Wczesne, pooperacyjne stężenie kortyzolu w surowicy w ocenie skuteczności przezklinowej operacji choroby Cushinga — badanie prospektywne

Introduction: Transsphenoidal surgery (TSS) is the treatment of choice for Cushing`s disease (CD). A proper assessment of the efficacy of surgical treatment is crucial in terms of patient prognosis. The aim of this study was to evaluate the usefulness of serum cortisol measurements performed on the first post-operative day as a predictor of TSS outcome. Material and methods: This prospective study involved 36 patients with CD who were operated on using the same surgical protocol and followed up for at least 18 months (median: 30 months). We investigated the relationship between serum cortisol measurements performed on the first post-operative day and the hormonal assessment of the pituitary-adrenal axis performed after 18 months of follow-up. The adopted criteria for remission were: serum cortisol within the referral range, normal circadian rhythm, and the ability of serum cortisol to suppress to values ≤ 1.8 μg/dL after 1 mg of dexamethasone. Results: The median serum cortisol on the first post-operative day was 1.98 μg/dL. 23 patients (63.9%) were regarded as cured. In all these cured cases, the post-op cortisol was ≤ 2.5. On the other hand, in the cases of the 13 patients (36.1%) for whom the remission of CD was not confirmed, the post-op cortisol was ≥ 2.5. Conclusion: Our prospective study demonstrated that early post-operative serum cortisol measurements can serve as a simple and useful test that predicts the remission of CD. Furthermore, a post-operative cortisol ≤ 2.5 can be considered as a forecast of CD remission.Wstęp: Leczeniem z wyboru w chorobie Cushinga jest selektywna przezklinowa adenomectomia. Ocena skuteczności operacji ma kluczowe znaczenie z punktu widzenia rokowania chorych. Celem pracy była prospektywna ocena przydatności oznaczeń kortyzolu w surowicy wykonanych w 1 dobie po operacji przezklinowej gruczolaka kortykotropowego dla oceny skuteczności leczenia operacyjnego. Materiał i metody: Badanie prospektywne obejmujące 36 pacjentów z chorobą Cushinga operowanych według identycznego protokołu operacyjnego i obserwowanych przez co najmniej 18 miesięcy (mediana: 30 mies.). Oceniano związek pomiędzy stężeniem kortyzolu w surowicy o godzinie 6.00 w 1 dobie po operacji przezklinowej a oceną hormonalną osi przysadkowo-nadnerczowej wykonaną w 18 miesiącu obserwacji pooperacyjnej. Jako kryteria remisji przyjęto: normalizację stężenia kortyzolu w surowicy, prawidłowy rytm dobowy oraz obniżenie stężenia kortyzolu do wartości poniżej 1,8 μg/dl w teście z 1 mg deksametazonu. Wyniki: Mediana stężenia kortyzolu w 1 dobie po operacji przysadki wyniosła 1,98 μg/dl. 23 pacjentów (63,9%) zostało uznanych za wyleczonych z choroby Cushinga. We wszystkich tych przypadkach stężenie kortyzolu w surowicy w 1 dobie po operacji było mniejsze lub równe 2,5 μg/dl. Jednocześnie u żadnego z 13 pacjentów (36,1%) ze stężeniem kortyzolu w 1 dobie po operacji powyżej 2,5 μg/dl nie potwierdzono remisji choroby Cushinga. Wnioski: W badaniu prospektywnym wykazano, iż wczesne, pooperacyjne oznaczanie stężenia kortyzolu w surowicy jest prostym i użytecznym badaniem zapowiadającym remisję choroby Cushinga. Wykazanie stężenia kortyzolu w surowicy mniejszego lub równego 2,5 μg/dL w 1 dobie po operacji przezklinowej może być traktowane jako czynnik prognozujący remisję choroby

Choroba Cushinga: brak normalizacji stężeń fibrynogenu i D-dimerów u pacjentów z wczesną remisją hiperkortyzolemii — badanie prospektywne

