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Query: UMLS:C0039730 (thalassemia)
 10,305 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A large number of children treated from the time of diagnosis with modern transfusion and chelation therapy are now entering early adolescence or early adulthood, and only now can we evaluate how many complications, secondary to iron overload, can be prevented by daily s.c. desferrioxamine (DFX) therapy. In 1989, we planned a multi-centre study on growth and endocrine complications in patients who started chelation therapy with DFX early in life. Height, weight, endocrine complications, haematological variables and compliance with DFX were evaluated in a study group of 238 patients aged 2-17 years with beta-thalassaemia major regularly followed in 13 paediatric and haematological Italian centres. The LMS method by Cole and Green and the Mann-Whitney test were applied for statistical analysis. Twenty-six patients with thalassaemia (12.4%) had growth hormone insufficiency, five patients (2.1%) had primary hypothyroidism and four patients (1.7%) had hypoparathyroidism. Delayed puberty was present in 18.4% of boys and 17.7% of girls. At the beginning of chelation, standing height was in the normal range when compared to Swiss standards, while in the following years a progressive decline of growth was observed in both sexes. In conclusion, our study noted a positive effect of DFX therapy on sexual maturation and endocrine complications. Nevertheless, short stature has persisted despite major advances in treatment.
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PMID:Impact of long-term iron chelation therapy on growth and endocrine functions in thalassaemia. 1675 31

Over a 2-month period, 200 type 1 diabetic patients attending a paediatric diabetic clinic in Cairo, Egypt were screened for anaemia and other complications of diabetes. The mean age was 11.2 years and the mean duration of diabetes was 4.0 years. Anaemia was diagnosed in 75 patients (37.5%) overall: 45 had microcytic hypochromic anaemia, 18 normocytic normochromic and 12 macrocytic hyperchromic. Of the 75, 41 patients (54.7%) had iron deficiency, 14 (18.7%) had folate deficiency and 14 (18.7%) had thalassaemia minor. Three patients (4%) had coeliac disease, and 18 patients (24%) had parasitic infections. None of the patients had hypothyroidism, renal failure or vitamin B12 deficiency.
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PMID:Prevalence and type of anaemia in young Egyptian patients with type 1 diabetes mellitus. 1676 66

Patients with beta-thalassemia (thal) major are subject to peroxidative tissue injury by iron overload. Glutathione S-transferases work as antioxidants, and their activity is determined genetically. In this study, we used multiplex polymerase chain reaction (m-PCR) to analyze polymorphisms of two endogenous antioxidant agents, glutathione S-transferase M1 (GSTM1) and glutathione S-transferase T1 (GSTT1), and to determine their roles in 41 patients with beta-thal major. Our results showed that the GSTM1 and GSTT1 null genotypes were not associated with any incidence of endocrine dysfunction (including diabetes mellitus, hypogonadism, hypothyroidism, and growth hormone deficiency), liver function, or impaired left ventricular ejection fraction (LVEF). The GSTM1 null genotype, but not the GSTT1 null genotype, was associated with a decreased signal intensity ratio on cardiac magnetic resonance imaging (MRI). Our results suggest that genetic variations of the GSTM1 enzyme are associated with cardiac iron deposition in patients with beta-thal major.
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PMID:Glutathione S-transferase M1 gene polymorphisms are associated with cardiac iron deposition in patients with beta-thalassemia major. 1679 50

