EFFECT OF ANTERIOR PITUITARY IRON OVERLOAD IN BETA THALASSEMIA MAJOR PATIENTS

Abstract

Ba~kgrQund: Thalassemia major is a hereditary baemolytic anaemia which is treated with repeated blood transfusions. About 240 million beta thalassemia carriers are present all over the world. Every year about 100,000 children are born with the disease of thalassemia. Thalassemia major is a homozygous trait in whiGh there is defective Hemoglobin synthesis that leads to the devei-opmenrorsevere-anemia:-Periudic-transfnsions along with chelation therapy have markedly improved the life span of thalassemic patients. Citrate toxicity and consequent iron overload leads to increase prevalence of endocrine complications in children, adolescents and young adults. Transfusion with chelation therapy has significantly extended life expectancy but, leads to complicatLQl1s due to iron overload. Beta thalassemia patients are more prone to develop different organ damage due to metabolic dysfunction, the actual mechanism is not clear but anemia and iron overload are most important factors leading to increase mortality and morbidity rate along with lipid peroxidation, .oxidative stress and free radical release that cause such condition. Maierials ~md Methods: The present study wa3conduct~d on a total of 300 individuals out of which 200 were patients suffering from beta thalassemia major and 100 were control matched for f age and gender with the thalassemic group. The total 300 individuals were further divided into 4 groups of <13 years female (50 thalassemic and 25 control), ~13 years female (50 thalassemic and 25 control), <13 years inale (50 thalassemic and 25 . control) and ~ 13 years male (50 thalassemic and 25 control). Height, Body Mass Index BMI, Hemoglobin and serum Ferritin levels were analyzed. Kisspeptin (Kp), FollIcle stimulating hormone (FSH), Luteinizing hormone (LH) and sex steroids were analyzed and correlation of these hOlmones with body mass . ' . . . index (BMI), serum FelTitin and Hemoglobin (Hb) levels in beta thalassemic patients undergoing regular blood transfusion was ~;tudied. GroVvih hom10ne ( GH), thyroid stimulating hormone (TSH), Triiodothyronine (T3), Thyroxine (T4) were analyzed and correlation of these hormones with body mass index (BMI), serum Ferritin, Hemoglobin (Bb) and Kisspeptin levels were done. Hepatitis Band C were detected in all thalassemic groups along with estimation of serum AL T levels. CorrelatiOll of serum Alanine Transaminase ALT levels with BMI, Hemoglobin and serum Ferritin levels was done along with estimation of prevalence of hepatitis and liver enlargement. Results: All groups had reduced height, BMI, Hb and high Fenitill levels as compare to the tt.Qllg.. PQsiti¥e..(P <O .-OO l)~lation oLBlV1l with Hemoglobin was seen in 2: 13 correlation. emales 2: 13 years bad significant (p<0.001) positive correlation of BMI with serum Ferritin levels. All groups had significantly reduced (P<O.OOI) erriin high in all thalassemic groups on comparison with control. Kisspeptin leve'Is in thalassemic females of <13 years females and ll1ales were significantly (P<O.OOl) low as compared to the control group. While thalassemic males of 2:13 years had significantly (P<O.OI) high Kisspeptin levels as compared to the control group. FSH levels in <13 and 2:13 years thalassemic male and female patients were significantly raised (P<O.OOI) as compared to the control group. LH levels in thalassemic males in <13 years were significantly high (P<O.OOI) as compared to the control group. While 2: 13 years thalassemic males had significantly (P<O. 001 ) reduced LH levels as compared-to the control group. Significantly high Testosterone (P<O.OOl) were observed in thalassemic males of <13 years as compared to the control group. While Estradiol levels were significantly low (P<O.OO 1) in <13 years thalassemic females. In <13 years thalassemic females FSH had a negative significant cOlTeiation (P<O.OOl) with Ferritin (r= -0.511). In thalassemic males of <13 years FSH had a significant (P<0.05) positive correlation with BMI (1'= 0.296) and negative significant correlation (P<O.OOI) with Hemoglobin (r= -0.479). In <13 years female LH had a significant (P<O.Ol) negative con'elation with Hemoglobin (r=-0.386). Estradiol in 2: 13 year females had a positive significant (P<O.05) con-elation with BMI (r= 0.318) and Hemoglobin (r=0.286). Growth hormone levels were significantly reduced in <13 years male and female thalassemic patients while the· levels were significantly raised in 2: 13 male and female thalassemic patients. T 3 levels in ? 