Bone Mineral Density and Dickkopf-1 in Adolescents with Non-Deletional Hemoglobin H Disease.

BACKGROUND: Low bone mineral density (BMD) is prevalent in individuals with ß-thalassemia and is associated with increased circulating dickkopf-1 concentration. These data are limited in α-thalassemia. Therefore, we aimed to determine the prevalence of low BMD and the association between BMD and serum dickkopf-1 in adolescents with non-deletional hemoglobin H disease, a form of α-thalassemia whose severity is comparable to ß-thalassemia intermedia. METHODOLOGY: The lumbar spine and total body BMD were measured and converted into height-adjusted z-scores. Low BMD was defined as BMD z-score ≤ -2. Participant blood was drawn for measurement of dickkopf-1 and bone turnover marker concentrations. RESULTS: Thirty-seven participants with non-deletional hemoglobin H disease (59% female, mean age 14.6 ± 3.2 years, 86% Tanner stage ≥2, 95% regularly transfused, 16% taking prednisolone) were included. Over one year prior to the study, mean average pretransfusion hemoglobin, ferritin and 25-hydroxyvitamin D concentrations were 8.8 ± 1.0 g/dL, and 958 ± 513 and 26 ± 6 ng/mL, respectively. When participants taking prednisolone were excluded, the prevalence of low BMD at the lumbar spine and total body was 42% and 17%, respectively. BMD at both sites was correlated positively with body mass index z-score, and negatively with dickkopf-1 (all p-values <0.05). There were no correlations among dickkopf-1, 25-hydroxyvitamin D, osteocalcin and C-telopeptide of type-I collagen. Multiple regression analysis showed dickkopf-1 inversely associated with total body BMD z-score adjusting for sex, bone age, body mass index, pre-transfusion hemoglobin, 25-hydroxyvitamin D, history of delayed puberty, type of iron chelator and prednisolone use (p-value = 0.009). CONCLUSIONS: We demonstrated a high prevalence of low BMD in adolescents with non-deletional hemoglobin H disease. Moreover, dickkopf-1 inversely associated with total body BMD suggesting it may serve as a bone biomarker in this patient population.

Elevated bone turnover markers predict bone mineral density accrual in adolescents with 21-hydroxylase deficiency.

CONTEXT: Prognostic biomarkers for monitoring bone health in adolescents with 21-hydroxylase deficiency (21OHD) are needed. OBJECTIVES: To assess associations between concentrations of baseline bone turnover markers (BTMs) including osteocalcin (OC) and type-I collagen C-terminal telopeptide (CTX) and changes in lumbar spine bone mineral density (LSBMD) in adolescents with classic 21OHD. DESIGNS AND PATIENTS: A retrospective-prospective study of 33 adolescents with classic 21OHD who had baseline data for LSBMD, bone age (BA), and BTM concentrations. METHODS: BTM concentrations were converted into z-scores according to BA. We measured LSBMD at the follow-up study visit and calculated the annual percentage change in LSBMD (%∆LSBMD). RESULTS: At baseline, participants (55% female, 79% Tanner 5) had mean (±SD) age of 14.6 ± 3.6 years, BA 16.7 ± 2.9 years, and average glucocorticoid (GC) dose 17.3 ± 5.6 mg/m2 /day of hydrocortisone equivalent. The mean follow-up duration was 14.4 ± 5.6 months. Median (Q1-Q3) %∆LSBMD was 3.6% (0-8.5)/year. %∆LSBMD was similar among genders or 21OHD subtypes. Prednisolone versus hydrocortisone replacement resulted in lower %∆LSBMD (p = .004). %∆LSBMD was increased across tertiles of CTX z-score (p = .014). %∆LSBMD correlated negatively with GC dose (p = .01) and positively with CTX and OC z-scores (p < .01). In regression analyses, only CTX z-score positively associated with %∆LSBMD (p = .003), adjusting for sex, BA, body mass index, testosterone, 25-hydroxyvitamin D, and GC type and dose. CONCLUSIONS: Higher GC dose and the use of prednisolone were associated with decreased LSBMD accrual in adolescents with 21OHD. CTX z-score independently associated with LSBMD accrual, suggesting its potential for prognostic bone biomarker.

