Pituitary Iron Research Articles

MRI of the liver and the pituitary gland in patients with beta-thalassemia major: does hepatic siderosis predict pituitary iron deposition?

Our objective was to study, in thalassemic patients, if hepatic siderosis evaluated by MRI could predict the pituitary iron overload. In 36 thalassemic patients (age range 6-44 years, mean age 21.7 years) the liver/fat ratio (L/F), the pituitary/fat ratio (P/F), the liver and pituitary T2 relaxation times were evaluated, by using a multiecho spin-echo sequence. Serum ferritin levels were measured and an extensive endocrine evaluation was performed. The L/F, the P/F and pituitary T2 showed a good correlation with serum ferritin ( r=-0.55, r=-0.55 and r=-0.53, respectively; p<0.01). Liver T2 did not show significant correlation with serum ferritin. The variability of L/F explained only the 10.8% of the variability of pituitary T2 and of the P/F. When ferritin was added to the model it predicted only the 26.85% and the 30.8% of the variability of pituitary T2 and of the P/F, respectively. The P/F and pituitary T2 were lower in patients with hypogonadotropic hypogonadism (group 1) compared with those without pituitary dysfunction (group 2). No significant differences of L/F were found between the two groups. Hepatic iron overload evaluated by MR is a poor predictor of pituitary siderosis. The MR studies of the pituitary gland might be necessary to evaluate the pituitary iron overload.

T2 relaxation rate as an index of pituitary iron overload in patients with beta-thalassemia major.

In transfusion-dependent ss-thalassemia major, increased iron deposition in the pituitary gland has a cytotoxic effect, leading mainly to hypogonadotropic hypogonadism. Early detection and quantification of iron in the pituitary gland are of particular importance for successful treatment. The purpose of this study was to evaluate the T2 relaxation rate (1/T2) as a marker of pituitary siderosis. In 29 patients with ss-thalassemia major and 40 controls, we assessed the 1/T2 of the pituitary gland in a 1.5-T MR unit, using a multiecho spin-echo sequence. In all patients, an extensive endocrine evaluation was performed, including measurements of spontaneous and stimulated levels of gonadotropins, thyroid hormones, growth hormone, insulinlike growth factor, and adrenal hormones. A positive correlation was found between the 1/T2 and the serum ferritin level (r = 0.73, p < 0.001). The 1/T2 was higher in patients (mean, 0.020 msec(-1); SD, 0.006) compared with that of controls (mean, 0.011 msec(-1); SD, 0.001; p < 0.001). The 1/T2 was higher in patients with hypogonadotropic hypogonadism (mean, 0.024 msec(-1); SD, 0.006) in comparison with that of patients without any pituitary dysfunction (mean, 0.017 msec(-1); SD, 0.004; p < 0.05). The T2 relaxation rate could be used as an index of pituitary iron overload, and it might be of value to monitor treatment with deferoxamine in patients with ss-thalassemia major.

Hypogonadotrophic Pituitary Insufficiency in Transfusional Hemochromatosis Complicating Thalassemia Major: MR Imaging

To identify pituitary iron overload in patients with transfusion-dependent thalassemia major causing secondary hypogonadism, we prospectively evaluated signal intensity abnormalities of the anterior lobe of the pituitary gland of 30 patients comparing spin-echo, gradient-echo imaging and pituitary T2 relaxation times measurement. We found that pituitary iron overload can best be assessed by MR imaging using gradient-echo T2*-weighted technique to establish signal reduction in the anterior lobe of the pituitary gland. This finding is correlated to increasing serum ferritin level — a parameter that reflects the severity of iron overload, and is more evident in patients with secondary hypogonadism. This finding is consistent with the hypothesis of hypogonadotrophic pituitary insufficiency due to iron-induced cellular damage.

Pituitary-testicular axis in men with beta-thalassaemia major.

