Cardiometabolic Disease Burden and Steroid Excretion in Benign Adrenal Tumors : A Cross-Sectional Multicenter Study.

BACKGROUND: Benign adrenal tumors are commonly discovered on cross-sectional imaging. Mild autonomous cortisol secretion (MACS) is regularly diagnosed, but its effect on cardiometabolic disease in affected persons is ill defined. OBJECTIVE: To determine cardiometabolic disease burden and steroid excretion in persons with benign adrenal tumors with and without MACS. DESIGN: Cross-sectional study. SETTING: 14 endocrine secondary and tertiary care centers (recruitment from 2011 to 2016). PARTICIPANTS: 1305 prospectively recruited persons with benign adrenal tumors. MEASUREMENTS: Cortisol excess was defined by clinical assessment and the 1-mg overnight dexamethasone-suppression test (serum cortisol: <50 nmol/L, nonfunctioning adrenal tumor [NFAT]; 50 to 138 nmol/L, possible MACS [MACS-1]; >138 nmol/L and absence of typical clinical Cushing syndrome [CS] features, definitive MACS [MACS-2]). Net steroid production was assessed by multisteroid profiling of 24-hour urine by tandem mass spectrometry. RESULTS: Of the 1305 participants, 49.7% had NFAT (n = 649; 64.1% women), 34.6% had MACS-1 (n = 451; 67.2% women), 10.7% had MACS-2 (n = 140; 73.6% women), and 5.0% had CS (n = 65; 86.2% women). Prevalence and severity of hypertension were higher in MACS-2 and CS than NFAT (adjusted prevalence ratios [aPRs] for hypertension: MACS-2, 1.15 [95% CI, 1.04 to 1.27], and CS, 1.37 [CI, 1.16 to 1.62]; aPRs for use of ≥3 antihypertensives: MACS-2, 1.31 [CI, 1.02 to 1.68], and CS, 2.22 [CI, 1.62 to 3.05]). Type 2 diabetes was more prevalent in CS than NFAT (aPR, 1.62 [CI, 1.08 to 2.42]) and more likely to require insulin therapy for MACS-2 (aPR, 1.89 [CI, 1.01 to 3.52]) and CS (aPR, 3.06 [CI, 1.60 to 5.85]). Urinary multisteroid profiling revealed an increase in glucocorticoid excretion from NFAT over MACS-1 and MACS-2 to CS, whereas androgen excretion decreased. LIMITATIONS: Cross-sectional design; possible selection bias. CONCLUSION: A cardiometabolic risk condition, MACS predominantly affects women and warrants regular assessment for hypertension and type 2 diabetes. PRIMARY FUNDING SOURCE: Diabetes UK, the European Commission, U.K. Medical Research Council, the U.K. Academy of Medical Sciences, the Wellcome Trust, the U.K. National Institute for Health Research, the U.S. National Institutes of Health, the Claire Khan Trust Fund at University Hospitals Birmingham Charities, and the Mayo Clinic Foundation for Medical Education and Research.

Resistin is Associated with Inflammation and Renal Function, but not with Insulin Resistance in Type 2 Diabetes.

The aim of the study was to investigate the association of adipokines (resistin, leptin and adiponectin) with obesity, insulin resistance (IR) and inflammation in type 2 diabetes mellitus (T2DM). A total of 284 patients with T2DM were included. Concentrations of resistin, leptin, adiponectin, and inflammatory markers [high sensitivity C-reactive protein (hsCRP), tumor necrosis factor α (TNF-α), and interleukin 6 (IL-6)] were measured and homeostatic model assessment for IR (HOMA-IR) index was calculated. Resistin correlated negatively with estimated glomerular filtration rate (eGFR) and positively with hsCRP, TNF-α, IL-6, and white blood cell count (WBC). Leptin correlated positively with HOMA-IR, whereas adiponectin correlated negatively. Leptin also correlated positively with body mass index (BMI), waist circumference, IL-6, WBC and negatively with eGFR. Adiponectin correlated negatively with waist circumference, WBC, and eGFR. Multivariate logistic regression indicated lower eGFR and higher WBC and IL-6 as independent predictive factors of resistin concentration above the upper quartile (CAQ3), whereas female sex and higher BMI and HOMA-IR of leptin CAQ3, and lower HOMA-IR and older age of adiponectin CAQ3. In conclusion, in contrast to leptin and adiponectin, in T2DM patients, resistin is not associated with BMI and IR, but with inflammation and worse kidney function.

Resistin is a prognostic factor for death in type 2 diabetes.

