Thalassemic Group Research Articles

Dental Arch Dimensions in Subjects with Beta-thalassemia Major

Thalassemia is a group of inherited hemoglobinopathies with thalassemia major representing the severe form of the disease characterized by craniofacial deformities. The aim of this study is to provide a detailed description of dental arch dimensions in subjects with thalassemia major. The sample consisted of 43 thalassemic subjects, 24 males and 19 females, aged 7.3 to 15.4 years (mean ± SD = 10.6 ± 3.5 years) and control group matched by age and sex. Dental casts of the participants were measured for arch lengths, arch widths, using a digital sliding caliper. Student t-test was used for comparison of mean values between males and females as well as between thalassemic and control groups. The results show that all means of maxillary and mandibular arch dimensions in thalassemic males and females were smaller than their controls, with 14 of the 16 comparisons being statistically significant (ranged from p < 0.05 to p < 0.001).The segmental arch lengths in the maxilla and mandible of thalassemic group were reduced by an average of 2.59 and 2.55 mm respectively, compared with the control group. The mean maxillary and mandibular arch depths (lengths) in the thalassemic group were shorter by 3.21 and 2.63 mm respectively, relative to the controls (p < 0.001). All arch widths thalassemic patients were significantly reduced by an average ranged from 1.33 to 1.90 mm in the maxilla and 1.37 to 1.77 mm in the mandible. The present study showed that the maxillary and mandibular dental arches dimensions are significantly reduced in patients with thalassemia major compared with healthy control subjects. Changes in the size of dental arches and tooth dimensions in thalassemic patients have an impact on the occlusal relationships.These changes should be taken into account when planning orthodontic treatment and orthognathic surgery.

Profile of Behavior and IQ in Anemic Children.

Study the profile of behavior and intelligence of children with anemia and their possible association to the hematological parameters. Fifty-eight children (42 anemic; 16 controls), matched by age, sex, and culture with the patients, were subjected to both behavioral and IQ testing using Revised Behavior Problem Checklist (RBPCL) and Wechsler intelligence scale for children-revised and hematological laboratory evaluation After controlling for age, sex and culture, the mean IQ was lower in the iron deficiency group than both thalassemic and control groups (P<.000). The mean scores of conduct disorder, socialized aggression, and anxiety withdrawal of RBPCL were higher in thalassemic group while the mean scores of motor excess and attention problems score were higher in the iron deficiency group. Regression analysis showed that hemoglobin concentration in gram/dl was the predictor of IQ in both anemic group and for attention problems in iron deficiency group while the mean corpuscular volume was the predictor of motor excess score in iron deficiency group. Other associations were not statistically significant. Behavior problems and low intelligence were significantly high among anemic children. Their association with the hematological parameters varies according to the type of behavior and the type of anemia. These results cannot exclude the role of other factors in shaping the profile of behavior and IQ.

Reproductive Hormones and Hypothalamic-Pituitary-Ovarian Axis in Female Patients With Homozygous β-Thalassemia Major

Homozygous beta-thalassemia major (hbeta-TM) is an autosomal recessive hemoglobinopathy with prominent endocrine complications. Our aims were to evaluate reproductive hormones, hypothalamic-pituitary-ovarian axis, and fertility in female patients with hbeta-TM. One hundred forty-four female patients with hbeta-TM, aged 18 years or above were enrolled in the study. Seventy-four age-matched healthy female volunteers served as controls. Two blood samples were drawn from each subject at 20-minute intervals for the determination of the resting levels of the following hormones: luteinizing hormone, follicle-stimulating hormone, estradiol, insulin-like growth factor-1, and insulin-like growth factor binding protein-3. The hypothalamic-pituitary-ovarian axis was also assessed using the gonadotropin-releasing hormone test. Menstruation status and growth rate were also noted. Puberty was assessed in both groups by Tanner classification. The mean age of puberty in the control group and hbeta-TM patients was 10.8+/-1.2 and 16.4+/-2.2 years, respectively (P=0.01). The mean age of menarche was 11.4+/-1.3 and 16.8+/-2.1 years in control subjects and patients with thalassemia, respectively (P=0.01). Of studied subjects with hbeta-TM, 61 (42.4%) were short in stature (height below the third percentile and below -2 SD scores). The baseline and peak levels of luteinizing hormone, follicle-stimulating hormone, and estradiol after gonadotropin-releasing hormone test in thalassemic group were significantly lower than in the control group. Further interventional studies are warranted to better clarify the treatment options to attain normal puberty and sexual maturation in patients with thalassemia.