Delayed puberty and hypogonadism are frequently observed in patients with homozygous beta-thalassaemia. We evaluated the pituitary-testicular axis in 30 thalassaemic men, aged from 17 to 35 years who were regularly transfused and underwent chelation therapy, while emphasis was given to pituitary reserves of gonadotrophins and the correlation of hormones with serum ferritin (SF). The investigation included endocrinological examination, evaluation of serum basal levels of follicle stimulating hormone (FSH), luteinizing hormone (LH), free testosterone and gonadotrophin-releasing hormone (GnRH) test and also spermiograms. According to the results, patients were divided into three groups: group A, which included 18 eugonadal patients with moderately elevated SF, group B which included six patients who had hypogonadotrophic hypogonadism and excessive elevation of SF, and group C, which included six patients characterized as intermediate, with regard to sexual maturation and SF levels. In conclusion, beta-thalassaemia major leads to variable pituitary iron overload and thus hypophyseal damage. This endocrine disturbance is becoming less frequent nowadays with early and intensive chelation therapy.

MRI in haemochromatosis: pituitary versus testicular iron deposition in five patients with hypogonadism

MRI in haemochromatosis: pituitary versus testicular iron deposition in five patients with hypogonadism

Current Concepts in Rational Therapy for Haemochromatosis

Genetic haemochromatosis is characterised by an inappropriately high rate of iron absorption by the small intestine. The disease is transmitted as an autosomal recessive condition. The gene frequency in the Caucasian population is approximately 1 in 20 and the disease frequency is 1 in 400. Excessive iron deposition occurs in the liver, pancreas, heart, pituitary and joints and hepatic iron concentrations above approximately 400 mumol/g dry weight are always associated with fibrosis and usually with cirrhosis and progressive liver failure. Accurate diagnosis depends upon the demonstration of elevated hepatic iron stores. An hepatic iron index [hepatic iron concentration (in mumol/g dry weight) divided by patient age] of greater than 2.0 distinguishes homozygous subjects from the other conditions in which slight increases in hepatic iron concentration may occur, e.g. in a subject heterozygous for haemochromatosis or alcoholic liver disease. If cirrhosis is present, patients are at a high risk of developing hepatocellular carcinoma. Therefore, they should undergo regular abdominal ultrasound and alpha-fetoprotein estimation. In the absence of cirrhosis, phlebotomy restores life expectancy to normal. Venesection should be continued until all excess iron stores are removed as judged by failure of a rise in haemoglobin concentration on cessation of phlebotomy. Screening of first degree relatives should commence from a young age (e.g. 10 years). If serum ferritin or transferrin saturation are abnormal, liver biopsy should be undertaken. HLA typing of the family allows for the identification of those siblings who are most likely to develop the disease. Secondary iron overload is often multifactorial in origin. Iron chelation therapy with subcutaneous deferoxamine (desferrioxamine) should only commence after careful consideration of the potential benefits in each individual patient.

Effect of Age at the Start of Iron Chelation Therapy on Gonadal Function in β-Thalassemia Major

Patients with transfusion-dependent thalassemia major tend to have abnormal growth and sexual maturation at puberty, presumably as a result of pituitary iron overload. This study was designed to determine whether chelation therapy with deferoxamine before the age of puberty would ameliorate this problem. We examined 40 patients over 14 years of age with transfusion-dependent thalassemia major. The 19 patients in group A (mean [+/- SD] age at study, 17.0 +/- 1.5 years) had begun nightly treatment with subcutaneous deferoxamine before the age of 10 (mean age at start of treatment, 7.5 +/- 1.8 years). The 21 patients in group B (mean age, 24.1 +/- 3.8 years) had begun treatment after the age of 10 (mean age at start of treatment, 14.4 +/- 4.7 years). The abnormal findings were essentially confined to sexual development. The final height did not differ between groups or from the mean parental height in each group. Ninety percent of the patients in group A had normal sexual development, as compared with 38 percent of those in group B (P = 0.001). Outcomes were correlated with indexes of iron overload; the patients in group A had lower serum ferritin levels before chelation treatment (P = 0.01) and lower average serum ferritin levels during treatment (P = 0.005). Beginning chelation treatment with deferoxamine before the age of puberty can help children with transfusion-dependent thalassemia major to attain normal sexual maturation.