PURPOSE: To investigate the association of leptin, resistin, and tumour necrosis factor α (TNF-α) with prognosis in type 2 diabetes (T2D). METHODS: Analysis included 284 T2D patients. Apart from routine laboratory parameters, baseline leptin, resistin, and TNF-α concentrations were measured. Patients were followed for a median of 5.4 years. The primary endpoint was all-cause death at follow-up. The secondary endpoint was a composite of death, acute coronary syndrome, and stroke or transient ischemic attack. RESULTS: At baseline, median age was 68 years, and 48% of patients were female. Data on the primary endpoint were obtained for all patients: 32 (11%) died during follow-up. Data on the secondary endpoint were available for 230 patients, of whom 45 (20%) reached the secondary endpoint. In univariate analyses, older age, heart failure, lower-glomerular filtration rate, and higher resistin, TNF-α and NT-proBNP concentrations were predictors of the study endpoints. Of these variables, only resistin remained an independent predictor of both study endpoints in multivariate models. In receiver-operating characteristic analysis, area under the curve for resistin was 0.7. Resistin concentration of greater than or equal to 11.4 ng/mL had sensitivity of 41% and specificity of 91% for prediction of death at follow-up (Youden's index). CONCLUSIONS: Higher resistin is associated with reduced survival in T2D, irrespectively of TNF-α. Resistin concentration of above 11 ng/mL indicates T2D patients at an increased risk of unfavourable outcomes. Leptin was not a prognostic factor. These results suggest that in T2D, association of resistin with unfavourable outcomes might, at least in part, result from its pro-inflammatory properties.

Salivary testosterone may not serve as a screening test in the diagnosis of biochemical hyperandrogenism.

AIM: The diagnosis of biochemical hyperandrogenism is still challenging because a set of appropriate, recommended diagnostic tests has not been established. In our study, we aimed to answer the question of whether salivary testosterone is a reliable test to establish the diagnosis of biochemical hyperandrogenism as compared to serum total testosterone (TT) measured either by liquid chromatography-tandem mass spectrometry (LC-MS/MS) or immunoassay and to assess which set of biochemical tests would be the most appropriate for the identification of biochemical hyperandrogenism. METHODS: A total of 39 women, aged 18-45 years, with clinical or biochemical hyperandrogenism and 41 healthy individuals, aged 19-45 years, were enrolled in the study. Salivary testosterone was measured using the Salimetrics test. Serum TT was measured either using the LC-MS/MS method or immunoassay, and dehydroepiandrosterone sulphate (DHEA-S) and androstenedione were measured using LC-MS/MS. RESULTS: In 15 of 17 (88%) patients with elevated serum TT measured by LC-MS/MS and in 14 of 16 (87%) measured with immunoassay, salivary testosterone showed normal levels. In 11 of 39 women (28%) with normal serum testosterone levels, DHEA-S was elevated. All patients with elevated androstenedione presented with an elevated concentration of either serum testosterone or DHEA-S. CONCLUSION: Salivary testosterone measurement may lead to the underdiagnosis of biochemical hyperandrogenism. Both serum testosterone and DHEA-S should be measured in the endocrine work-up toward biochemical hyperandrogenism.

Clinical utility of TSH receptor antibody levels in Graves' orbitopathy: a comparison of two TSH receptor antibody immunoassays.

INTRODUCTION: Thyroid stimulating hormone (TSH) receptor antibodies (TRAB) play a role in the development of Graves' orbitopathy (GO), and measurements of the TRAB level may be helpful in monitoring GO treatment. AIM OF THE STUDY: To assess the correlation of TRAB levels measured with two different assays: third-generation TRAB assay (TRAB Cobas) and novel Immulite assay (TRAB Immulite), in patients with moderate-to-severe GO treated with intravenous glucocorticoid pulse therapy (ivGCs). MATERIAL AND METHODS: Forty patients with active, moderate-to-severe GO underwent clinical and laboratory evaluation before, in the middle, and after ivGCs therapy. The correlation of TRAB levels with GO signs was evaluated. Laboratory and clinical findings were compared according to the response to ivGCs. TRAB concentration was measured with Immulite TSI assay and with Elecsys IMA. RESULTS: All patients were TRAB positive in both assays at the beginning of the treatment. The decrease of both TRAB Immulite and Cobas levels in serum during ivGCs was statistically significant. We observed strong correlation between both TRAB levels before and after ivGCs. There was no statistically significant difference in antibody levels between patients with good response and no response to the treatment. We did not find any correlation between antibody levels and GO features before the therapy, but measurements during ivGCs showed comparable correlation of both TRAB levels with GO activity. CONCLUSIONS: We found similarity between Immulite assay and third-generation TRAB assay in the assessment of patients with GO treated with ivGCs. Both TRAB levels showed comparable correlation with GO activity during ivGCs therapy.

Total testosterone to dihydrotestosterone ratio assessed by LC-MS/MS predicts a worse metabolic profile not only in PCOS patients.

