The Role of Vitamin D Receptor Gene Polymorphisms in Thyroid-Associated Orbitopathy.

Purpose: Thyroid-associated orbitopathy (TAO) is an autoimmune disease that typically occurs in the course of Graves' disease. VDR gene has been tested for its association with autoimmune thyroid diseases, with conflicting results. The study aimed to evaluate the association of selected VDR polymorphisms (rs2228570, rs1544410, rs7975232, rs731236, and rs11568820) with susceptibility to TAO.Methods: 108 TAO patients and 130 control subjects were enrolled. Polymorphisms were studied by PCR-RFLP or TaqMan real-time PCR.Results: Genotype distributions of rs2228570 differed significantly between TAO and controls under a dominant model (OR = 2.05; 95% CI: 1.03-4.08; p = .04). TAO patients also had slightly increased frequency of C allele of rs2228570 comparing to controls (p = .05). However, the study failed to find any associations between VDR polymorphisms and the analyzed clinical features of the disease.Conclusions: These preliminary results have shown that C allele of rs2228570 may contribute to the development of TAO in patients of Caucasian Polish origin.

Effect of methylprednisolone pulse therapy with and without alendronate on biochemical markers of bone turnover in patients with Graves' ophthalmopathy.

INTRODUCTION:  Immunosuppression with glucocorticoids is the method of choice in the treatment of active Graves' ophthalmopathy (GO). However, glucocorticoid therapy may have side effects, among others, it affects bone metabolism. OBJECTIVES:  The aim of the study was to compare the effect of methylprednisolone pulse therapy (MPPT) with and without alendronate on bone turnover markers in patients with GO with normal and reduced bone mineral density (BMD). PATIENTS AND METHODS:  The study included 53 patients with GO and 20 sex- and age­matched healthy controls. Twenty patients with normal BMD (17 women, 3 men, aged 45 ±1.0 years) received only MPPT (8 g intravenously during 4 weeks). The remaining patients, with reduced BMD, were randomly assigned either to MPPT without alendronate (10 women, 2 men, aged 47 ±1.0 years) or MPPT with alendronate (18 women, 3 men, aged 47 ±1.0 years). BMD of the lumbar spine and femoral neck was assessed using dual energy X­ray absorptiometry  (DEXA) before treatment. The markers of bone formation (serum osteocalcin, carboxyterminal propeptide of type I collagen [PICP], alkaline phospatase) and the markers of bone resorption (serum carboxyterminal telopeptide of type I collagen [ICTP], cross­linked C­terminal telopeptide of type I collagen [CTX], serum calcium [Ca] and potassium [P], as well as urinary excretion of deoxypyridinoline, Ca, and P) were determined before and after treatment. RESULTS:  MPPT caused a decrease in bone formation markers and an increase in some bone resorption markers. MPPT with alendronate decreased bone formation and bone resorption markers. CONCLUSIONS:  A negative effect of MPPT on bone turnover is observed both in patients with GO with normal and with reduced BMD. Simultaneous use of MPPT and alendronate in patients with GO and reduced BMD suppresses bone resorption caused by methylprednisolone.

Methylprednisolone and hepatotoxicity in Graves' ophthalmopathy.