Iron-overload associated endocrinopathy is the most frequently reported complication of chronic transfusion therapy in patients with thalassaemia (Thal). This study compared iron-overloaded subjects with Thal (n = 142; 54%M; age 25.8 +/- 8.1 years) and transfused sickle-cell disease (Tx-SCD; n = 199; 43%M, 24.9 +/- 13.2 years) to non-transfused SCD subjects (non-Tx-SCD; n = 64, 50%M, 25.3 +/- 11.3 years), to explore whether the underlying haemoglobinopathy influences the development of endocrinopathy. Subjects were recruited from 31 centres in the USA, Canada and the UK. Subjects with Thal had more evidence of diabetes (13% vs. 2%, P < 0.001), hypogonadism (40% vs. 4%, P < 0.001), hypothyroidism (10% vs. 2%, P = <0.001) and growth failure (33% vs. 7%, P < 0.001), versus Tx-SCD. Fifty-six per cent of Thal had more than one endocrinopathy compared with only 13% of Tx-SCD (P < 0.001). In contrast, Tx-SCD was not different from non-Tx-SCD. Multivariate analysis indicated that endocrinopathy was more likely in Thal than SCD [Odds Ratio (OR) = 9.4, P < 0.001], with duration of chronic transfusion a significant predictor (OR = 1.4 per 10 years of transfusion, P = 0.04). Despite iron overload, endocrinopathy was not increased in Tx-SCD versus non-Tx-SCD, suggesting that the underlying disease may modulate iron-related endocrine injury. However, because transfusion duration remained a significant predictor of endocrinopathy, these data should be confirmed in SCD subjects that have been chronically transfused for longer periods of time.
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PMID:Increased prevalence of iron-overload associated endocrinopathy in thalassaemia versus sickle-cell disease. 1705 76

Hemolytic anemias can induce various anomalies of the endocrine glands which can already be observed in children. Endocrine dysfunction is also found in the course of therapy for aplastic anemias, usually as undesirable side effects. In Europe, 2-9% of the population belongs to ethnic minorities at risk for developing hemolytic anemia. Pituitary affinity to iron deposition explains the high incidence of hypogonadism, puberty delay and growth retardation although other factors have to be considered. Growth hormone deficiency has to be ruled out as it can occur in a minority of subjects with thalassemia and sickle-cell disease (drepanocytosis). Diabetes mellitus, hypothyroidism and hypoparathyroidism may also develop. Follow-up includes close monitoring of growth and pubertal development in order to guide therapeutic interventions.
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PMID:[Severe chronic anemia and endocrine disorders in children]. 1752 72

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> or =12 years and liver iron concentration> or =10 mg/g dry wt or serum ferritin> or =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 years), 203 subjects with TxSCD (44% Male, 24.7+/-0.9 years: Mean+/-SE), and 65 NonTxSCD (50% Male, 22.2+/-1.3 years) 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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PMID:Fracture prevalence and relationship to endocrinopathy in iron overloaded patients with sickle cell disease and thalassemia. 1843 Jun 24

Osteopenia and osteoporosis cause severe problems in thalassemic patients. The pathogenesis of bone loss in thalassemia is multifactorial. The delay in sexual maturation, the presence of diabetes and hypothyroidism, the parathyroid gland dysfunction, the accelerated hemopoiesis with progressive marrow expansion, the direct iron toxicity on osteoblasts, the iron chelators, the deficiency of growth hormone or insulin growth factors, all have been identified as major causes of osteoporosis in thalassemia. However, despite the normalization of hemoglobin levels, adequate hormone replacement and effective iron chelation, patients continue to show an unbalanced bone turnover with an increased resorptive phase resulting in seriously diminished bone mineral density (BMD). During the last decade bisphosphonates have been used for the management of osteoporosis in thalassemia. Alendronate, pamidronate and zoledronic acid have shown efficacy in increasing BMD in thalassemic patients. However, further trials must be conducted in order to clarify the exact role of each bisphosphonate, the long-term benefit and side-effects as well as the effects of the combination of bisphosphonates with other effective agents, such as hormonal replacement, on thalassemia osteoporosis.
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PMID:Pathogenesis and management of osteoporosis in thalassemia. 1933 61