OBJECTIVES: Total testosterone/dihydrotestosterone ratio (TT/DHT) was found to determine metabolic risk in polycystic ovary syndrome (PCOS). The aim of this study was to analyze whether (TT/DHT) may be helpful in predicting metabolic risk not only in PCOS patients but also in healthy women. MATERIAL AND METHODS: Total testosterone (TT), dihydrotestosterone (DHT), androstendione and dehydroepiandrosterone sulphate (DHEA-S) were measured by LC-MS/MS in 36 women with PCOS and in 29 age-matched controls without clinical hyperandrogenism. In all participants, anthropometric data, lipids, adipose tissue percent (%fat), HOMA-IR were also assessed. RESULTS: The studied groups were not different in terms of age, BMI, waist circumference, %fat and HOMA-IR. In the patients group, mean TT and androstendione levels were significantly higher as compared to controls (1.4 nmol/L vs. 1.0 nmol/L, P < 0.001) and (6.6 nmol/L vs. 4.9 nmol/L, P < 0.01), respectively. In the patients group, mean TT/DHT ratio was significantly higher compared to controls (3.6 vs. 2.7, P < 0.01) and correlated with BMI (r = 0.37, P < 0.05), waist circumference (r = 0.44, P < 0.01), %fat (r = 0.30, P < 0.05), as well as with insulin levels (r = 0.38, P < 0.05) and HOMA-IR (r = 0.44, P < 0.05). The association between TT/DHT ratio and unfavorable metabolic parameters was also seen in controls. CONCLUSION: Total testosterone/dihydrotestosterone ratio assessed by LC-MS/MS correlates with a worse metabolic profile not only in PCOS patients, but also in healthy women.

The morning and late-night salivary cortisol ranges for healthy women may be used in pregnancy.

OBJECTIVES: The diagnosis of adrenal dysfunction in pregnancy and in women taking oral contraceptives remains a diagnostic challenge. Salivary cortisol seems to be a useful tool for the diagnosis of Cushing's syndrome and adrenal insufficiency. However, the changes in salivary cortisol concentration in healthy pregnancy are not clearly defined. DESIGN: The aim of our study was to compare diurnal changes in salivary cortisol in healthy pregnant women, healthy controls and women on oral contraceptives. PATIENTS: The study groups consisted of (i) 41 healthy pregnant women, (ii) 42 healthy women and (iii) 12 healthy women on oral contraceptives. MEASUREMENTS: Serum and salivary cortisol in the morning and salivary late-night cortisol were measured with Roche ECLIA cortisol test (Elecsys 2010) in each trimester and postpartum. RESULTS: Despite the elevation of morning serum cortisol in the second and third trimesters of pregnancy, the morning salivary values as well as late-night salivary cortisol throughout all trimesters were not significantly different from control values (P > 0·5). In the postpartum period, the morning and late-night salivary cortisol values were significantly lower than in late pregnancy. The morning and late-night salivary cortisol values in women on contraceptives were also not different from those in the healthy women group. CONCLUSION: The results of our study suggest that reference values for salivary cortisol established for a healthy adult population can be used for pregnant women and women on oral contraceptives in the initial diagnostic testing for Cushing's syndrome and adrenal insufficiency.

HLA DQ2 HAPLOTYPE, EARLY ONSET OF GRAVES DISEASE, AND POSITIVE FAMILY HISTORY OF AUTOIMMUNE DISORDERS ARE RISK FACTORS FOR DEVELOPING CELIAC DISEASE IN PATIENTS WITH GRAVES DISEASE.

OBJECTIVE: The diagnosis of celiac disease (CD) in patients with different autoimmune diseases including Graves disease (GD) remains a challenge. The aims of our study were to: (1) assess the prevalence of CD in Polish patients with GD and (2) evaluate the prevalence of CD in the subgroups of patients with GD divided on the basis of clinical and human leukocyte antigen (HLA) typing criteria. METHODS: The prospective study was conducted at an academic referral center. The study groups consisted of consecutive, euthyroid patients with GD (n = 232) and healthy volunteers without autoimmune thyroid diseases (n = 122). The diagnosis of CD was based on elevated immunoglobulin A autoantibodies to the enzyme tissue transglutaminase (IgA-TTG) and small intestine biopsy findings. RESULTS: CD was diagnosed in 8 patients with GD (3.4%) and 1 healthy volunteer (0.8%). The development of CD in patients with GD was strongly associated with HLA-DQ2 haplotype (as predicted from linkage disequilibria, 14.6% vs. 1.5%, P = .009; odds ratio [OR] = 11.3; 95% confidence interval [CI] 1.3-252.7): 6 patients with CD carried HLA-DRB1(*)03, 1 carried an HLA-DRB1(*)04 allele, and 1 had an HLA-DRB1(*)07/(*)11 genotype. Multivariate analysis showed independent associations between CD and early GD onset (P = .014, OR = 9.6), autoimmunity in family (P = .029, OR = 6.3) and gastroenterologic symptoms (P = .031, OR = 8.1). CONCLUSIONS: The results of our study suggest that serologic screening for CD may be considered in GD patients (1) with the HLA alleles typical for CD, (2) with an early onset of GD, or (3) a family history of autoimmunity. Moreover, the diagnosis of CD should be explored in euthyroid GD patients with nonspecific gastrointestinal symptoms.