BACKGROUND: Immunosuppressive therapy with glucocorticoids alone or in combination with radiotherapy is first-choice treatment for the active phase of Graves' ophthalmopathy (GO). Intravenous methylprednisolone (mPRED) pulse therapy is much more effective, safer, and better tolerated than steroids orally administered. There have been some reports, however, of unfavorable reactions to mPRED pulse therapy on liver function. Here, we report laboratory test results in patients with GO before and after intravenous mPRED therapy. METHODS: Thirty patients (24 women and 6 men) whose mean age was ± standard error of the mean 53±1.3 participated in the study. All patients were treated with mPRED for their history of GO. None had received radiotherapy before mPRED. There was no history of liver disease including viral hepatitis in any of the patients. A battery of tests including general serum chemistries and liver function tests as well as those relating to clotting parameters and viral forms of hepatitis were performed a week before and 2 days after mPRED therapy. RESULTS: mPRED pulse therapy caused a significant, below reference range, decrease in alkaline phosphatase activity from 119.43±14.98 to 105.53±13.98 IU/L and an increase in gamma-glutamyltranspeptidase activity (above reference range, but not statistically significant) from 23.76±2.93 to 25.3±1.52 IU/L. No significant changes were noted in other liver enzymes activities. We also observed a significant, below reference range, decrease in serum total protein as well as a significant, above reference range, increase of alpha-1 globulins, and low-density lipoproteins cholesterol levels. Pulse therapy also resulted in a significant, but still within reference range, decreases in activated partial thromboplastin time (APTT) from 29.03±0.86 to 26.13±1.16 s, fibrinogen from 3.85±0.2 to 3.05±0.13 g/L, and increase of International Normalized Ratio (INR) from 1.06±1.06 to 1.11±0.06. Despite a lack of a history of viral hepatitis, six patients had positive tests for anti-Hepatitis B e (HBe) antibodies before mPRED administration. In two of these patients, anti-HBe antibody tests became negative after mPRED treatment. In two of the six patients who had positive anti-HBe antibodies, anti-HBc antibodies in the IgG class were also present before and after mPRED treatment. Another patient was found to have anti-HBc IgG both before and after mPRED treatment. Other markers of A and C viral hepatitis were negative in all patients. CONCLUSIONS: Patients who are on anticoagulents need careful monitoring of their INR, APTT, and fibrinogen while on mPRED therapy. We recommend at least once a week. In patients without evidence for active viral replicating disease, but with past hepatitis B, as judged by the presence of pertinent markers, mPRED pulse therapy for GO does not appear to reactivate hepatitis B.

[Pharmacokinetics of digoxin in hyperthyroidism. Effect of methimazole]. / Farmakokinetyka digoksyny u chorych z nadczynnoscia tarczycy. Wplyw metimazolu.

INTRODUCTION: Cardiovascular abnormalities may be the only manifestations of overt hyperthyroidism. In patients with heart failure and atrial fibrillation digoxin can be beneficial in controlling the symptoms and signs, but hyperthyroid patients show an impaired response or even resistance to digoxin treatment. The aim of the study is to establish: 1. Are there any differences in the pharmacokinetics of a single oral dose of digoxin between hypertyroid and euthyroid patients? 2. Does simultaneous administration of digoxin and methimazole affect the pharmacokinetics of a single oral dose of dogoxin? 3. Does methimazole-induced euthyroidism change the pharmacokinetics of a single oral dose of digoxin? MATERIAL AND METHODS: The subject of the study were 28 patients with hyperthyroidism and 15 healthy persons. We evaluated the pharmacokinetics of a single oral dose of digoxin. Moreover we evaluated pharmacokinetics of a single dose of digoxin after simultaneous administration of digoxin and methimazole in 12 patients and 12 methimazole treated patients werere-assessed once they had become euthyroid. RESULTS: Hyperthyroid patients showed significantly lower serum digoxin concentrations, shorter T1/2 beta and a significantly smaller area under the concentration curve (AUC) that the control group. Administration of methimazole did not affect digoxin pharmacokinetics. CONCLUSIONS: In hyperthyroid patients: 1. the pharmacokinetics of a single oral dose of digoxin does differ from that observed in healthy subjects. 2.methimazole do not alter digoxin pharmacokinetics.

Interleukin-1beta gene (IL-1beta) polymorphisms (SNP -511 and SNP +3953) in thyroid-associated ophthalmopathy (TAO) among the Polish population.

OBJECTIVE: The aim of this study was to evaluate whether the IL-1beta gene could be a genetic marker of the thyroid-associated ophthalmopathy (TAO) development. MATERIALS AND METHODS: The IL-1beta gene polymorphisms at -511 and +3953 regions in 117 TAO patients of Polish origin (ATA/NOSPECS class III or greater) and in 106 controls were studied. RESULTS: We found no significant differences in the frequencies of genotypes and allelic variants for SNP -511 and SNP +3953 between the controls and the studied groups. CONCLUSIONS: No association between the IL-1beta polymorphisms and the TAO existed, so those polymorphisms are not suitable genetic markers for TAO.

