Hypothyroidism in children with Hb E/ß-thalassemia compared between those who received regular transfusion and those who underwent hematopoietic stem cell transplantation.

The studies of hypothyroidism in children with transfusion-dependent hemoglobin E/ß-thalassemia (TDT), especially in those who underwent hematopoietic stem cell transplantation (HSCT) are limited. We performed a longitudinal retrospective analysis of thyroid function test (TFT) results among TDT patients aged <25 years who received regular transfusion compared to those who underwent HSCT in Faculty of Medicine Siriraj hospital, Thailand during October 2003 to March 2019. Fifty patients (23 TDT, 27 HSCT) were included. The mean age at the last follow-up was 20.1 ± 2.8 vs. 14.5 ± 4.61 years, respectively. The median age at HSCT was 6 (range: 1.9-13.7) years. The prevalence of hypothyroidism among TDT and post-HSCT was 47.8% and 52.2%, respectively. No study patients showed symptoms or signs of hypothyroidism. Subclinical hypothyroidism was the most common type (63.6% of TDT, and 100% of post-HSCT). We found persistent hypothyroidism in 30.4% of TDT, and in 22.2% of post-HSCT. Thyroxine was given in 1 TDT patient with overt hypothyroidism, and in 3 of 6 post-HSCT patients with persistent subclinical hypothyroidism. The ex-thalassemia patients who underwent HSCT after the age of 10 years had a significantly higher risk of post-HSCT hypothyroidism compared to those who underwent HSCT at the age ≤10 years (hazard ratio: 12.01, 95% confidence interval: 1.65-87.41; p = 0.014). In conclusion, hypothyroidism was found to be common in both TDT and post-HSCT patients. Subclinical hypothyroidism without symptoms and signs was the most common type, and was diagnosed only by TFT screening. Long-term regular surveillance of TFT should be performed in both groups of patients.

Bone Mineral Density and Serum 25OHD in Children and Adolescents With Juvenile Idiopathic Arthritis.

Low bone mass is one of the complications of juvenile idiopathic arthritis (JIA). However, a study focusing on the low bone mass in children and adolescents with JIA in Southeast Asian countries is limited. This study aimed to evaluate the bone mineral density (BMD) of Thai patients with JIA and identify factors correlated with BMD. A cross-sectional study was conducted at a tertiary-care center. The BMD of the lumbar spines (BMDLS) and the total body (BMDTB) were measured by dual-energy X-ray absorptiometry. Thirty-eight patients were enrolled between July 2015 and January 2016. No patient had low BMDLS, and only 2 (5.3%) had low BMDTB. Serum 25-hydroxyvitamin D (25OHD) levels were significantly positively correlated with the BMDTB Z-score (coefficient: 0.047; 95% confidence interval = 0.011-0.082; P = .012). Our study demonstrated a very low prevalence of low bone mass. Optimization of the serum 25OHD level should be encouraged.

Reference values of bone mineral density of proximal femur for Southeast Asian children and adolescents.

Bone mineral density (BMD) of the proximal femur helps evaluate bone density in children with reduced mechanical loading of the lower extremities. This study provides the first reference values of bone mineral density of proximal femur according to age and sex for Southeast Asian children and adolescents.   OBJECTIVES: The study aimed to (1) establish normative data of BMD of the proximal femur (femoral neck and total hip), measured by dual-energy X-ray absorptiometry (DXA), for healthy Thai children aged 5 to 18 years and (2) ascertain the relationships between BMD, growth, and puberty. METHODS: Proximal femur scans of 170 boys and 191 girls obtained from DXA (Lunar Prodigy Pro, GE, and software enCORE version 7.53) were un-analyzed and then re-analyzed with the upgraded software enCORE version 17 SP2 for BMD assessment. The bone mineral apparent density of the femoral neck (FNBMAD) was calculated. RESULTS: Sex and Tanner stage-specific BMD normative data were generated. BMD values of the femoral neck and total hip increased with age and pubertal progression. FNBMAD values were not markedly influenced by age and puberty. Using multiple linear regression analysis, age and weight affected FNBMD and total hip BMD in boys and girls, but height and Tanner stage only influenced girls. Age did not significantly influence FNBMAD in either sex. Tanner stage weakly influenced FNBMAD only in boys. CONCLUSIONS: We established normative reference data for BMD of the proximal femur measured by DXA in Thai children aged 5 to 18 years. Our reference data will help clinicians and researchers assess and interpret the BMD of the proximal femur for Southeast Asian children.

