Serum secreted frizzled-related protein 5 in relation to insulin sensitivity and its regulation by insulin and free fatty acids.

PURPOSE: Secreted frizzled-related protein 5 (SFRP5) is an adipokine, which acts as an inhibitor of noncanonical WNT signaling pathway. It has been suggested to exert anti-inflammatory and insulin-sensitizing effects, however, contradictory data has also been reported. The aim of this study was to assess serum SFRP5 concentration in a young healthy population in relation to insulin sensitivity and its regulation by hyperinsulinemia and/or serum free fatty acids (FFA) elevation. METHODS: We examined 150 healthy subjects (83 normal-weight and 67 overweight/obese). Insulin sensitivity (M) was measured with hyperinsulinemic-euglycemic clamp. In 20 male subjects, clamp was prolonged to 6 h and after 1 week another clamp with the concurrent Intralipid/heparin infusion was performed. Independent group of 10 male subjects received infusions of Intralipid/heparin or saline in 1-week interval. RESULTS: Baseline SFRP5 was lower in the overweight/obese group (p = 0.01) and was positively associated with M (r = 0.23, p = 0.006) and serum adiponectin (r = 0.55, p < 0.001) and negatively with BMI (r = -0.18, p = 0.03). In multiple regression analysis, adiponectin was independently associated with SFRP5. Insulin infusion resulted in a decrease in serum SFRP5, both at 120' (p = 0.02) and 360' (p = 0.031). This effect was not observed during the clamp with Intralipid/heparin as well as during Intralipid/heparin alone or saline infusions. CONCLUSIONS: The relation between SFRP5 and insulin sensitivity is mainly dependent on adiponectin. FFA abolish a decrease in circulating SFRP5 caused by insulin, but Intralipid/heparin infusion alone does not regulate SFRP5 concentration. Insulin seems to be more important factor in the regulation of circulating SFRP5 levels than FFA.

Expression of zinc transporter 8 in thyroid tissues from patients with immune and non-immune thyroid diseases.

INTRODUCTION: Recent studies have revealed the presence of zinc and the expression of zinc transporter (ZnT) family members in most endocrine cell types. It was demonstrated that ZnT family plays an important role in the synthesis and secretion of many hormones. Moreover, recently ZnT8 was described as a newly islet autoantigen in type 1 diabetes. MATERIALS AND METHODS: We studied the expression of ZnT8 transporter in thyroid tissues from patients with immune and non-immune thyroid diseases. The study was performed in thyroid tissues after thyroidectomy from patients with thyroid non-toxic nodular goitre (NTNG; n = 17, mean age 15.8 ± 2.2 years) and cases with Graves' disease (n = 20, mean age 15.6 ± 2.8). In our study we investigated the expression of ZnT8 in human thyroid tissues from patients with immune and non-immune thyroid diseases using immunohistochemistry, Western Blot as well as immunofluorescence analyses. To the best of our knowledge, this is the first investigation which identified ZnT8 protein expression in human thyroid tissues, moreover, confirmed by three different laboratory techniques. Results and Conclusions Expression of ZnT8 transporter was identified by immunohistochemistry in the thyroid tissues from paediatric patients with Graves' disease (on +++) and non-toxic nodular goitre (on ++). ZnT8 transporter expression was found both in thyroid follicular cells (within the cytoplasm and cytoplasmic membrane in follicular cells) and C cells (membrane-cytoplasmic reaction) in fluorescence. Predominant expression of ZnT8 in band 41 kDa in immune than in non-immune thyroid disorders may suggest potential role of ZnT8 as a new thyroid autoanitgen but it requires further study on a larger cohort.

Analysis of diabetes-associated autoantibodies in children and adolescents with autoimmune thyroid diseases.

