Czynnik wzrostu fibroblastów 21 i jego związek z wrażliwością na insulinę u krewnych pierwszego stopnia chorych na cukrzycę typu 2

  Introduction: Fibroblast growth factor 21 (FGF 21) has been suggested as a predictor for the development of type 2 diabetes mellitus (T2DM). Material and methods: We aimed to determine FGF 21 levels in normoglycaemic (Group 1) and prediabetic (Group 2) first-degree relatives (FDR) of patients with T2DM in comparison with normoglycaemic subjects without a history of T2DM in their FDR (Group 3). Results: There was a significant difference between Group 1, 2, and 3 with respect to plasma FGF 21 concentrations (143.3 ± 93.8, 221.9 ± ± 171.7 and 121.2 ± 119.8 pg/mL, respectively, p = 0.01). FGF 21 levels were significantly increased in prediabetic FDR of patients with T2DM compared to normoglycaemic subjects without a history of T2DM in their FDR (p = 0.02). FGF 21 levels did not differ between normoglycaemic FDR of patients with T2DM and normoglycaemic subjects without a history of T2DM in their FDR (p > 0.05). In the whole group, FGF 21 correlated positively with age (r = 0.31, p = 0.003), BMI (r = 0.38, p < 0.001), systolic blood pressure (r = 0.38, p = 0.001), diastolic blood pressure (r = 0.26, p = 0.02), fasting blood glucose (r = 0.24, p = 0.02), HOMA-IR (r = 0.23, p = 0.03), AUC glucose (r = 0.35, p = 0.001), and AUC insulin (r = 0.32, p = 0.003) and negatively with HDL cholesterol (r = –0.24, p = 0.02) and Matsuda ISI (r = –0.33, p = 0.002). In the regression analysis, BMI was the most predictive factor for FGF 21 levels (beta = 0.41, r2 = 0.17, p < 0.001). Conclusions: We showed that FGF 21 concentrations are increased in prediabetic FDR of patients with T2DM and that there is a significant association between FGF 21 and obesity and insulin sensitivity. (Endokrynol Pol 2016; 67 (3): 260–264)    Wstęp: Sugerowano, że stężenie czynnika wzrostu fibroblastów 21 (FGF 21) jest czynnikiem predykcyjnym rozwoju cukrzycy typu 2 (T2DM). Materiał i metody: Celem badania było ustalenie stężenia FGF 21 u osób z normoglikemią (grupa 1) i ze stanem przedcukrzycowym (grupa 2) będących krewnymi pierwszego stopnia (FDR) chorych na T2DM w porównaniu z osobami z normoglikemią z ujemnym wywiadem rodzinnym w kierunku T2DM (grupa 3). Wyniki: Stwierdzono istotne różnice między grupami 1, 2 i 3 pod względem stężenia FGF 21 w osoczu (odpowiednio 143,3 ± 93,8; 221,9 ± 171,7 i 121,2 ± 119,8 pg/ml; p = 0,01). Stężenia FGF 21 były istotnie wyższe w grupie krewnych pierwszego stopnia chorych na T2DM ze stanem przedcukrzycowym niż u osób z normoglikemią bez dodatniego wywiadu rodzinnego w kierunku T2DM (p = 0,02). Stężenia FGF 21 nie różniły się istotnie między krewnymi pierwszego stopnia chorych na T2DM z normoglikemią a osobami z normoglikemią bez T2DM u krewnych pierwszego stopnia (p > 0,05). W całej badanej grupie stwierdzono dodatnią korelację między stężeniem FGF 21 a wiekiem (r = 0,31; p = 0,003), BMI (r = 0,38; p < 0,001), skurczowym ciśnieniem tętniczym (r = 0,38; p = 0,001), rozkurczowym ciśnieniem tętniczym (r = 0,26; p = 0,02), glikemią na czczo (r = 0,24; p = 0,02), wskaźnikiem HOMA-IR (r = 0,23; p = 0,03), AUC glukozy (r = 0,35; p = 0,001), AUC insuliny (r = 0,32; p = 0,003) oraz ujemną korelację ze stężeniem cholesterolu frakcji HDL (r = –0,24; p = 0,02) i wskaźnikiem ISI według Matsudy (r = –0,33; p = 0,002). W analizie regresji najsilniejszym czynnikiem prognostycznym stężenia FGF 21 był wskaźnik BMI (beta = 0,41; r2 = 0,17; p < 0,001). Wnioski: Podsumowując, autorzy wykazali, że stężenia FGF 21 są zwiększone u krewnych pierwszego stopnia chorych na T2DM ze stanem przedcukrzycowym i że istnieje silny związek między stężeniem FGF 21 a otyłością i wrażliwością na insulinę. (Endokrynol Pol 2016; 67 (3): 260–264)