[Nail susceptibility to fungal infection in patients with type 1 and 2 diabetes under long term poor glycaemia control]. / Podatnosc paznokci na zakazenie grzybicze u chorych na cukrzyce typu 1 i 2 z dlugoterminowa zla kontrola glikemii.

Onychomycosis is a common disorder in adults. Its prevalence increases also in diabetics. The objective of the study was: 1) evaluation of finger and toe nail susceptibility to Candida albicans and Trichophyton mentagrophytes infection in patients with type 1 and type 2 diabetes with long term glycaemia under poor control as compared with healthy persons, and 2) checking whether or not various aetiology of type 1 and type 2 diabetes may influence the intensity of fungal nail infection. The materials comprised finger and toe nails sampled from 26 patients with type 1 diabetes (20 females and 6 males at average age 51 +/- 10 years), 25 patients with type 2 diabetes (17 females and 8 males at average age 58 +/- 4 years). Twenty two healthy volunteers (18 females and 4 males at average age 47 +/- 14 years) served as controls. All of the diabetics (except one with type 1 diabetes and four with type 2 diabetes) had increased fasting glycaemia; moreover, all of them had poor controlled long term glycaemia because the concentration of glycated haemoglobin HbAlc exceeded 7.5%. The patients with type 1 diabetes were treated with insulin while those with type 2 diabetes with diet only (one person), with gliclazide (sixteen persons), with glimepirid (five persons), and with metformin (four persons). Enhanced fingernail susceptibility to Candida albicans infection was detected in 38.5% of the patients with type 1 diabetes, in 28% of those with type 2 diabetes, and in 22.7% of the controls. Intensive toenail infection was found in 34.6%, 20%, and 22.7% respectively. Enhanced fingernail susceptibility to Trichophyton mentagrophytes infection was found in 30.8% of the patients with type 1 diabetes, in 48% of those with type 2 diabetes, and in 4.54% of the controls while intensive toenail infection in 15.4%, 20%, and 18,2% respectively. Statistical analysis gave evidence of statistically significant higher susceptibility to infection of finger and toe nails with T. mentagrophytes but not with C. albicans in both type 1 and type 2 diabetics, as compared with the controls. In the diabetics, no significant correlation was found between the susceptibility to C. albicans and T. mentagrophytes infection and the age of the patients, metabolic diabetes control (evaluated on the basis of serum glucose level and blood HbAlc concentration), as well as the duration of diabetes.

[Long-term consequences of surgical excision of cortisol producing adrenocortical adenoma]. / Odlegle nastepstwa chirurgicznego usuniecia gruczolaka kory nadnercza wytwarzajacego kortyzol.

INTRODUCTION: Surgical excision of adrenocortical tumour in patients with ACTH-independent Cushing syndrome gives a chance for their entire cure. However in some patients after adrenalectomy persistent arterial hypertension, obesity and diabetes mellitus is observed. The aim of the study was to analyse long term consequences of surgical excision of cortisol producing adrenocortical adenoma with a special attention on the influence of adrenalectomy on arterial blood pressure. MATERIAL AND METHODS: 15 patients (mean age 54 years) suffering from arterial hypertension (n = 15), obesity or overweight (n = 12) and diabetes mellitus (n = 7) were subjected to analysis. Mean follow up time was 45 months. RESULTS: Improvement of blood pressure control after unilateral adrenalectomy was observed in 66.7% of patients. The risk factor of no improvement of blood pressure control was BMI > 30.5 kg/m(2) (RR = 4.0 [1.07-14.90]). During the follow up period decrease of maximal values of systolic and diastolic blood pressure was observed (34 [17-50] and 25 [16-35] mm Hg respectively; p < 0.01). In the entire group of patients a 3.4 kg/m(2) decrease of BMI was observed p = 0.01. BMI decreased significantly (more than 1 kg/m(2)) in 66.7% of patients. Only in 2 patients a complete regression of diabetes was observed. 46.7% of patients required supplementation with adrenal steroids. 40% of patients reported a subjective withdrawal of all symptoms of the disease after surgery and 46.7% only partial remission. CONCLUSION: Surgical excision of cortisol producing adrenocortical adenoma results in improvement of blood pressure control and body weight reduction in a large percentage of patients with Cushing syndrome. Obesity before adrenalectomy is the factor that reduces a chance for improvement of blood pressure control after surgery.

