Incidences of newly diagnosed childhood diabetes and onset severity: a multicenter regional study in Thailand over two decades and during the COVID-19 pandemic.

OBJECTIVES: While global  incidence rates (IR) of childhood diabetes are increasing, there is a notable lack  of current information on the incidence of childhood-onset diabetes in Thailand. This study aims to illustrate the age-standardized IR and types of childhood diabetes using multicenter regional data in Northern Thailand from 2005 to 2022 and to assess the impact of the COVID-19 pandemic. METHODS: Data on newly diagnosed childhood diabetes were retrospectively collected between 2005 and 2016 and prospectively recorded for all incident cases between 2016 and 2022. The capture-recapture method was applied to estimate the completeness of ascertainment. The age-standardized IR of diabetes was calculated. The IR of diabetes and the prevalence/severity of DKA at onset were compared between the pre-pandemic and pandemic periods. RESULTS: Among 210 patients, type 1 diabetes (T1D) accounted for 56.2 %, type 2 diabetes (T2D) for 39 %, and other types for 4.8 %. The T1D age-standardized IR significantly increased from 0.30 in 2005 to 3.11/100,000 person/year in 2022, mirroring the T2D trend, which increased from 0.33 to 3.15/100,000 person/year. The average T1D age-standardized IR, including the prevalence/severity of DKA at diagnosis, did not significantly differ between the pre-pandemic and pandemic periods (2.11 vs. 2.36/100,000 person/year, p-value=0.67). However, the average T2D age-standardized IR significantly increased from 0.83 to 2.15/100,000 person/year during the pandemic (p-value=0.0057). CONCLUSIONS: This study highlights an increased incidence of childhood T1D and T2D in Northern Thailand over a two-decade period. Notably, during the COVID-19 pandemic, the T1D incidence remained stable, while a significant rise in T2D incidence was observed.

Iatrogenic hyperthyroidism in primary congenital hypothyroidism: prevalence and predictive factors.

OBJECTIVES: Primary congenital hypothyroidism (CH) is a preventable cause of mental retardation. Iatrogenic hyperthyroidism has occasionally been reported using the recommended LT4 dosage. Currently, information regarding iatrogenic hyperthyroidism and predictive factors for permanent hypothyroidism (P-CH) among Thai patients is lacking. The aim of this study is to determine the prevalence and factors for predicting iatrogenic hyperthyroidism at one month after LT4 initiation and for predicting P-CH in primary CH infants. METHODS: This retrospective cohort study involved 87 infants with primary CH. Patients were classified by thyroid status at one month after LT4 initiation. At 3 years, patients were reevaluated after LT4 cessation and assigned as P-CH or transient CH (T-CH). Differences between groups were analyzed. RESULTS: One month after LT4 initiation, 35.6% of patients were classified as having iatrogenic hyperthyroidism. An initial LT4 dose of 10.2 µg/kg/day (sensitivity 64.5%, specificity 71.4%) was a suitable cutoff value for predicting iatrogenic hyperthyroidism, wherein 55.6 and 21.6% of patients were treated with initial doses of ≥10.2 and <10.2 µg/kg/day, respectively (p=0.004). Initial LT4 dose was the only predictive factor for thyroid status after initial treatment. At reevaluation, 47.4% of patients were diagnosed with P-CH. LT4 dosage at 3 years of age was significantly higher in patients with P-CH (3.3 vs. 2.85 µg/kg/day, p=0.02) and the only relevant factor for predicting P-CH. CONCLUSIONS: Iatrogenic hyperthyroidism is common among infants with primary CH when treated with the recommended LT4 dosage. LT4 dose was the only factor for predicting iatrogenic hyperthyroidism after LT4 initiation and the diagnosis of P-CH.

Near final adult height, and body mass index in overweight/obese and normal-weight children with idiopathic central precocious puberty and treated with gonadotropin-releasing hormone analogs.