273 patients with thalassaemia major followed from diagnosis in the Ferrara Centre were divided into 3 cohorts (C) according to the year of birth (C1=1954-1964, 85 patients; C2=1965-1974, 129 patients; C3=1975-2001, 59 patients) in order to study the trends of endocrine complications. Menarche occurred in 52 out of 112 patients (46%), without significant differences among the 3 groups, at the mean age of 13.9+/-1.4 years. Sixty-five percent of these patients had secondary amenorrhoea at the mean age of 18.8+/-3.7 years. In males complete pubertal development occurred in 48% of patients (C1:31%, C2: 44%, C3: 63%, p<0.05) followed by secondary hypogonadism in 24% of patients above 21 years of age. Primary (80%) and central 20%) hypothyroidism were diagnosed in 31% of patients (C1: 55%, C2: 31.5%, C3: 13.4%, p<0.05), diabetes mellitus (DM) in 17% of patients (C1: 28.6%, C2: 17.2%, C3: 3.4%, p<0.05), and hypoparathyroidism in 10.6% of cases (C1: 18.7%, C2: 10.1%, C3: 3.4%, p<0.05). No difference was found in patient mean age of diagnosis of hypothyroidism, DM or hypoparathyroidism (20.4+/-8.2 years, 19+/-5 yrs and 18.5+/-5.8 yrs respectively) but in all three groups age at diagnosis significantly increased over time (hypothyroidism and DM: p<0.001; hypoparathyroidism: p<0.01). Over time the prevalence of hypothyroidism, diabetes mellitus and hypoparathyroidism increased to 24.4%, 14.7%, and 6.7%, respectively, at the time of the study. Incidences peaked in the early 1980's, and declined in the following years (primary hypothyroidism from 6.5% in 1981 to 0.9% in 2007, p<0.01; DM from 3.9% in 1986 to 0.8% in 2007, p<0.05; hypoparathyroidism 2.4% in 1984 to 0% in 2007, p<0.01) and correlated with the decrease in annual mean serum ferritin levels in all patients (p<0.001). The main risk factors associated with endocrine complications were high serum ferritin levels, poor compliance with desferioxamine (DFO) therapy, early onset of transfusion therapy (only for hypogonadism) and splenectomy (only for hypothyroidism). Serum ferritin levels of approximately 2000 ng/ml were found to correlate with hypogonadism, and 3000 ng/ml for hypothyroidism, hypoparathyroidism and DM. The incidences of hypothyroidism, DM and hypoparathyroidism were not significantly different in 18 patients on long term treatment with deferiprone (DPO) compared with 64 patients continuously treated with DFO, from 1995 to 2007. In conclusion, our longitudinal study shows that in the last 30 years in the Ferrara Centre the incidences of hypothyroidism, diabetes mellitus, and hypoparathyroidism declined, and pubertal development in males with thalassemia major improved in patients, on DFO treatment, born after 1976. The efficacy of alternative chelation regimes with deferiprone or deferasirox to monotherapy with desferioxamine remains to be established.
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PMID:Hypogonadism, diabetes mellitus, hypothyroidism, hypoparathyroidism: incidence and prevalence related to iron overload and chelation therapy in patients with thalassaemia major followed from 1980 to 2007 in the Ferrara Centre. 1933 72

The severity of thyroid dysfunction in patients with beta-thalassaemia major is variable in different series. An exaggerated thyrotropin response to thyrotropin-releasing-hormone (TRH) has been found in 1 out of 5 beta-thalassaemia major patients. Because it is not well known how many of these patients will develop overt or subclinical hypothyroidism, we reviewed retrospectively the thyroid status (thyroid hormones, TBG, TG basal and TSH peak after TRH test) of 24 children and adolescents with beta-thalassemia major (mean age 12.1+/-3.9 years) on periodic transfusion therapy, regularly followed in our Centre during the last 20 years. As controls we studied 30 normal subjects aged 13.4+/-2.5 years. In our group of 24 thalassaemics an exaggerated TSH response to TRH test was found in 8 (33.3%), 3 of whom developed subclinical or overt hypothyroidism from 3 to 11 years later. TSH peak values correlated directly with ferritin levels, ALT, and compliance index to chelation therapy. Our data suggest that an exaggerated TSH response to TRH test is frequent in beta-thalassemia major, and may evolve into subclinical or overt hypothyroidism as we found in 37.5% of our patients with sub-biochemical hypothyroidism.
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PMID:Exaggerated TSH response to TRH ("sub-biochemical" hypothyroidism) in prepubertal and adolescent thalassaemic patients with iron overload: prevalence and 20-year natural history. 1933 73