Elevated Random Luteinizing Hormone is an Unreliable Indicator for Pubertal Suppression in Girls Treated with Monthly Leuprolide for Idiopathic Central Precocious Puberty

Objective: Longitudinal data regarding random luteinizing hormone (LH) concentrations in patients with idiopathic central precocious puberty (ICPP) during treatment are limited. Therefore, we sought to evaluate random LH and estradiol concentrations during monthly leuprolide injection and their associations with pubertal progression and final adult height (FAH) in girls with ICPP. Methods: Medical records of 27 girls with ICPP who had attained FAH were reviewed. Patients' height, weight, Tanner stage, growth rate (GR), bone age, random LH measured by both immunoradiometric and immunochemiluminescent methods, follicular-stimulating hormone (FSH) and estradiol levels were monitored until FAH. Results: Treatment was started at a mean (±standard deviation) age of 8.1±0.6 years with mean duration of 3.9±0.2 years. At six months of follow-up, random LH (p=0.048), FSH (p<0.001) and estradiol (p=0.023) concentrations were decreased compared with baseline. Thereafter, random LHs were well suppressed. GRs gradually decreased to prepubertal norm by month 12. Seventeen patients (63%) exhibited pubertal LH concentrations at least once during treatment visits. Furthermore, 43 of a total 116 (37%) LH measurements were found elevated. However, those patients with elevated random LH did not show signs of pubertal progression. After treatment, mean FAH was greater than predicted adult height (p<0.0001) and target height (p=0.03). At no time points of treatment did random LH, FSH and estradiol correlate with GRs or FAH. Conclusion: Elevated random LH is commonly found in ICPP girls during monthly leuprolide treatment. However, these elevations were not associated with clinical progression of puberty or decreased FAH, suggesting that it is not a reliable method for CPP monitoring.

INCREASED LEVELS OF MEDIAN URINARY IODINE EXCRETION OF PRIMARY SCHOOL CHILDREN IN THE SUBURBAN AREA, KHON KAEN, THAILAND.

Iodine deficiency disorder (IDD) is associated with a low IQ in children and is an important public health problem in northeastern Thailand. Despite campaigns to reduce IDD in northeastern Thailand, studies showed people in this region continue to have the lowest median urinary iodine (UI) excretion and Intelligence Quotient scores. We conducted a cross sectional study of median urinary iodine excretion among primary school children in suburban Khon Kaen Province, in northeastern Thailand, during December 2012 to evaluate the current status of IDD in this population. We studied 377 school children. Urine samples were collected and measured for UI using a simple microplate method. The median UI level was 229.0 µg/l (range 15.0-1,124.1). Forty school children (10.6%) had UI levels less than 100 µg/l and 10 children (2.7%) had UI levels less than 50 µg/l. One hundred nine children (28.9%) had UI levels greater than 300 µg/l. Our study shows that there are still children in the study population and study area with inadequate UI levels. Programs to prevent IDD need to include this population in this area.

Effectiveness and Safety of Radioactive Iodine Therapy in Childhood Graves' Disease in Khon Kaen, Thailand.

Background: Graves' disease (GD) is the most common cause of hyperthyroidism in children and adolescents. Treatments consist of medication, radioactive iodine (RAI) therapy and surgery. Currently, radioactive iodine therapy is the first line treatment in many medical centers. Objective: To evaluate the effectiveness and safety of RAI therapy in childhood GD. Material and Method: A retrospective study was performed in 46 GD patients, aged at onset <15 years, who had undergone RAI therapy at the age >10 years. Goiter grading, evidence of hypothyroidism, severity of ophthalmopathy, RAI dosage and side effects of RAI therapy were evaluated. Results: The cure rate was 95.6%. All participating patients had goiter reduction (p = 0.005). Hypothyroidism was induced in 33 (71.7%) and 11 (23.9%) patients after the first and second RAI therapy. The total RAI dosage was significantly higher in the patients with failure response (p = 0.001). The average time to induce hypothyroidism after the first RAI therapy was 127.5 (IQR: 94.5-223.0) days. All of the patients had improvement of ophthalmopathy and none had thyroid carcinoma during the follow-up period of 42.5 (IQR: 17-52) months. Conclusion: Radioactive iodine therapy is effective and safe in the treatment of children and adolescents with Graves' disease.

Prevalence and type of associated syndromes in patients with cleft lip and cleft palate who received the treatment in Tawanchai Center until 4-5 years of age.

BACKGROUND: Understanding the genetic etiologies of cleft lip and palate (CLP) is important for improved prevention, treatment, and prognosis for patients affected by CLP. OBJECTIVE: To report the prevalence and the type of associated syndromes in Northeastern Thai patients with CLP. MATERIAL AND METHOD: A retrospective study of123 cleft lip/palate children aged 4-5 years was carried out at the Tawanchai Cleft Centel; Khon Kaen University during the period from October to December 2011. Data were collected by reviewing the patient 's medical records. RESULTS: Seventeen (14%) of the 123 children had multiple malformations and five (4%) of these children had associated syndromes. Syndromes were identified in 5 (29%) of the 17 children who had associated malformations. The syndromes were Apert, Cleft lip/palate-ectodermal dysplasia, Kabuki, Oculo-Auriculo-Vertebral Spectrum, and Velocardiofacial syndrome. CONCLUSION: Recognition of the associated syndrome in a patient with CLP is essential to assess the problem of the patient, provide necessaty treatment and the appropriate methodology of prevention.