Background Zinc transporter 8 autoantibodies (ZnT8Abs) together with glutamic acid decarboxylase autoantibodies (GADAbs), insulinoma antigen 2 autoantibodies (IA-2Abs) and insulin autoantibodies (IAbs) are markers of type 1 diabetes mellitus (T1DM). We studied the prevalence of ZnT8Ab in children with autoimmune thyroid diseases (AITDs) to assess the association of AITDs and T1DM at the serological level. Methods The study groups consisted of 44 children with Graves' disease (GD), 65 children with Hashimoto's thyroiditis (HT), 199 children with T1DM with or without AITDs and 58 control children. ZnT8Ab, GADAb, IA-2Ab, IAb, 21-hydroxylase autoantibodies (21-OHAbs) and acetylcholine receptor autoantibodies (AChRAbs) were measured. Results ZnT8Abs were found in 4/44 (9.1%) patients with GD, and 4/44 (9.1%) patients with GD were positive for GADAb. Of the 65 HT patients, six (9.2%) were positive for ZnT8Ab, while four (6.2%) were positive for GADAb. In the T1DM group, 128/199 (64%) of the patients were positive for ZnT8Ab, 133/199 (67%) for GADAb and 109/199 (55%) for IA-2Ab. One GD patient and one HT patient were positive for all the four diabetes-associated autoantibodies. Two HT patients were positive for three diabetes autoantibodies. Two GD (4.5%) and five HT (7.7%) patients were positive for 21-OHAb only. None of the patients had AChRAb. In the control group, 2/58 (3.4%) were positive for GADAb and 2/58 (3.4%) were positive for ZnT8Ab. Conclusions Diabetes-associated autoantibodies including ZnT8Ab were found in children and adolescents with GD and HT.

Analysis of chosen polymorphisms rs2476601 a/G - PTPN22, rs1990760 C/T - IFIH1, rs179247 a/G - TSHR in pathogenesis of autoimmune thyroid diseases in children.

BACKGROUND: Autoimmune thyroid diseases are multifactorial diseases with a genetic susceptibility and environmental factors. A potential role of the protein tyrosine phosphatase non-receptor type 22 (PTPN22) gene, the interferon-induced helicase domain 1 (IFIH1) gene, the thyroid-stimulating hormone receptor (TSHR) gene polymorphisms on autoimmune thyroid diseases (AITDs) in adults has been established unequivocally, but there is still lack of research articles including group of children. Objective and hypotheses: To estimate the association of polymorphisms of PTPN22, IFIH1 and TSH-R genes with the pre-disposition to Graves' disease (GD) and Hashimoto's thyroiditis (HT) in children. METHODS: The study was performed in 142 patients with GD, 57 with HT and 160 healthy volunteers. The three single-nucleotide polymorphisms (SNPs): rs2476601 - PTPN22, rs1990760 - IFIH1 and rs179247 - TSHR were genotyped by TaqMan SNP genotyping assay using the real-time PCR. RESULTS: Rs2476601 A alleles were more frequent in patients with GD in comparison to healthy subjects (p = .009 with odds ratio [OR] = 2.13). Rs2476601 A alleles were more frequent in patients with HT in comparison to healthy subjects (p = .008, OR = 2.48). Rs1990760 T alleles were more frequent in male patients with GD in comparison to healthy males (p = .003, OR = 3.00). In case of HT patients, rs1990760 T alleles were also more frequent in males compared to healthy subjects (p = .086, OR =2.47). Rs179247 A alleles were more frequent in patients with GD in comparison to healthy subjects (p = 0.039, OR = 1.51). CONCLUSIONS: Rs2476601 A/G, Rs1990760 C/T and Rs179247 A/G polymorphisms could contribute to the development of AITDs in children. The main risk factor for rs2476601 and rs179247 is allele A. In case of rs1990760, the main risk factor is allele T.

Role of the T and B lymphocytes in pathogenesis of autoimmune thyroid diseases.

Autoimmune thyroid disorders (AITD) broadly include Graves' disease and Hashimoto's thyroiditis which are the most common causes of thyroid gland dysfunctions. These disorders develop due to complex interactions between environmental and genetic factors and are characterized by reactivity to self-thyroid antigens due to autoreactive lymphocytes escaping tolerance. Both cell-mediated and humoral responses lead to tissue injury in autoimmune thyroid disease. The differentiation of CD4+ cells in the specific setting of immune mediators (for example cytokines, chemokines) results in differentiation of various T cell subsets. T cell identification has shown a mixed pattern of cytokine production indicating that both subtypes of T helper, Th1 and Th2, responses are involved in all types of AITD. Furthermore, recent studies described T cell subtypes Th17 and Treg which also play an essential role in pathogenesis of AITD. This review will focus on the role of the T regulatory (Treg) and T helper (Th) (especially Th17) lymphocytes, and also of B lymphocytes in AITD pathogenesis. However, we have much more to learn about cellular mechanisms and interactions in AITD before we can develop complete understanding of AITD pathophysiology.