  Introduction: Effective transsphenoidal surgery (TSS) for Cushing`s disease (CD) normalizes cortisol levels and reduces complications of hypercortisolism. However, there is evidence of increased cardiovascular morbidity even after successful surgery. Objective. A prospective, controlled study on the dynamics of fibrinogen and D-dimer levels with a six-month follow-up after an effective TSS for CD. Material and methods: Forty patients with CD and forty healthy age- and sex-matched subjects were included. We assessed ACTH, urinary and serum cortisol, and fibrinogen and D-dimer levels before TSS and during follow-up. Results: Baseline BMI (P < 0.001), fibrinogen (P = 0.002), and D-dimer (P = 0.001) levels in CD patients were significantly higher than those in healthy controls. High fibrinogen levels in the CD group were independent of BMI, and were positively associated with hsCRP (rS = 0.61, P < 0.001) and arterial hypertension (P = 0.029). After the six-month follow-up we confirmed a sustained difference between the remission group and controls in fibrinogen and D-dimer levels (P = 0.001 and P = 0.017, respectively). Conclusions: Despite early biochemical remission of CD the levels of fibrinogen and D-dimer failed to decrease. This probably contributes to the high risk of thrombotic events and indicates the need for a close follow-up for signs of thromboembolic and cardiovascular complications in patients with early CD remission. (Endokrynol Pol 2016; 67 (3): 283–291)    Wstęp: Skuteczne leczenie chirurgiczne choroby Cushinga prowadzi do normalizacji stężenia kortyzolu i redukcji powikłań hiperkortyzolemii. Istotnym spostrzeżeniem jest jednak fakt utrzymywania się zwiększonego ryzyka związanego z powikłaniami sercowo-naczyniowymi, nawet po skutecznym leczeniu operacyjnym. Celem pracy była prospektywna ocena zmian stężenia fibrynogenu i D-dimerów w okresie 6 miesięcy po przeprowadzonym leczeniu chirurgicznym choroby Cushinga. Materiał i metody: Do badania włączono 40 pacjentów dobranych pod względem płci i wieku z rozpoznaną chorobą Cushinga i 40 osób zdrowych. U badanych wykonano oznaczenia stężeń: ACTH, kortyzolu w moczu i surowicy, fibrynogenu i D-dimerów przed leczeniem chirurgicznym i w okresie obserwacji. Wyniki: Wartości BMI (P < 0,001), fibrynogenu (P = 0,002) i D-dimerów (P = 0,001) były istotnie wyższe w grupie pacjentów z choroba Cushinga w porównaniu ze zdrowymi osobami. Wysokie stężenie fibrynogenu wśród pacjentów z chorobą Cushinga było niezależne od wartości BMI, ale wykazywało dodatnią zależność od wartości hsCRP (rS = 0,61, P < 0,001) i występowania nadciśnienia tętniczego (P = 0,029). Potwierdzono utrzymywanie się istotnej różnicy stężeń fibrynogenu i D-dimerów (P = 0,001 i P = 0,017, odpowiednio) po 6 miesiącach od operacji pomiędzy chorymi, u których uzyskano remisję hiperkortyzolemii i osobami zdrowymi. Wnioski: Mimo wczesnej remisji hiperkortyzolemii w chorobie Cushinga, stężenia fibrynogenu i D-dimerów nie ulegają obniżeniu. Prawdopodobnie jest to przyczyną wysokiego ryzyka incydentów zakrzepowo-zatorowych u tych chorych, a także wskazanie do ścisłej obserwacji pooperacyjnej chorych w okresie remisji. (Endokrynol Pol 2016; 67 (3): 283–291)

The influence of hypothyroidism and substitution treatment on thyroid hormone conversion ratios and rT3 concentration in patients with end-stage renal failure

Introduction: The increasing number of patients with end-stage renal disease (ESRD) requires seeking new opportunities to improve their quality of life, not only because of kidney disease but also due to other disturbances, such as thyroid hormone disorders. The objective of the study was to evaluate the influence of coexisting hypothyroidism and thyroid hormone therapy in patients with ESRD on thyroid hormone conversion ratios and rT3 concentration. Material and methods: The study involved 85 patients aged 26 to 87 years, with a mean age of 59.62 ± 15.45 years. Four groups of patients were examined: G1 group — 25 persons without RF and hypothyroidism, G2 — 26 patients with ESRD treated with haemodialysis (HD), G3 — 12 patients with ESRD treated with HD and newly diagnosed hypothyroidism, and G4 — 22 HD patients with hypothyroidism treated with thyroid hormones substitution. The concentrations of TSH, T4, T3, fT4, fT3, and rT3 were measured and the fT3/fT4, T3/T4, and rT3/T4 conversion ratios and rT3/T3 ratio were calculated. Concentrations of protein, hsCRP, Hg, and blood gases were also checked; the anion gap was calculated. Results: Patients from group G1 through G2 to G3 were older (ptrend = 0.002), with lower Hb level (ptrend < 0.001), with lower pH (ptrend < 0.001), with increased anion gap (ptrend < 0.013) and CRP concentrations (ptrend < 0.001), and decreased total protein level (ptrend < 0.001). There were increased TSH values (ptrend < 0.001) and lower T4 (ptrend = 0.024), fT3 (ptrend < 0.001), T3 (ptrend < 0.001), and rT3 (ptrend = 0.008) levels. rT3/T3 ratio did not change, the rT3/T4 ratio tended to decrease (ptrend = 0.065) similarly to T3/T4 ratio (ptrend = 0.063), and the fT3/fT4 ratio also decreased (ptrend = 0.005). It seems that the treatment of thyroid disease in patients with renal failure, treated with haemodialysis, is not associated with change of rT3 and conversion factor levels. Conclusions: The concentration of rT3 in HD patients in relation to healthy persons tends to decrease, and hypothyroidism increases this tendency in these patients. Hormone substitution treatment does not eliminate the influence of RF on inhibition of rT3 production. In patients with ESRD, hypothyroidism additionally reduces the conversion of thyroid hormones examined by fT3/fT4 and to a lesser extent T3/T4 ratios