Detecting the interferences in adrenocorticotropic hormone measurement - three cases reinforcing the efficiency of the complementary clinical and laboratory audit

Highlights Comparing test results to clinical data enhances the identification of interferences Misinterpretation of ACTH as a result of interference may lead to unnecessary testing Despite the interference, ACTH concentration can be in the reference interval Accurate measurement of adrenocorticotropic hormone (ACTH) is crucial in the evaluation of pituitary and adrenal disorders. Although great progress has been achieved in ACTH measurement with immunometric assays, interference may occur and adversely affect the clinical management. The report contributes to compiling the evidence on the clinical challenges with the management of the interferences in the ACTH measurement by presenting three cases: two with clinically overt hypercortisolism and discrepant ACTH concentrations within the reference interval; the third case describes the falsely elevated ACTH in a patient with secondary adrenal insufficiency. In all patients, the results obtained with the two immunometric platforms, chemiluminescence (CLIA) immunoassay (Siemens, Immulite) and electrochemiluminescence (ECLIA) immunoassay (Roche, Cobas), were discordant. Serial dilution of plasma samples revealed nonlinearity. After polyethylene glycol (PEG) precipitation recoveries were less than 22%, 26%, and 3%, respectively, supporting interference. Moreover, a decrease in ACTH concentration after incubation in a heterophile antibody-blocking tube was observed in the second case. In the first case, misinterpretation of ACTH led to inferior petrosal sinus sampling (IPSS), whereas timely detection of assay interference prevented further investigations in other cases. Increasing awareness regarding ACTH interference and comprehensive approach in evaluation could allow timely detection, helping to prevent unnecessary testing and perplexing clinical outcomes

46 XX male syndrome with hypogonadotropic hypogonadism: A case report.

We report a 46 XX male syndrome diagnosed after failure of gonadotropin therapy taken for hypogonadotropic hypogonadism due to a pituitary macroadenoma. A 39-year-old man with a non-functioning pituitary macroadenoma was admitted to our clinic due to vision loss and infertility. After pituitary surgery, vision loss improved while infertility still existed. Low testosterone levels without elevated gonadotropins were established suggesting hypogonadotropic hypogonadism due to pituitary adenoma. Gonadotropin treatment was initiated. There was no response to treatment after 12 months. A karyotype analysis was ordered to investigate other causes of infertility. Karyotype analysis showed a 46 XX male syndrome that can explain the failure of gonadotropin therapy. Testosterone therapy was started instead of gonadotropin therapy. 46 XX male syndrome usually presents with hypergonadotropic hypogonadism. However, in our case, it presented with hypogonadotropic hypogonadism due to pituitary mass not responding to gonadotropin therapy. It is important to keep in mind to obtain a genetic analysis of patients whose gonadotropin therapy failed, even if their gonadotropin levels are not elevated

Proprotein convertase subtilisin/kexin type 9 (PCSK9), soluble lectin-like oxidized LDL receptor 1 (sLOX-1) and ankle brachial index in patients with differentiated thyroid cancer.

The cardiovascular effects of short-term overt hypothyroidism are not well known. We investigated proprotein convertase subtilisin/kexin type 9 (PCSK9), soluble lectin-like oxidized LDL receptor 1 (sLOX-1) and the ankle brachial index (ABI) in thyroid cancer patients with short-term overt hypothyroidism due to thyroid hormone withdrawal (THW). Twenty-one patients requiring radioactive iodine (RAI) ablation or scanning and 36 healthy control subjects were enrolled. Patients were evaluated in the subclinical thyrotoxic phase when they were on suppressive levothyroxine therapy and in the overt hypothyroid phase due to THW for four weeks. PCSK9, sLOX-1, lipids and ABI were measured in the patient and control groups. Total cholesterol, LDL cholesterol, triglycerides and Apo B levels were increased in short overt hypothyroidism compared with the control group (p<0.001). PCSK9 levels increased before THW and after THW in the patients compared to control group (p<0.001, p=0.004, respectively). sLOX-1 levels were not different between patients with short term overt hypothyroidism and control group (p=0.27). ABI was found to be significantly decreased in patients with thyroid cancer before and after THW compared to control group (p=0.04, p=0.002 respectively). PCSK9 levels were correlated negatively with ABI (r=-0.38, p=0.004). In conclusion; our study demonstrated that patients with differentiated thyroid cancer both before and after THW which is a short term overt hypothyroid phase, had increased PCSK9 levels and decreased ABI. Short term overt hypothyroidism also leads to increased HDL, LDL, total cholesterol, Apo A and Apo B levels

Fibroblast growth factor 21 and its relationship with insulin sensitivity in first-degree relatives of patients with type 2 diabetes mellitus

