Krzysztof Sworczak

Role of adipokines in complications related to obesity. A review

Worldwide, the prevalence of overweight and obesity and associated complications is increasing. Cardiovascular complications are the most important factor determining survival and influencing clinical management. However, obesity is also associated with an increased risk of metabolic syndrome, type 2 diabetes, cancer and other diseases. The development of complications depends on the amount of body fat and its endocrine function. The hormones (leptin, adiponectin, resistin) and cytokines (TNF alpha, IL-6, PAI-1) produced by the adipose tissue are the link between obesity and obesity-related complications. The present article discusses the structure, function and clinical significance of adipokines.

Urine metabolomics analysis for adrenal incidentaloma activity detection and biomarker discovery

This study describes the development of a method suitable for the analysis of nineteen major urinary steroid metabolites in human urine. The analytes of interest were isolated from urine using solid phase extraction, subjected to enzymatic hydrolysis and again extracted applying solid phase extraction. After derivatization, methyloxime-trimethylsilyl ether derivatives of steroid hormones were identified by gas chromatography-mass spectrometry (GC/MS) and quantified by gas chromatography with flame ionization detector (GC/FID). The quantification method was validated for linearity, trueness, precision and selectivity. The limits of detection were between 6.2 and 7.2 ng/mL and limits of quantification were between 12.3 and 14.8 ng/mL. The established method was applied to analyze 28 urine samples from patients diagnosed with non-functioning adrenal incidentalomas (AIs) and 30 healthy subjects. Hierarchical cluster analysis (HCA) and principal component analysis (PCA) were employed to visualize the differences between metabolic profiles of patients and the control group and to determine possible markers of AIs activity. Both multivariate methods separated seven patients from the rest of the examined individuals. Five urinary metabolites including α-cortol, tetrahydrocorticosterone, tetrahydrocortisol, allo-tetrahydrocortisol and etiocholanolone were identified as potential biomarkers of pathological adrenal function. The altered metabolites reflected pathological metabolism mainly of cortisol and cortisone. This research proved that metabolomics is a suitable tool for disease research.

Natural Killer Activity and Thyroid Hormone Levels in Young and Elderly Persons

Background: On the basis that (1) multiple interactions exist between the hormonal and immune systems, and (2) aging is accompanied by changes in thyroid hormone metabolism and responsiveness, we postulate that thyroid hormones may be involved in the observed decrease in natural killer (NK) activity in a population of apparently healthy elderly subjects. The purpose of the study is to compare NK cytotoxic activity and serum concentrations of TSH and thyroid hormones in healthy old and young people, and to assess in vitro the effects of triiodothyronine (T3) on NK activity. Materials and Methods: Sixteen of the 47 healthy old people (mean age 64 ± 5.2) were classified as optimally healthy, and the remainder as ‘almost healthy’ (according to the criteria of the Senieur protocol) [Ligthart et al., Mech Ageing Dev 1984;28:47–55]; the mean age of the healthy young people was 23.3 ± 2.3 years. NK cytotoxic activity of peripheral blood mononuclear cells was assessed using 51Cr release from K562 target cells. The cutoff level for defining low and high NK responses was set at a value of 20%. Serum concentrations of TSH, total thyroxine (T4) and total triiodothyronine (T3) were measured by radioimmunoassay. Results: NK activity in the ‘optimally healthy’ elderly was high (mean 41 ± 12%, SE), whereas ‘almost healthy’ subjects showed low NK activity (mean 6 ± 5%). Serum T4 and TSH levels, but not T3 concentrations were similar in both the young and old. We observed a significant correlation (r = 0.53, n = 21, p < 0.05) between the serum total T3 level and the NK activity in the elderly individuals. Under in vitro conditions exogenous T3 significantly increased NK activity in the elderly subjects who had serum T3 values at the lower end of the reference range. However, no effect of T3 on NK activity was observed in peripheral blood mononuclear cells obtained from either old or young individuals who had serum T3 levels at the midpoint of the range. Conclusion: Decreased serum concentrations of total T3 may contribute to low NK activity in the ‘almost healthy’ subgroup of the elderly.

