Macro-GH - A clinical entity causing a diagnostic challenge - A case report.

AIM: Presentation of a new case of a patient with macro-GH, that may interfere with different GH assays leading to false-positive results in serum samples. CASE PRESENTATION: A 61-year-old female was referred with a pituitary macroadenoma and elevated growth hormone levels. The laboratory tests showed increased fasting GH level, measured by a sandwich chemiluminescence immunoassay (LIAISON® XL) without suppression on oral glucose tolerance test and normal IGF-1. The patient did not have the typical signs and symptoms of acromegaly. The patient underwent a transsphenoidal resection of a pituitary tumor, showing only α-subunit immunostaining. Postoperative GH levels remained elevated. An interference in the determination of GH level was suspected. GH was analyzed by three different immunoassays, UniCel DxI 600, Cobas e411 and hGH-IRMA. Heterophilic antibodies and rheumatoid factor were not detected in serum sample. GH recovery after precipitation with 25 % polyethylene glycol (PEG) was 12 %. Size-exclusion chromatography confirmed the presence of macro-GH in serum sample. CONCLUSION: If results of laboratory tests are not consistent with the clinical findings, the presence of an interference within immunochemical assays could be suspected. To identify interference caused by the macro-GH, the PEG method and size-exclusion chromatography should be used.

Therapeutic plasma exchange with albumin as a valuable method of preparing thyrotoxic patients for a life-saving thyroidectomy.

Hyperthyroidism affects approximately 1.2% of the population and its routine treatment includes antithyroid drugs (ATDs), radioiodine and surgery. Management of patients with resistance or contraindications to ATDs who require thyroidectomy may be challenging. We present the experience of our department in preparing thyrotoxic patients for life-saving thyroidectomy by using therapeutic plasma exchange (TPE) with albumin: one patient with Graves' disease and previous history of agranulocytosis and cholestatic jaundice after ATDs and two patients with amiodarone-induced thyrotoxicosis. Five to six TPEs were applied to each patient resulting in a decrease of fT3 by 57% to 83%, fT4 by 21% to 60% and decrease/normalization of total thyroid hormones. All patients underwent surgery successfully. In case of drug-resistant thyrotoxicosis or contraindications to ATDs, TPE can be a valuable tool in preparing patients for surgery. Albumin used as a replacement fluid appears to be effective in ameliorating clinical and laboratory symptoms of thyrotoxicosis.

Epstein-Barr Virus and Human Adenovirus Viremia in Renal Tumors Is Associated with Histological Features of Malignancy.

BACKGROUND: There is growing evidence that viral infections may impact the risk and clinical course of malignancies, including solid tumors. The aim of this study was to assess the possible association of selected chronic/latent viral infections with the clinical course of renal cell carcinoma (RCC). METHODS: In this prospective study we enrolled 27 patients undergoing partial or radical nephrectomy due to the histologically confirmed RCC and followed them up for one year post-operation. Isolation of the nucleic acids was performed using the NucleoSpin Tissue Kit (Macherey-Nagel, Düren, Germany) from tumor tissue and using the EZ1 Virus Mini Kit v2.0 from plasma. The number of viral copies of human adenovirus (ADV), herpes simplex virus HSV-1 and HSV-2, Epstein-Barr virus (EBV), cytomegalovirus (CMV), BK virus (BKV) and John Cunningham virus (JCV) in the tissue and plasma was assessed with real-time PCR. RESULTS: Viral infections were diagnosed in ten patients (37.0%), including three ADV cases (11.1%) and eight EBV cases (29.6%). Infected patients tended to be significantly older (71.3 vs. 57.6 years, p < 0.05), more commonly presented with chronic renal disease (OR 2.4, p < 0.05), diabetes (OR 4.2, p < 0.05) and overweight (OR 2.0, p < 0.05). Regarding oncological data, infected patients were found to have a higher rate of high-grade cancers (OR 5.0, p < 0.05) and a higher rate of papillary RCCs (OR 8.3, p < 0.05). Status of viral infections had no influence on the clinical cancer stage, surgical procedure or survival. CONCLUSIONS: EBV and ADV infections are common in renal cancer patients and increase the risk of high-grade RCC presence. While there is no significant impact on short term survival, further studies are needed to assess the relevance of these findings in a long run.

Comparison of chromogranin A (CgA) levels in serum and plasma (EDTA2K) and the respective reference ranges in healthy males.