LC-MS/MS improves screening towards 21-hydroxylase deficiency.

Basal serum 17OHP measurement remains the first screening step for nonclassic congenital adrenal hyperplasia (NCCAH) and the accuracy of the test is of high value. The aim of this study was to compare the accuracy of immunoassays to LC-MS/MS in the assessment of serum 17OHP and androgens concentration in women with hyperandrogenism and controls. 17OHP, total testosterone, androstendione and DHEA-S were measured in 39 women with clinically and/or biochemically evident hyperandrogenism and in 29 age-matched controls without clinical hyperandrogenism. 17OHP and androgens were measured by immunoassays and by LC-MS/MS. In patients group median 17OHP level measured by immunoassays was significantly higher compared to LC-MS/MS (5.49 nmol/l-ELISA NovaTec® and 3.57 nmol/l-ELISA DRG® versus 1.56 nmol/l-LC-MS/MS p < 0.0001) as well as in the control group (2.58 nmol/l-ELISA DRG® versus 1.14 nmol/l-LC-MS/MS p < 0.0001). Additional, unnecessary diagnostic procedures explaining elevated 17OHP level were undertaken in 85% of patients when NovaTec® test was used, in 50% when ELISA DRG® and in none when LC-MS/MS method was applied. Total testosterone, androstendione and DHEA-S concentrations in the patients and the controls assessed by the immunoassays were also significantly higher compared to LC-MS/MS. LC-MS/MS is more reliable diagnostic tool in the measurement of serum 17OHP and androgens concentrations compared to immunoassays in women with hyperandrogenism.

Younger age, higher body mass index and lower adiponectin concentration predict higher serum thromboxane B2 level in aspirin-treated patients with type 2 diabetes: an observational study.

BACKGROUND: Evidence from the literature suggests diminished acetylsalicylic acid (ASA) treatment efficacy in type 2 diabetes (DM2). High on-aspirin platelet reactivity (HAPR) in DM2 has been linked to poor glycemic and lipid control. However, there are no consistent data on the association between HAPR and insulin resistance or adipose tissue metabolic activity. The aim of this study was to assess the relationship between laboratory response to ASA and metabolic control, insulin resistance and adipokines in DM2. METHODS: A total of 186 DM2 patients treated with oral antidiabetic drugs and receiving 75 mg ASA daily were included in the analysis. Response to ASA was assessed by measuring serum thromboxane B2 (TXB2) concentration and expressed as quartiles of TXB2 level. The achievement of treatment targets in terms of glycemic and lipid control, insulin resistance parameters (including Homeostatic Model Assessment-Insulin Resistance, HOMA-IR, index), and serum concentrations of high-molecular weight (HMW) adiponectin, leptin and resistin, were evaluated in all patients. Univariate and multivariate logistic regression analyses were performed to determine the predictive factors of serum TXB2 concentration above the upper quartile and above the median. RESULTS: Significant trends in age, body mass index (BMI), HOMA-IR, HMW adiponectin concentration, C-reactive protein concentration and the frequency of achieving target triglyceride levels were observed across increasing quartiles of TXB2. In a multivariate analysis, only younger age and higher BMI were independent predictors of TXB2 concentration above the upper quartile, while younger age and lower HMW adiponectin concentration were predictors of TXB2 concentration above the median. CONCLUSIONS: These results suggest that in DM2, the most important predictor of HAPR is younger age. Younger DM2 patients may therefore require total daily ASA doses higher than 75 mg, preferably as a twice-daily regimen, to achieve full therapeutic effect. Higher BMI and lower HMW adiponectin concentration were also associated with less potent ASA effect. This is the first study to demonstrate an association of lower adiponectin concentration with higher serum TXB2 level in patients treated with ASA.

Effect of common single-nucleotide polymorphisms in acetylsalicylic acid metabolic pathway genes on platelet reactivity in patients with diabetes.