Determining the enzymatic activities of iodothyronine 5’-deiodinases in renal medulla and cortex

Wstęp: Zaburzenia hormonów tarczycy u pacjentów z przewlekłą chorobą nerek (PChN) są wynikiem zaburzeń konwersji T4 do T3. Znaczenie nerek w konwersji hormonów tarczycy nie jest w pełni poznane. Działania różnych typów dejodynaz jodotyroninowych w strukturach nerek, nie zostały jeszcze określone. Celem badań było określenie aktywności dejodynazy typu 1 (D1) i typu 2 (D2) w korze i rdzeniu nerek u chorych z rakiem nerki. Materiał i metody: Próbki kory i rdzenia nerek (10 pacjentów) lub tylko samej kory (13 pacjentów) były pobrane z przeciwnego bieguna tej samej nerki do guza , z nerek usuniętych z powodu raka. Resekcje wykonano u 23 chorych (7 kobiet i 16 mężczyzn) w wieku 52&#8211;82 lat. Wyniki: Aktywność D1 w korze nerki wynosiła 3,785 &#177; 2,041 fmol 125I/mg białka/min., a aktywność D2 wynosiła 0,236 &#177; 0,125 fmol 125I/ mg białka/min. Znaleziono silną, dodatnią korelację pomiędzy aktywnością D1 i D2 w korze nerki (r = 0,890, p < 0,001). Aktywność D1 w rdzeniu nerek wynosiła 2,157 &#177; 2,176 fmol 125I/mg białka /min., a aktywność D2 wynosiła 0,168 &#177; 0,095 fmol 125I/mg białka/min. Zaobserwowano również dodatni związek pomiędzy aktywnością D1 i D2 w rdzeniu nerek (r = 0,661, p = 0,038). Stwierdzono silną dodatnią korelację aktywności D1 w korze i rdzeniu (r = 0,794, p = 0,006) oraz brak korelacji aktywności D2 w korze i rdzeniu (r = 0,224, p = 0,553). Wnioski: Wyniki przedstawionej pracy sugerują, że aktwność dejodynaz 1 i 2 zarówno w korze jak i w rdzeniu nerki może miec wpływ na metabolizm hormonów tarczycy. To ustalenie może mieć znaczenie kliniczne dla chorych z upośledzoną funkcją nerek. (Endokrynol Pol 2013; 64 (3): 182&#8211;185)Introduction: Thyroid hormone disorders in patients with chronic kidney disease (CKD) are a result of impaired conversion of T4 to T3. The importance of kidneys in thyroid hormones conversion is not fully understood. The activities of different types of iodothyronine deiodinases in the kidney structures have not been determined yet. The aim of this study was to determine the activity of deiodinase type 1 (D1) and type 2 (D2) in renal cortex and medulla in renal cancer patients. Material and methods: Samples of renal cortex and medulla (ten patients) or renal cortex alone (13 patients) were taken from kidneys resected because of malignant cancer, from a site opposite to the cancer. Resections were performed in the 23 patients (seven female and 16 male) who were 52&#8211;82 years old. The material was stored at &#8211;72 oC. Results: Activity of D1 in renal cortex was 3.785 &#177; 2.041 fmol 125I/mg protein/minute and activity of D2 was 0.236 &#177; 0.125 fmol 125I/mg protein/minute. There was a strong positive correlation between D1 and D2 activities in renal cortex (r = 0.890, p < 0.001). Activity of D1 in renal medulla was 2.157 &#177; 2.176 fmol 125I/mg protein/minute, and activity of D2 was 0.168 &#177; 0.095 fmol 125I/mg protein/minute. A positive correlation between D1 and D2 in renal medulla (r = 0.661, p = 0.038) was observed as well. Activities of D1 in cortex and medulla were strongly and positively associated (r = 0.794, p = 0.006), whereas there was no correlation between the activities of D2 in cortex and medulla (r = 0.224, p = 0.553). Conclusions: Results presented in this study suggest that both cortical and medullary D1 and D2 may be involved in thyroid hormone metabolism. This finding could be of clinical relevance in patients with impaired renal function. (Endokrynol Pol 2013; 64 (3): 182&#8211;185