Background The standard treatment of central precocious puberty (CPP) is gonadotropin-releasing hormone analogues (GnRHa). It is a concern that children treated with GnRHa are at risk of developing obesity which could impair the treatment outcomes. This study aimed to investigate the effect of GnRHa on body mass index (BMI) standard deviation score (SDS), and the influence of BMI status on treatment outcomes in children with idiopathic CPP (iCPP). Methods A retrospective cohort study in children with iCPP who completed GnRHa treatment and had attained near final adult height (NFAH) was conducted. Children with a history of disease or drug ingestion which could affect their BMI were excluded. BMI, BMI SDS, height (Ht), Ht SDS, predicted adult height (PAH), and NFAH were compared at baseline, 1 and 2 years during treatment, and at NFAH according to the baseline BMI status; normal weight and overweight/obesity. Results Fifty-eight children with iCPP treated with GnRHa were enrolled. The BMI SDS was significantly increased at 1 and 2 years during treatment in the overweight/obese group and at 1 year during treatment in the normal-weight group. However, at NFAH (2 years after treatment discontinuation), the BMI SDS was not statistically different from baseline in both groups. Ht gain, change in Ht SDS and BMI SDS were not statistically different from the baseline in both groups. Conclusions GnRHa results in a transient increase in BMI SDS during treatment and returned to baseline after treatment cessation. The benefit of GnRHa treatment on final Ht improvement is similar between overweight/obese and normal-weight patients.

Role of Leucine 341 in Thyroid Hormone Receptor Beta Revealed by a Novel Mutation Causing Thyroid Hormone Resistance.

Leucine 341 has been predicted from crystal structure as an important residue for thyroid hormone receptor beta (TRß) function, but this has never been confirmed in functional studies. Here, a novel p.L341V mutation as a cause of resistance to TRß is described, suggesting an important role for L341 in TRß function. In silico and in vitro studies confirmed that substituting L341 with valine and other non-polar amino acids impairs sensitivity of TRß for triiodothyronine to various degrees, depending on their side-chain size and orientation.

Vitamin D deficiency and its relationship with cardiac iron and function in patients with transfusion-dependent thalassemia at Chiang Mai University Hospital.

BACKGROUND: Vitamin D deficiency is common in patients with thalassemia. Vitamin D deficiency could be related to cardiac dysfunction. Increased parathyroid hormone (PTH) is also known to be associated with heart failure. OBJECTIVES: To determine the prevalence of Vitamin D deficiency and to explore the impact of Vitamin D deficiency on cardiac iron and function in patients with transfusion-dependent thalassemia. METHOD: A cross-sectional study in patients with Transfusion-dependent thalassemia was conducted. Patients with liver disease, renal disease, type 1 diabetes, malabsorption, hypercortisolism, malignancy, and contraindication for MRI were excluded. Calcium, phosphate, PTH, vitamin D-25OH were measured. CardiacT2* and liver iron concentration (LIC) and left ventricular ejection fraction (LVEF) were determined. Results Sixty-one (33M/28F) patients with Transfusion-dependent thalassemia were enrolled. The prevalence of Vitamin D deficiency was 50.8%. Patients with cardiac siderosis had tendency for lower D-25OH than those without siderosis (15.9 (11.7-20.0) vs. 20.2 (15.85-22.3) ng/mL); p = 0.06). Serum calcium, phosphate, PTH, LIC, cardiac T2*, and LVEF were not different between the groups with or without Vitamin D deficiency. Patients with Vitamin D deficiency had significantly lower hemoglobin levels compared to those without Vitamin D deficiency (7.5 (6.93-8.33) vs. 8.1 (7.30-8.50) g/dL; p = 0.04). The median hemoglobin in the last 12 months was significantly correlated with D-25OH. Cardiac T2* had significant correlation with PTH. CONCLUSION: Vitamin D deficiency is prevalent in patients with Transfusion-dependent thalassemia. Vitamin D level is correlated with hemoglobin level. Vitamin D status should be routinely assessed in these patients. Low PTH is correlated with increased cardiac iron. This study did not demonstrate an association between Vitamin D deficiency and cardiac iron or function in patients with Transfusion-dependent thalassemia.