BACKGROUND: Platelet reactivity in patients on acetylsalicylic acid (ASA) therapy can be influenced by physiological or pathological conditions affecting ASA pharmacokinetics or pharmacodynamics. The mechanism of such variability in the therapeutic response to ASA, particularly in diabetic patients, is poorly understood. The rate of elimination of ASA and its metabolite, salicylic acid (SA), is likely a major factor determining drug efficacy. The objective of this study was to investigate the effect of genetic polymorphisms in the selected candidate genes within the ASA metabolic pathway on the platelet reactivity and concentration of ASA and thromboxane A(2) (TxA(2)) metabolites in a population of patients with type 2 diabetes mellitus (T2DM). MATERIAL AND METHODS: The study cohort consisted of 287 Caucasians with T2DM who had been taking ASA tablets at the dose of 75 mg per day for at least 3 months. Platelet reactivity analyses were performed using VerifyNow Aspirin and PFA-100 assays. The measured ASA metabolite included salicylic acid (ASA), and TxA(2) metabolites included serum TxB(2) and urinary 11-dh-TxB(2). Genotyping for the selected 18 single-nucleotide polymorphisms (SNPs) within 5 genes of the ASA metabolic pathway was performed using a Sequenom iPLEX platform. RESULTS: No statistically significant association was observed between the investigated SNPs genotypes, platelet reactivity, and measured metabolites in the investigated cohort of patients. CONCLUSIONS: The results of our study failed to confirm that the selected variants in the genes within the ASA metabolic pathway might contribute to platelet reactivity in a diabetic population treated with ASA.

[Assessment of neuropeptide Y, leptin and leptin-receptor concentrations in teenagers suffering from anorexia nervosa]. / Ocena wartosci stezen neuropeptydu Y, leptyny oraz receptora leptyny u nastolatek chorych na anoreksje.

INTRODUCTION: Anorexia nervosa (AN) is the third most common chronic disorder affecting adolescents and is associated with high mortality risk. The predominant symptom of anorexia nervosa is persistent and intentional striving to achieve weight loss initiated and/or sustained by the patient, leading to cachexia. Until now the cause of the condition remains unknown, but seems to be multifactoral. Patients with AN develop multi-organ complications and endocrine disorders affecting multiple disturbances of energy metabolism. Neuropeptide Y and leptin can be found between chemical substances regulating feelings of hunger and satiety. Neuropeptide Y plays the main role in the regulation of energetic homeostasis of the organism, feeding customs, sexual and reproductive functions. Concentration of neuropeptide Y increases during starvation and decreases after feeding. In anorexia nervosa the concentration of neuropeptide Y increases and, by doing that, decreases the excrection of gonadoliberines and gonadotropines. Leptin influences the feeling of hunger and its synthesis takes part, among others, in adiposal tissue. It also influences the menstruation disturbances. Rising leptin concentrations, with accompanying increasing adiposity is known to be the main factor influencing the puberty and the reverse of the malfunction of hypothalamic-pituitary-gonadal axis in malnourished persons. During hunger and low calorie intake, leptin concentration decreases, independently of adiposity. AIM: The main aim of the study was to assess concentrations of neuropeptide Y, leptin and leptin receptor in teenagers treated for anorexia nervosa. MATERIALS AND METHODS: The study was conducted between 2007- 2011 in a group of 45 female teenagers with anorexia nervosa and a control group consisting of 59 healthy regularly menstruating female age peers. Concentrations of leptin, leptin receptor and neuropeptide Y (NPY) have been determined by using immunoenzymatic tests. Blood samples were obtained in fasting state. The Ethics Committee of the Medical University of Lodz approved of the study. RESULTS: There were statistically significant differences between mean values of BMI (14.6 vs. 19.83), median value of leptin concentration (3.79 vs. 12.09), proportions of LEP/BMI (0.1986 vs. 0.5701) in the study group when compared to controls. Higher values were found in the study group if compared to the percentage of body mass insufficiency--(23.09 vs. 3.97), neuropeptide Y concentration--(0.33 vs. 0.19), proportions of NPY/BMI--(0.023 vs. 0.0095), concentration of leptin receptor--(30.25 vs. 19.45), proportions of LR/BMI--(2.1048 vs. 0.9744). CONCLUSIONS: Low concentrations of leptine correlate to high concentrations of leptin receptor. A positive correlation between low body mass index and leptin receptor concentration and proportions of LR to BMI was found. A negative correlation was found between body mass loss and leptin concentration. The increasing concentration of neuropeptide Y, correlated to body mass deficency with existing high concentrations of leptin, could suggest disturbances of their regulatory axis.

Vitamin D insufficiency in healthy pregnant women living in Warsaw.