Bone mineral density in primarily preadolescent children with hemoglobin E/ß-thalassemia with different severities and transfusion requirements.

BACKGROUND: Children with ß-thalassemia major and ß-thalassemia intermedia frequently have low bone mass. However, studies of bone mineral density (BMD) in children with transfusion-dependent (TD) or non-transfusion-dependent (NTD) hemoglobin (Hb) E/ß-thalassemia are scarce. OBJECTIVES: To determine the prevalence of low bone mass among mostly preadolescent children with NTD and TD Hb E/ß thalassemia and the related factors. METHODS: We investigated the BMD of the lumbar spine (LSBMD) and total body (TBBMD), measured by dual-energy X-ray absorptiometry, of 59 children with NTD Hb E/ß-thalassemia and 50 with TD Hb E/ß-thalassemia. RESULTS: The median age of the patients was 10.4 (6.2-13.5) years in the NTD group and 10.3 (5.9-14.1) years in the TD group. These children had a relatively low prevalence of low bone mass (NTD: 1.7%-10.2%; TD: 4%-14%). The values varied with the bone site measured and the BMD size-adjustment method used (height age vs. bone age). The NTD group had significantly lower TBBMD Z-scores (adjusted for height age) than the TD group. The proportion of patients with low lumbar spine bone mass (adjusted for bone age) was significantly higher for the TD group than for the NTD group. CONCLUSIONS: Our study demonstrates that most children with either disease had normal BMD. Patients with the NTD form had a lower TBBMD than those with the TD form. Low bone mass affected the lumbar spine of patients with TD Hb E/ß-thalassemia more than those with the NTD form.

Differences in longitudinal growth patterns of children and adolescents with transfusion-dependent hemoglobin E/ß-thalassemia and those achieving successful hematopoietic stem-cell transplantation.

BACKGROUND: Short stature is a very common endocrinopathy among children with transfusion-dependent (TD) thalassemia. Hematopoietic stem-cell transplantation (HSCT) is the only effective curative treatment for TD thalassemia. This study aimed to identify and compare the longitudinal growth patterns of children with TD hemoglobin E (Hb E)/ß-thalassemia against those of children successfully undergoing HSCT. MATERIALS AND METHODS: We reviewed the medical records of 39 patients with TD Hb E/ß-thalassemia receiving regular blood transfusions, and 39 post-HSCT patients. Longitudinal weight and height Z-scores at each year of age were recorded for TD patients, and longitudinal weight and height Z-scores at each year before and after HSCT were obtained for post-HSCT patients. RESULTS: The mean weight and height Z-scores of TD patients decreased gradually and were lowest at age 13. However, post-HSCT subjects saw significant improvement in their mean weight and height Z-scores 6 and 3 years after HSCT, respectively, relative to pre-HSCT baseline values. CONCLUSIONS: Longitudinal growth patterns differed between patients successfully undergoing HSCT and children and adolescents with TD Hb E/ß-thalassemia. HSCT significantly improved height outcomes of children and adolescents with TD Hb E/ß-thalassemia.

Early development of decreased ß-cell insulin secretion in children and adolescents with hemoglobin H disease and its relationship with levels of anemia.

BACKGROUND: Diabetes mellitus (DM) associated with iron overload has been reported among adults with transfusion-dependent thalassemia and those with non-transfusion-dependent thalassemia (NTDT), especially in ß-thalassemia disease. However, little is known about glucose metabolism and how early its dysregulation can develop in α-thalassemia hemoglobin H (Hb H) disease, which is one of the most common types of NTDT worldwide. PROCEDURE: We prospectively calculated glucose metabolism index in 40 patients (aged 10-25 years) with Hb H disease. Glucose metabolism data were compared between patients with deletional versus nondeletional Hb H, and between patients with normal versus abnormal insulin secretion/sensitivity. RESULTS: Despite normal glucose tolerance in all patients, 52.5% had abnormal insulinogenic index indicating decreased ß-cell insulin secretion. Patients with functional hemoglobin < 8 g/dL had significantly higher percentages of abnormal insulinogenic index. There was no significant difference in abnormal insulinogenic index between deletional and nondeletional Hb H. CONCLUSION: Decreased ß-cell insulin secretion is highly prevalent among children and adolescents with Hb H disease, and it is associated with levels of functional anemia at baseline, but not with the type of Hb H disease. This result warrants heightened awareness among hematologists due to potentially increased risk of DM later in life.