13 years thalassemic females were significantly raised as compared to control. T 4 and TSH in <13 year thalassemic male were significantly reduced than control and 2:13 thalassemic males had significantly raised as compared to the control.GH in <13 years had a positive correlation with Kisspeptin (r=0.31 0). T3 in 2:13 years thalassemic females had a significant negative correlation with BMI(1=-OA08) and (P<0.05) with Hb ( r=0.329) and a positive correlation with Kisspeptin (r=0.317).1n <13 years thalassemic males T3 had a positive correlation with Ferritin (r=0.523).T4 in 2:13 thalassemic female had a positive correlation with BM! (r=O.333), Ferritin (R=O.317) and Hb(r=O.328). There was a positive correlation of T4 with Hb(r=0.422) in <13 year thalassemic males. TSH in ~13 thalassemic females had a positive correlation (P<O.OOl) with BMI (1'=0.487), Ferritin(r=0.S31) and (P<O.OI) with Hb (r=0.394). In_ > 13 thalassemic males TSH had a ~--------------~----~----------- Ferritin levels were significantly (P<O.OOl) high in all thalassemic groups on comparison with ignificant. correlation exist between serum ALT and Ferritin levels. Prevalence of hepatitis is greater than SO % in all four thalassemic groups. Conclusion: In beta thalassemic patients growth disturbance or delay is the main clinical feature that effects the life and wellbeing of these individuals. Our study has revealed that patients with beta thalassemia suffer from reduced height, BMI which is enhanced in patients having high levels of serum Ferritin (ng/rnL) and low Hemoglobin (gmldl). The growth retardation seen in these patients with thalassemia major is multifactorial, it can be due to under-nutrition, hypogonadism, hypothyroidism, and other complications of thalassemia such as tissue hypoxia • ' . , ' ... . . • • , f • " and side effects of chelating therapy with desfell'ioxamine. So, lifelong care and management of such patients is mandatory which :requires significant cost for proper treatment of these patients in aU aspects. Our study revealed that the levels of Kisspeptin in thalssemic females and males of < 13 years had reduced levels but, 2:13 years were raised but, at. the same time the levels FSH and LH were significantly deranged. These findings are suggestive that hormone production by hypothalmus was correctly secreting Kisspeptin according to the pubertal time frame but, the levels of hormones secreted by anterior pituitalY and the gonads were deranged due to damage caused by iron overload at pituitatY and gonadal level. Along with disturbed hypothalamic pituitary gonadal axis there was decreasedBMI, low Henioglobin and raised serum FelTitin levels. These findings are indicating that treatment with double chelation from early life should be considered for better outcomes in thalassemic patients. Regular blood transfusion followed by iron chelation therapy is just a supportive treatment for the disease of thalassemia which is associated with serious complications. But, during this suppOliive treatment, the magnitude of the body iron burden is the . principal deterrninant of clinical outcome for the prime goal i.e of iron-chelating therapy in patients with thalassemia major is to control body iron. The optimal body iron should be reduced both to prevenUbeadverse effects from the iron-chelating agent to prevent the risk of complications from iron overload. The apparent facts is that upon reaching ,.--___ --a, e o(pub.erty"J alassellliJ patients deyelop growth..retardatiol1 and pubertal failure. Thalassemic therapy. These defects stmt early in life but, become becomes obvious after the age of 8 years. In . =TIerefore, effective alternate chelation regImens should be considered to improve the complication resulting from chelation therapy. Serum FelTitin concentration is an important determinant of liver enzyme levels, and increased serum Ferritin level is an independent predictor of liver damage in thalassemic patients, so it is useful to identify patients at risk of steatohepatitis and advanced fibrosis. Hepatitis also effects the condition of such patients along with anemia and low BMLwhich reduce the ability of thalassemic patients to fight against such infections. Careful monitoring should be done at early stage of disease and serum Ferritin levels should also be maintained and frequently monitored to prevent further liver damage during the course of treatment