INTRODUCTION: Chromogranin A (CgA) is a major, nonspecific marker of neuroendocrine tumours (NET). There are a few routinely used assays for the measurement of CgA concentration in serum or plasma. These assays differ in analytical techniques (radioimmunoassay, ELISA, CLIA, TRACE), have different calibrators, and use different antibodies which recognise different epitopes of CgA molecule. Our study was designed to confirm the noted earlier differences in CgA levels measured in serum and plasma, and to establish respective reference ranges in a group of healthy males. MATERIAL AND METHODS: In 145 male blood donors (age 19-61 years, mean = 35.7), blood was collected into two tubes: one with EDTA2K (plasma) and one with clot activator (serum). Chromogranin A was measured by immunoradiometric kit (CIS bio, France). RESULTS: In blood donors, the median (and the range) of CgA concentration were as follows for serum samples - 42.0 ng/mL (16-108 ng/mL) and for plasma (EDTA2K) samples - 58.0 ng/mL (23-153 ng/mL). The differences between serum and plasma ranged 15-75% (median 26%). Plasma CgA levels were significantly higher in relation to serum CgA levels (p < 0.0001). Correlation of CgA in serum and plasma was r = 0.8493; p < 0.01. The reference ranges for CgA measured in serum and plasma in males, expressed as 2.5 to 97.5 percentiles, were: 21.0-108.0 ng/mL and 31.0-153.0 ng/mL respectively. CONCLUSIONS: 1. Significant differences in the concentrations of CgA measured in plasma and in serum demand the application of separate reference ranges adjusted to the type of investigated material. 2. Each laboratory should recommend only one sort of sample material for CgA assay.

Associations of vitamin D concentration with metabolic and hormonal indices in women with polycystic ovary syndrome presenting abdominal and gynoidal type of obesity.

GOAL: The aim of the study was to estimate potential associations of vitamin D concentration with metabolic and hormonal indices in women with polycystic ovary syndrome (PCOS) presenting abdominal and gynoidal type of obesity. MATERIAL AND METHODS: Twenty-six women with PCOS (19-49 years old, BMI: 26.8-53.8 kg/m2), presenting predominantly abdominal and gynoidal type of obesity were recruited. Anthropometric measures, body composition using dual-energy absorptiometry, fasting serum 25-hydroxyvitamin D, leptin, glucose, insulin, homeostatic model of assessment (HOMA), lipids, androgens and sex hormone-binding globulin (SHGB) were estimated. RESULTS: Vitamin D insufficiency was found in 2, and deficiency or deep deficiency in 12 patients. Levels of vitamin D were lower in obese than non-obese women, and in patients with abdominal as compared to gynoidal obesity (9.60±3.7 vs. 16.02±3.3 ng/mL, p<0.04). In obese women, vitamin D correlated negatively with all, except for gynoidal fat, measures of obesity fasting glucose levels, and HOMA. No correlations with androgens were found. In women with abdominal obesity vitamin D correlated with luteinizing hormone/follicle-stimulating hormone ratio (LH/FSH) and SHBG. CONCLUSIONS: We demonstrated that women with PCOS are often vitamin D deficient. Its concentration was lower in patients with predominantly abdominal obesity as compared to subjects with gynoidal fat excess. In overweight/obese subjects with PCOS, vitamin D correlated with fasting glucose and HOMA. The correlation with LH/FSH suggests that vitamin D status may contribute to hormonal dysregulation. Further studies are needed to elucidate a potentially different impact of abdominal and subcutaneous fat on vitamin D metabolism.

Phenotype and metabolic disorders in polycystic ovary syndrome.

The polycystic ovary syndrome (PCOS) is one of the most frequent endocrinopathies in women. Its incidence is assessed at 6-8% of the female population in the reproductive age. It is characterised by oligomenorrhea (Oligo), hyperandrogenism (HA), and the presence of polycystic ovaries (PCOs). Carbohydrate and lipid metabolism is being disturbed in many women with PCOS. The pathogenesis of PCOS is still unexplained. Following the main criteria of diagnosis (Rotterdam Consensus 2003), Dewailly, Welt and Pehlivanov divided the patients with PCOS into 4 phenotype groups: A, B, C, and D. In our studies of 93 patients with PCOS, we found (1) the most frequent appearance (60,2%) of the phenotype A [Oligo + HA + PCO]; (2) an increased androstenedione concentration in a group with HA (A, B, C); (3) an increased HOMA-ß and insulin concentration after 30 min an oral 75 g glucose tolerance test (OGTT) in a group of obese women with BMI > 30 kg/m(2); (4) high levels of total testosterone, total cholesterol, and LDL cholesterol concentrations in a group A with classic phenotype of PCOS: Oligo + HA + PCO-increasing the risk of development of cardiovascular diseases, type 2 diabetes, or metabolic syndrome. The average androstenedione concentrations could be a good diagnostic and prognostic parameter.