[Tryptase- and chymase-positive mast cells as possible prognostic factor in patients with Hodgkin's lymphoma]. / Mastocyty tryptazo- i chymazododatnie jako potencjalny czynnik rokowniczy u chorych na chloniaka Hodgkina.

UNLABELLED: Aim of the study was to reveal potential prognostic factors in Hodgkin's lymphoma (HL) patients by means of assessment of the influence of mast cells on clinical characteristics of the disease. PATIENTS AND METHODS: Paraffin-fixed lymph node biopsies taken from the group of 72 patients treated for Hodgkin's lymphoma in the Department of Internal Medicine and Oncological Chemotherapy of Silesian Medical Academy in Katowice from 1990 to 2002. The analyzed group consisted of 44 men (age 16-73, mean 39.2) and 28 women (age 15-73, mean 36.5) presenting with 5 histological types of HL according to WHO classification. Overall survival (OS) for the group ranged from 3 to 169 month (mean 64.5) while disease-free survival (DFS) was from 4 to 167 months (mean 44.8). Tryptase and chymase-positive mast cell density was assessed in order to correlate it with histological type, staging, sex and age of patients. Tissue specimens were immunohistochemically stained for mast cell tryptase and counted at 200x magnification. Tryptase-positive mast cell density (MCD-T) was assessed in 10 randomly selected fields and the score was averaged. RESULTS: The highest density of MCD-T and MCD-C was observed in NS type while the lowest characterized LD. A statistically significant difference in MCD-T was noted between NS and LD (p=0.0002). Despite the fact that increased density of MCD-T and MCD-T was observed in stage III and the lowest in stage IV of the disease, no correlation was found between MCD and stage, sex or age. Overall survival was assessed in correlation with histological type and showed to be longest in MC and worst in NS type. CONCLUSIONS: Tryptase and chymase-positive mast cell density is related to histological type of Hodgkin's lymphoma. Increased mast cell density correlates with worse prognosis in patients with HL.

[Difficulties in the diagnosis of Cushing's disease--usefulness of desmopressin test]. / Trudnosci w rozpoznaniu ACTH-zaleznego zespolu cushinga pochodzenia przysadkowego -- rola testu z desmopresyna.

A 39-year-old man with occult eutopic corticotropin microadenoma leading to Cushing's syndrome was presented. Magnetic resonance imaging was unable to identify the pituitary microadenoma. In another department bilateral adrenalectomy was justified. In our department to identify or exclude a pituitary source of autonomous corticotropin secretion desmopressin test was performed. Intravenous desmopressin administration enhanced both circulating concentrations ofACTH and cortisol by 217.36% (peak vs. baseline) and 67% respectively. The patient underwent a transsphenoidal adenomectomy. Immunostaining demonstrated ACTH in adenoma cells. After surgery cortisol levels returned to the normal range, moreover no ACTH and cortisol response was elicited by desmopressin administration. This clinical case represents the demonstration of the possibility to unmask an occult eutopic Cushing's syndrome with the desmopressin test.

Focal lesions in the ultrasonographic examination of the spleen as a symptom of various disease statuses: literature survey and case descriptions.

