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

Presentation of Graves' orbitopathy within European Group On Graves' Orbitopathy (EUGOGO) centres from 2012 to 2019 (PREGO III)

Background: Graves' orbitopathy (GO) is subject to epidemiological and care-related changes. Aim of the survey was to identify trends in presentation of GO to the European Group On Graves' Orbitopathy (EUGOGO) tertiary referral centres and initial management over time. Methods: Prospective observational multicentre study. All new referrals with diagnosis of GO within September-December 2019 were included. Clinical and demographic characteristics, referral timelines and initial therapeutic decisions were recorded. Data were compared with a similar EUGOGO survey performed in 2012. Results: Besides age (mean age: 50.5±13 years vs 47.7±14 years; p 0.007), demographic characteristics of 432 patients studied in 2019 were similar to those in 2012. In 2019, there was a decrease of severe cases (9.8% vs 14.9; p<0.001), but no significant change in proportion of active cases (41.3% vs 36.6%; p 0.217). After first diagnosis of GO, median referral time to an EUGOGO tertiary centre was shorter (2 (0-350) vs 6 (0-552) months; p<0.001) in 2019. At the time of first visit, more patients were already on antithyroid medications (80.2% vs 45.0%; p<0.001) or selenium (22.3% vs 3.0%; p<0.001). In 2019, the initial management plans for GO were similar to 2012, except for lid surgery (2.4% vs 13.9%; p<0.001) and prescription of selenium (28.5% vs 21.0%; p 0.027). Conclusion: GO patients are referred to tertiary EUGOGO centres in a less severe stage of the disease than before. We speculate that this might be linked to a broader awareness of the disease and faster and adequate delivered treatment

Insulin Like Growth Factor-I and IGF-Binding Protein-3 Levels in A Healthy Adult Turkish Population

Tuzun, Hakan/0000-0002-6376-8979WOS: 000298720200004Objective: Insulin-like growth factor-I (IGF-I) and IGF binding protein-3 (IGFBP-3) levels are important markers in diagnosis of growth hormone (GH) related disorders. The normal levels of IGF-I and IGFBP-3 vary among different ethnic groups, and using the references derived from different populations may sometimes be misleading during diagnosis, treatment and follow-up. We examined the levels of IGF-I and IGFBP-3 in healthy adult Turkish population. Material and Methods: Eight hundred and thirty-three subjects (512 females, 321 males) were enrolled in the study. Serum IGF-I and IGFBP-3 levels were measured by immunoradiometric assay in all participants. The study population was divided into age groups (18-20, 21-23, 24-25, 26-30, 31-40, 41-50, >50 years of age) and gender groups (females and males separately in the population 30 years of age (p<0.05). Conclusion: Serum IGF-I concentrations of our study population are generally higher than the reference values of the commercial kit. Centers dealing with GH disorders might benefit from defining their own population's normal values for IGF-I and IGFBP-3 to overcome possible diagnostic and follow-up pitfalls

Neuropsychological Changes and Health-related Quality of Life in Patients with Asymptomatic Primary Hyperparathyroidism

Purpose: Data about neuropsychological impairment and health-related quality of life (HRQOL) in patients with asymptomatic primary hyperparathyroidism (APHPT) is limited. We aimed to investigate the HRQOL, neuropyschological impairment, including depression, anxiety in patients with APHPT who have mildly elevated serum calcium (Ca) levels. Material and Method: Thirty-seven patients with APHPT and 37 controls were included. The Beck Depression Inventory (BDI), Spielberger State-Trait Anxiety Inventory (STAI), and the General Health Questionnaire were administered in all patients, HRQOL was investigated using the Medical Outcomes Study 36-Item Short Form Health Survey (SF-36). Results: Serum levels of Ca and parathyroid hormone (PTH) were significantly higher in patients than in controls [(10.92 +/- 0.66 vs. 9.49 +/- 0.66, p= 0.016, and 133 (34-736) vs. 52.95 (25-75.50), p< 0.001), respectively]. The levels of serum vitamin D were lower in patients than in controls [12.85 (4.0-62.50) vs. 20.30 (5.90-55.00), p= 0.041)]. The patient group had higher BDI scores than controls (12.49 +/- 10.34 vs. 7.46 +/- 5.33, p= 0.011). Patients with APHPT showed lower scores in SF-36 mental health (60.55 +/- 20.75 vs. 69.62 +/- 14.31, p= 0.034), SF-36 physical functioning (55.83 +/- 27.30 vs. 75.67 +/- 24.18, p= 0.002), SF-36 social functioning (66.32 +/- 27.69 vs. 82.08 +/- 14.89, p= 0.003), and SF-36 emotional role functioning (42.55 +/- 37.85 vs. 69.30 +/- 35.43, p= 0.003). The patients showed higher STAI-1 scores (39.95 +/- 11.52 vs. 34.70 +/- 8.01, p= 0.026). We observed that STAI-1 score positively correlated with serum Ca level (r= 0.391; p= 0.018); and PTH (r= 0.341; p= 0.042). Discussion: Our study demonstrated that patients with APHPT have more depressive and anxiety symptoms and lower HRQOL. Our results suggest that HRQOL and neuropsychological changes should also be considered during the clinical follow-up of patients with APHT

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