Factors influencing chronic diabetic complications in type 1 diabetes.

Although type 1 diabetes mellitus (T1DM) usually begins in childhood or adolescence, the prevalence of complications increases in adulthood. The objective of this study was to determine the complications of T1DM and the factors that influence them. This retrospective study of 43 patients with T1DM was carried out during 2006-2007. We collected and analyzed demographic data, the clinical status of their diabetes, the complications and treatment. The subjects consisted of 16 males (37.2%) and 27 females (62.8%) with a mean age of 17.8 +/- 7.1 years (range 4.1 - 37.5), a mean age at onset of T1DM of 11.3 +/- 5.9 years (range 0.9 - 28.1) and a mean duration of T1DM of 6.8 +/- 4.3 years (range 1.1 - 19.0). The mean HbA1c of the most recent visit of 9.6 +/- 3.1% (range 5.2-17.6). Self - monitoring of blood glucose (SMBG) was performed by 21 patients (48.8%). Acute complications (diabetic ketoacidosis and hypoglycemia) had occurred in 29 patients (67.4%); chronic (microvascular and macrovascular) complications were documented in 13 patients (30.2%). Older age of onset and longer disease duration were factors associated with chronic diabetic complications (p = 0.004 and 0.006, respectively). There were no significant differences in HbA1c level, frequency of daily insulin injections, and presence of SMBG between patients with and without complications. Our results suggest patients with T1DM who had older age at onset or longer disease duration are at higher risk for complications.

The rising incidence of type 1 diabetes in the northeastern part of Thailand.

OBJECTIVE: To determine the incidence of T1DM in children under 15 years in 19 provinces in northeast Thailand. MATERIAL AND METHOD: Data of new cases of T1DM during 10 years between 1996 and 2005 were collected retrospectively by a mail survey from 275 hospitals in northeast Thailand. RESULTS: Three hundred forty cases, 134 (39.4%) boys and 206 (60.6%) girls were identified. The incidence rate of T1DM was 0.6/100,000/year (95% confidence interval 0.57; 0.71), a two-fold increased from the previous study between 1991 and 1995. More than half of the cases were diagnosed between the ages of 10 and 14 and the incidence rate in girls was 1.5 fold that of boys. CONCLUSION: Though the increased in incidence rate, the study indicated that the incidence of T1DM in northeast Thailand is still one of the very low incidence rates in the world.

Prevalence of type II diabetes and metabolic syndrome among overweight school children in Khon Kaen, Thailand.

BACKGROUND: Childhood obesity has been accompanied by an increase in the prevalence of type 2 diabetes mellitus (T2DM) and metabolic syndrome (MetS) among children and adolescents worldwide. OBJECTIVE: To determine the prevalence of T2DM and MetS among overweight children and adolescents in Khon Kaen province, Northeast Thailand. MATERIAL AND METHOD: A cross-sectional, prospective pilot study was performed in school children between 10 and 15 years of age. The weight and height measurements and body mass index (BMI) calculations for 2156 school children were analyzed. The BMI for the age and sex value at > or = 85th percentile was considered overweight and the overweight children were evaluated for family history of diabetes, signs of insulin resistance, plasma fasting glucose and lipid level. RESULTS: Five hundred and ninety four (27.6%) overweight children were identified, of whom 186 (31.3%) participated in the present study. T2DM was documented in 4 (2.2%) while MetS was documented in 6 (3.2%) children. At least one type of dyslipidemia was found in 87 (46.8%) children. CONCLUSION: T2DM and MetS are common among overweight school children in Khon Kaen, Thailand Preventive interventions to reduce overweight and consequently prevent T2DM in Thai children should be provided at school and the community level.

Acute suppurative thyroiditis with thyrotoxicosis.

