Evaluation of the glucocorticoid, mineralocorticoid, and adrenal androgen secretion dynamics in a large cohort of patients aged 6–18 years with transfusion-dependent β-thalassemia major, with an emphasis on the impact of cardiac iron load

Endocrine ◽  
2016 ◽  
Vol 53 (1) ◽  
pp. 240-248 ◽  
Author(s):  
Ahmet Uçar ◽  
Nergiz Öner ◽  
Gülcihan Özek ◽  
Mehmet Güli Çetinçakmak ◽  
Mahmut Abuhandan ◽  
...  
Keyword(s):  
Thalassemia Major ◽  
Large Cohort ◽  
Adrenal Androgen ◽  
Cardiac Iron ◽  
Iron Load ◽  
Androgen Secretion ◽  
The Impact

Reduction of Hepatic Iron in Patients with Thalassemia Major According to Iron Chelation Regime Assessed by MRI T2*

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 5410-5410
Author(s):  
Vassilios Ladis ◽  
Giorgos Chouliaras ◽  
Kirikos Zannikos ◽  
Panagiotis Moraitis ◽  
Eleni Berdoussi ◽  
...  
Keyword(s):  
Statistical Significance ◽  
Linear Regression Analysis ◽  
Thalassemia Major ◽  
Rate Of Change ◽  
Hepatic Iron ◽  
Iron Loading ◽  
Liver Iron ◽  
Cardiac Iron ◽  
Iron Load ◽  
Number Of Patients

Abstract In 212 thalassemia major patients, repeated assessments for cardiac and hepatic iron (LIC) assessed by Magnetic Resonance Imaging (MRI – T2*) have been performed. The chelation regimes were either desferrioxamine (DFO), deferiprone (DFP), combination of DFO and DFP (Comb) or deferasirox (DFX). In general over the last few years, tailoring of chelation therapy has been principally guided by the cardiac iron loading. As many patients had been found to have excess cardiac iron, the majority (48%) had been placed on Comb. Patients were grouped according to the degree of siderosis. A T2* of <1.6ms was regarded as heavy LIC, between 1.6–4.0 moderate, 4.1–9.0 mild and > 9.1 acceptable. Taking into account that the change in T2* is not necessarily linear with respect to time and as the overall time of exposure to DFO, DFP and Comb regimes was significantly greater than that with DFX it was unjustified to perform comparative analysis using the total time period of the patients who were on any of the non DFX regimes. Therefore, to compare the efficacy of the four regimes on LIC, we performed an analysis using student T test to assess the rate of change only between the first and second MRI in patients with comparable LIC according to each chelation regime with adjustment for overall time of exposure (Table 1). Using the same data and applying linear regression analysis (Table 2) we compared the effect of DFO to the other three regimes in the annual rate of increasing hepatic T2*. Only Comb is effective at all levels of hepatic iron loading in reducing the iron content. DFX is effective in the mildly iron loaded patients and for the moderately iron loaded patients, its efficacy approaches statistical significance. DFP does not seem to significantly decrease LIC at any level of hepatic iron load however the numbers of patients in that group are very small. Interestingly DFO seems the least effective at all levels of hepatic iron loading and particularly in the heavy loaded patients. This factor may be related to poor compliance to its use as the patients who have reached such levels of iron load are more often those who are not compliant. In the comparison analysis to DFO, only Comb is significantly better and DFP and DFX are equivalent to it. In addition Comb is more effective than DFX and DFP in that over 12 months it would increase the T2* by 3.8ms (p <0.001) and 3.9ms (p 0.012) respectively. DFX and DFP are similar in efficacy in that they maintain the liver iron at the same levels (DFP vDFX 0.009ms p=0.95). In patients with hepatic T2* >9ms, 4 of 11 on DFO, 5 of 6 on DFX, 7 of 11 on DFP and 3 of 22 on Comb fell below 9. It is of note that DFO only maintains LIC and that a number of patients in the normal range increased LIC. Taking this data into account the DFX and DFP results are compatible with those seen both in the clinic and in trials. It is apparent however that combination therapy is the most effective regime for reducing hepatic iron significantly. As with cardiac iron loading, by knowing the degree of hepatic iron loading by the non-invasive T2* measurement and being able to manipulate patients chelation regimes, it seems possible to be able to have patients free of excess hepatic iron and potentially reduce other iron related morbidities as well. Table 1 Annual estimated mean change in T2* according to severity of hepatic siderosis Regime Heavy Moderate Mild ΔT2* p ΔT2** p ΔT2* p *tm= mean time (in months) between MRI studies DFO n= 42 tm*= 24.6 0.05 0.5 0.57 0.37 0.1 0.7 DFP n= 11 tm= 23.8 0.56 0.25 0.88 0.31 3.5 0.19 Comb n= 101 tm=21.7 1.17 0.0064 3.6 <0.001 5.9 <0.001 DFX n=58 tm=15.2 3.1 0.11 1.25 0.06 3.8 0.014 Table 3 Mean estimated difference in T2* Standard Error p DFP v. DFO −0.7 1.6 0.7 Comb v DFO 3.1 1.05 0.03 DFX v DFO −0.7 1.2 0.5