Prevalence of low bone mass among adolescents with nontransfusion-dependent hemoglobin E/ß-thalassemia and its relationship with anemia severity.

BACKGROUND: Low bone mass is common among adolescents with transfusion-dependent ß-thalassemia despite adequate transfusion and iron chelation. However, there are few reports regarding bone mineral density (BMD) among adolescents with nontransfusion-dependent thalassemia (NTDT). Indeed, only BMD data in patients with nontransfusion-dependent (NTD) ß-thalassemia intermedia have been reported. No previous study has investigated BMD among adolescents with NTD hemoglobin (Hb) E/ß-thalassemia. OBJECTIVE: To determine the prevalence of low bone mass among adolescents with NTD Hb E/ß-thalassemia and factors relating to low bone mass. METHODS: We investigated BMD of lumbar spine (L2-L4; BMDLS) and total body (BMDTB), as measured by dual-energy X-ray absorptiometry, in 22 adolescents (aged 13.2-20 years) with NTD Hb E/ß-thalassemia. RESULTS: Low bone mass was found to be 18.2% and 22.7% at the lumbar spine (BMDLS Z-score adjusted for bone age and height age) and 13.6% and 9.1% at the total body (BMDTB Z-score adjusted for bone age and height age). Patients with mean Hb level <8 g/dl were more likely to have low bone mass (BMDLS and BMDTB Z-scores adjusted for bone age) compared to those with Hb level ≥ 8 g/dl. Mean Hb level correlated with BMDLS and BMDTB Z-scores adjusted for bone age. CONCLUSION: We demonstrated that a low Hb level was associated with low bone mass among adolescents with NTD Hb E/ß-thalassemia. A significant proportion of low bone mass among these patients highlights the importance of appropriate management, including red cell transfusion, vitamin D and calcium supplementation for improved long-term bone health.

A normal reference of bone mineral density (BMD) measured by dual energy X-ray absorptiometry in healthy thai children and adolescents aged 5-18 years: a new reference for Southeast Asian Populations.

Ethnic-specific normative data of bone mineral density (BMD) is essential for the accurate interpretation of BMD measurement. There have been previous reports of normative BMD data for Caucasian and Asian children including Japanese, Chinese, Korean and Indian. However, the normative BMD data for Southeast Asian including Thai children and adolescents are not currently available. The goals of our study were 1) to establish normative data of BMD, bone mineral content (BMC), bone area (BA) and lean body mass (LBM) for healthy Thai children and adolescents; aged 5-18 years measured by dual energy X-ray absorptiometry (DXA, Lunar Prodigy) and 2) to evaluate the relationships between BMD vs. age, sex, puberty, weight, height, calcium intake and the age of menarche in our population. Gender and age-specific BMD (L2-4; LS and total body; TB), BMADLS (apparent BMD of the lumbar spine), BMC (L2-4 and total body), BA (L2-4 and total body) and LBM were evaluated in 367 children (174 boys and 193 girls). All parameters increased progressively with age. A rapid increase in BMD, BMC and BMADLS was observed at earlier ages in girls. Gender and Tanner stage-specific BMD normative data were also generated. The dynamic changes of BMD values from childhood to early and late puberty of Thai children appeared to be consistent with those of Caucasian and Asian populations. Using a multiple-regression, weight and Tanner stage significantly affected BMDLS, BMDTB and BMADLS in both genders. Only in girls, height was found to have significant influence on BMDTB and BMADLS. The positive correlation between BMD and several demographic parameters, except the calcium intake, was observed. In summary, we established a normal BMD reference for Thai children and adolescents and this will be of useful for clinicians and researchers to appropriately assess BMD in Thais and other Southeast Asian children.

Children with hemoglobin E/ß-thalassemia have a high risk of being vitamin D deficient even if they get abundant sun exposure: a study from Thailand.

