Increasing prevalence of type 2 diabetes mellitus in Thai children and adolescents associated with increasing prevalence of obesity.

Type 2 diabetes mellitus (DM) is being diagnosed more frequently in children and adolescents. Thailand has a low incidence of childhood DM. This study reviewed patients with DM in the Division of Pediatric Endocrinology, Faculty of Medicine, Siriraj Hospital compared to our previous study. The results demonstrate that type 2 DM in Thai children and adolescents has increased from 5% during 1986-1995 to 17.9% during 1996-1999. Mean age was 11.6 years. Mean BMI was 27.8 kg/m2. Fifty-six percent were diagnosed on routine examination. The period of increase in type 2 DM is associated with an increase of obesity prevalence from 5.8% in 1990 to 13.3% in 1996. This result emphasizes the importance of encouraging daily physical activity and healthy diet in our populations and also alerts our pediatricians and endocrinologists to the possibilities of type 2 DM in these age groups.

Satoyoshi syndrome.

Satoyoshi syndrome is a very rare disorder of unknown etiology, characterized by progressive, intermittent, painful muscle spasms, alopecia universalis, diarrhea or unusual malabsorption, various endocrine disorders, and secondary skeletal abnormalities. This report describes a 9-year-old Thai girl who developed alopecia universalis when she was 6 years old. At age 7 years, she began to have recurrent, painful muscle spasms. The spasms progressed in time, producing recurrent patella dislocation. The laboratory investigations and radiologic study were compatible with Satoyoshi syndrome. She was treated with oral corticosteroid therapy, with marked improvement of her muscle spasms and alopecia. She underwent corrective surgery for deformities of both knees with a normal healing process.

Measurement of serum free IGF-I in diagnosis of growth hormone deficiency.

Serum levels of total insulin-like growth factor-I (IGF-I) are growth hormone (GH) dependent and can be used as the screening tool for GH deficient status. However, most of them are bound to IGF-binding proteins, leaving less than 1 per cent in the free or unbound forms which represent the active biological fractions. Serum free IGF-I levels were measured by radioimmunoassay (IRMA) in 48 short children with various conditions. We found that the means +/- SEM of free IGF-I in children with panhypopituitarism (PAN) and complete growth hormone deficiencies (cGHD) were significantly lower than those in sex and age matched normal children (0.02 +/- 0.01 vs 2.01 +/- 0.7 ng/ml, p = 0.0006 and 0.42 +/- 0.18 vs 1.72 +/- 0.27 ng/ml, p = 0.0007 respectively) but not in children with partial growth hormone deficiencies (pGHD) (0.91 +/- 0.3 vs 1.97 +/- 0.4 ng/ml, p = 0.27) and idiopathic short stature (ISS) (0.94 +/- 0.3 vs 1.95 +/- 0.6 ng/ml, p = 0.13). However, when we classified the pGHD children into 2 groups according to IGFBP-3 SDS for normal Thai children, we found that the mean of free IGF-I levels in pGHD children with IGFBP-3 SDS < or = -1.3 was significantly lower than that of the controls. (0.68 +/- 0.55 vs 2.66 +/- 0.71 ng/ml, p = 0.04) In conclusion, the measurement of free IGF-I level can be used to evaluate the GH status of short children and might be used as a guide when starting treatment.

An identical neo-mutation in the thyroid hormone receptor beta gene (A317T) in 2 unrelated Thai families with resistance to thyroid hormone.

We reported two unrelated Thai girls with resistance to thyroid hormone. The affected patients presented with goiter and no other stigmata of hyperthyroidism. Their serum T4, T3, free T4 and free T3 concentrations were high and they had normal levels of TSH. The affected girl in family 1 was treated with an antithyroid drug for 1-9/12 years. The affected girl in family 2 was only observed her thyroid function tests. TRH test showed normal TSH response in both girls. Analysis of the thyroid hormone receptor beta gene of both affected girls revealed the same missense mutation, changing the guanine in nucleotide 1234 to an adenine which results in the replacement of the normal alanine (GCT) with a threonine (ACT) at codon 317. Two proposita were heterozygous, and this mutation was not present in their parents compatible with a neo-mutation.