Glutathione S-Transferase Gene Polymorphism and Heart Iron Overload in Thalassemia Major.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2767-2767
Author(s):  
Raffaella Origa ◽  
Stefania Satta ◽  
M. Dolores Cipollina ◽  
Lucia Perseu ◽  
Annalisa Agus ◽  
...  
Keyword(s):  
Iron Overload ◽  
Serum Ferritin ◽  
Thalassemia Major ◽  
Myocardial Iron ◽  
Gstm1 Null Genotype ◽  
Glutathione S Transferase ◽  
Body Iron ◽  
Cardiac Iron ◽  
Iron Load ◽  
Allelic Distribution

Abstract Heart is the target lethal organ for iron accumulation in thalassemia major. Currently, magnetic resonance imaging (MRI) is the only non-invasive method with the potential to assess myocardial iron. MRI T2* has proven to be a fast, simple, robust and clinically useful tool for the assessment of cardiac iron load. In chelated patients, myocardial iron is usually inversely related to compliance with chelation while there is no meaningful correlation with liver iron and serum ferritin concentration measured at the time of T2* assessment. However, in a subset of patients, myocardial iron overload occurs despite an history of good compliance with chelation therapy, suggesting the possible role of genetic factors. Several gene polymorhisms including apolipoprotein epsylon and HLA haplotypes have been described as protective or predisposing factors for cardiac iron dysfunction. Wu et al. (2006) analyzed polymorphisms of two endogenous antioxidant enzymes, glutathione S-transferase M1 (GSTM1) and glutathione S-transferase T1 (GSTT1). They found that the GSTM1 null (deleted) genotype was associated with a decreased signal intensity ratio on MRI, suggesting that genetic variations of the GSTM1 enzyme are associated with cardiac iron deposition. The aim of the current study was to evaluate if the GSTM1 null genotype is a predisposing factor for myocardial iron overload in thalassemia major patients on chelation treatment with desferrioxamine with low body iron load as assessed by serum ferritin levels. Allelic distribution of wild and null GSTM1 genotype was assessed in 24 patients with thalassemia major in whom the severe myocardial iron overload (T2* <10 msec) was unexpected based on low body iron load (mean of lifelong serum ferritin determinations 1360 ± 268 ng/ml), and in 26 thalassemia patients in whom the myocardial iron overload was expected based on high body iron load (mean of lifelong serum ferritin determinations 4724 ± 1530 ng/ml). Twenty-six healthy subjects were analyzed as controls. We found that the GSTM1 null genotype was more frequent in thalassemia patients with unexpected myocardial iron load (p=0.02) than in patients with expected myocardial iron load (Table 1). The presence of the GSTM1 null genotype can therefore explain in part the development of severe myocardial iron overload in thalassemia major patients who have been adequately chelated since their first years of life. Based on the inhibition of the cardiac ryanodine receptor calcium channels by members of the glutathione transferase structural family, and given the little difference in permeability among divalent cations in those channels, we hypothesized that the deletion of GSTM1 is associated with increased entry of iron into the myocites, in patients with thalassemia major. Further studies are needed to understand the mechanisms that underlie the association between GSTM1 gene polymorphisms and predisposition to myocardial iron overload. Table 1. Allelic distribution of wild and null GSTM1 genotype in beta thalassemia patients with expected and unexpected heart iron overload, and in 26 healthy controls GSTM1 wild GSTM1 wild GSTM1 null GSTM1 null n % n % χ2 test : A vs C p>0.05; A vs B p=0.02; B vs C p=0.04 A. Thalassemic patients with expected heart iron overload 17 65.4 9 34.6 B. Thalassemic patients with unexpected heart iron overload 8 33.3 16 61.5 C. Healthy controls 16 61.5 10 38.4

Hepatic and Cardiac Iron-load in Children on Long-term Chelation with Deferiprone for Thalassemia Major

2018 ◽  
Vol 55 (7) ◽  
pp. 573-575 ◽  
Author(s):  
Sidharth Totadri ◽  
Deepak Bansal ◽  
Amita Trehan ◽  
Alka Khadwal ◽  
Anmol Bhatia ◽  
...  
Keyword(s):  
Thalassemia Major ◽  
Cardiac Iron ◽  
Iron Load

scholarly journals Cardiac Iron Load and Novel P-Wave Measurements in Patients with Thalassemia Major: The role of P index and Interatrial Block