PTCSC3 Is Involved in Papillary Thyroid Carcinoma Development by Modulating S100A4 Gene Expression

CONTEXT We previously showed that a long noncoding RNA gene, PTCSC3, located close to the variant rs944289 that predisposes to papillary thyroid carcinoma (PTC) might target the S100A4 gene. OBJECTIVE The aim was to investigate the impact of PTCSC3 on S100A4 expression and its role in cancer development. DESIGN S100A4 abundance was analyzed by quantitative PCR (qPCR) in unaffected and tumor tissue from n = 73 PTC patients. The expression of PTCSC3 and S100A4 was studied in BCPAP and TPC-1 cell lines with forced expression of PTCSC3 by qPCR. Expression of S100A4 target genes (VEGF and MMP-9) was studied in the BCPAP cell line with forced expression of PTCSC3 by qPCR, reverse transcriptase PCR, and Western blot. The impact of PTCSC3 on BCPAP motility and invasiveness was analyzed by the Transwell and Matrigel assays, respectively. SETTING This was a laboratory-based study using cells from clinical samples and thyroid cancer cell lines. MAIN OUTCOME AND MEASURE We aimed to find evidence for a link between the expression of PTCSC3 and thyroid carcinogenesis. RESULTS Expression data from PTC cell lines pinpointed S100A4 as the most significantly downregulated gene in the presence of PTCSC3. S100A4 was upregulated in tumor tissue (P = 9.33 × 10(-7)) while PTCSC3 was strongly downregulated (P = 2.2 × 10(-16)). S100A4 transcription was moderately correlated with PTCSC3 expression in unaffected thyroid tissue (r = 0.429, P = .0001), and strongly in unaffected tissue of patients with the risk allele of rs944289 (r = 0.685, P = 7.88 × 10(-5)). S100A4, VEGF, and MMP-9 were suppressed in the presence of PTCSC3 (P = .0051, P = .0090, and P =.0037, respectively). PTC cells expressing PTCSC3 showed reduction in motility and invasiveness (P = 4.52 × 10(-5) and P = 1.0 × 10(-4), respectively). CONCLUSIONS PTCSC3 downregulates S100A4, leading to a reduction in cell motility and invasiveness. We propose that PTCSC3 impacts PTC predisposition and carcinogenesis through the S100A4 pathway.

Ectopic ACTH syndrome associated with ovarian steroid-cell tumor

Several cases of ovarian neoplasms resulting in Cushing’s syndrome due to ectopic secretion of ACTH or ectopic secretion of F have been reported. Tumors producing ACTH include adenocarcinoma, androblastoma, Sertoli cell carcinoma, carcinoid tumor and teratoma. Cortisol secretion has been reported in ovarian steroid cell tumor (unclassified steroid cell tumor). We present a case of a 19-year-old woman with Cushing’s syndrome in course of an ovarian steroid cell tumor with ectopic ACTH production. To our knowledge, it is the first reported case of ACTH secreting ovarian steroid cell tumor causing Cushing’s syndrome.

The Role of Immunohistochemistry in Histopathological Diagnostics of Clinically Silent Incidentally Detected Adrenal Masses

BACKGROUND The detectability of adrenal incidentalomas (incidentally found adrenal tumours) in the whole population is estimated at 0.1%; 0.42% in non-endocrine patients and at 4.3% in oncologically diagnosed ones. Even up to 16% of incidentalomas of adrenal glands can be malignant lesions. The issue of crucial importance is the histopathological differentiation between benign lesions and malignant tumours of the adrenal cortex and medulla. OBJECTIVES To evaluate whether the immunohistochemical analysis of the expression of p53, p21, PCNA and Ki67 in the tumours tissue can be useful in the histopathological diagnostics of adrenal incidentalomas and whether it is important for prognosis. MATERIAL AND METHODS Our series consisted of 74 tumour samples from 164 patients operated for incidentalomas. There were 43 cortical adenomas, 11 cortical adrenocarcinomas and 20 PHEOs (including 5 malignant lesions). Using monoclonal antibodies, the expression of p53, p21, PCNA and Ki67 was evaluated. RESULTS We found a statistically significant correlation between the expression of p53, p21, Ki67 and the differential diagnosis of adrenal cortical adenoma and adrenocortical carcinoma (for proteins: p53 p=0.010, for p21 p=0.010, for Ki67 p<0.001). The statistical significant correlation between PCNA protein and diagnosis of adrenal cortical adenoma and adrenocortical carcinoma was not found. The statistically significant correlation between p21, PCNA proteins and the diagnosis of benign and malignant PHEOs was not estimated. There was no expression of Ki67 or p53 protein above the assumed level in benign and malignant pheochromocytomas. The statistically significant correlation between p53, p21, PCNA or Ki67 and the occurrence of metastases in adrenocarcinoma and malignant PHEOs was not found.