From 1990 to 1991, the Pediatric and Adolescent Endocrine Outpatient Clinic of Arcispedale S. Anna admitted 97 thalassaemia major (TM) patients for endocrine evaluation. Their mean age was 14.2+/-5.7 years (range 5-28 years). Sixty-eight (70%) had normal thyroid function and twenty-one (21.6%) were discharged with a diagnosis of hypothyroidism of different degrees of severity. Thirteen patients out of 21 (61.9%) were females. Twelve patients (57.1%) fulfilled the criteria for subclinical hypothyroidism (SH). Their mean age was 15.7+/-3.5 years (range 9-22 years). A positive direct correlation was observed between the following variables: TSH and serum ferritin, TG and basal TSH, basal TSH and peak levels after TRH stimulation test. In 6 out of 12 TM patients (50%) with SH type a, the basal ejection fraction assessed by MUGA scan was normal; 1 TM patient (8.3%) showed mild abnormality and 5 TM patients (41.6%) showed severe abnormalities. A normal response during exercise (increase in LVEF greater than 5 percentage units) occurred in 10 patients (83.3%). Global or segmental left ventricular dysfunction at rest and during exercise were found in 8 patients (66.6%) and 10 patients (83.3%), respectively. These cardiac abnormalities were more common in TM patients with severe iron overload and poor compliance to DFX treatment (group A: serum ferritin above 2500 ng/ml) compared to TM patients with mild-moderate iron overload (group B: serum ferritin below 2500 ng/ml). In the control group of TM patients (group C) with normal thyroid function the assessment of MUGA scan was normal in all subjects at rest and after exercise. Global or segmental left ventricular dysfunction was observed only during exercise in 50% of TM patients with normal thyroid function (group C). Our patients with SH exhibited three different thyroid function patterns during follow-up: a. 3 (25%) of 12 studied TM patients showed a normalization of serum TSH levels b. 2 patients (16.6%) showed intermittent elevation of serum TSH with normal serum FT4 concentrations c. 3 patients (25%) had a persistent mild elevation of serum TSH concentration (from 6.3 to 7.6 microU/ml) with serum FT4 concentrations within the normal range. Two TM patients (16.6%) were treated with L-thyroxine. The reason for starting therapy was an abnormality of basal LVEF in the presence of mild iron overload (serum ferritin levels 665 ng/ml and 523 ng/ml). One TM patient with persistent SH type a developed a papillary carcinoma, and another, a multinodular goiter. The serum ferritin levels at diagnosis were 4739 ng/ml and 744 ng/ml,respectively. The thyroid function in TM patients from group C remained normal during the follow-up period. Two patients (Group A: patients no. 1 and 2) with severe iron overload and poor compliance to chelation therapy died during the follow-up, due to heart failure and arrhythmia. The time intervals between the first abnormal LVEF value and the development of symptomatic heart failure were 3.8 and 4.3 years. An improvement of LVEF was observed in three TM patients from group A after 24 months of intensive subcutaneous chelation therapy with DFX, and in two patients from Group B after 12-14 months of L-thyroxine replacement therapy in association with regular iron chelation therapy. In those two TM patients the basal LVEF increased from 37% to 45% and from 45% to 49%. In conclusion, although the findings are limited to a small group of TM patients with SH type a, our results show a high prevalence of primary hypothyroidism with the predominance of its mildest form, its stable course over years in most patients, and the presence of cardiac involvement in patients with severe-moderate iron overload. Regular iron chelation therapy should be advised for these patients to prevent thyroid dysfunction and the development of clinically significant myocardial dysfunction. In addition, therapy with L-thyroxine should be considered in iron overloaded TM patients with SH and a poor response to chelation therapy and in patients with SH and mild iron overload.
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PMID:Mild subclinical hypothyroidism in thalassaemia major: prevalence, multigated radionuclide test, clinical and laboratory long-term follow-up study. 1933 74


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