2012 ◽  
Vol 9 (1) ◽  
Author(s):  
Kadir Acar ◽  
Mehmet Kayrak ◽  
Enes Elvin Gul ◽  
Turyan Abdulhalikov ◽  
Orhan Özbek ◽  
...  
Keyword(s):  
Thalassemia Major ◽  
P Wave ◽  
Cardiac Iron ◽  
Wave Measurements ◽  
Iron Load ◽  
P Index ◽  
Interatrial Block

Premature Adrenarche and its Association with Cardiovascular Risk in Females

2020 ◽  
Vol 26 (43) ◽  
pp. 5609-5616
Author(s):  
Sarantis Livadas ◽  
Christina Bothou ◽  
Djuro Macut
Keyword(s):  
Polycystic Ovary ◽  
Dehydroepiandrosterone Sulfate ◽  
Adrenal Androgen ◽  
Premature Adrenarche ◽  
Adrenal Hyperandrogenism ◽  
Long Term Follow Up ◽  
History Of ◽  
Hormonal Milieu ◽  
The Impact

Early activation of the adrenal zona reticularis, leading to adrenal androgen secretion, mainly dehydroepiandrosterone sulfate (DHEAS), is called premature adrenarche (PA). The fact that adrenal hyperandrogenism in females has been linked to a cluster of cardiovascular (CV) risk factors, even in prepubertal children, warrants investigation. Controversial results have been obtained in this field, probably due to genetic, constitutional, and environmental factors or differences in the characteristics of participants. In an attempt to understand, in depth, the impact of PA as a potential activator of CV risk, we critically present available data stratified according to pubertal status. It seems that prepubertally, CV risk is increased in these girls, but is somewhat attenuated during their second decade of life. Furthermore, different entities associated with PA, such as polycystic ovary syndrome, non-classical congenital adrenal hyperplasia, heterozygosity of CYP21A2 mutations, and the impact of DHEAS on CV risk, are reviewed. At present, firm and definitive conclusions cannot be drawn. However, it may be speculated that girls with a history of PA display a hyperandrogenic hormonal milieu that may lead to increased CV risk. Accordingly, appropriate long-term follow-up and early intervention employing a patient-oriented approach are recommended.

scholarly journals The Impact of Illicit Drug Use on Spontaneous Hepatitis C Clearance: Experience from a Large Cohort Population Study

PLoS ONE ◽  
2011 ◽  
Vol 6 (8) ◽  
pp. e23830 ◽  
Author(s):  
Hossein Poustchi ◽  
Saeed Esmaili ◽  
Ashraf Mohamadkhani ◽  
Aghbibi Nikmahzar ◽  
Akram Pourshams ◽  
...  
Keyword(s):  
Hepatitis C ◽  
Drug Use ◽  
Population Study ◽  
Illicit Drug ◽  
Illicit Drug Use ◽  
Large Cohort ◽  
The Impact

Dissociation of cortisol and adrenal androgen secretion in poorly controlled insulin-dependent diabetes mellitus

1992 ◽  
Vol 127 (2) ◽  
pp. 115-117 ◽  
Author(s):  
RM Couch
Keyword(s):  
Diabetes Mellitus ◽  
Good Control ◽  
Insulin Dependent Diabetes Mellitus ◽  
Dehydroepiandrosterone Sulfate ◽  
Insulin Dependent Diabetes ◽  
Dependent Diabetes Mellitus ◽  
Poor Control ◽  
Adrenal Androgen ◽  
Insulin Dependent ◽  
Androgen Secretion

In acute illness, cortisol secretion increases whereas that of the adrenal androgens, dehydroepiandrosterone and dehydroepiandrosterone sulfate declines. The present study examined if a similar dissociation of cortisol and adrenal androgen secretion occurs in poorly controlled diabetes mellitus. Serum concentrations of cortisol, dehydroepiandrosterone and dehydroepiandrosterone sulfate obtained at 08.00 were compared in 13 post-pubertal diabetics (mean age 18.0 years) in good control (HbA1C<8.0%) and 10 post-pubertal diabetics (mean age 17.0 years) in poor control (HbA1C> 10.0%). Those in poor control had significantly higher serum cortisol (597±94 nmol/l vs 479±208, p < 0.05), lower dehydroepiandrosterone (13.1±5.5 nmol/l vs 25.3±16.9, p<0.025) and lower dehydroepiandrosterone sulfate (4.5±2.4 μmol/l vs 7.0±3.7, p<0.025). The ratios of dehydroepiandrosterone and dehydroepiandrosterone sulfate to cortisol were also significantly lower in those with poor control. It is concluded that poor control of insulin-dependent diabetes mellitus results in a dissociation of cortisol and adrenal androgen secretion.

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