The differences in chromogranin A (CgA) concentrations measured in serum and in plasma by IRMA and ELISA methods.

INTRODUCTION: Chromogranin A (CgA) is regarded as a major, nonspecific marker of neuroendocrine tumors (NET). Its estimation appears helpful for diagnostic purposes and is particularly useful for monitoring the treatment of NET. It must be kept in mind, however, that various factors, drugs, or coexisting diseases may influence the outcome of CgA measurement in blood. One such analytical factor is the sort of studied biological material, whether it is plasma or serum. The aim of our study was to compare directly the results of CgA concentrations measured in serum and in plasma by IRMA and ELISA. MATERIAL AND METHODS: We analysed 122 samples of EDTA-plasma and 122 samples of serum by IRMA method, 20 samples of EDTAplasma and 20 samples of serum by IRMA and ELISA, 25 heparinised-plasma samples and 25 samples of EDTA-plasma by IRMA and ELISA methods, and 8 EDTA-plasma, heparinised-plasma, and serum samples by IRMA and ELISA. The material for comparative study was obtained during the same blood collection from the same subjects (volunteers and patients with NET). CgA was measured with the use of kits manufactured by CIS bio International (France). RESULTS: CgA concentrations were markedly higher in plasma than in serum. Using the IRMA method, the difference in the CgA range between 10-100 ng/mL approached 20-70% (median 61 v. 42), in the range 101-300 ng/mL--12-60% (median 147 v. 101), and in the CgA range 301-1076 ng/mL--14-40% (median 486 v. 356). The differences between results in serum and plasma using ELISA were similar but slightly smaller. There was no significant difference between CgA levels in EDTA and heparinised-plasma samples, and the results of measurements performed by IRMA and ELISA in most cases were similar. CONCLUSIONS: Referring each individual CgA result to the proposed reference range (or cut-off value) we must take into account whether the measurement is performed in plasma or in serum.

[Evaluation of neutrophils adhesive molecules CD11b/CD18 in the course of photochemotherapy (PUVA) for psoriasis vulgaris]. / Ocena czasteczek adhezyjnych CD11b/CD18 granulocytów obojetnochlonnych w przebiegu fotochemoterapii (PUVA) luszczycy pospolitej.

Psoriasis is a common, chronic dermatological disorder. Inflammatory cells assemble in epidermis in the early stage of acute psoriasis. Accumulation of neutrophils at the site of inflammation depends on the expression of adhesion molecules. A variety of stimuli--mediators or selectins can active CD11b/CD18 molecules on the neutrophils surface. The aim of our study was expression of CD11b/CD18 molecules without and after stimulation by fMLP (formyl-Met-Leu-Phe) in patients with psoriasis vulgaris treated by PUVA. Expression of beta2-integrins was estimated with MFI (mean fluorescence intensity). Neutrophils in patient with acute psoriasis showed an increase in CD11b/CD18 expression. It means about an activation of neutrophils and particular role of those molecules in granulocyte adhesion to epidermis in psoriasis.

[Cytofluorimetric assay for evaluation of CD16 receptor expression and myeloperoxidase (MPO) activity of neutrophils in patients with psoriasis vulgaris treated with PUVA]. / Cytofluorymetryczna ocena ekspresji receptora CD16 oraz aktywnosci mieloperoksydazy (MPO) granulocytów obojetnochlonnych u chorych na luszczyce pospolita, leczonych fotochemoterapia PUVA.

Early histological changes indicate the collecting of neutrophils in the stratum corneum, mainly in the acute psoriasis. Fc gammaRIIIB (CD16) is the specific functional neutrophilic receptor, which is responsible for phagocytosis. Myeloperoxidase (MPO) is granulocyte enzyme playing main role in metabolic activity of neutrophils. We have evaluated CD16 expression and MPO activity of polymorphonuclear granulocytes in the acute psoriasis vulgaris and the influence of photochemotherapy PUVA (psoralen plus ultraviolet light of A wavelength) treatment on these parameters. The expression of CD16 and MPO activity were significantly higher in neutrophils of patients after PUVA.