BACKGROUND/OBJECTIVES: Ensuring the optimal level of 25-hydroxy-vitamin D (250HD) in serum (concentration above 30 ng/ml) is essential for protecting the health of the mother and the developing fetus. Vitamin D plays an important role in maintaining proper bone structure, preventing infections, reducing the risk of premature birth and gestational diabetes. The aim of the study was to verify whether healthy pregnant residents of Warsaw were deficient in vitamin D. MATERIAL AND METHODS: The material consisted of 150 serum samples of 50 healthy women in 1st, 2nd and 3rd trimester of pregnancy 72.7% of the sera were from women who reported taking multivitamin supplements containing vitamin D3 (71% out of that group was taking 400 IU daily). The concentration of 250HD was measured using the vitamin D total assay on Elecsys 2010 automatic analyzer (Roche Diagnostics). RESULTS: The average serum 250HD concentrations of 50 women in 1st, 2nd and 3rd trimester of pregnancy were respectively: 23.1 ng/ml, 24.8 ng/ml, and 25.1 ng/ml, with no statistically significant differences. The optimal levels of 250HD (30-80 ng/ml) were found in 30.0% of samples, hypovitaminosis (20-30 ng/ml) occurred in 38.7%, deficiency (10-20 ng/ml) in 24.0% and severe deficiency (less than 10 ng/ml) in 7.3% of cases. Mean concentration of 250HD in winter season (October 1 - March 31) was 23.6 ng/ml and in summer season (April 1 - September 30) was 25.5 ng/ml, with no statistically significant difference. On the basis of the BMI in 1st trimester two subgroups were distinguished from the studied subjects: BMI <21 (13 patients, 39 samples) and BMI >25 (14 patients, 42 samples). Mean 250HD concentration in these groups were 27.3 and 23.5 ng/ml respectively (p<0.05). High statistical significance (p<0.001) was found among the total number of samples with 250HD deficiency and severe deficiency (<20 ng/ml) and samples with hypovitaminosis and optimal 250HD level (>20 ng/ml) in these groups. CONCLUSIONS: Regardless of trimester and season, vitamin D below the optimal level is a common occurrence during pregnancy and the current level of supplementation among Polish pregnant women appears to be insufficient. Our data suggest that special attention should be paid to the problem of vitamin D insufficiency in overweight pregnant women.

[Iodine supply and thyroid function in the group of healthy pregnant women living in Warsaw]. / Zaopatrzenie wjod oraz czynnosc tarczycy w grupie zdrowych kobiet ciezarnych zamieszkujacych Warszawe.

UNLABELLED: Iodine deficiency and thyroid gland disorders are especially harmful for pregnant women and normal fetal development. After initiation in 1997 of obligatory iodine prophylaxis, Poland has been found since 2003 a country with sufficient delivery of this microelement. However, in the population of pregnant women, slight deficiency of this element still exists. Insufficient iodine supply results in abnormalities of thyroid hormones'biosynthesis. Simultaneously, adaptive changes, occurring in pregnancy, make the proper interpretation of hormone's assays difficult. Lack of normative data for the thyroid hormones concentration in the each pregnancy trimester for Polish population cause additional difficulties in the interpretation of these results. The aim of the study was prospective observation of iodine intake and thyroid function in healthy pregnant women supplemented with 150 pg of iodine daily MATERIALS AND METHODS: 62 healthy pregnant women living in Warsaw in the early weeks of pregnancy, confirmed by ultrasonographic examination, were included to this study. Pregnancies were singleton resulting in birth of healthy neonates. Urinary iodine concentrations (UIC), serum TSH, fT4, fT3, antyTPO, thyroid volume and morphology by the ultrasonography examination were assessed in consecutive trimesters of pregnancy. TSH level was measured in the each newborn. RESULTS: Low urinary iodine concentrations (UIC)-median 96 microg/l was found at the beginning of pregnancy Only in 14% of pregnant women UIC exceeded 150 microg/l. In spite of intended supplementation of at least 150 microg of extra iodine per day, medians of UIC in the next trimesters were 122 microg/l and 129 microg/l, respectively. TSH levels kept reference values for the 1st trimester of pregnancy in 86% of participants and in the next trimesters in 85% and 95%, respectively. Levels of fT4 were within reference range for the women in the 1st trimester. In 2nd trimester 12% and in 3rd trimester 33% of pregnant women had fT4 level below the reference value. Concentrations of fT3 were within reference values during whole pregnancy. Median thyroid volume was respectively 11.12 ml; 13.0 ml and 15.75 ml (range: 6.8-26.8 ml) in subsequent trimesters.Median neonatal' TSH level on the 3rd day of life, as a screening of thyroid insufficiency, was 1.34 mlU/l (range: 0.01-6.6 mlU/l) and in 4.41 % of newborns TSH concentrations were higher than 5 mlU/I. CONCLUSION: Despite the sufficient supply of iodine in the whole population, iodine consumption among the pregnant women is still not satisfactory. The increase of TSH values above the upper reference level for pregnant women in 15% of patients may be related to iodine deficiency. It is important to educate pregnancy planning women about this problem. Our observations confirm the importance of the recommendations that during the pregnancy every woman should receive supplementation of iodine at the minimal amount of 150 microg daily.

Insulin autoimmune syndrome.

Not required for Clinical Vignette.

[Saliva as an alternative diagnostic material in determination of hormone--advantages and limitations]. / Slina jako alternatywny material laboratoryjny dla oznaczen hormonalnych--zalety i ograniczenia.