Vitamin D deficiency during winter months among an adult, predominantly urban, population in northern Poland

INTRODUCTION Vitamin D is vital in the regulation of the calcium-phosphate metabolism, has a direct impact on the musculoskeletal system, and also affects numerous other systems. Widespread vitamin D deficiency and its detrimental effect on health have been reported globally. Data concerning vitamin D status in Polish adult population is scarce. MATERIAL AND METHODS Ambulatory patients of an outpatient clinic in Gdańsk were included in the study. Serum concentrations of 25(OH) D, parathyroid hormone (PTH), alkaline phosphatase (ALP), calcium and phosphorus were determined. In a questionnaire declared UVB exposure, dietary vitamin D and calcium intake, and health status of the subjects were assessed. Non- and parametric tests, logistic regression and population attributable risk were applied in data analysis. RESULTS 448 adults were examined from February to mid-April 2012, 305 women and 143 men, aged 19 to 86 (mean 46.3 ± 14.9 years). Mean 25-hydroxyvitamin D concentration was 14.3 ± 6.6 ng/mL. 84.4% of subjects were vitamin D deficient (25(OH)D < 20 ng/mL); 13.2% presented insufficient (20-30 ng/mL), and 2.5% (or 11 subjects) sufficient 25(OH)D concentrations. Significantly higher 25(OH)D concentrations were found in subjects who reported more UVB exposure, supplemented vitamin D orally and those who declared more physical activity. 21% of subjects had elevated serum PTH concentration (i.e. > 62 pg/mL); mean parathormone was 48.6 ± 25.2 pg/mL. A linear correlation was found between the logarithm of PTH and logarithm of 25(OH)D concentrations (r = -0.21, p < 0.001). CONCLUSIONS Results obtained here demonstrate the necessity of implementing a monitoring and prophylaxis programme of vitamin D deficiency in Poland.

Ovarian thecoma with androgenic manifestations in a postmenopausal woman

A 50-year-old woman, who presented with progressive androgenization, central obesity and severe hypertension, was initially suspected to have an adrenal virilizing tumor. Her serum testosterone level was in the male range (9.3–11.6 ng/ml) and was not suppressed with dexamethasone. Although no pathological abdominal or pelvic mass was detected, total hysterectomy and bilateral salpingo-oophorectomy was performed. Histopathological examination revealed a theca-cell tumor of the right ovary. Postoperatively the testosterone level returned to normal and the patient had regression of virilism. Our case illustrates that a virilizing ovarian tumor can be small and elude imaging studies, but may be detected by means of well-considered clinical management.

The estimation of selected endogenous anticoagulation system parameters in patients with subclinical Cushing's syndrome

OBJECTIVE An increased tendency towards thromboembolic events is observed in patients with Cushings syndrome. There are much fewer publications available about thromboembolic complications in patients with subclinical Cushings syndrome (SCS). Therefore, a question arises whether hemostatic disturbances appear in this particular disease phase. AIM OF STUDY Estimation of protein C (PC), free protein S (FPS), antithrombin (AT) activity, thrombomodulin (TM) concentration and activated PC resistance (APCR) in patients with SCS. MATERIALS AND METHODS We studied 35 patients with SCS. The control group consisted of 33 healthy volunteers. The activity of PC, AT, FPS, APCR and the concentration of TM was estimated in all representatives. RESULTS The comparison of the examined coagulation parameters between the patients with SCS and the healthy individuals revealed significantly higher mean PC activity and mean FPS activity in the SCS group. Mean TM concentration was significantly lower in patients with SCS compared with the control group. The differences in APCR and AT activity were not significant. We did not prove any statistically significant correlations between the examined coagulation parameters and hormonal parameters. We did not find any correlation between the concentration of cortisol and basic coagulation parameters such as international normalized ratio, activated partial thromboplastin time or fibrinogen in the group with SCS either. CONCLUSIONS The patients with SCS present disturbances in endogenous anticoagulation system defined as PC, FPS activity and TM concentration. This finding suggests an impact of mild autonomic cortisol overproduction on coagulation system.

Paraneoplastic syndromes in olfactory neuroblastoma

Olfactory neuroblastoma (ONB) is a rare malignant neoplasm of sinonasal tract, derived from olfactory epithelium. Unilateral nasal obstruction, epistaxis, sinusitis, and headaches are common symptoms. Olfactory neuroblastoma shows neuroendocrine differentiation and similarly to other neuroendocrine tumors can produce several types of peptic substances and hormones. Excess production of these substances can be responsible for different types of endocrinological paraneoplastic syndromes (PNS). Moreover, besides endocrinological, in ONB may also occur neurological PNS, caused by immune cross-reactivity between tumor and normal host tissues in the nervous system. Paraneoplastic syndromes in ONB include: syndrome of inappropriate ADH secretion (SIADH), ectopic ACTH syndrome (EAS), humoral hypercalcemia of malignancy (HHM), hypertension due to catecholamine secretion by tumor, opsoclonus-myoclonus-ataxia (OMA) and paraneoplastic cerebellar degeneration. Paraneoplastic syndromes in ONB tend to have atypical features, therefore diagnosis may be difficult. In this review, we described initial symptoms, patterns of presentation, treatment and outcome of paraneoplastic syndromes in ONB, reported in the literature.