (6.1%) of nodules larger than 10 mm in diameter was found (14 in males and 75 in females). In this study the nature of nodules remained unidentified, since all subjects were referred to additional examinations. Malignant nodules were suspected in 3 females with high serum thyroglobulin level and in one additional female with occasionally found very large nodule. The estimation of urinary iodine showed a majority of values in optimal range (> 100-200 microg/l). CONCLUSIONS: Thyroid volume in about 75% examined subjects of all age groups may be considered as relatively small which is apparently due to 45 years of effective iodine prophylaxis. In spite of that the volume of remaining about 25% thyroids were apparently increased which may be presubambly explained by the effect of mainly genetic, but also environmental factors.

[Occurrence of primary aldosteronism in a group of ambulatory hypertensive patients]. / Výskyt primárneho aldosteronizmu v súbore ambulantných hypertonikov.

Findings pertaining to the diagnosis and treatment of primary aldosteronism are rapidly expanding. In the present work the authors focused attention on the clinical application of some progressive methods. They examined a group of 115 ambulatory patients with arterial hypertension, not suspected of secondary arterial hypertension, in the course of one year. As a screening method of primary aldosteronism they selected the aldosterone renin ratio (ARR). Using this method the authors diagnosed 125 cases of primary aldosteronism, i.e. a 13% prevalence in the examined group. Only in one instance they detected an adenoma by computed tomography (CT), in the remaining patients, i.e. four times, the adenoma was verified by selective catheterization of adrenal veins and assessment of aldosterone and cortisol. The authors did not confirm a more accurate localization of the adenoma by the aldosterone/cortisol ration than when assessing aldosterone only. In two patients adrenalectomy was performed by laparoscopy and this surgical technique, as regards adrenal glands, was implemented for the first time in Slovakia in our department. It has certain advantages over classical adrenalectomy.

[Cushing's syndrome in pregnancy]. / Cushingov syndróm v gravidite.

Active Cushing's syndrome during pregnancy is a rare phenomenon which was so far described in the literature only in 85 women. The authors give an account of a patient who developed Cushing's syndrome during pregnancy and who was delivered during the eighth month of a healthy foetus by caesarean section, afterwards the hypercortisolism associated with hyperaldosteronism was treated by dextrolateral adrenalectomy. In the removed adrenal gland was a cortical adenoma made up of clear cells and cells reminding of the zona glomerulosa. Subsequently the authors summarize data from the literature on the prevalence of different pathogenetic forms of Cushing's syndrome in pregnant women, on the influence of hypercortisolism on mother and foetus, on the optimal diagnosis and therapy of this syndrome during pregnancy.

[Parenteral, depot and repeatable forms of Parlodel LAR bromocriptine in the treatment of hyperprolactinemia syndrome. Comparison with oral Parlodel]. / Parenterální, depotní, opakovatelný bromokriptin Parlodel LAR v lécbe hyperprolaktinemického syndromu. Porovnání s perorálním Parlodelem.

Parenteral, depot, repeatable bromocriptine Parlodel LARR (PLO LAR) was used in the treatment of 10 women with hyperprolactinaemia. Two of them had previously an operation of a prolactinoma, eight did not have adenomas. Twenty eight days following administration of 50 mg PLO LAR, the PRL levels ere significantly lower than before treatment; in patients without adenomas they were quite normal. The action of the mentioned 50 mg PLO LAR corresponded roughly to a daily dose of 7.5 mg ParlodelR (PLO) by the oral route, i.e. in 28 days a total of 185 mg bromocriptine. After administration of five PLO LAR injections (50 and later 100 mg), the mean PRL levels in patients without adenomas were normal after 6 months. There were no significant nor pathological changes 28 days following i.m. PLO LAR 50 mg as regards T3, T4 levels, the blood sugar, cholesterol, FSH, LH, STH, TSH, testosterone cortisol, progesterone, 17 beta-estradiol, androstendione, 11 beta-OH androstendione, DHEA-S, 17 alpha-OH progesterone, aldosterone, 17-ketosteroids and 17-ketogenic steroids (in urine). LHRH + TRH + insulin tolerance tests were made repeatedly. Significant changes were found only in PRL levels (decline). In three amenorrhoic patients the originally low progesterone level rose significantly to levels of postovulation progesterone. One of these three women became pregnant after 18 years of unsuccessful treatment of sterility, incl. various oral dopaminergic preparations. The patients tolerated the preparation well and various biochemical and haematological tests were normal. The effect on galactorrhoea was favourable, seven amenorrhoic women had normal menstruation.

Circadian pattern of serum androgens in women with Cushing's syndrome.

Circadian profiles of the serum levels of cortisol and five androgens were studied in 20 females including 8 controls, 7 patients with ACTH-dependent Cushing's syndrome and 5 with hypercortisolism due to adrenal adenoma. A significant 24-h periodicity was found for each steroid in all groups. Besides hypercortisolaemia, a significant increase of 11-hydroxyandrostenedione was shown in both forms of Cushing's syndrome. The most conspicuous finding was a decreased dehydroepiandrosterone and its sulphate in adrenal adenoma. The peaks for the studied steroids were shifted from the morning hours towards the noon in ACTH-dependent Cushing's syndrome and towards the evening (for cortisol) and night hours (for androgens) in adrenal adenoma.

Organ distribution and autoradiography after administration of 125I-16 alpha-iodo-estradiol in female rats.

Tissue distribution experiments with 125I-1 16 alpha-iodo-estradiol (Amersham) showed the highest tissue-to-blood ratio of 3 to 8 in the liver, uterus, mammary gland, ovaries and adrenals up to 2 h after the injection. Satisfactory images with a simple autoradiographical techniques according to Stumpf [1971] have been achieved at 2 h after the injection of drug.

[An intracranial tumor in an unusual location associated with Cushing's syndrome]. / Intrakraniálni nádor neobvyklé lokalizace s Cushinogvým syndromem.

In a 58 year-old woman with peracute Cushing's syndrome high levels of ACTH were proved by RIA method. Autopsy showed normal pituitary gland in addition to a voluminous tumour situated in planum sphenoidale and lamina cribrosa ossis ethmoidalis. Tumour cells with epithelial features produced ACTH which was found by an indirect immunoperoxidase technique. Tumour was classified as ectopic corticotropic pituitary adenoma.