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      Relationship Between Pituitary Siderosis and Endocrinological Disorders in Pediatric Patients with Beta-Thalassemia

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      1 , 2 , 3 , 4 , 5 , 6 , 6 ,
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      Cureus
      Cureus
      beta thalassemia, pituitary mri, t2, siderosis

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          Abstract

          Introduction

          Excess iron accumulation occurs mainly in organs such as reticuloendothelial cells, the pituitary gland, and the pancreas in beta-thalassemia because of blood transfusions. In the present study, it was aimed to investigate the relationship between T2* values on magnetic resonance imaging (MRI) and clinically diagnosed pituitary endocrinological disorders in children with thalassemia major.

          Methods

          This study enrolled patients diagnosed with beta-thalassemia at pediatric hematology outpatient clinics. In the study, in addition to the medical history of the patients, routinely performed tests, including hemoglobin electrophoresis, routine biochemical tests, and tests for pubertal development (follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol, testosterone, etc.), as well as iron deposition measured by hepatic MRI T2* (STAR) sequence, were retrospectively assessed. A total of 29 patients were enrolled.

          Results

          Hypothyroidism was detected in 34.6% (9/26) of patients, short stature in 37% (10/27), and pubertal retardation in 50% (14/28) of the patients. There was no significant correlation between hypothyroidism and pituitary MRI T2* values. No significant correlation was found between laboratory parameters and pituitary MRI examination. Although the sensitivity of T2* levels could rise above 80%, their specificity remained low. This is one of the major limitations of the pituitary MR T2* study for the prediction of short stature. The best lower cut-off level of MR T2* to predict short stature was found 14.6 ms.

          Conclusion

          The diagnostic specificity pituitary MR examination levels for short stature were detected as low. Thus, the clinical standardization and validation of pituitary MR T2* values examination are needed before clinical follow-up and multifaceted studies are needed.

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          Most cited references30

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          Cardiovascular T2-star (T2*) magnetic resonance for the early diagnosis of myocardial iron overload.

          To develop and validate a non-invasive method for measuring myocardial iron in order to allow diagnosis and treatment before overt cardiomyopathy and failure develops. We have developed a new magnetic resonance T2-star (T2*) technique for the measurement of tissue iron, with validation to chemical estimation of iron in patients undergoing liver biopsy. To assess the clinical value of this technique, we subsequently correlated myocardial iron measured by this T2* technique with ventricular function in 106 patients with thalassaemia major. There was a significant, curvilinear, inverse correlation between iron concentration by biopsy and liver T2* (r=0.93, P<0.0001). Inter-study cardiac reproducibility was 5.0%. As myocardial iron increased, there was a progressive decline in ejection fraction (r=0.61, P<0.001). All patients with ventricular dysfunction had a myocardial T2* of <20 ms. There was no significant correlation between myocardial T2* and the conventional parameters of iron status, serum ferritin and liver iron. Multivariate analysis of clinical parameters to predict the requirement for cardiac medication identified myocardial T2* as the most significant variable (odds ratio 0.79, P<0.002). Myocardial iron deposition can be reproducibly quantified using myocardial T2* and this is the most significant variable for predicting the need for ventricular dysfunction treatment. Myocardial iron content cannot be predicted from serum ferritin or liver iron, and conventional assessments of cardiac function can only detect those with advanced disease. Early intensification of iron chelation therapy, guided by this technique, should reduce mortality from this reversible cardiomyopathy.
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            Noninvasive measurement and imaging of liver iron concentrations using proton magnetic resonance.

            Measurement of liver iron concentration (LIC) is necessary for a range of iron-loading disorders such as hereditary hemochromatosis, thalassemia, sickle cell disease, aplastic anemia, and myelodysplasia. Currently, chemical analysis of needle biopsy specimens is the most common accepted method of measurement. This study presents a readily available noninvasive method of measuring and imaging LICs in vivo using clinical 1.5-T magnetic resonance imaging units. Mean liver proton transverse relaxation rates (R2) were measured for 105 humans. A value for the LIC for each subject was obtained by chemical assay of a needle biopsy specimen. High degrees of sensitivity and specificity of R2 to biopsy LICs were found at the clinically significant LIC thresholds of 1.8, 3.2, 7.0, and 15.0 mg Fe/g dry tissue. A calibration curve relating liver R2 to LIC has been deduced from the data covering the range of LICs from 0.3 to 42.7 mg Fe/g dry tissue. Proton transverse relaxation rates in aqueous paramagnetic solutions were also measured on each magnetic resonance imaging unit to ensure instrument-independent results. Measurements of proton transverse relaxivity of aqueous MnCl2 phantoms on 13 different magnetic resonance imaging units using the method yielded a coefficient of variation of 2.1%.
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              Normalisation of total body iron load with very intensive combined chelation reverses cardiac and endocrine complications of thalassaemia major.

              Cardiac and endocrine disorders are common sequelae of iron overload in transfused thalassaemia patients. Combined chelation with desferrioxamine (DFO) and deferiprone (DFP) is well tolerated and produces an additive/synergistic effect superior to either drug alone. 52 thalassaemia major patients were transitioned from DFO to combined chelation with DFO and DFP. Serum ferritin, cardiac and hepatic iron levels were monitored regularly for up to 7 years, as were cardiac and endocrine function. Patients' iron load normalized, as judged by ferritin and cardiac and hepatic magnetic resonance imaging findings. In all 12 patients receiving treatment for cardiac dysfunction, symptoms reversed following combined chelation, enabling nine patients to discontinue heart medications. In the 39 patients with abnormal glucose metabolism, 44% normalized. In 18 requiring thyroxine supplementation for hypothyroidism, 10 were able to discontinue, and four reduced their thyroxine dose. In 14 hypogonadal males on testosterone therapy, seven stopped treatment. Of the 19 females, who were hypogonadal on DFO monotherapy, six were able to conceive. Moreover, no patients developed de novo cardiac or endocrine complications. These results suggest that intensive combined chelation normalized patients' iron load and thereby prevented and reversed cardiac and multiple endocrine complications associated with transfusion iron overload.
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                Author and article information

                Journal
                Cureus
                Cureus
                2168-8184
                Cureus
                Cureus (Palo Alto (CA) )
                2168-8184
                23 January 2021
                January 2021
                : 13
                : 1
                : e12877
                Affiliations
                [1 ] Pediatrics, Dicle University School of Medicine, Diyarbakir, TUR
                [2 ] Pediatric Allergy, Dicle University School of Medicine, Diyarbakir, TUR
                [3 ] Radiology, Memorial Regional Hospital, Diyarbakir, TUR
                [4 ] Pediatric Oncology, Dicle University School of Medicine, Diyarbakir, TUR
                [5 ] Pathology, Dicle University School of Medicine, Diyarbakir, TUR
                [6 ] Radiology, Dicle University School of Medicine, Diyarbakir, TUR
                Author notes
                Article
                10.7759/cureus.12877
                7899051
                255b4d33-5455-4dbe-a1be-8c122e50ec67
                Copyright © 2021, Yılmaz et al.

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 23 January 2021
                Categories
                Pediatrics

                beta thalassemia,pituitary mri,t2,siderosis
                beta thalassemia, pituitary mri, t2, siderosis

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