Metabolic and endocrinologic complications in beta-thalassemia major: a multicenter study in Tehran

Abstract

BackgroundThe combination of transfusion and chelation therapy has dramatically extended the life expectancy of thalassemic patients. The main objective of this study is to determine the prevalence of prominent thalassemia complications.MethodsTwo hundred twenty patients entered the study. Physicians collected demographic and anthropometric data and the history of therapies as well as menstrual histories. Patients have been examined to determine their pubertal status. Serum levels of 25(OH) D, calcium, phosphate, iPTH were measured. Thyroid function was assessed by T3, T4 and TSH. Zinc and copper in serum were determined by flame atomic absorption spectrophotometry. Bone mineral density (BMD) measurements at lumbar and femoral regions have been done using dual x-ray absorptiometry. The dietary calcium, zinc and copper intakes were estimated by food-frequency questionnaires.ResultsShort stature was seen in 39.3% of our patients. Hypogonadism was seen in 22.9% of boys and 12.2% of girls. Hypoparathyroidism and primary hypothyroidism was present in 7.6% and 7.7% of the patients. About 13 % of patients had more than one endocrine complication with mean serum ferritin of 1678 ± 955 micrograms/lit. Prevalence of lumbar osteoporosis and osteopenia were 50.7% and 39.4%. Femoral osteoporosis and osteopenia were present in 10.8% and 36.9% of the patients. Lumbar BMD abnormalities were associated with duration of chelation therapy. Low serum zinc and copper was observed in 79.6% and 68% of the study population respectively. Serum zinc showed significant association with lumbar but not femoral BMD. In 37.2% of patients serum levels of 25(OH) D below 23 nmol/l were detected.ConclusionHigh prevalence of complications among our thalassemics signifies the importance of more detailed studies along with therapeutic interventions.

Associated Complications In Beta Thalassemia Patients

“…This figure is quite less than earlier reports. This figure is lower than 57% reported by Satwani et al and 88% reported by Shamshirsaz et al [18,9]. In a multicentre study from Italy involving 1861 patients, hypogonadism was present in 47% of girls older than 15 years of age and secondary amenorrhoea in 23%, menstrual irregularity in 14% and arrest of sexual maturation in 13%.…”

“…These complications have contributed little to morbidity and mortality in the past; however as a result of increased longevity, these have become more common and contribute significantly to the morbidity in these patients [17]. Endocrine complications along with osteoporosis, trace elements deficiency and other metabolic disturbances also lead to growth failure and short stature [9,10]. Hypogonadism is the most frequent endocrine complication in patients with thalassemia and is an important cause of growth retardation in adolescence.…”

“…In our study the growth failure (49.4%) was found to be the most common complication. It is due to growth hormone neuro-secretary disturbance and secondary growth hormone insensitivity [9,10]. Chronic anaemia, congestive cardiac failure, haemosiderosis and other endocrine and metabolic disturbances may also be contributory factors [11].…”

Effect of Iron Overload on Gonadotrophins and Organ Sex Steroids in Pubertal Thalassemia Patients

“…Thus, these cells are most affected, resulting in declining synthesis of luteinizing hormone (LH) and follicle-stimulating hormone (FSH). A study found significant difference in mean serum ferritin level between thalassemic patients with primary amenorrhea, irregular mense, hypogonadism and those without endocrinopathies [10].The current study shows statistically significant low FSH and LH levels as well as significant negative correlation between ferritin and the gonadotrophins in both male and female thalassemic group.…”

“…It is still not known whether iron deposition in the pituitary gonadotrophic cells or gondal iron deposition or both causes the hypogonadism. Some studies [10] found significant difference in mean serum ferritin level between thalassemic patients with primary amenorrhea, irregular mense, hypogonadism and those without endocrinopathies. These findings yield the importance of iron overload in development of endocrine disorders among which hypogonadism is most frequent.…”