The Study of G/T Polymorphism in COLIA1 Gene and Osteoporosis in b-Thalassemia Patients.

Abstract 4078Poster Board III-1013 IntroductionOsteoporosis is an important cause of morbidity in patients with β thalassemia major. Several genes are thought to be involved in the pathogenesis of osteoporosis. Collagen type I alpha 1 (COLIA1) is one of the most prominent candidate genes, which has been consistently associated with osteoporosis in different populations. Polymorphism at the Sp1 binding site within a key regulatory region of COLIA 1 has been reported to be associated with susceptibility to osteoprotic fractures. Our objective was to detect the allelic distribution of COLIA1 gene in beta thalassemia patients and its relation to bone mineral density (BMD). Patients and methodsThe study included 25 beta thalassemia major patients (12-28 years, mean = 18.12±5.077 years) and 20 controls (mean age = 23.05±2.3 years) with no family history of thalassemia. Anthropometric measurements were done to all patients .Femoral and lumbar BMD was measured in all patients and control groups using dual energy absorbiometry (DXA). Assessment of the COLIA1 genotypes (SS, Ss, ss) and G/T polymorphism were done using PCR amplification and restriction enzyme digestion (Bal1) of DNA amplified products to thalassemic patients and control groups. ResultsHigh prevalence of growth retardation was observed in β thalassemia major patients in the form of short stature (36%), truncal shortening (48%) and under weight (8%). Osteopenia and osteoporosis were detected in 68% of the thalassemia patients with a highly significant lower lumbar and femoral BMD compared to controls (P<0.01) (Table 1). There was a non significant difference between genders regarding BMD, significant negative correlation was observed between long duration of desferroxamine (DFO) intake and low femoral and lumbar BMD (R=-0.571& P<0.01,R=-0.571&P<0.05) in β thalassemia patients. A negative correlation was observed between ferritin level and fat free mass% (FFM%) in thalassemic patients (R=-0.48& P<0.05) and low lumbar BMD in female patients (R=-0.55& P<0.05). There was a positive correlation between age of starting DFO and decreased sitting height in male patients (R=0.74&P<0.01). In the thalassemic group, frequency of COLIA1 alleles was S (94%), s (6%), 12% showed the G/T polymorphism while 88% had the G/G polymorphism (Table 2). Non significant difference was observed in most of the parameters between the 2 different groups of polymorphism. In the control group allele frequencies were S (87.5%) and s (12.5%), G/T polymorphism was present in 25%.and G/G in 75%. No association was detected between COLIA1 gene polymorphism and BMD in the lumbar spine or in femur bone in the thalassemia patients (P>0.05) while the s allele was associated with femoral and lumbar BMD in the control group (P<0.05, P<0.01) (Table 3). ConclusionHigh prevalence of growth impairment, osteopenia and osteoporosis in our β thalassemia major patients. Desferroxamine duration therapy was related to osteoporosis in our patients. The absence of association between BMD and COLIA 1 polymorphism and the low frequency of s allele in our thalassemic group may be due to the small sample size of the thalassemia patients together with the fact that BMD is determined by a variety of genetic and environmental factors. Further studies including larger number of patients are needed to evaluate these findings. Disclosures:No relevant conflicts of interest to declare.

CARACTERIZAÇÃO ERITROCITOMÉTRICA DIFERENCIAL ENTRE PORTADORES DE ANEMIA POR DEFICIÊNCIA DE FERRO, TRAÇO FALCIFORME E BETA TALASSEMIA MENOR