Saliva can be an excellent alternative diagnostic material in determination of hormone concentration substituting the routinely used serum, plasma and urine. Particularly useful is the measurement of nonconjugated steroid hormones and cyclic amines (melatonin), the concentration of which is not dependent on saliva production, and correlates well with hormone concentration in blood. In routine laboratory diagnostic saliva is mainly used for multiple measurement of hormone concentration (establishing of diurnal cycle, monitoring the function of endocrine system with dynamic tests ex. Synacthen and dexamethasone), monitoring the concentration and metabolism of hormones used as a drugs (hormone replacement therapy) or when the determination of free (bioactive) fraction of hormone is required. Noninvasive saliva collection at patient's home, which does not need medical staff assistance, may reduce the costs of hormonal diagnostics in specialty clinics and hospitals.

Iodine status of pregnant women from central Poland ten years after introduction of iodine prophylaxis programme.

INTRODUCTION: Until 1997, Poland was one of the European countries suffering from mild/moderate iodine deficiency. In 1997, a national iodine prophylaxis programme was implemented based on mandatory iodisation of household salt with 30 ± 10 mg KI/kg salt, obligatory iodisation of neonatal formula with 10 µg KI/100 mL and voluntary supplementation of pregnant and breast-feeding women with additional 100-150 µg of iodine. Our aim in this study was to evaluate the iodine status of pregnant women ten years after iodine prophylaxis was introduced. MATERIAL AND METHODS: A cross-sectional study was undertaken in 100 healthy pregnant women between the fifth and the 38th week of gestation with normal thyroid function, singleton pregnancy, normal course of gestation, without drugs known to influence thyroid function except iodine. Serum TSH, fT(4), fT(3), thyroglobulin (TG), anti-peroxidase antibodies (TPO-Ab), anti-thyroglobulin antibodies (TGAb) and urinary iodine concentration (UIC) were determined. Thyroid volume and structure were evaluated by ultrasonography. RESULTS: Fifty nine per cent of studied pregnant women had a diet rich with iodine carriers and 35% obtained iodine supplements. Twenty eight per cent appeared to have a goitre: 11 diffuse and 17 a nodular one, median goitre volume was 18.7 mL (range 6.8-29.0 mL). Median UIC was 112.6 µg/L (range 36.3-290.3 µg/L), only 28% of women had UIC ≥ 150 µg/L. Median UIC was significantly higher in the group receiving iodine supplements than in the group without iodine supplements: 146.9 µg/L v. 97.3 µg/L respectively, p 〈 0.001. Serum TSH, fT(3) and fT(3)/fT(4) molar ratio increased significantly during pregnancy while fT(4) declined. Median serum TG was normal: 18.3 ng/mL (range 0.4-300.0 ng/mL) and did not differ between trimesters. Neonatal TSH performed on the third day of life as a neonatal screening test for hypothyroidism was normal in each case: median value was 1.49 mIU/L (range 0.01-7.2 mIU/L). Less than 3% (2 out of 68) of results were 〉 5 mIU/L. CONCLUSION: Iodine supplements with 150 µg of iodine should be prescribed for each healthy pregnant woman according to the assumptions of Polish iodine prophylaxis programme to obtain adequate iodine supply. (Pol J Endocrinol 2010; 61 (6): 646-651).

Are adipokines associated with atrial fibrillation in type 2 diabetes?

INTRODUCTION: The potential effect of adipokines on the development of AF is yet to be established. The aim of this study was to investigate the association of baseline serum adipokines with 1) the presence of AF at baseline and 2) future risk of AF development. MATERIAL AND METHODS: The current study is a sub-analysis of the prospective, randomised AVOCADO (Aspirin Vs./Or Clopidogrel in Aspirin-resistant Diabetics inflammation Outcomes) trial. The AVOCADO study included patients with type 2 DM burdened with at least two additional cardiovascular risk factors and receiving acetylsalicylic acid. In patients included in the current analysis adipokines and inflammatory biomarker levels were measured. Information on the subsequent AF diagnosis was collected after a median of 5.4 years of follow-up. RESULTS: A total of 273 patients with type 2 DM (median age 68 years; 52% male) were included in the initial analysis comparing patients with and without AF at baseline. Patients with diagnosed AF (12%) had higher levels of serum resistin [8.5 (5.8-10.5) vs. 6.9 (5.6-8.7) ng/mL; p = 0.034], adiponectin [6.9 (5.6-8.7) vs. 2.7 (1.8-4.2) ng/mL; p = 0.032], and N-terminal pro-B-type natriuretic peptide [336 (148-473) vs. 108 [45-217]; p < 0.001) than non-AF patients. There were no significant differences in serum leptin, IL-6, and TNF-alpha concentrations between the two groups. From subjects without known AF at study entry, 19% developed AF at follow-up. In logistic regression analysis, baseline adipokine levels did not predict AF development. CONCLUSION: In type 2 DM, patients with AF have higher resistin and adiponectin concentrations than patients with no AF. None of the studied adipokines proved a predictor of future AF development.