BACKGROUND: Ultrasonography (US) is an easy and non-invasive technique of visualizing spleen. Thanks to its repeatability, it plays an important role in the diagnostics of, among others, developmental anomalies, such as supernumerary or lobated spleens, as well as focal lesions. It is also used in monitoring the size of the spleen and it considerably facilitates diagnosis after certain injuries. Thanks to the application of the Doppler method, it also facilitates the diagnostics of pathologies within the spleen's vessels. CASE REPORT: This paper presents six different cases of focal lesions in the spleen, including lesions in the course of histiocytosis, in the course of sarcoidosis, as well as isolated abscesses of the spleen. The authors also present the case of a spleen with numerous metastatic lesions, the case of a near-splenic cyst, and the case of asymptomatic focal lesions of unknown origin. In all the presented cases, the lesions were accidentally revealed during ultrasonographic examination, which was the starting point for further diagnostics. CONCLUSIONS: Though rare, morphologic lesions in the spleen should always be taken into consideration when performing a routine ultrasonographic examination of the abdominal cavity, and the organ itself should not be ignored. US is a widely available, noninvasive, and useful method for diagnosing splenic abnormalities, including focal changes.

[CD20 antigen of Hodgkin and Reed-Sternberg cells as possible prognostic factor in patients with Hodgkin's lymphoma--preliminary reports]. / Antygen CD20 komórek Hodgkina i Reed-Sternberga jako potencjalny czynnik prognostyczny u chorych na chloniaka Hodgkina--doniesienia wstepne.

UNLABELLED: THE AIM of the study was to asses the validity of CD20 expression on H-RS cells as independent prognostic factor in patients with Hodgkin's lymphoma. METHODS: 72 patients (44 men and 28 women) between 15 and 73 y.o. (av. 36,5 y.o) treated in the Department of Oncological Chemotherapy of Silesian Medical Academy (1992-2002) were included in the study. Tissue specimens were immunohistochemically stained with monoclonal antibodies for CD20. RESULTS: Analyzed group was classified according to histological subtype as follows: LP - n = 3, NS - n = 26, MC - n = 23, LR - n = 7 and LD - n = 13. Overall survival (OS) for the group was from 3 to 169 months (av. 64,5), disease free survival (DFS) - 4 to 167 months (av. 44,8) respectively. CD20 expression on H-RS cells was found in 13,9% subjects. Statistically significant difference (p = 0,0001) in DFS has been found between groups with and without CD20 expression. Results of this study are preliminary and should be confirmed in larger prospective studies.

[Nail susceptibility to fungal infections in patients with hypothyroidism and hyperthyroidism]. / Podatnosc paznokci na zakazenie grzybicze u chorych z niedoczynnoscia i nadczynnoscia tarczycy.

Onychomycosis is a frequent disorder in adults. The objective of the study was evaluation of finger and toe nails susceptibility to Candida albicans and a dermatophyte Trichophyton mentagrophytes infection in patients with symptomatic hypothyroidism and hyperthyroidism as compared with healthy persons. The materials comprised finger and toe nails from 23 patients with hypothyroidism (in 8 cases postoperative, and in 15 cases caused by Hashimoto type thyroiditis), and from 27 patients with hyperthyroidism (including 17 cases of Graves-Basedow disease, and 10 with nodular goitre). Nails from 22 healthy persons of similar sex and age distribution served as controls. A significantly more frequent and more intensive than in control group toe nail infection with C. albicans was found in the patients with both hypothyroidism and hyperthyroidism. The enhanced toe nail susceptibility to C. albicans infection did not depend on autoimmunological aetiology of both hypothyroidism and hyperthyroidism.

[Primary lymphoma of the thyroid--diagnostic and treatment problems. The case report]. / Pierwotny chloniak tarczycy--trudnosci diagnostyczne i terapeutyczne. Opis przypadku.

The authors present the case of primary malignant thyroid lymphoma and problems with distinguishing between Hashimoto's thyroiditis and primary thyroid lymphoma. Primary malignant thyroid lymphoma (PMTL) is a rare disease and difficult to diagnose. The appearance of PMTL may be preceded by Hashimoto's thyroiditis. The biopsy is useful but often only surgical treatment allows to establish diagnosis. The treatment of PMTL includes surgical treatment, chemo- and radiotherapy. The prognosis depends on the disease period.