BACKGROUND: Vitamin D is a key component in calcium homeostasis, bone mineralization and immune function, and people with a vitamin D deficiency may therefore be at higher risk of osteoporosis, osteopenia, delayed growth and fractures. Vitamin D deficiency is a known clinical complication of patients with ß-thalassemia major; however, as yet there are limited data on the vitamin D status of patients with Hb E/ß-thalassemia. Hb E/ß-thalassemia is characterized by a wide clinical heterogeneity ranging from non-transfusion dependency to transfusion dependency. Because patients with Hb E/ß-thalassemia are so clinically diverse, the prevalence of vitamin D deficiency might differ among Hb E/ß-thalassemia patients. PROCEDURE: We investigated the vitamin D status of 109 children with Hb E/ß-thalassemia who attended the Pediatric Hematology Clinic at the Siriraj Hospital in Bangkok, Thailand, from April 2009 to March 2010. RESULTS: Forty-nine of the children were classified as transfusion-dependent (TD) and the remainder (n = 60) as non-transfusion-dependent (NTD). Only 10.1% of the children in our study had normal vitamin D levels, despite Thailand's geographic position 15° N and 100° E and climate, which provides abundant sunlight exposure and therefore efficient vitamin D synthesis. In addition, NTD children were significantly more likely to be vitamin D deficient than TD children (P = 0.01). CONCLUSIONS: Our results highlight the importance of monitoring serum vitamin D levels in children with Hb E/ß-thalassemia regardless of their clinical severity or the amount of sunlight they are exposed to.

Adrenal insufficiency is prevalent in HbE/ß-thalassaemia paediatric patients irrespective of their clinical severity and transfusion requirement.

OBJECTIVES: Transfusion dependency is known to cause endocrinopathies in patients with thalassaemia such as adrenal insufficiency, because transfusion-related iron overload is injurious to endocrine organs. Children with HbE/ß-thalassaemia vary greatly in red cell transfusion requirement and some are transfusion dependent (TD), whereas others are nontransfusion dependent (NTD). Because iron overload is thought to be the primary cause of adrenal insufficiency, TD children with HbE/ß-thalassaemia are considered likely candidates for the development of adrenal insufficiency, while the adrenal function of NTD children is generally considered to be normal. As yet, the prevalence of adrenal insufficiency among children with NTD HbE/ß-thalassaemia is not known. The present study was performed to (i) assess the prevalence of adrenal insufficiency in children with both TD and NTD HbE/ß-thalassaemia and to evaluate whether there is any difference in the prevalence of adrenal insufficiency between both groups and (ii) determine the type of adrenal insufficiency (primary or secondary). METHODS: We investigated the prevalence of adrenal insufficiency among TD (n = 42) and NTD (n = 43) children with HbE/ß-thalassaemia by assessing morning serum cortisol levels, and we distinguished between primary and secondary adrenal insufficiency by assessing the cortisol responses following the 1- and 250-µg ACTH stimulation tests. RESULTS: The prevalence of adrenal insufficiency among TD and NTD children with HbE/ß-thalassaemia was 50% and 53·5%, respectively. By using the 250-µg ACTH stimulation test, at least 39% and 23·5% were diagnosed with adrenal gland hypofunction in TD and NTD children, respectively. CONCLUSION: This is the first study to show that adrenal insufficiency is common among all children with HbE/ß-thalassaemia, irrespective of their transfusion history or requirement. Our findings have important implications for the clinical management of these children.

Prevalence and risk factors of low bone mineral density among perinatally HIV-infected Thai adolescents receiving antiretroviral therapy.

BACKGROUND: Low bone mineral density (BMD) has been reported among 10%-54% of HIV-infected adolescents in developed countries. We studied the prevalence and predictors of low BMD among HIV-infected Thai adolescents receiving antiretroviral therapy. METHODS: A cross-sectional study of lumbar spine (L2-L4) BMD as measured by dual-energy X-ray absorptiometry in Thai HIV-infected adolescents aged 12-20 years was performed. The BMD Z score was analyzed using age-matched healthy Thai children as a reference. Serum 25-hydroxyvitamin D was performed. Osteopenia was defined as BMD Z score ≤ -2. RESULTS: From October 2010 to February 2011, 101 adolescents, 50% male, with a median age of 14.3 (range: 13.0-15.7) years were enrolled. The median [interquartile range (IQR)] current CD4 T-cell count was 646 (506-796) cells per cubic millimeter and 90% had plasma HIV-1 RNA <50 copies per milliliter. The mean BMD among HIV-infected adolescents and controls were 0.855 and 0.980 g/cm (P < 0.001). The median (IQR) L2-L4 spine BMD Z score was -1.0 (-1.9 to -0.1), of which 24% had BMD Z score ≤ -2.0. The median (IQR) of 25-hydroxyvitamin D level was 24.8 (20.0-31.4) ng/mL, of which 25% had vitamin D level < 20 ng/mL. In multivariate analysis, the height for age Z score < -1.5 (adjusted odds ratio: 6.2; 95% confidence interval: 2.2 to 17.7) and history of World Health Organization clinical stage 4 before antiretroviral therapy (adjusted odds ratio: 3.7; 95% confidence interval: 1.3 to 10.7) were significantly associated with osteopenia. CONCLUSION: One fourth of HIV-infected Thai adolescents have osteopenia. Children with history of advanced-staging or having low height for age are at risk of osteopenia. Preventive measures to prevent osteopenia should be incorporated in routine care for these adolescents.

