Pairunyar Nakavachara

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/cm2 (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.

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

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 β‐thalassemia major; however, as yet there are limited data on the vitamin D status of patients with Hb E/β‐thalassemia. Hb E/β‐thalassemia is characterized by a wide clinical heterogeneity ranging from non‐transfusion dependency to transfusion dependency. Because patients with Hb E/β‐thalassemia are so clinically diverse, the prevalence of vitamin D deficiency might differ among Hb E/β‐thalassemia patients.

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

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/β‐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/β‐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).

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

Low bone mass is common among adolescents with transfusion‐dependent β‐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) β‐thalassemia intermedia have been reported. No previous study has investigated BMD among adolescents with NTD hemoglobin (Hb) E/β‐thalassemia.

Clinical and mutational spectrum of patients with congenital lipoid adrenal hyperplasia in Southeast Asia

Aims Mutations in Steroidogenic Acute Regulatory protein (StAR) cause congenital lipoid adrenal hyperplasia (lipoid CAH), characterized by absent steroidogenesis, potentially lethal salt loss, 46,XY sex reversal and massively enlarged adrenals engorged with cholesterol esters. Nonclassic lipoid CAH is a recently recognized disorder caused by StAR mutations that retain partial function. We aim to delineate the clinical and mutational spectrum of StAR mutations in patients with lipoid CAH.

Non-transfusion dependent hemoglobin E/β thalassemia had high prevalence of vitamin D deficiency than more severe patients who received regular blood transfusion and iron chelation therapy

Hb E/β thalassemia is the most common β thalassemia syndrome in Asia-Pacific due to a high prevalent of Hb E and β thalassemia genes. Management of this condition can be cumbersome due to its clinical heterogeneity and various disease severity ranging from severe end in which patients are transfusion dependent thalassemia (TD) similar to that of β thalassemia major (TM) to moderate and mild severity which are non-transfusion dependent thalassemia (NTDT) akin to β thalassemia intermedia. Although, clinical diagnosis of Hb E/β thalassemia might be identical, the natural history and disease related complications can vary greatly due to different baseline severity and management received. In this study, we evaluated vitamin D deficiency, one of the most common endocrine complications described in TM, in Thai HbE/β thalassemia children who were TD and NTDT. 109 children aged 5.9 to 14.1 years with HbE/β-thalassemia were enrolled. 60 patients who received no or occasional transfusion were classified into NTDT group. While 49 patients who received regular transfusion every 3 weeks to keep pre-transfusion Hb at 9-10 g/dL were classified into TD group. All TD patients except two received iron chelation. Blood samples were collected to determine hemoglobin, serum ferritin and 25-OHD levels. Mean Hb of NTDT was lower than TD patients (8.1+1.0 vs. 10.0+1.0 g/dL, P<0.001). In contrast, TD had higher mean serum ferritin than NTDT patients (4104+2336 vs. 347+488 ng/mL, P<0.001). However, mean serum 25-OHD of NTDT was lower than in TDT patients (22.7+5.2 vs. 25.0+6.1 ng/mL, P=0.043). Moreover, the percentage of patients who were vitamin D deficient (serum 25-OHD < 20 ng/mL) in NTDT was higher than TD patients (33.3% vs. 12.2%, P=0.01). We found no correlation between serum 25-OHD vs. ferritin and Hb levels. Although patients with HbE/b thalassemia do not require regular blood transfusion due to their ‘milder’ clinical severity, they remain at high risk of having vitamin D deficiency. A better standard of care for these neglected patients is in an urgent need and a regular monitoring of serum 25-OHD with adequate vitamin D supplementation for deficient patients is highly recommended for all Hb E/b thalassemia regardless of their clinical severity.

Thyrotoxic periodic paralysis and chorea: two uncommon neuromuscular complications in an adolescent with newly diagnosed Graves disease

Both thyrotoxic periodic paralysis (TPP) and choreoathetosis are unusual complications of childhood thyrotoxicosis. We hereby report a boy who presented with both TPP and choreoathetosis at the initial presentation of his Graves disease. A 14 year-old Thai boy presented with acute generalized proximal muscle weakness and myalgia for 5 hours. Detailed history revealed the increased appetite, heat intolerance and labile mood for 6 months. Physical examination revealed tachycardia, goiter and mild exopthalmos. Generalized proximal muscle weakness and hyporeflexia were noted. Abnormal movement including ballism and mild spooning of hands were also noted. The milk maid sign was positive. The abnormal movement was consistent with choreoathetosis. Labs showed serum T3 > 651 ng/dL, Free T4 > 7.77 ng/dL, TSH < 0.005 uU/mL, K 2.1 mmol/L and CPK 1555 U/L. Autoimmune profile showed high titer of the anti-microsomal antibodies of 1:25000. The final diagnosis of Graves disease with TPP and choreoathetosis were made. Methimazole and propranolol were started. Intravenous K was administered to correct hypokalemia. Serum K was normalized within 7 hours after K replacement. The patient was able to stand and walk normally on the 2nd day of admission. After 4 weeks of treatment with Methimazole, the thyroid function test was consistent with hypothyroidism, therefore the dose of Methimazole was decreased. The choreoathetosis resolved completely within 4 weeks. Our case report demonstrates the first pediatric patient with Graves disease who developed combined neuromuscular complications which were TPP and choreoathetosis. There has been a previous case report of a 21-year-old man with Graves disease who had both muscular complication and choreoathetosis. The muscular involvement in that patient was different from our patient. In that particular patient, he developed acute severe thyrotoxic myopathy which involved both bulbar and skeletal muscle. TPP is an alarming and potentially lethal complication of hyperthyroidism. It usually resolves completely after the normalization of serum K levels. Effective control of hyperthyroidism can prevent the recurrence of TPP. While, choreoathetosis usually resolves after the patient recovers from hyperthyroid state. We should always be aware of Graves disease in any children who present with either muscle weakness or choreoathetosis since the signs and symptoms of Graves disease itself might not be very obvious.