[Endothelin ET-1 in patients with non-toxic nodular goiter]. / Endotelina ET-1 u chorych z wolem guzkowym obojetnym.

Endothelin ET-1 plays an important, however not entirely identified role in physiology and pathology of thyroid gland. The aim of the study was to determine if in patients with non-toxic nodular goiter there is relationship between size of goiter and ET-1 concentration in plasma of peripheral venous blood and plasma of venous blood taken from thyroid vein in patients undergoing strumectomy. The study included 30 patients with non-toxic nodular goiter (29 women and 1 man, mean age 48 year) and 15 healthy persons of control group. In all ET-1 concentration in plasma of venous peripheral blood and T3, T4, TSH serum concentration were estimated using radioimmunologic methods, as well as size of thyroid gland were evaluated in ultrasonography. Patients with nodular goiter underwent strumectomy. During the operation, before strumectomy, blood from thyroid vein was sampled to estimate plasma ET-1 concentration. Patients were divided into two groups: with adenomatous goiter (14 patients) and colloid goiter (16 patients). The goiter size was similar in each group. In all of the groups there was no relationship between goiter size and ET-1 concentration in plasma of peripheral and thyroid vein. Lack of correlation between ET-1 concentration in plasma and goiter size does not exclude possible ET-1 role in goitrogenesis, it suggests that ET-1 may play a role in control of thyroid gland trophic regulation and vascularity as paracrine or autocrine factor. Significantly higher concentration of ET-1 in plasma of thyroid vein in comparison to plasma of peripheral venous blood and positive correlation between ET-1 concentration in thyroid and peripheral plasma were found in both studied groups of patients with goiter and this may speak for increased ET-1 production within the goiter.

[Insulinoma exclusively localized during intraoperative ultrasonography]. / Insulinoma zlokalizowany wylacznie podczas ultrasonografii sródoperacyjnej.

The case of the patient surgically treated for diagnosed pancreatic insulinoma is reported. Pancreatic insulinomas are the most often diagnosed hormonally active tumors of pancreas. They are small in size, localized evenly in the head, body or tail of pancreas. Their precise location is not easy. This case confirms that the preoperative localization of the tumor is very difficult and preoperative image tests often fail. The performance of intraoperative ultrasonography (IOUS) led to the visualization of the tumor and the curative surgery.

[The influence of adrenalectomy on the treatment of arterial hypertension in patients with benign adrenal medullary and cortical tumors]. / Wplyw adrenalektomii na leczenie nadcisnienia tetniczego u chorych z lagodnymi guzami rdzenia i kory nadnerczy.

One of the reasons of secondary arterial hypertension (HA) are pathological lesions of adrenal glands. The aim of the study was to estimate the influence of performed adrenalectomy on the values of arterial blood pressure (RR) in patients with adrenal tumours and HA observed at least one year after surgical treatment. Data of 54 patients were analysed. Hormonal activity of adrenal tumours was diagnosed in 57.4% of patients. 83.3% of patients underwent unilateral and 16.7% bilateral adrenalectomy. Pathological examination revealed the presence of pheochromocytoma in 14.8% of patients, adenoma in 59.3% and hyperplasia in 25.9%. The observation time was 43.0 +/- 21.3 months from the operation. The mean maximal value of SBP measured during the time of observation was significantly lower than observed before surgery and amounted to 152.4 +/- 27.0 mm Hg and DBP 96.6 +/- 17.7 mm Hg. The decrease of maximal value of SBP amounted to 52.7 +/- 40.9 mm Hg and DBP 26.8 +/- 24.8 mm Hg. In 87.0% of patients performed surgery caused that symptoms of the disease accompanying HA regressed or decreased, and in 72.2% allowed to reduce the number and doses of antihypertensive drugs. Surgical excision of adrenal tumours in patients with pheochromocytoma as well as with Conn and Cushing syndrome leads to significant reduction of maximal RR values. In patients without confirmation of hormone activity of the tumour qualification to the surgical treatment should be based on clinical symptoms accompanying HA as well as on the size of the tumour.