Urine steroid metabolomics for the differential diagnosis of adrenal incidentalomas in the EURINE-ACT study: a prospective test validation study.

BACKGROUND: Cross-sectional imaging regularly results in incidental discovery of adrenal tumours, requiring exclusion of adrenocortical carcinoma (ACC). However, differentiation is hampered by poor specificity of imaging characteristics. We aimed to validate a urine steroid metabolomics approach, using steroid profiling as the diagnostic basis for ACC. METHODS: We did a prospective multicentre study in adult participants (age ≥18 years) with newly diagnosed adrenal masses. We assessed the accuracy of diagnostic imaging strategies based on maximum tumour diameter (≥4 cm vs <4 cm), imaging characteristics (positive vs negative), and urine steroid metabolomics (low, medium, or high risk of ACC), separately and in combination, using a reference standard of histopathology and follow-up investigations. With respect to imaging characteristics, we also assessed the diagnostic utility of increasing the unenhanced CT tumour attenuation threshold from the recommended 10 Hounsfield units (HU) to 20 HU. FINDINGS: Of 2169 participants recruited between Jan 17, 2011, and July 15, 2016, we included 2017 from 14 specialist centres in 11 countries in the final analysis. 98 (4·9%) had histopathologically or clinically and biochemically confirmed ACC. Tumours with diameters of 4 cm or larger were identified in 488 participants (24·2%), including 96 of the 98 with ACC (positive predictive value [PPV] 19·7%, 95% CI 16·2-23·5). For imaging characteristics, increasing the unenhanced CT tumour attenuation threshold to 20 HU from the recommended 10 HU increased specificity for ACC (80·0% [95% CI 77·9-82·0] vs 64·0% [61·4-66.4]) while maintaining sensitivity (99·0% [94·4-100·0] vs 100·0% [96·3-100·0]; PPV 19·7%, 16·3-23·5). A urine steroid metabolomics result indicating high risk of ACC had a PPV of 34·6% (95% CI 28·6-41·0). When the three tests were combined, in the order of tumour diameter, positive imaging characteristics, and urine steroid metabolomics, 106 (5·3%) participants had the result maximum tumour diameter of 4 cm or larger, positive imaging characteristics (with the 20 HU cutoff), and urine steroid metabolomics indicating high risk of ACC, for which the PPV was 76·4% (95% CI 67·2-84·1). 70 (3·5%) were classified as being at moderate risk of ACC and 1841 (91·3%) at low risk (negative predictive value 99·7%, 99·4-100·0). INTERPRETATION: An unenhanced CT tumour attenuation cutoff of 20 HU should replace that of 10 HU for exclusion of ACC. A triple test strategy of tumour diameter, imaging characteristics, and urine steroid metabolomics improves detection of ACC, which could shorten time to surgery for patients with ACC and help to avoid unnecessary surgery in patients with benign tumours. FUNDING: European Commission, UK Medical Research Council, Wellcome Trust, and UK National Institute for Health Research, US National Institutes of Health, the Claire Khan Trust Fund at University Hospitals Birmingham Charities, and the Mayo Clinic Foundation for Medical Education and Research.

[The role of bone metabolic markers in qualification for treatment of osteoporosis. Results of POMOST study]. / Rola markerów metabolizmu kostnego w kwalifikacji do leczenia osteoporozy. Wyniki programu POMOST.

INTRODUCTION: Increased bone turnover markers (BTM) level is consider as independent risk factor of bone fracture. However, it was not used in 10-year probability of bone fracture method (FRAX) proposed by WHO, which helps in qualification of patients for pharmacological treatment of osteoporosis. The aim of the study was to evaluate the usefulness of BTM in qualification for pharmacological treatment of osteoporosis. MATERIAL AND METHODS: The study was performed in 152 subjects (20 men and 132 women) referred to Krajowe Centrum Osteoporozy. One-hundred thirty two of them were qualified for pharmacological treatment and 20 for prophylaxis on the basis of qualitative method. The following BTM were examined in all patients: of bone formation - N-terminal propeptide of procolagen type I (PINP) and N-mid osteocalcin (OC) and of bone resorption - C-terminal cross-linked telopeptide of collagen type I (CTx). RESULTS: The values over that considered as independent fracture risk (in women only, no data for men) were found in 39 women with PINP, 39 with OC and 41 with CTx. Part of women had decreased serum BTM (10 women 3 BTM and 35 with 1 at least). There were not significant differences in serum BTM depending on the presence of clinical fracture risk factors: osteoporotic fracture in past, osteoporotic hip fracture in parents, chronic treatment with glucocorticosteroids and qualification for pharmacological treatment on the basis of qualitative and FRAX method. There was no significant difference in the presence of fracture risk factors depending on increased or decreased serum BTM. CONCLUSIONS: Results of the study did not show the practical use of BTM in qualification for pharmacological treatment of osteoporosis.