Anhelli Syrenicz

Association between serum osteocalcin, adiposity and metabolic risk in obese children and adolescents

INTRODUCTION Childhood obesity has been associated with the development of insulin resistance, potentially leading to several metabolic disorders. Osteocalcin has been reported to contribute to the regulation of glucose tolerance and insulin sensitivity. The purpose of this study was to examine the relationship between serum osteocalcin and metabolic risk factors in obese children and adolescents. MATERIAL AND METHODS Age, gender, pubertal stage, adiposity markers (standard deviation score of body mass index: BMI-SDS, percentage of body fat, waist circumference), blood pressure, serum osteocalcin (OC), fasting plasma glucose and insulin, glycated haemoglobin level (HbA1c), insulin resistance estimated by homeostasis model assessment (HOMA-IR), lipid profile, C-reactive protein (CRP), fibrinogen (FB), white blood cell count (WBC) and 25-hydroxyvitamin D (25-OH-D) were evaluated in 142 obese children and adolescents. Stepwise multiple regression analysis was used to determine the relationship between serum osteocalcin and metabolic risk parameters. RESULTS Mean serum osteocalcin level was 72.0 ± 20.5 μg/L (range: 16.8-181.5 µg/L). After adjustment for multiple potential confounders, serum osteocalcin concentration was inversely associated with adiposity markers as well as HOMA-IR, HbA1c, triglycerides, CRP, FB and positively with 25-OH-D and HDL-cholesterol. In stepwise multiple linear regression analysis adjusted for age, gender and pubertal stage, osteocalcin was significantly negatively related to HOMA-IR, triglycerides and waist circumference. CONCLUSIONS Serum osteocalcin concentration is associated with blood markers of dysmetabolic phenotype and measures of adiposity, suggesting that osteocalcin is important not only for bones but also for glucose and fat metabolism as early as during childhood.

Insulin resistance and brain-derived neurotrophic factor levels in chronic kidney disease

Introduction: Insulin resistance is a frequent abnormality in chronic kidney disease (CKD) appearing in early stages. Factors known to promote insulin resistance in CKD patients include disorders of ion and acid–base equilibrium and circulating uremia toxins. Recent research has focused on the central nervous system as the source of the brain-derived neurotrophic factor (BDNF). The aim of our work was to study plasma BDNF concentrations in stage 3 and 4 CKD patients in relationship with insulin resistance and distribution of adipose tissue. Method: Plasma BDNF concentrations were measured in a study group of 31 patients, including a subgroup of 20 non-diabetic subjects. Additionally dual-energy X-ray absorptiometry (DXA) was performed. Homeostatic model assessment of insulin resistance (HOMA-IR) and homeostatic model assessment of B-cell function (HOMA-beta) indices were calculated. Results: Two separate analyses were performed. In the first analysis performed in all 31 CKD patients, there were no correlations between BDNF and: body mass index (BMI), android, gynoid fat distribution, HOMA-IR and HOMA-beta. In the second analysis performed in 20 CKD patients without diabetes, BDNF was negatively related to gynoid fat (Rs = −0.47, P = 0.034) and women revealed significantly lower levels of BDNF than men (P = 0.046). Normotensive patients disclosed significantly higher BDNF levels than hypertensive patients in the whole CKD group (P = 0.039) and in the non-diabetic subgroup (P = 0.028). No correlations between BDNF and eGFR were found. Conclusions: Female sex and arterial hypertension are associated with lower BDNF plasma concentration in CKD patients.

Case report: rare case of infiltration of small lymphocytic B-cell lymphoma in the thyroid gland of female patient with B-cell chronic lymphocytic leukemia (CLL-B/SLL-B)

The article presents a case of 57-year-old woman with the infiltration of rare small lymphocytic B cell lymphoma in the thyroid gland. Initially, the patient was followed-up due to chronic lymphocytic B-cell leukemia diagnosed on the basis of histopathological examination of cervical lymph node. Eight months later, general symptoms occurred along with lymphocytosis and exacerbation of lesions in lymph nodes, and therefore, chemotherapy was started according to COP regimen. After four chemotherapy cycles, further progression of the disease was observed during chemotherapy. Computed tomography (CT) performed at that time showed generalized lymphadenopathy and the presence of an irregular area in left thyroid lobe. On palpation, the thyroid was asymmetrical, with enlarged left lobe and palpable lymph node packages on the left side of the neck. The levels of thyroid hormones and anti-thyroid antibodies were normal. Ultrasound examination of the thyroid gland showed non-homogeneous hypoechogenic structure of the left lobe and complete focal remodeling. Cytological examination of left-lobe lesion obtained during fine needle aspiration biopsy showed multiple small lymphoid cells, suggestive of small lymphocytic lymphoma. To confirm this diagnosis, flow cytometry of the biopsy material sampled from the left lobe was performed showing B cellimmunophenotype: CD19+/CD20+/CD22 dim/FMC-7, CD23+/CD5+, sCD79b-+, CD38-, CD10-, kappa and lambda-/weak reaction. The results of flow cytometry of the thyroid bioptate and blood were nearly identical, confirming leukemic nature of the infiltration in left thyroid lobe. Cytogenetic findings included the presence of 17p deletion (TP53 gene). The patient received immunochemotherapy with alemtuzumab. The progression of the disease occurred in the sixth week of therapy. The treatment was discontinued after 8 weeks due to worsening of patient’s general status. The patient died 15 months after the diagnosis.