Subtle inflammation: a possible mechanism of future cardiovascular risk in obese children.

PURPOSE: The risk of cardiovascular disease (CVD) has been shown to be associated with systemic inflammation in obese adults with metabolic syndrome (MetS). The aims of this study were to evaluate the prevalence of MetS and its relation to inflammatory markers in obese Thai children. METHODS: A cross-sectional study was conducted. Children with history of endogenous obesity, chronic diseases, drug ingestion, and any acute illness within 2 weeks prior to enrollment were excluded. Their fasting blood glucose (FBG) levels, oral glucose tolerance tests, insulin, lipid profiles, and selected inflammatory markers, including interleukin-6, tumor necrosis factor-alpha, and high-sensitivity C-reactive protein (hs-CRP) levels, were tested. RESULTS: In this study, 58 obese Thai children (female, 20; male, 38) with a mean body mass index z score of 5.1±2.2 were enrolled. The prevalence of MetS and prediabetes was 31% and 17.2%, respectively. None of the children had diabetes. FBG levels, 2-hour glucose levels, and lipid profiles were not statistically different between those with and without MetS. However, obese children with MetS had higher insulin levels and homeostasis model assessment of insulin resistance values. Elevated hs-CRP levels were found in 69% of the cases, although it was not statistically different between the 2 groups. CONCLUSION: We described a substantial prevalence of MetS in Thai obese children. Regardless of MetS status, two-thirds of the obese children had elevated hs-CRP level, indicating subtle ongoing inflammatory process. This chronic inflammation feasibly predisposes them to CVD in the future, even in children without MetS.

Isolated methylmalonic acidemia with unusual presentation mimicking diabetic ketoacidosis.

BACKGROUND: Hyperglycemic ketoacidosis is an acute, life threatening condition requiring early etiologic recognition and management to prevent serious morbidity/mortality. The most common cause is diabetic ketoacidosis (DKA). Organic acidemias (OAs) are inheritable disorders caused by defects in protein metabolism resulting in acid accumulation. Patients with metabolic decompensation usually present with acidosis, with/without hypoglycemia. Hyperglycemia is a very rare manifestation. At least 16 cases of OAs presenting with hyperglycemia have been reported. Six of the 16 were diagnosed with isolated methylmalonic academia (MMA) and three of the six passed away from late diagnosis. CASE DESCRIPTION: We describe a 2-year-old Thai girl who presented with hyperglycemia, acidosis and ketosis. She has underlying delayed development, seizures, optic atrophy and poor growth. An initial diagnosis of DKA was made and standard treatment was started. After 4 h of treatment, the patient partially responded to treatment; blood sugar decreased but acidosis and ketonemia persisted. HbA1c was normal. Investigations to rule out OAs were performed. Markedly elevated urinary methylmalonic acid consistent with MMA was observed. Molecular and enzyme analyses confirmed the diagnosis with isolated MMA. Specific treatment for MMA including protein restriction, high caloric fluid, carnitine and vitamin B12 was promptly started. Clinical improvement was seen 4 days after initiating specific treatment. CONCLUSIONS: Inherited metabolic disorders should be included in differential diagnosis in hyperglycemia ketoacidosis patients who respond poorly to standard DKA treatment. Unusual findings, e.g. hyperammonemia, lactic acidosis, pancytopenia, abnormal basal ganglia in MRI or underlying delayed development may indicate underlying OAs. Determining the etiology of hyperglycemic ketoacidosis is important and can lead to good outcomes.

Insulin resistance and lipid profiles in HIV-infected Thai children receiving lopinavir/ritonavir-based highly active antiretroviral therapy.