BACKGROUND: Acute suppurative thyroiditis (AST) is a rare condition in children, and most children with AST usually have normal thyroid function. OBJECTIVE: To report a case of thyrotoxicosis complicating AST in a child. CASE REPORT: A 6-year-old boy with AST presented with the unusual clinical features of severe thyrotoxicosis. Two palpable masses were found to be of firm to hard consistency with tenderness without any acute inflammatory signs on the overlying skin of the thyroid gland. The diagnosis of AST was confirmed by ultrasonography and fine needle aspiration. Thyroid function tests were normal within a week after antibiotic treatment and surgical drainage. CONCLUSION: Transient thyrotoxicosis complicating AST is very rare in children. Awareness of this unusual complication is important to avoid inappropriate treatment of hyperthyroid disease.

Propylthiouracil associated antineutrophil cytoplasmic antibodies (ANCA) in patients with childhood onset Graves' disease.

Propylthiouracil (PTU) can induce anti-myeloperoxidase (MPO-ANCA) positive vasculitis. We performed a cross-sectional study to estimate the prevalence of MPO-ANCA in patients with childhood onset Graves' disease (GD) receiving PTU and to assess the relationship between ANCA and clinical manifestations of vasculitis. We studied 60 patients (59 girls and one boy) between 7.3 and 25.0 years of age (mean +/- SD, 14.71 +/- 4.49). GD, diagnosed at the age of 3.0 to 14.5 years (11.3 +/- 2.48), was designated as: newly diagnosed, on PTU therapy, and after PTU discontinuation in 4, 50 and 6 patients, respectively. Manifestations of vasculitis were noted and the patients were tested for MPO-ANCA, antinuclear antibodies, blood urea nitrogen, creatinine and urine analysis. Twenty-six patients (43.3%) reacted positively for MPO-ANCA, 23 were on PTU therapy (0.42 to 6.00, median 3.00 years) and three had discontinued PTU. There were 34 (56.7%) ANCA-negative patients and 27 patients on PTU therapy (0.25 to 5.17, median 1.00 years, p = 0.012). Vasculitis presented in 16 patients (26.7%), all of whom were receiving PTU at the time of the study. The percentage of vasculitis among MPO-ANCA positive patients was 27.6% more than in the negative group, p = 0.017. PTU was discontinued in patients with vasculitis and positive for MPO-ANCA. Our findings show a high prevalence of MPO-ANCA positivity and a significantly higher percentage of vasculitis among these patients, suggesting that patients taking PTU should be closely observed for the appearance of MPO-ANCA and signs of vasculitis, especially patients GD who have been treated for a long time.

Evolution of valve damage in Sydenham's chorea during recurrence of rheumatic fever.

BACKGROUND: The evolution of valve damage during a recurrence, in a patient who did not have apparent carditis in the initial attack of Sydenham's chorea, has been a subject of debate. METHODS: Thirty-six patients with an initial episode of acute rheumatic fever and Sydenham's chorea (3 patients with subclinical mitral regurgitation) were followed up prospectively for 5 years. Clinical examinations and transthoracic color Doppler echocardiography were done for each patient at initial attacks of Sydenham's chorea and at recurrences of rheumatic fever. RESULTS: Six recurrences of rheumatic fever occurred in 6 of the 36 patients. One recurrence developed in the regular secondary prophylaxis group (27 patients) with a recurrence rate of 0.007 per patient-year. Three of the 18 patients who initially had no heart murmur and no echocardiographic finding of valvular regurgitation had three recurrences of pure chorea with no echocardiographic evidence of significant valvular regurgitation. Interestingly, one of the 3 patients with previous pure chorea and echocardiographic finding of significant mitral regurgitation had a recurrence of pure chorea and new echocardiographic evidence of mitral, aortic and tricuspid regurgitations. Furthermore, two recurrences occurring in 2 of the 15 patients with previous carditis developed echocardiographic evidence of new carditis. CONCLUSIONS: Rheumatic recurrence can develop new valve damage evident by echocardiography for the patient with pure Sydenham's chorea who had previous subclinical valvulitis. Longer duration of secondary prophylaxis is recommended to prevent a recurrence of rheumatic fever in the patient with pure Sydenham's chorea who initially had subclinical valvulitis.

Galactorrhea in a 14-year-old girl.

The authors report a 14-year-old girl who had galactorrhea with regular menstruation. Furthermore, this galactorrhea case was associated with hyperprolactinemia and prolactinoma. The patient tolerated and responded well to therapy with bromocriptine. The serum prolactin levels decreased from 103.27 ng/mL to 24.25 ng/mL after 8 weeks of treatment and 12.48 ng/mL after 6 months of treatment. No pituitary tumor was demonstrated after 12 months of therapy and the galactorrhea had not recurred 1 year after ending the bromocriptine treatment.

Ocular myasthenia gravis and auto-immune thyroiditis in children.