Bone mineral density in girls with functional hypothalamic amenorrhea subjected to estroprogestagen treatment – a 4-year prospective study

The aim of this study was to evaluate the effects of 4-year estroprogestagen therapy (EP) on the bone mineral density (BMD) of 16- to 17-year-old girls with functional hypothalamic amenorrhea (FHA, n = 78). Baseline values of hormonal parameters, bone fraction of alkaline phosphatase (BALP), and cross-linked n-telopeptide of type I collagen (Ntx) were taken along with BMD measurements. Follow-up measurements of laboratory parameters were performed after 6 months of EP treatment. BMD was measured on a yearly basis. Six-month treatment resulted in a marked increase in estradiol levels and a significant decrease in BALP and Ntx. The relative increase in BMD was highest after the second year of treatment. Based on the dynamics of BMD changes during the first year of treatment, we identified a subgroup with no or insignificant reactions to the treatment. It was characterized by significantly higher baseline BMD and markedly lower baseline Ntx compared to the patients who responded to 1-year therapy well or extremely well. Further follow-up proved, however, that this subgroup did not differ significantly in terms of the long-term prognosis for BMD normalization. In conclusion, this study showed that EP therapy is effective in the treatment of BMD disorders associated with FHA.

New insights into the diagnosis of nodular goiter.

Preoperative diagnostic investigations of nodular goiter are based on two main examinations: ultrasonography of the thyroid gland and ultrasound-guided fine-needle aspiration biopsy. So far, FNAB has been the best method for the differentiation of nodules, but in some cases it fails to produce a conclusive diagnosis. Some of the biopsies do not provide enough material to establish the diagnosis, in some other biopsies cytological picture is inconclusive.Determining the eligibility of thyroid focal lesions for surgery has been more and more often done with molecular methods. The most common genetic changes leading to the development of thyroid cancer include mutations, translocations and amplifications of genes, disturbances in gene methylation and dysregulation of microRNA. The mutations of Ras proto-oncogenes and BRAF gene as well as disturbances of DNA methylation in promoter regions of genes regulating cell cycle (e.g. hypermethylation of RASSF1A gene and TIMP-3 gene) play an important role in the process of neoplastic transformation of thyreocyte. The advances in molecular biology made it possible to investigate these genetic disturbances in DNA and/or RNA from peripheral blood, postoperative thyroid tissue material and cytology specimens obtained through fine-needle aspiration biopsy of focal lesions in the thyroid gland.As it became possible to analyze the mutations and methylation of genes from cell material obtained through fine-needle aspiration biopsy, it would be beneficial to introduce the techniques of molecular biology in the pre-operative diagnosis of nodular goiter as a valuable method, complementary to ultrasonography and FNAB. The knowledge obtained from molecular studies might help to determine the frequency of follow-up investigations in patients with nodular goiter and to select patients potentially at risk of developing thyroid cancer, which would facilitate their qualification for earlier strumectomy.

Successful outcome of pregnancy complicated by Werner's syndrome

Werners syndrome is an extremely rare genetic disorder of the autosomal recessive type, characterized by features suggesting premature aging in young adulthood. Because of the concomitant hypogonadism, pregnancy among patients with Werners syndrome occurs extremely rarely. We present a case of a successful outcome of pregnancy complicated by Werners syndrome in a 34-year-old primigravida. The reason for early delivery by caesarean section, at 34th week of pregnancy, was exacerbation of coronary symptoms, with early signs of cardiac insufficiency. A healthy female child was born in a good condition, with birth weight of 1950 g.

The Common C49620T Polymorphism in the Sulfonylurea Receptor Gene SUR1 (ABCC8) in Patients with Gestational Diabetes and Subsequent Glucose Metabolism Abnormalities

Aim. The aim of this study is to investigate the relationship between the common C49620T polymorphism in the sulfonylurea receptor (SUR1) gene and glucose metabolism, β-cell secretory function and insulin resistance in women with a history of gestational diabetes (GDM). Material and Methods. Study group included 199 women, diagnosed GDM within the last 5–12 years and control group of comparable 50 women in whom GDM was excluded during pregnancy. Blood glucose and insulin levels were measured during oral glucose tolerance test. Indices of insulin resistance (HOMA-IR) and β-cell function (HOMA %B) were calculated. In all patients, the C49620T polymorphism in intron 15 of the SUR1 gene was determined. Results. The distribution of the studied polymorphism in the two groups did not differ from each other (χ 2 = 0.34, P = 0.8425). No association between the distribution of polymorphisms and coexisting glucose metabolism disorders (χ 2 = 7,13, P = 0, 3043) was found. No association was also observed between the polymorphism and HOMA %B or HOMA-IR. Conclusions. The polymorphism C49620T in the SUR1 gene is not associated with insulin resistance and/or insulin secretion in women with a history of GDM and does not affect the development of GDM, or the development of glucose intolerance in the studied population.