BACKGROUND: Lopinavir/ritonavir (LPV/r) is associated with insulin resistance (IR). We aim to determine the prevalence of IR, dyslipidemia and their inter-relationships with adipokines in HIV-infected children treated with LPV/r-based highly active antiretroviral therapy (HAART). METHODS: Twenty-eight children were enrolled. Fasting glucose, insulin, lipid profiles, adipokines, and oral glucose tolerance tests were performed. RESULTS: The prevalence of IR, pre-diabetes mellitus, and hypertriglyceridemia was 42.9(12/28), 10.7(3/28), and 75.0(21/28)% respectively. No case met the definition for diabetes mellitus (DM) and lipodystrophy. Children with IR had higher BMI z-score, triglyceride levels but unchanged leptin or adiponectin levels compared to those without IR. Longer duration of LPV/r-based HAART was associated with increased levels of triglyceride and total cholesterol. CONCLUSIONS: We describe high prevalence of IR, pre-diabetes mellitus, and dyslipidemia among HIV-infected children receiving LPV/r-based HAART. Pre-diabetes mellitus or DM or IR screening might be important for early diagnosis and intervention in these children.

Radioactive iodine for thyrotoxicosis in childhood and adolescence: treatment and outcomes.

OBJECTIVE: The aim of the present study was to evaluate the outcome of radioiodine treatment in thyrotoxicosis in childhood and adolescence. METHODS: This was a retrospective study of 27 patients (ages 7.2- 19.8 years) with a diagnosis of thyrotoxicosis who received iodine-131 (I-131) treatment from January 2007 to December 2011 in the Nuclear Medicine Division, Department of Radiology, Faculty of Medicine, Chiang Mai University. Gender, duration of antithyroid drug (ATD) treatment, 24-hour I-131 uptake, thyroid weight, total dose and number of treatments with I-131, and thyroid status at 6 months after treatment were recorded. RESULTS: The outcomes of 27 patients (85.2% female, 14.8% male) treated with radioactive iodine were analyzed to assess the effectiveness of therapy as related to dose and gland size. All children and adolescents received 150 µCi of I-131/g of thyroid tissue (n=27). Six 6 months after treatment, 44.5% of the patients were hyperthyroid, 14.8% were euthyroid, and 40.7% were hypothyroid. Of the 12 cases with hyperthyroidism, 2 cases needed a second dose of I-131 treatment, and they finally reached a hypothyroid state. The patients were classified into 2 groups according to treatment success (euthyroid and hypothyroid) and treatment failure (hyperthyroid). There were no significant differences in age, gender, duration of ATD treatment, 2- and 24-hour I-131 uptake, thyroid weight, and total I-131 dose between these two groups. CONCLUSIONS: Radioiodine treatment is safe and effective for thyrotoxicosis in childhood and adolescence. It is suitable as a good second-line therapy for patients with severe complications, those who show poor compliance, and those who fail to respond to ATD treatment.

Persistent hyperinsulinemic hypoglycemia of infancy associated with congenital neuroblastoma: a case report.

The authors report a rare case of persistent hyperinsulinemic hypoglycemia of infancy (PHHI) with congenital neuroblastoma without feature(s) of Beckwith-Wiedemann syndrome. A term newborn with a birth weight of 3,900 g developed hypoglycemia one hour after birth and required up to 20 mg/kg/min of intravenous glucose infusion to maintain euglycemia. Investigations during the critical period revealed an inappropriately high insulin level. An abdominal CT scan revealed a normal pancreas, right suprarenal mass, and liver nodules. A condition of stage 4S neuroblastoma was suspected and supported by an increased ratio of urine vanillylmandelic acid to creatinine. The bone marrow smear was normal. She underwent near total pancreatectomy at the age of 2 months. The suprarenal mass and liver nodules were not found during the operation or during repeated abdominal CT scans at 3 month of age. Spontaneous regression of neuroblastoma was suspected. The pathology of the pancreas was compatible with PHHI.