O número de funções discriminantes baseadas na automação, incorporou vários parâmetros relacionados ás células eritrocitárias, que foram desenvolvidas para diferenciar as várias formas de anemia. O objetivo deste trabalho, foi estabelecer padrões de diferenciação através dos índices eritrocitométricos em três estados patológicos do metabolismo da hemoglobina: a deficiência de ferro, o traço falciforme e a beta talassemia menor. A deficiência de ferro foi caracterizada em pacientes com níveis de ferritina abaixo de 10 ng/dL, enquanto que a beta talassemia menor e o traço falciforme foram definidas pela resistência osmótica alterada, teste de solubilidade para a hemoglobina S e eletroforese de hemoglobina. O grupo de talassêmicos revelou característica marcante em relação à elevada contagem de eritrócitos (acima de 5 milhões/mm3), diminuição do VCM e HCM (respectivamente abaixo de 71 fL e 24 pg) e presença de ponteado basófilo em todas as extensões sangüíneas analisadas, já no grupo deficiente de ferro houve grande variação quanto ao grau de microcitose e hipocrômia, podendo apresentar parâmetros semelhantes aos encontrados na beta talassemia menor. Por outro lado, o grupo de portadores do traço falciforme, apresentaram normocitose e normocromia . A elevação do RDW acima de 20% foi encontrada apenas no grupo deficiente de ferro, porém valores acima do normal (14,5%) foram encontrados nas três patologias, dificultando uma diferenciação por este parâmetro. Nosso estudo permite concluir que é possível presumir os portadores de beta talassemia menor, diferenciando-os daqueles portadores de anemia por deficiência de ferro e solicitar eletroforese de hemoglobina quantitativa, mas não é possível suspeitar dos que seriam portadores do traço falciforme, apenas pelos dados do eritrograma.

Renal function in children with β-thalassemia major and thalassemia intermedia

In beta-thalassemia, profound anemia and severe hemosiderosis cause functional and physiological abnormalities in various organ systems. In recent years, there have been few published studies demonstrating proteinuria, aminoaciduria, low urine osmolality, and excess secretion of the tubular damage markers, such as urinary N-acetyl-D-glucosaminidase (U(NAG)) and beta2 microglobulin, in patients with thalassemia. The object of this study was to analyze renal tubular and glomerular function in pediatric patients with beta-thalassemia and to correlate the renal findings to iron overload. Thirty-seven patients with beta-thalassemia major and 11 with thalassemia intermedia were studied. Twelve children without iron metabolism disorders or renal diseases served as a control group. No difference in blood urea nitrogen (BUN), serum creatinine, creatinine clearance, electrolytes, fractional excretion of sodium and potassium, and tubular phosphorus reabsorption was found. Serum uric acid was equal in the two groups, but its urine excretion was significantly higher in the thalassemic group. U(NAG) and U(NAG) to creatinine ratio (U(NAG/CR)) were elevated in all patients with thalassemia compared with the control group (p < 0.001) and were directly correlated to the amount of transfused iron but not to actual ferritin level. We found that renal tubular function is impaired in children with beta- thalassemia major and intermedia. It is not known whether these functional abnormalities would have any long-term effects on the patients. Further studies are needed, and means of preventing these disturbances should be sought.

ZINC STATUS IN PATIENTS WITH MAJOR β-THALASSEMIA

To determine the zinc status in patients with major β-thalassemia and its effect on their growth, the authors studied 64 thalassemic patients in comparison with 64 healthy matched individuals. Demographic and anthropometric data and history of the therapies were collected. Serum zinc level in both groups and ferritin in the thalassemic group were assigned. Interestingly, mean serum zinc level was significantly higher in the thalassemic group. No significant correlation between serum zinc level and short stature, serum ferritin level, desferrioxamine dose, initiating time of blood transfusion, and chelation therapy was found. The study indicates zinc deficiency in thalassemic patients who are on regular blood transfusion is rare and it seems that routine zinc supplementation is not necessary.

Quantitative determination of 8-hydroxy-2′-deoxyguanosine as a biomarker of oxidative stress in thalassemic patients using HPLC with an electrochemical detector

A simple and robust HPLC method with electrochemical detection was developed for the quantitative determination of 8-hydroxy-2′-deoxyguanosine (8-OHdG), a DNA damage product excreted in urine. Sample cleanup was carried out using solid-phase extraction (SPE) prior to chromatographic separation. 8-OHdG was well separated on an Eclipse XDB®-C18 column (150 × 4.6 mm i.d., 5 μm) with an Eclipse XDB®-C18 guard column (12 × 4.6 mm i.d., 5 μm). Two mobile phases containing methanol and 10 mM sodium formate (pH 4.5) at a ratio of 10: 90 and 50: 50 v/v, respectively, were used. The retention time of 8-OHdG was 9.8 ± 0.5 min. The recovery of 8-OHdG was found to be 97.2 ± 3.3% (n = 6). Intraday and interday precisions of the method were 4.0 ± 2.9% (n = 6) and 6.6 ± 1.7% (n = 6), respectively. The detection limit was 5 ng/mL. Preliminary investigation showed that the mean value of 8-OHdG, normalized with the amount of creatinine in the sample, from the thalassemic group was significantly higher than that from healthy subjects (211 ± 214 ng/mg creatinine vs. 31.4 ± 32.2 ng/mg creatinine, respectively), indicating oxidative stress.

