Increased prevalence of iron‐overload associated endocrinopathy in thalassaemia <i>versus</i> sickle‐cell disease

Fung, Ellen B.; Harmatz, Paul; Lee, Phillip; Milet, Meredith; Bellevue, Rita; Jeng, Michael; Kalinyak, Karen; Hudes, Mark; Bhatia, Sangeeta; Vichinsky, Elliott

doi:10.1111/j.1365-2141.2006.06332.x

Cited by 168 publications

(160 citation statements)

References 31 publications

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“…43,44 Cardiac and endocrine iron overload occur in sickle cell disease, but they are not particularly common. [45][46][47] Future impact of MRI With routine cardiac screening, patients are now living long enough to encounter increasing iron-mediated endocrine morbidities. Diabetes, hypothyroidism, and hypogonadism remain common among thalassemia patients 2,48 and are probably underdiagnosed.…”

Section: Mri In Iron Overload Disorders Other Than Thalassemiamentioning

confidence: 99%

Impact of Iron Assessment by MRI

Wood

2011

Hematology

118

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The use of magnetic resonance imaging (MRI) to estimate tissue iron was conceived in the 1980s, but has only become a practical reality in the last decade. The technique is most often used to estimate hepatic and cardiac iron in patients with transfusional siderosis and has largely replaced liver biopsy for liver iron quantification. However, the ability of MRI to quantify extrahepatic iron has had a greater impact on patient care and on our understanding of iron overload pathophysiology. Iron cardiomyopathy used to be the leading cause of death in thalassemia major, but is now relatively rare in centers with regular MRI screening of cardiac iron, through earlier recognition of cardiac iron loading. Longitudinal MRI studies have demonstrated differential kinetics of uptake and clearance among the difference organs of the body. Although elevated serum ferritin and liver iron concentration (LIC) increase the risk of cardiac and endocrine toxicities, some patients unequivocally develop extrahepatic iron deposition and toxicity despite having low total body iron stores. These observations, coupled with the advent of increasing options for iron chelation therapy, are allowing clinicians to more appropriately tailor chelation therapy to individual patient needs, producing greater efficacy with fewer toxicities. Future frontiers in MRI monitoring include improved prevention of endocrine toxicities, particularly hypogonadotropic hypogonadism and diabetes.

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Section: Mri In Iron Overload Disorders Other Than Thalassemiamentioning

confidence: 99%

Impact of Iron Assessment by MRI

Wood

2011

Hematology

118

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“…Though beneficial, transfusion therapy results in iron overload and iron-related organ toxicities in patients without strict adherence to chelation therapy. Although iron-related endocrine abnormalities are observed more frequently in Thal [20], the relationship of endocrinopathy to fracture prevalence has not been investigated in detail in either Thal or SCD.…”

Section: Introductionmentioning

confidence: 99%

Fracture prevalence and relationship to endocrinopathy in iron overloaded patients with sickle cell disease and thalassemia

Fung¹,

Harmatz²,

Milet³

et al. 2008

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Transfusional iron overload leads to gonadal failure and low bone mass in patients with thalassemia (Thal). However, gonadal failure is rarely reported in transfused patients with sickle cell disease (SCD) and the literature regarding fracture prevalence in SCD is limited. The objective of this study was to assess self-reported fracture prevalence and its relationship to endocrinopathy in transfused Thal or SCD subjects and compare to non-transfused subjects with SCD (NonTxSCD). Eligibility was based on age ≥12 years and liver iron concentration ≥ 10 mg/g dry wt or serum ferritin ≥ 2000 ng/mL (Thal or TxSCD) or for NonTxSCD, ferritin < 500 ng/mL. Data were collected by patient interview and chart review at 31 clinical centers in the U.S., Canada and the U.K. 152 subjects with Thal (52% Male; 25.6±0.7 yrs), 203 subjects with TxSCD (44% Male, 24.7 ±0.9 years: Mean ± SE), and 65 NonTxSCD (50% Male, 22.2 ±1.3 yrs) were enrolled. Overall, male subjects with Thal were more likely to have sustained a fracture in their lifetime (51%) compared to TxSCD (28%) or NonTxSCD (32%) (p=0.005). There was no difference in fracture prevalence among women (Thal: 26%, TxSCD 17%, NonTxSCD: 16%). Fracture was most frequently reported in the upper extremities (53.3% of all fractures) while spine and pelvic fractures were relatively common for such a young cohort: 10.6%. Though overall fracture prevalence was not distinctly different from published healthy cohorts, fewer fractures occurred during the adolescent years. In multivariate analysis, the significant predictors of fracture prevalence were Thal diagnosis (Odds Ratio: 2.3; 1.2-4.6; 95%CI), male gender (OR: 2.6; 1.5-4.5), hypothyroidism (OR: 3.3; 1.1-9.8) and age (OR: 1.1; 1.03-1.08). These data suggest that despite similar iron burden, transfused patients with Thal are at greater risk for fracture than subjects with SCD. Male subjects with Thal and hypothyroidism are at particular risk for fracture, in contrast, transfused subjects with SCD had no greater risk of fracture compared to non-transfused SCD. Though ethnic differences in fracture risk cannot be ignored, endocrinopathy is rare in TxSCD which may also provide some protection from fracture.

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“…A major concern with this therapy is the development of transfusional iron overload, which can cause endocrinopathies, liver inflammation and fibrosis, and cardiac toxicity [3][4][5], although some of these complications appear to occur less commonly in SCA compared with thalassemia patients [6,7]. The use of modified transfusion programs that allow higher pretransfusion hemoglobin S levels [8] and automated exchange transfusions may limit iron loading in SCA [9,10].…”

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confidence: 99%