Thyroid functions in children with Down's syndrome.

OBJECTIVE: To evaluate thyroid function in children with Down's syndrome, and to ascertain the presence of a relationship between overt thyroid diseases and congenital anomalies. MATERIAL AND METHOD: One hundred and forty Down's syndrome patients, aged from 3 days to 13 years 9 months, were evaluated for karyotype, thyroid functions and the coexistence of congenital anomalies. RESULTS: Trisomy 21 was found in the majority of cases (95.7%). Fifty-six patients (40%) had abnormal thyroid functions: 53 (37.9%) hypothyroidism and 3 (2.1%) hyperthyroidism. Ten patients (7.1%) were diagnosed with overt thyroid disease: congenital hypothyroidism 3.6%, acquired hypothyroidism associated autoimmune thyroiditis 1.4% and hyperthyroidism 2.1%. None of the patients with congenital hypothyroidism had athyreosis or ectopic thyroid gland. Sub-clinical hypothyroidism accounted for 32.9% of all cases; 10.7% showed a spontaneous decrease to normal TSH levels and 13.6% had persistently elevated TSH levels with the median follow-up time of 6 and 12 months, respectively. Congenital heart disease, gastrointestinal anomalies and hematological disease were found in 73.6, 10 and 3.6 percent of patients, respectively. There was no statistical correlation between the coexistence of cardiovascular or gastrointestinal disease in Down's syndrome patients with overt thyroid diseases or sub-clinical hypothyroidism to those having normal thyroid functions. CONCLUSION: Sub-clinical hypothyroidism was the most common thyroid abnormality in children with Down's syndrome. A longitudinal and timely-scheduled evaluation of thyroid function is needed to establish the natural course of this abnormality and the proper management guideline.

Infantile osteopetrosis in four Thai infants.

Four Thai infants, aged between 4 and 23 months, had progressive abdominal distension, pallor and delayed or regressed developmental milestones, with age at onset of 1 month, 3 months, 4 months and 1 month, respectively. Clinical findings consisted of growth and developmental retardation, anemia, frontal bossing, marked hepatosplenomegaly, and hearing and visual impairment. Laboratory findings revealed moderate anemia, leukocytosis and thrombocytopenia. The radiographic findings comprised generalized sclerosis of all bones, including the cranial base, and obliteration of the medullary canals and trabecular patterns. The first and second patients, who had swelling of the wrist joints and prominent costochondral junctions, had hypophosphatemia, elevated levels of serum alkaline phosphatase, and metaphyseal flaring on their radiographs, which was consistent with infantile osteopetrosis complicated by rickets. After Stoss therapy, there were biochemical and radiological responses suggesting vitamin D deficiency in the first patient, but not in the second. The third patient, who had hypocalcemia, hypophosphatemia and normal levels of serum alkaline phosphatase, received vitamin D at 3000 units per day, without improvement. Despite frequent blood transfusions, all patients continued to deteriorate and were finally lost to follow-up. Rickets should be identified and treated at the onset, because treatment of rickets leads to improvement in well-being and an adequate clinical response to bone marrow transplantation.

Diencephalic syndrome: a rare and easily overlooked cause of failure to thrive.

BACKGROUND: Diencephalic syndrome (DS) is an uncommon cause of failure to thrive in infants and young children. The major manifestations are emaciation, hyperkinesia, and euphoria. Most patients have a tumor in the hypothalamic-optic chiasma region. CASE REPORT: Two children, aged 14 months and 5 years 9 months, who presented with classic features of DS at an onset of 2 and 3 months respectively, were reported. Neurologic examination was normal, except for papilledema in the second child. Imaging of the brain showed a suprasellar mass, identified as pilocytic astrocytoma in both cases. The first case was lost to follow up. The latter underwent partial resection of the tumor and received radiotherapy postoperatively. He gradually gained in weight and height. CONCLUSION: DS should be a differential diagnosis in any children with emaciation despite adequate caloric intake and an inappropriately euphoric mood. Awareness of this syndrome, careful history taking, general detail as well as neurological examination including fundoscopic examination and appropriated investigations are crucial.