Elevated F 2-isoprostanes in thalassemic patients

This study was aimed at investigating oxidative stress in thalassemic patients by measurement of the oxidative damage biomarker, F 2-isoprostanes (F 2-IsoPs), using gas chromatography-mass spectrometry. The results showed that the mean value of urinary F 2-IsoPs, normalized with creatinine, in the thalassemic group was significantly higher than that from healthy subjects (3.38 ± 2.15 ng/mg creatinine vs 0.86 ± 0.55 ng/mg creatinine, respectively), and the mean value of plasma total F 2-IsoPs in the thalassemic group was also significantly higher than that from healthy subjects (0.39 ± 0.15 ng/ml vs 0.18 ± 0.03 ng/ml, respectively). Serum ferritin, erythrocyte superoxide dismutase (SOD), glutathione peroxidase, glutathione, and TBARS levels after treatment of erythrocytes with H 2O 2 were also investigated, and serum ferritin and erythrocyte SOD levels were significantly higher in thalassemic patients. Our findings are consistent with oxidative stress in thalassemia patients.

H63D Mutation of the Hemochromatosis Gene and Serum Ferritin Levels in Thai Thalassemia Carriers

We determined the prevalence of the H63D and the IVS5#1G-A HFE mutations in 370 (169 males and 201 females) Thai thalassemia carriers and 201 normal subjects. While no IVS5#1G-A mutation was found, the H63D heterozygosity was identified in 5.5% (11/201) of normal subjects and 7.3% (27/370) of thalassemia carriers. Within the thalassemic group, the medians (ranges) of serum ferritin were 217.5 ng/ml (20.1–424.3) and 169.8 ng/ml (3.9–3,536.0) in male subjects and 30.4 ng/ml (11.9–130.7) and 49.3 ng/ml (0.6–931.0) in female subjects with (HD) and without (HH) H63D mutation, respectively. The proportions of subjects with elevated ferritin were found to be 37.5% (6/16) for HD and 14.0% (18/129) for HH in male and 0% (0/11) for HD and 3.0% (5/164) for HH in female subjects, respectively. Statistical analysis of all the data revealed no significant difference. Among 14 Hb E/β-thalassemia patients, no difference in hematological data as well as serum ferritin levels was observed between those with (HD) and without (HH) H63D mutation. Therefore, the H63D heterozygosity has no significant effect on the serum ferritin level and screening for this HFE mutation in thalassemic patients is not recommended.

Reticulocyte evaluation in α+‐thalassemia

Although it is almost certain that alpha(+)-thalassemia protects against malaria, the mechanisms for that are still unknown. It has been suggested that an increased number of young circulating red blood cells in alpha(+)-thalassemic children, as a result of some degree of ineffective erythropoiesis, could be related to the high frequencies of the alpha(+)-thalassemic allele in malaria endemic areas. Reticulocyte evaluation in this condition, however, has been poorly performed so far. Our objective was to determine the reticulocyte number and maturation degree, in addition to the soluble transferrin receptor and serum erythropoietin levels, in alpha(+)-thalassemia heterozygotes, comparing them with normal alpha-genotype controls. One hundred twenty-one alpha(+)-thalassemia carriers (-alpha(3.7)/alphaalpha) and 249 controls (alphaalpha/alphaalpha), all of them with normal serum ferritin levels, were subclassified according to age (1-5, 6-10, 11-15, 16-20, and over 20 years old). Reticulocyte analyzes were carried out by flow cytometry and sTfR and s-Epo levels determined by immunonephelometry and chemiluminescence, respectively. The comparisons did not show any significant difference between thalassemics and controls regarding the reticulocyte parameters [percentages and absolute values, P = 0.2643 and 0.5421; high, medium, and low maturation degree, P = 0.2579, 0.2196, and 0.4192; RET maturity index (RMI), P = 0.2471, respectively], as well as the s-Epo levels (P = 0.5711). The sTfR concentrations were higher in the thalassemic group (P = 0.0001), but statistical significance was due only to the 1-5 and over 20 subgroups (P = 0.0082 and 0.0436, respectively). The results found here are compatible with a compensated erythropoiesis and do not confirm the hypothesis mentioned above.