Type 1 diabetes in Thai children aged 0-14 years.

Fifty-nine patients were diagnosed with diabetes in the ten years from 1987 to 1996 in the Division of Endocrinology and Metabolism, Department of Pediatrics, Faculty of Medicine Siriraj Hospital, Bangkok, Thailand. All patients were less than fifteen years old. Fifty-five patients (93.3%) were type 1 diabetes, three (5%) were type 2 diabetes and MODY, and one (1.7%) was diabetes secondary to beta thalassemia major. Patients with type 2 diabetes, MODY, and secondary diabetes were excluded from this study, and fifty-five patients with type 1 diabetes were analysed. The aims of this study were to determine some of the general characteristics of Thai childhood type 1 diabetes and to see whether a seasonal variation is present. The results showed a female to male ratio of 1.39:1. The peak age at diagnosis was from 9 to 12 years. Seventy-seven per cent had diabetic ketoacidosis at the time of diagnosis. The majority of patients (93.9%) had a BMI of less than 20 kg/m2. A family history of diabetes was reported in 38 per cent but only 2 per cent were type 1 diabetes. We found a high prevalence of patients in the summer and winter seasons (35-48% and 37-50% respectively) and a lower prevalence in the rainy season (14.8-15%). These results are different from a previously reported study in 1984-1985 which found no differences in summer, winter, and rainy seasons. Further research study into Thai childhood type 1 diabetes is needed, especially the influence of seasonal factors, the incidence of the disease, and the significance of family history.

Thyroid scintigraphy in children with hypothyroidism: a five-year experience.

The presence or absence of thyroid glandular tissue demonstrated by thyroid scintigraphy is important for genetic and prognostic counseling and for acceleration of diagnosis in other affected siblings. Technetium-99m-pertechnetate thyroid scintigraphy was performed on 27 children with cretinism at the Division of Nuclear Medicine, Faculty of Medicine Siriraj Hospital during the 5-year period from June 1991. Based on scintigraphic findings, three main groups of thyroid localization were seen. Thirteen (48.1%) were athyrotic while 3 (11.1%) had an ectopic thyroid and 11 (40.8%) had gland in normal position. Perchlorate discharge test was performed in 8 children of the last group and the results were positive indicating an organification defect. Thyroid scintigraphy and perchlorate discharge test provided the useful information for diagnosis, follow-up, and prognosis in children with cretinism.

Serum IGF-I and IGFBP-3 levels for normal Thai children and their usefulness in clinical practice.

Serum IGF-I and IGFBP-3 levels are growth hormone (GH) dependent and reflect the endogenous GH secretion. Two hundred and forty-four healthy children were evaluated for serum IGF-I and IGFBP-3 levels and then the age-defined normal values for Thai children were constructed. The results showed that the serum IGF-I and IGFBP-3 levels were age dependent, gradually increased from birth and reached the peak values around the age of 14-16 years. In addition, we studied the IGF-I and IGFBP-3 values in 28 GH deficient children and 26 normal variant short stature (NVSS) by using our normal constructed values as the reference. To minimize the influence of age, both IGF-I and IGFBP-3 values were transformed to standard deviation score (SDS). In clinical practice, we recommend using the IGF-I SDS and IGFBP-3 SDS of -1 and -1.3 respectively as a cut-off point to discriminate between GH deficiency and NVSS to avoid risky GH provocative tests and unnecessary GH replacement with the sensitivity of 71 per cent and the specificity of 92 per cent.

Familial dysalbuminemic hypertriiodothyroninemia: a new, dominantly inherited albumin defect.