PvuII and XbaI polymorphisms of estrogen receptor-α and the results of estroprogestagen therapy in girls with functional hypothalamic amenorrhea – preliminary study

Introduction The aim of this study was the long-term prospective evaluation of the effects of estroprogestagen (EP) therapy on the bone mineral density (BMD) of girls with functional hypothalamic amenorrhea (FHA) carrying various PvuII and XbaI polymorphisms of ER-α. Material and methods Prospective observation included 84 FHA girls and 50 controls. The FHA patients were subjected to 4-year sequential therapy with 17β estradiol (2 mg from the 2nd to 25th day of the menstrual cycle) and dydrogesterone (10 mg from the 16th to the 25th day). Hormonal parameters, serum concentration of the bone fraction of alkaline phosphatase (BALP), urine concentration of cross-linked n-telopeptide of type I collagen (Ntx) and BMD were determined before and after the treatment. Results Six-month treatment resulted in a marked increase in estradiol (p = 0.001), testosterone and prolactin levels (p = 0.01 both) and a significant decrease in BALP and Ntx (p = 0.001 both). Patients with the PP polymorphism had significantly lower baseline BMD compared to carriers of other polymorphic variants of PvuII (p = 0.003). A significant increase in BMD was observed throughout the entire therapy period, with no significant differences in the yearly dynamics of BMD changes observed amongst various polymorphic variants and haplotypes of ER-α. Conclusions The EP therapy is effective in the treatment of BMD disorders associated with FHA, and treatment results do not depend on PvuII and XbaI polymorphisms of ER-α.

Prevalence and Clinical Outcome of CYP21A2 Gene Mutations in Patients with Nonfunctional Adrenal Incidentalomas.

Adrenal tumors, discovered incidentally in approximately 4.5% of imaging procedures, are known as adrenal incidentalomas. Nonclassic congenital adrenal hyperplasia, mild form of 21-hydroxylase deficiency, may lead to the development of adrenocortical tumors. The aim of the study was to evaluate prevalence of the most common nonclassic mutations of CYP21A2 gene in patients with adrenal incidentalomas and investigate possible relationship with clinical outcome. One hundred adult patients with such lesions were enrolled. Clinical, imaging and biochemical evaluation were performed to rule out hormonal overproduction or potential malignancy. All subjects and a control group of 100 neonates were genotyped for P30L, P453S, and V281L mutations of CYP21A2 gene using direct sequencing. Clinical and imaging features as well as hormone levels were analyzed. Heterozygous CYP21A2 gene mutations were detected in 8 subjects but not in the neonates. Thus, the risk of carrying mutant allele was significantly higher in subjects with adrenal tumors (OR=8.7; 95% CI=2.23-389.56; p=0.003). Mean concentrations of renin, basal, and stimulated 17-hydroxyprogesterone were higher and ACTH was lower in the carriers than in the remaining subjects. Furthermore, the carriers had higher incidence of hypertension (100 vs. 52.1%, p=0.008) and diabetes (50 vs. 11.9%, p=0.003). ACTH-stimulated 17-hydroxyprogesterone levels varied widely among the carriers. In summary, prevalence of P30L, P453S, and V281L mutations of CYP21A2 gene is increased in patients with adrenocortical tumors. In these subjects, carrying the analyzed mutant alleles may increase the risk of diabetes and hypertension. ACTH-stimulation test does not satisfactorily predict presence of heterozygous CYP21A2 mutations in patients with adrenal tumors.

Functional hypothalamic amenorrhoea – diagnostic challenges, monitoring, and treatment

Functional hypothalamic amenorrhoea (FHA) is associated with functional inhibition of the hypothalamic-pituitary-ovarian axis. Causes of FHA can be classified into the three groups: 1) stress-related factors, 2) consequences of weight loss and/or underweight, and 3) consequences of physical exercise or practicing sports. Diagnosis of FHA should be based on a history of menstrual disorders. During physical examination, patients with FHA present with secondary and tertiary sex characteristics specific for the pubertal stage preceding development of the condition and with the signs of hypoestrogenism. Laboratory results determine further management of patients with amenorrhea, and thus their correct interpretation is vital for making appropriate therapeutic decisions. Treatment of chronic anovulation, menstrual disorders, and secondary amenorrhea resulting from hypothalamic disorders should be aimed at the elimination of the primary cause, i.e. a decrease in psycho-emotional strain, avoidance of chronic stressors, reduction of physical exercise level, or optimisation of BMI in patients who lose weight. If menses do not resume after a period of six months or primary causative treatment is not possible, neutralisation of hypoestrogenism consequences, especially unfavourable effects on bone metabolism, become the main issue. Previous studies have shown that oestroprogestagen therapy is useful in both the treatment of menstrual disorders and normalisation of bone mineral density. Hormonal preparations should be introduced into therapeutic protocol on an individualised basis.