Degenerative disc disease as a cause of back pain in the thalassaemic population: a case-control study using MRI and plain radiographs

The aim of this study was to test our observation that back pain in thalassemic patients could be caused by premature and extensive lumbar degenerative disc disease, when compared to non-thalassemic patients with back pain. Sixteen thalassemic patients with their sex- and age-matched controls were recruited into the study, 12 with thalassemia major, and 4 with thalassemia intermedia. Both the thalassemia patients and control subjects suffered from back pain, which was subjective rather than measured/pain scored. All subjects underwent magnetic resonance (MR) imaging of the lumbar spine, and 11 of the cases and 8 controls had lumbar spine radiographs. Each lumbar disc was scored for radiographic appearances and MR features of disc degeneration and disc protrusion. Proportion values for these parameters and median scores were derived at each disc level, and were analyzed and compared. There was a statistically-significant difference between proportion values of cases and controls for the MR features (P value=0.01, n=16) and the radiographic features (P value=0.01, n=11 cases, n=8 controls) of disc degeneration. The median disc level scores for the thalassemic group were uniformly high across all lumbar discs, and at all levels except at L 4/5. The control group conversely demonstrated a predilection for disc degeneration at L4/5 level. The distribution of lumbar disc degeneration in thalassemic patients with back pain is more extensive, severe and multi-level in nature compared to matched controls, and disc degeneration should be considered as a significant cause of back pain in this population group.

Virological, immunological and histological aspects in adult beta-thalassemic patients with chronic hepatitis C virus infection.

Multitransfused adult beta-thalassemic patients constitute a population with high prevalence of hepatitis C virus (HCV) infection, because of transmission of HCV from infected blood donors prior to the introduction of anti-HCV screening. The aim of this study was to compare them with otherwise normal patients with HCV infection. Forty-two adult multitransfused beta-thalassemics and 49 otherwise normal patients of the same age, with chronic HCV infection were studied. Viral parameters, autoimmunity indices and liver histology were evaluated. Serum HCV RNA levels were found significantly lower in thalassemic (median: 65,150 international units per milliliter (IU/ml); range: 3 059 380 IU/ml) than in non-thalassemic (NT) patients (median: 580,000 IU/ml; range: 10,956,000 IU/ml; P=0.001). The most prevalent genotype in thalassemic group was genotype 4 (32.4%) while in NT group was genotype 3a (59.2%). Cryoglobulins were detected in 8/42 (19%) thalassemic patients and in 12/49 (24.5%) NTs. Thalassemic patients had significantly lower levels of C3 and C4 components of complement and higher incidence of anti-nuclear antibodies than those without thalassemia. In patients with thalassemia a lower grading score was noted in liver biopsy compared with those without thalassemia (4.41+/-1.98 vs 5.38 +/- 2.09, P=0.038). On the contrary, thalassemic patients were found to have a higher staging score (3.08 +/- 1.51 vs 2.33 +/- 1.34, P=0.024). Adult beta-thalassemic patients, compared with other patients with HCV infection, present lower necroinflammatory activity and lower viral load but higher staging score. Autoimmune features are marginally different. Age of acquiring the infection, iron overload and modulation of immune system by transfusions are the proposed causes of these differences.

Polyarthrite rhumatoïde associée à un trait bêta-thalassémique : aspect clinique, sérologique et immunogénétique

Objectives. – To investigate the clinical, serologic, radiologic and immunogenetic characteristics of rheumatoid arthritis occurring in patients with beta-thalassemic trait as compared with rheumatoid arthritis in control patients from the same geographical area. Materials and methods. – Twenty-eight patients with beta talassemic trait fulfilling the American College of Rheumatology criteria for rheumatoid arthritis were compared with a control group of twenty-eight rheumatoid arthritis patients matched for age, sex, disease duration and place of birth. Clinical and routine laboratory assessment, including anti-keratin antibodies and anti-citrullinated peptide antibodies, was carried out in the two groups. The patients were also evaluated for HLADRB1 alleles and radiologic damage. Results. – No differences were found with regard to clinical indexes of disease activity, laboratory parameters, and joint erosions. The immunogenetic analysis did not show any significant difference, the percentage of patients with alleles encoding for the shared epitope being similar in the two groups (61% vs 57%). As for the extra-articular features, we found a trend for a lower prevalence of sicca syndrome in the beta thalassemic group (14% vs 39%; P = 0.06). Rheumatoid nodules were not found in beta thalassemic patients while they were present in two rheumatoid arthritis patients in the control group. Conclusions. – The chronic polyarthritis occurring in beta thalassemic trait carriers can be regarded as a true rheumatoid arthritis similar to that found in Mediterranean countries, possibly characterized by a low prevalence of extra-articular-features.