A 7-year-old girl presented at a university hospital with ptosis of the left eye. This resolved spontaneously within 4 weeks but then the right eye became similarly affected but responded to prostigmine. Left hypertropia with restriction of the right inferior rectus, mild exophthalmos, non-tender diffuse enlargement of the thyroid, normal thyroid function tests, anti-thyroglobulin, and anti-microsomal antibodies indicated an association of autoimmune thyroiditis and ocular myasthenia. The ptosis was remedied with pyridostigmine and short-course oral prednisolone, but the hypertropia persisted.

Endocrine function in thai children infected with human immunodeficiency virus.

Most children infected by HIV show manifestations which mimic the clinical features of endocrine dysfunction, such as failure to thrive and hyperpigmentation. Our cross-sectional study was designed to assess the endocrine function of Thai children infected with HIV and to determine any relationship between disease severity, height and endocrine function. Thirty-six prepubertal children infected by HIV, 12 boys and 24 girls, aged 4-12 years (mean +/- SD 7 +/- 2 years), were tested for thyroid function (serum T4, T3, TSH and free T4), morning serum cortisol level, serum insulin-like growth factor-I (IGF-I) and IGF binding protein-3 (IGFBP-3). Disease severity was assessed using CD4+ T-lymphocyte percentage. Ten (28%) patients showed abnormal thyroid function. Five patients had euthyroid sick syndrome. Thyroid function tests indicated another five patients had a condition compatible with compensated hypothyroidism. Most patients had normal morning serum cortisol levels. Two-thirds and one-third of the patients showed low IGF-I and IGFBP-3 standard deviation scores (SDS), respectively. Twenty-six (72%) patients had CD4+ T-lymphocyte <15%, thus were classified as severely immune suppressed. A weak linear relationship was indicated between disease severity and endocrine function (r = -0.03 to 0.41). Statistical significance was found between CD4+ percentage and IGF-I SDS, IGFBP-3 SDS, serum T3 and free T4 (p-value = 0.03, 0.02, 0.02 and 0.01, respectively. Nearly half (44%) the patients were below the third percentile for height of Thai children. There was also a weak correlation between height SDS and endocrine function (r = -0.03 to 0.41). Statistical significance was observed between height SDS and IGF-I SDS, serum T3 and TSH (p-value = 0.02 and 0.01, respectively). We conclude that HIV-infected children with demonstrated growth failure and greater disease severity tend to have abnormal endocrine function, particularly disordered IGF-I levels.

Newborn screening for congenital hypothyroidism in Khon Kaen University Hospital, the first three years, a preliminary report.

Between January 2000 and December 2002, 9,558 of 10,868 live births at Srinagarind Hospital, Khon Kaen University, Khon Kaen, Thailand, were screened for congenital hypothyroidism (CH). Dried blood spot thyroid stimulating hormone (TSH) was collected at age 48 hours or older. The cut-off TSH level for recall test was > 25 mu/L. Serum thyroxine (T4), Free T4 and TSH were performed during the confirmatory test. Six of 24 infants recalled for confirmatory thyroid function tests had abnormal tests. Primary CH was confirmed in 3 infants and thyroxine treatment was given. Two of the three infants had thyroid dysgenesis, one had normal thyroid gland. Three infants showed borderline CH from the confirmatory test, only one had borderline CH from the second confirmatory test and also received thyroxine treatment. Twenty infants with false positives during the screening and confirmatory tests were regularly followed-up for growth, development and thyroid function tests. The incidence of primary CH in this sole tertiary care government hospital in Northeast Thailand was 1:3,186. Routine newborn CH screening would ensure early detection and treatment.

Molar pregnancy and hyperthyroidism in a 13 year-old girl.

A 13 year-old girl presented with secondary amenorrhea, vaginal bleeding and dyspnea. Hyperthyroidism was diagnosed based on clinical symptoms and thyroid function test. Ultrasonographic findings and tissue histology from curettage were consistent with a hydatidiform mole. She reached clinical euthyroidism 2 weeks after uterine curettage and propylthiouracil treatment. The diagnosis of putative adult diseases in pediatric patients should not be ruled out.

The epidemiology of type 1 diabetes in Thai children.

The incidence of type 1 diabetes in children aged 0-15 years in Thailand was reported to be as low as 0.2/100,000/year in 1984-1985. This survey from 1991 to 1995 by the same investigators using the same questionnaires distributed to hospitals in every province demonstrated increasing numbers. In Bangkok, the capital city, a survey was done by using the capture-recapture method, and found a significant incidence of 1.65/100,000/yr. This number is equal to the incidence in other countries in Asia. This result might be effectively considered as an exact incidence rate during this decade.