We report the abnormal albumin in members of a Thai family that presented with high serum total T3 but not T4 when measured by radioimmunoassay. In contrast, total T3 values were very low when measured by ELISA and chemiluminescence. The subjects have no goiter, and clinically euthyroid. Their serum free T4, free T3, and TSH were normal. Spiking of T3 to affected serum showed good recovery by radioimmunoassay, but very poor recovery by ELISA and by chemiluminescence. The immunoprecipitation with labeled T3 bound to albumin showed high percent precipitation in affected serum. T3-binding studies showed that the association constant of serum albumin in affected subjects was 1.5 x 10(6) M-1 or 40-fold that of unaffected relatives of 3.9 x 10(4) M-1. In contrast, the Ka of HSA for T4 in an affected subject was only 1.5-fold that of a normal. Albumin complementary DNA from leukocytes of affected member was amplified and sequenced. We found the second nucleotide of normal codon 66 (CTT), a thymine, was substituted by a cytosine (CCT), resulting in the replacement of the normal leucine by proline. This is the first report of variant albumin causing familial dysalbuminemic hypertriiodothyroninemia.

Growth hormone therapy update in Thailand.

There were 841 children in Thailand with growth hormone deficiency (GHD) from January 1992 to 1996. Idiopathic isolated GHD was the major diagnosis. Only 40.19% received recombinant DNA human growth hormone (rhGH) treatment. Also reported here is a 1-2 year study of rhGH therapy in 30 GH-deficient children (21 males, 9 females), aged (mean +/- SD) 10.41+/-3.16 years, and bone age 7.37+/-3.34 years. The height velocity 1 and 2 years posttreatment were 8.17+/-1.9 and 7.36+/-2.8 cm/year respectively, which were statistically significant compared to pretreatment values of 3.91+/-1.09 cm/ year. Improved height SDS was observed at the end of each treatment period. Thyroid function and glycosylated hemoglobin tests were normal during the treatment period. There were no reports of side effects.

Mutation in the thyroid hormone receptor beta gene (A317T) in a Thai subject with resistance to thyroid hormone.

Analysis of the thyroid hormone receptor beta (TRbeta) gene of a Thai female with the syndrome of resistance to thyroid hormone (RTH) revealed a missense mutation at codon 317, changing the guanine in nucleotide 1234 to an adenine that results in the replacement of the normal alanine (GCT) with a threonine (ACT). The proposita was heterozygous, and this mutation was not present in her parents and her sister, compatible with a neomutation. This is the first report of TRbeta gene mutation causing RTH in an individual of Thai origin.

'Exaggerated adrenarche' in children presenting with premature adrenarche.

OBJECTIVE: Previous reports of endocrinological profiles in children presenting with premature adrenarche have not shown consistent abnormalities. We therefore aimed to review the clinical and biochemical aspects of a large number of patients presenting with premature adrenarche without virilization and determine the relation between clinical and biochemical characteristics and the frequency of adrenal steroid disorders. DESIGN AND PATIENTS: Eighty-eight patients presenting with adrenarche without virilization during 1985-1992 were retrospectively reviewed. There were 72 girls and 16 boys. All were normotensive and had either prepubertal breasts or testes < 4 ml. In patients with high adrenal androgen levels, adrenal tumours had been excluded by either adrenal ultrasound or CT scan. MEASUREMENT: We recorded clinical manifestations, auxological data, bone age, biochemical results including basal 17OH-progesterone (b17OHP), dehydroepiandrosterone sulphate (DHEAS), androstenedione (delta 4A), testosterone, cortisol and stimulated 17OHP and cortisol. ACTH stimulation tests (using soluble Synacthen 250 micrograms intramuscularly and collecting blood at 0, 30 and 60 minutes) were performed when clinically indicated. 17OH-Pregnenolone (17OHPreg) was also measured during ACTH stimulation tests in 13 individuals to look for abnormalities of 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD). RESULTS: The age of onset ranged from 3 to 9.5 years (mean 6.8 +/- 1.3). There were no significant differences by sex for height SDS, weight SDS or % ideal body weight, but bone age advancement was greater in males (P < 0.02). The most common presenting clinical manifestation was premature appearance of pubic hair in 93.8%, the other 6.2% presenting with body odour, acne and/or hirsutism. Twelve patients had b17OHP > 6 nmol/l of whom 5 were diagnosed as having congenital adrenal hyperplasia (CAH) resulting from 21-hydroxylase deficiency after ACTH stimulation tests. A further 33 patients who had b17OHP < 6 nmol/l had normal 17OHP and cortisol responses to ACTH stimulation. Patients, after excluding those with CAH, were divided on the basis of their DHEAS levels into prepubertal (< 1.5 mumol/l), pubertal (1.5-6 mumol/l) and above pubertal range (> 6 mumol/l). The 8 patients with DHEAS values above the pubertal range were described as having 'exaggerated adrenarche'. There were no significant clinical differences between these 3 groups, but significant differences were found for bone age advancement and the steroids, b17OHP, delta 4A and testosterone. There was a strong correlation between DHEAS and delta 4A (r = 0.623, P < 0.001). The 'exaggerated adrenarche' group had higher 17 OHPreg/17OHP ratios at 60 minutes after stimulation but these were not diagnostic for 3 beta-HSD deficiency. CONCLUSION: The value of assessing basal steroids in children presenting with premature adrenarche is demonstrated in this series with 5.7% being diagnosed with 21-hydroxylase deficiency and 9.1% with 'exaggerated adrenarche'. No relation was found between adrenal steroids and clinical features except for the acceleration of bone age. The relation between 'exaggerated adrenarche' and future ovarian hyperandrogenism needs further evaluation.