A follow-up history of young man with apparent cortisone reductase deficiency (ACRD) - several years after diagnosis.

INTRODUCTION: Inactivating mutations in the enzyme hexose-6-phosphate dehydrogenase (H6PDH), the enzyme responsible for NADPH generation playing critical role in 11-hydroxysteroid dehydrogenase type 1 (11b-HSD1) activity, cause apparent cortisone reductase deficiency (ACRD). It leads to increased metabolic clearance rate of cortisol due to a defect in cortisone to cortisol conversion by 11b-HSD1. We want to analyse the process of the disease, efficacy of long-lasting treatment with glucocorticoids throughout childhood and adolescence in only male patient with ACRD. CASE PRESENTATION: A 23 year-old male patient was diagnosed with ACRD at the age of 7 years. The clinical manifestation of ACRD was presented by precocious pubarche. His bone age was assessed as 11.5 years old. Blood tests indicated increased the plasma androgen, with elevated 17-hydroxyprogesterone concentration. A steroid profile analysis of a 24-h urine collection showed extremely reduced THF + allo-THF/THE ratio - 0.021 (normal range: 0.7-1.2). Two months of hydrocortisone therapy was ineffective and dexamethasone was administered in initial dose of 0.375 mg/24 h. Next dosage beetwen 0.125 mg/24h and 0.375 mg/24h has been changed depending on the patient's results of laboratory tests and condition. Control laboratory studies indicated suppression of excess adrenal androgen synthesis, but we never got the THF + allo-THF/THE ratio in normal values. He did not develop any serious side effects, although dexamethasone is the most potent adrenal suppression drug. CONCLUSIONS: Hydrocortisone treatment is ineffective in ACRD patients because it was rapidly metabolized to cortisone. We have found the balance between the dexamethasone treatment effects of adrenal suppression and the achievement of full height potential considering the condition of our patient.

Cushing's syndrome in infancy due to ectopic ACTH secretion by a sacro-coccygeal teratoma.

BACKGROUND: Adenocorticotropic hormone (ACTH)-dependent Cushing's syndrome in infancy is extremely rare. We describe the case of a sacro-coccygeal ectopic ACTH-secreting immature teratoma in an infant who also presented the triad of defects characteristic of Currarino syndrome. CASE PRESENTATION: A girl was born with a large immature teratoma in the sacro-coccygeal region associated with anal atresia. At the age of 7 days, the concentration of α-fetoprotein (AFP) was above the age-specific normal range. Two non-radical surgical excisions of the tumour were performed. At the age of 7 months, she developed polyphagia, acne, hirsutism, hypertension and hypokalemia with elevated ACTH and absence of serum cortisol circadian rhythm. Immunostaining of tumour tissue showed ACTH-immunoreactive cells. Due to unsuccessful therapy with ketoconazole and resistance to antihypertensive medications [blood pressure (BP) 210/160 mmHg], metyrapone was administered, which controlled her ACTH and cortisol levels in the normal range. Following further removal of tumour bulk after three operations during the first year of life, there was a decrease of BP to normal values. CONCLUSIONS: A rare case of ectopic ACTH syndrome causing Cushing's syndrome in infancy in the context of Currarino syndrome is reported. Radical surgery has resulted in excision of the tumour and current control of Cushing's syndrome.

Anemia in diabetic kidney disease - underappreciated but still clinically relevant problem.

Anemia is the most common disorder of the blood with iron deficiency being the predominant cause. On the other hand, diabetes prevalence is increasing rapidly. Over time, diabetes can damage the heart, blood vessels, eyes, kidneys, and nerves. Diabetic kidney disease (DKD) may be present in both types 1 and type 2 diabetes mellitus. Anemia is one of the common feature of chronic kidney disease. The epidemiological data on anemia prevalence are limited. In this review data on epidemiology, pathogenesis, complication and treatment of anemia in diabetic kidney disease are presented.