Clarity and consistency in stillbirth reporting in Europe: why is it so hard to get this right?

Background Stillbirth is a major public health problem, but measurement remains a challenge even in high-income countries. We compared routine stillbirth statistics in Europe reported by Eurostat with data from the Euro-Peristat research network. Methods We used data on stillbirths in 2015 from both sources for 31 European countries. Stillbirth rates per 1000 total births were analyzed by gestational age (GA) and birthweight groups. Information on termination of pregnancy at ≥22 weeks’ GA was analyzed separately. Results Routinely collected stillbirth rates were higher than those reported by the research network. For stillbirths with a birthweight ≥500 g, the difference between the mean rates of the countries for Eurostat and Euro-Peristat data was 22% [4.4/1000, versus 3.5/1000, mean difference 0.9 with 95% confidence interval (CI) 0.8–1.0]. When using a birthweight threshold of 1000 g, this difference was smaller, 12% (2.9/1000, versus 2.5/1000, mean difference 0.4 with 95% CI 0.3–0.5), but substantial differences remained for individual countries. In Euro-Peristat, missing data on birthweight ranged from 0% to 29% (average 5.0%) and were higher than missing data for GA (0–23%, average 1.8%). Conclusions Routine stillbirth data for European countries in international databases are not comparable and should not be used for benchmarking or surveillance without careful verification with other sources. Recommendations for improvement include using a cut-off based on GA, excluding late terminations of pregnancy and linking multiple sources to improve the quality of national databases.publishedVersio

Perinatal health monitoring through a European lens: eight lessons from the Euro-Peristat report on 2015 births

International audienceNo abstract availabl

Socioeconomic inequalities in stillbirth rates in Europe: measuring the gap using routine data from the Euro-Peristat Project

Background Previous studies have shown that socioeconomic position is inversely associated with stillbirth risk, but the impact on national rates in Europe is not known. We aimed to assess the magnitude of social inequalities in stillbirth rates in European countries using indicators generated from routine monitoring systems. Methods Aggregated data on the number of stillbirths and live births for the year 2010 were collected for three socioeconomic indicators (mothers’ educational level, mothers’ and fathers’ occupational group) from 29 European countries participating in the Euro-Peristat project. Educational categories were coded using the International Standard Classification of Education (ISCED) and analysed as: primary/lower secondary, upper secondary and postsecondary. Parents’ occupations were grouped using International Standard Classification of Occupations (ISCO-08) major groups and then coded into 4 categories: No occupation or student, Skilled/ unskilled workers, Technicians/clerical/service occupations and Managers/professionals. We calculated risk ratios (RR) for stillbirth by each occupational group as well as the percentage population attributable risks using the most advantaged category as the reference (post-secondary education and professional/managerial occupations). Results Data on stillbirth rates by mothers’ education were available in 19 countries and by mothers’ and fathers’ occupations in 13 countries. In countries with these data, the median RR of stillbirth for women with primary and lower secondary education compared to women with postsecondary education was 1.9 (interquartile range (IQR): 1.5 to 2.4) and 1.4 (IQR: 1.2 to 1.6), respectively. For mothers’ occupations, the median RR comparing outcomes among manual workers with managers and professionals was 1.6 (IQR: 1.0–2.1) whereas for fathers’ occupations, the median RR was 1.4 (IQR: 1.2–1.8). When applied to the entire set of countries with data about mothers’ education, 1606 out of 6337 stillbirths (25 %) would not have occurred if stillbirth rates for all women were the same as for women with post-secondary education in their country. Conclusions Data on stillbirths and socioeconomic status from routine systems showed widespread and consistent socioeconomic inequalities in stillbirth rates in Europe. Further research is needed to better understand differences between countries in the magnitude of the socioeconomic gradient