Growth response in Turner syndrome with recombinant human growth hormone therapy.

Ten Turner syndrome girls whose mean age was 10.9 +/- 2.7 years were treated with recombinant human growth hormone (rhGH), dose 0.6 U/kg/week. Five of them had classical 45, XO karyotype. The mean height velocity increased from 2.8 +/- 1.3 cm/year before treatment to 6.1 +/- 2.06 cm/year after treatment for a period of 1.4 years. The response of treatment correlated well with pretreatment height velocity (<3 cm/year) but not with karyotype. However, the response has been decreasing and an increased dose after the first year of treatment is recommended.

Congenital generalized lipodystrophy, a case report.

Generalized lipodystrophy is a rare condition which can be divided into congenital and acquired types, based on the age at presentation and pattern of inheritance. The congenital type of generalized lipodystrophy or Lawrence-Seip syndrome presents in first two years of life and is inherited in an autosomal recessive pattern. The diagnosis is made on the basis of loss of body fat, muscular hypertrophy, acanthosis nigricans, hirsutism, hepatomegaly with fatty liver, hyperlipidemia and hyperglycemia with insulin resistance. A 2 1/2-year-old Thai girl with the clinical features of Lawrence-Seip syndrome is reported. Abnormal platelet function was detected in this girl.

The epidemiology of insulin-dependent diabetes mellitus (IDDM): report from Thailand.

The epidemiology of diabetes mellitus in Thai children aged 0-15 years was studied in 1985 and compared with a previous study done in 1984. Four hundred and seventy-six questionnaires were sent each year to hospitals in Thailand. In 1984, thirty-six cases of newly diagnosed diabetes mellitus were found of which 35 were IDDM and one was NIDDM. In 1985, twenty-seven cases of new IDDM were found, no case of NIDDM was reported. Two cases of MRD were reported from the Northeastern and Southern part of Thailand. The incidence of IDDM in the whole kingdom of Thailand was 0.19/100,000/year in 1984 and 0.14/100,000/year in 1985. The male to female ratio was 1:1.5 in 1984 and 1:2 in 1985. The peak age at diagnosis showed the main peak at 14 years old in boys. The peak age of girls preceded boys by 1-2 years in 1984 and 1985. Similar findings in 1984 and 1985 were the onset of symptoms showing a seasonal variation with highest frequency in winter with a slight change of increased incidence in the rainy season of 1985. There was an increased incidence of IDDM in families with lower educational and socioeconomic levels. The newly diagnosed IDDM with DKA was 16.2, and 19.5 per cent in 1984 and 1985. The incidence of IDDM in Thai children, aged 0-15 years seems to be the lowest compared to other countries previously described which might be due to some genetic and environmental including diet, micronutrient, eating habits and life-style which might play a role in the difference.

Effect of recombinant DNA human growth hormone in Thai children with growth hormone deficiency.

We conclude that recombinant DNA methionine-free hGH treatment of GH-deficient Thai children is very effective in the first year of treatment. No patients reported any side effects or resistance to treatment.