Successful strategy to improve glucose tolerance in Thai obese youth.

BACKGROUND: Childhood obesity is an emerging national health problem in Thailand. Our previous study found that one third of obese children and adolescents had impaired glucose tolerance (IGT) and 2.6 percent had already developed type 2 diabetes mellitus. An immediate strategy needs to be established in order to improve these metabolic problems. OBJECTIVE: To determine whether diet and exercise education for lifestyle modification with or without metformin therapy in our diabetes clinic is enable to improve these metabolic problems. MATERIAL AND METHOD: Twenty-six Thai obese children and adolescents with IGT, who received at least 6 months of treatment consisting of lifestyle modification alone or lifestyle modification and metformin (combined treatment) were enrolled into this study. Each patient underwent the second 2-hour oral glucose tolerance test (OGTT). Plasma glucose, insulin levels, HbA1C and lipid profiles were measured. The results were compared with historical pre-treatment data. RESULTS: Approximately 1 year after intervention, 19 out of 26 patients with IGT completed the second 2-hour OGTT. Sixteen patients (84.2%) successfully reversed to be normal glucose tolerance whereas 3 patients (15.8%) remained IGT. Body mass index (BMI), BMISDS, 2-hour plasma glucose, basal insulin level, 2-hour insulin level were significantly decreased after treatment in normal OGTT group (Ps < 0.05). Treatment with lifestyle modification alone and combined treatment indifferently improved the abnormal glucose tolerance in our patient (83.3% vs. 84.6%). CONCLUSION: Impaired glucose tolerance in obese youth is a reversible abnormality by lifestyle modification with or without metformin.

Glycemic control and the psychosocial benefits gained by patients with type 1 diabetes mellitus attending the diabetes camp.

OBJECTIVE: The aim of this study was to evaluate the effectiveness of diabetes camp on glycemic control, knowledge, and psychosocial benefits among patients with type 1 diabetes (T1D). Glycemic control among patients with infrequent and frequent self-monitoring of blood glucose (SMBG) was also compared. METHODS: During a 5-day camp, 60 patients were taught diabetes self-management education (DSME). After camp, patients were divided into two groups based on frequency of SMBG (<3 versus 3-4 times/day) and were followed up until 6-month post-camp. Patients' HbA1c levels and knowledge were assessed at baseline, 3- and 6-month post-camp. Patients' impressions towards camp were assessed. RESULTS: In both SMBG groups, HbA1c levels decreased significantly at 3-month post-camp but did not sustain at 6-month monitoring. The patients with frequent SMBG had a lower mean HbA1c level. A significant improvement in knowledge was noted and sustained up to 6-month post-camp. The patients found diabetes camp of benefit and felt they could better cope with diabetes. CONCLUSIONS: Although the effect of the diabetes camp on glycemic control was short-lived, an improvement in knowledge and a better attitude towards having diabetes were seen among participants. PRACTICE IMPLICATIONS: The psychosocial benefits and knowledge gained by patients attending diabetes camp underline the importance of including a camp in a diabetes management plan. To improve patients' long-term glycemic control, a continuous education is required.

Etiology and glycemic control among Thai children and adolescents with diabetes mellitus.

BACKGROUND: There is little data on etiology and metabolic control in children and adolescents with diabetes in developing countries. OBJECTIVE: Determine the etiology of diabetes in Thai youths and to evaluate their glycemic control. MATERIAL AND METHOD: The authors retrospectively reviewed the case records of 157 patients seen at the Department of Pediatrics, Siriraj Hospital between 2003 and 2004. RESULT: Type 1 diabetes (T1D) comprised 83%, type 2 diabetes (T2D) 13%, and other types 4%. GAD65 and IA-2 antibodies were positive in 63% and 61% of T1D patients, and 0% and 9% of T2D patients, respectively. There were an increasing number of new cases, both T1D and T2D, during the study period compared with a previous study conducted at the hospital. Mean HbA1c in T1D and T2D were 8.9 +/- 2.1% and 6.2 +/- 1.80%, respectively (p < 0.001). CONCLUSION: Based on the present study, glycemic control appeared to be more satisfactory in T2D patients than those with T1D. Glycemic control among T1D patients was comparable to others in developed countries.