Introduction: Fibroblast growth factor 21 (FGF 21) has been suggested as a predictor for the development of type 2 diabetes mellitus (T2DM). Material and methods: We aimed to determine FGF 21 levels in normoglycaemic (Group 1) and prediabetic (Group 2) first-degree relatives (FDR) of patients with T2DM in comparison with normoglycaemic subjects without a history of T2DM in their FDR (Group 3). Results: There was a significant difference between Group 1, 2, and 3 with respect to plasma FGF 21 concentrations (143.3 +/- 93.8, 221.9 +/- 171.7 and 121.2 +/- 119.8 pg/mL, respectively, p = 0.01). FGF 21 levels were significantly increased in prediabetic FDR of patients with T2DM compared to normoglycaemic subjects without a history of T2DM in their FDR (p = 0.02). FGF 21 levels did not differ between normoglycaemic FDR of patients with T2DM and normoglycaemic subjects without a history of T2DM in their FDR (p > 0.05). In the whole group, FGF 21 correlated positively with age (r = 0.31, p = 0.003), BMI (r = 0.38, p < 0.001), systolic blood pressure (r = 0.38, p = 0.001), diastolic blood pressure (r = 0.26, p = 0.02), fasting blood glucose (r = 0.24, p = 0.02), HOMA-IR (r = 0.23, p = 0.03), AUC glucose (r = 0.35, p = 0.001), and AUC insulin (r = 0.32, p = 0.003) and negatively with HDL cholesterol (r = -0.24, p = 0.02) and Matsuda ISI (r = -0.33, p = 0.002). In the regression analysis, BMI was the most predictive factor for FGF 21 levels (beta = 0.41, r(2) = 0.17, p < 0.001). Conclusions: We showed that FGF 21 concentrations are increased in prediabetic FDR of patients with T2DM and that there is a significant association between FGF 21 and obesity and insulin sensitivity

Proprotein convertase subtilisin/kexin type 9 (PCSK9), soluble lectin-like oxidized LDL receptor 1 (sLOX-1) and ankle brachial index in patients with differentiated thyroid cancer

The cardiovascular effects of short-term overt hypothyroidism are not well known. We investigated proprotein convertase subtilisin/kexin type 9 (PCSK9), soluble lectin-like oxidized LDL receptor 1 (sLOX-1) and the ankle brachial index (ABI) in thyroid cancer patients with short-term overt hypothyroidism due to thyroid hormone withdrawal (THW). Twenty-one patients requiring radioactive iodine (RAT) ablation or scanning and 36 healthy control subjects were enrolled. Patients were evaluated in the subclinical thyrotoxic phase when they were on suppressive levothyroxine therapy and in the overt hypothyroid phase due to THW for four weeks. PCSK9, sLOX-1, lipids and ABI were measured in the patient and control groups. Total cholesterol, LDL cholesterol, triglycerides and Apo B levels were increased in short overt hypothyroidism compared with the control group (p<0.001). PCSK9 levels increased before THW and after THW in the patients compared to control group (p<0.001, p=0.004, respectively). sLOX-1 levels were not different between patients with short term overt hypothyroidism and control group (p=0.27). ABI was found to be significantly decreased in patients with thyroid cancer before and after THW compared to control group (p=0.04, p=0.002 respectively). PCSK9 levels were correlated negatively with ABI (r=-0.38, p=0.004). In conclusion; our study demonstrated that patients with differentiated thyroid cancer both before and after THW which is a short term overt hypothyroid phase, had increased PCSK9 levels and decreased ABI. Short term overt hypothyroidism also leads to increased HDL, LDL, total cholesterol, Apo A and Apo B levels

GDF-15 and Hepcidin Levels in Nonanemic Patients with Impaired Glucose Tolerance

Aims. Growth Differentiation Factor-15 (GDF-15) has been suggested as one of the regulators of hepcidin, an important regulatory peptide for iron deposition. Current data is conflicting about the relationship between hepcidin and disorders of glucose metabolism. We aimed to investigate serum hepcidin and GDF-15 concentrations and their associations with each other, in nonanemic subjects with impaired glucose tolerance (IGT) in comparison with the nonanemic subjects with normal glucose tolerance (NGT). Methods. Thirty-seven subjects with IGT and 32 control subjects with NGT, who were age-, gender-, and body mass index- (BMI-) matched, were included in the study. Results. Serum GDF-15 levels were significantly higher in IGT compared to NGT. There were no differences in hepcidin, interleukin-6, and high sensitive C-reactive protein levels between the groups. We found a positive correlation between GDF-15 and hepcidin levels. There were also positive correlations between GDF-15 and age, uric acid, creatinine, and area under the curve for glucose (AUC-G). Hepcidin was correlated positively with ferritin levels. In the multiple regression analysis, GDF-15 concentrations were independently associated with age, uric acid, and AUC-G. Conclusions. Impaired glucose tolerance is associated with increased GDF-15 levels even in the absence of anemia, but the levels of hepcidin are not significantly altered in prediabetic state