Bone marrow transplantation for hematological disorders--Shiraz experience.

In the past 8 years, 120 cases of hematological disorders were transplanted from the HLA identical donors. Using chemotherapy based conditioning regimen with cyclophosphamide 200 mg/kg and busulfan 15-16 mg/kg, 80 cases of beta-thalassemia major and 35 cases of leukemia and five patients with aplastic anemia had received bone marrow transplantation. The five-year-survival in thalassemic group was 72%, for leukemic group (acute and chronic) was 58%, and also for aplastic anemia 65%. Transplantation related mortality was the cause of death in 29 cases. The two major causes of death were acute graft versus host disease and poor medical condition of patients before marrow transplantation. At the present time, allogenic marrow transplantation is curative mode of treatment for many hematological diseases.

EVALUATION OF OSTEOPOROSIS IN THALASSEMIA BY QUANTITATIVE COMPUTED TOMOGRAPHY: Is It Reliable?

This study was conducted to quantify the degree of osteoporosis in thalassemic patients by single energy quantitative computed tomography (SEQCT) and to test the reliability of this method. On 38 thalassemic patients with osteoporosis and 38 normal control subjects, bone mineral density (BMD) measurements were done by SEQCT. BMD and standard deviation (SD) of the x-ray attenuation numbers of pixels within region of interest (ROI) of the measurement areas were compared between two groups. Mean BMD values for thalassemic patients and control group were 173.4 and 158.2 mg/cm3, respectively. Mean BMD value for thalassemic patient group was significantly higher. Mean SD values of ROI for control group and thalassemic patients were 41.4 and 71.1, respectively. The difference between the SD values was also statistically significant. Positive correlation was noted between SD values and patients' ages in the thalassemic group. Results of SEQCT method may not reflect the clinical and conventional radiographic findings of osteoporosis seen in thalassemic patient group and should be used cautiously. Other methods of BMD measurement, such as photon absorbsiometry and x-ray absorbsiometry, should also be investigated for their accuracy in this patient group.

The Prevalence of Viral Hepatitis lnfections in lmmunodepressive Patient Groups

The frequency of HAV, HBV, HCV and HDV infections were evaluated in children with thalassemia and haematologic by ELİSA. A total of 136 serum specimens were tested for this purpose. Hepatitis B surface antigen (HBsAg) positivity was found in 46 % of patients with leukemia, 50 % of patients with lymphoma and 16.6 % of thalassemic children. Anti HCV was present in 8 % of leukeınia group and 16.6 % in thalassemic group. in our opinion, vira! hepatitis infections that have a great prevalence in multitransfused patient groups can be reduced by screening of blood donors for markers of viral hepatitis before transfusion.

Hereditary Red Cell Disorders in Southeast Asian Refugees and the Effect on the Prevalence of Thalassemia Disorders in the United States

This investigation established the frequency and prevalence of hemoglobin E, alpha and beta thalassemia, and glucose-6-phosphate dehydrogenase deficiency in a group of Southeast Asian individuals and determined the impact upon the prevalence of thalassemia disorders in the United States. The resettlement program of Southeast Asian refugees has significantly increased the total number of serious thalassemic disorders in the United States. For several generations Southeast Asian children will be the principal thalassemic group.

Sexual maturation and adrenal function in girls with thalassemia.

Adrenal steroid production was evaluated in 12 thalassemic girls aged between 18 and 22 years and at stage P1 of sexual maturation according to Tanner. The values found in these patients were compared with those in 12 normal girls of the same age at stage P4-5 of sexual maturation. Pregnelone, dehydroepiandrosterone, dehydroepiandosterone sulfate, progesterone, 17-OH-P, androstenedione, testosterone, dihydrotestosterone and estradiol were found to be significantly reduced (p less than 0.001) in the thalassemic group, while cortisol levels showed a slight but not statistically significant reduction. Plasma ferritin levels were greatly increased and showed a highly significant (p less than 0.001) correlation coefficient when plotted against each hormone. The present results suggest that the impaired adrenal function plays an important role in determining the delayed sexual maturation almost always present in the thalassemic patients and that this disorder may be due to iron overload.