Microcephalic osteodysplastic primordial dwarfism with severe microdontia and skin anomalies: confirmation of a new syndrome.

We report two related Thai children having a new syndrome of microcephalic osteodysplastic primordial dwarfism (MOPD). The findings which classify them as having MOPD include IUGR, microcephaly, prominent nose and nasal bridge, small pinnae, short stature, cone-shaped and ivory-epiphyses, delayed bone age, slender long bones, and abnormal pelvis. The findings that distinguish them as having newly recognized syndrome consist of severe microdontia, malformed teeth, single-rooted or rootless teeth, severely hypoplastic alveolar bone, café au lait spots, acanthosis nigricans, and areas of hypo- and hyperpigmented skin. The reported patients appear to have the same condition as the family reported by Kantaputra [2002: Am J Med Genet 111:420-428]. This article contains supplementary material, which may be viewed at the American Journal of Medical Genetics website at http://www.interscience.wiley.com/jpages/0148-7299/suppmat/index.html.

Primary congenital hypothyroidism: clinical characteristics and etiological study.

Forty-eight children with primary congenital hypothyroidism, who attended Chiang Mai University Hospital, during 1977-2000, were reviewed. The female to male ratio was 2:1. The age at diagnosis ranged from 1 month to 12 years 4 months, with 27% of the cases diagnosed within the first three months of life, 37.5% within the first year, and 62.5% after one year of age. Constipation, delayed development and growth, feeding problems, prolonged neonatal jaundice and goiter were more common. Prolonged neonatal jaundice was found in every case diagnosed within the first three months. The other common signs were dry or mottled skin, abdominal distension, macroglossia, short stature, puffy face and umbilical hernia. Kocher-Debré-Semelaigne syndrome comprised 18.7% of cases with a 2:1 female to male ratio, and it was found in various forms of hypothyroidism. Thyroid scintigrams were done in 47 patients. Thyroid dysgenesis was the most common etiology (80.9%), which consisted of 40.4% athyreosis, 4.3% hypoplasia, and 36.2% thyroid ectopy. Thyroid dyshormonogenesis accounted for 18.9%, in which only 4 of 9 presented with goiter. Two-thirds of these patients showed a positive result to the perchlorate discharge test, indicating an organification defect. A 11 patients had elevated serum TSH level greater than 50 mU/L. The serum T4 level below 2 microg/dL was observed in 17 of 19 patients with athyreosis, 11 of 1 7 with thyroid ectopy, and 6 of 9 with thyroid dyshormonogenesis. These findings including retarded bone age were unable to differentiate among different groups of hypothyroidism.

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.

Primary hypomagnesemia in Thai infants: a case report with 7 years follow-up and review of literature.

A female Thai baby born to non-consanguineous parents, presented with primary hypomagnesemia at 10 weeks of age, and suffered recurrent convulsions that responded to magnesium supplementation. She was found to have hypomagnesemia (Mg 0.35-1.02 mEq/L) and a low urinary magnesium excretion of less than 10 mg per day, or urinary Mg/Cr that ranged from 0.005-0.01 mg/mg. Intermittent hypomagnesemia and one episode of hypocalcemia with occasional convulsions developed, due to irregular consumption of oral magnesium sulfate, which had a bitter taste, caused frequent loose stools and black staining of the teeth. Better compliance after switching from magnesium sulfate to magnesium oxide resulted in an increased level of serum magnesium and the gradual disappearance of the black staining of the teeth and frequent loose stools. The patient required an oral elemental magnesium dosage of 15-30 mg/kg/day to maintain the serum magnesium level at between 1.02-1.33 mEq/L and keep her free from convulsions. The follow-up period was 7 years during which the patient showed normal physical growth and a mild degree of mental retardation.