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.

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.

Serum IGF-I and IGFBP-3 levels by immunoeadiometric assay (IRMA) in diagnosis of growth hormone deficiency.

The anabolic actions of growth hormone (GH) are mediated by insulin-like growth factor-I (IGF-I) which circulates in blood bound with high affinity to specific carrier proteins, IGF-binding proteins (IGFBP) especially IGFBP-3. Serum levels of IGF-I and IGFBP-3 reflect 24-hour growth hormone status. We divided 44 children into 4 groups depending on growth hormone status. Group I (n=9), complete growth hormone deficiency (GHD). Group II (n=9), partial GHD. Group III (n=12), idiopathic short stature Group IV (n=14), normal children. Measurement of serum IGF-I and IGFBP-3 was performed by immunoradiometric assay (IRMA). The results showed the serum IGF-I and IGFBP-3 levels in group I were 123.1 + 106.8 ng/ml and 1825.1+ 966.6 ng/ml respectively which were significantly different from the levels in group 4, IGFI=270.7+ 139.4 ng/ml (p=0.025) IGFBP-3 = 2702.7+ 500.4 ng/ml (p=0.009) but not in group 2 and 3. In conclusion serum IGF-I and IGFBP-3 levels were proved to by useful for diagnosis of complete GHD.

Molecular examination of GH gene deletion in familial growth hormone deficiency.

The human growth hormone gene (GH gene) from nine members of a family with familial growth hormone deficiency was examined. The patients were diagnosed as having growth hormone deficiency clinically and by response to hormonal treatment. PCR amplification was carried out using total DNA extracted from leukocytes. The flanking regions of the GH gene which are highly homologous were amplified by one pair of primers. PCR products of 1900 bp and 1919 bp were obtained. By using the combination of restriction enzymes BgII, HaeII and SmaI to digest these PCR products, the various sizes of GH gene deletion can be detected. None of the possible deletions was found in these patients and their relatives by either PCR or Southern blot analysis.

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.

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.

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.

Hormonal and growth status in long term survivors of acute lymphoblastic leukemia (ALL) in children.

Nineteen children and adolescents in long-term complete remission from acute lymphoblastic leukemia (ALL) were studied for hormonal and growth status after cessation of therapy. Cranial irradiation of 600-2,400 cGy was given for C.N.S. prophylaxis in 18 out of 19 patients, and additional irradiation of 2,000 cGy was given to both testes of a prepubertal boy because of testicular infiltration. The time ranges after cranial irradiation and cessation of therapy at the time of study were 61-137 months and 5-127 months respectively. Thyroid hormone, cortisol and peak cortisol response after ACTH stimulation were normal in every tested children. Basal serum gonadotropin and sex steroid values were appropriate in the majority of patients. A child who received testicular irradiation, had elevated levels of gonadotropins. Glucagon stimulation test (GST) and/or L-Dopa propranolol test (DP test) were used to study growth hormone (GH) response. None had peak GH value less than 7 ng/ml. Ten patients had peak GH values of over 15 ng/ml. Nine female patients had normal puberty and regular menstruation. Eight out of ten male children also had normal puberty. All except two male patients had normal linear growth within 2 standard deviations of the mean. The mean attained final height of 11 children was not significantly different when compared to the mean predicted heights obtained from Bayley-Pinneau and Tanner methods. Excessive weight gain during and after cessation of chemotherapy was observed in the majority of children. Continuing long-term review of these children is essential.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

Insulin Dependent Diabetes Mellitus (IDDM): Clinical data and HLA antigen.

We studied 34 cases of IDDM attending diabetic clinic at Siriraj Hospital from May to November 1988. The study covered background personal, clinical history, diabetic control, diabetic knowledge, socioeconomic status, frequency and cause of admission. HAL antigen was performed in 20 cases. The age of IDDM ranged from 4 to 22 years with peak age at 11 to 15 years. Male to female ratio was 1:1 Majority had low socioeconomic status. Total admission of 26 IDDM were 57 occasions in the part 10 years, consisted of diabetic ketoacidosis (DKA), poor control and infections, malnutrition and hypoglycemia in 29, 20, 4 and 4 episodes respectively. However there was no statistically significant between socioecomic status and frequency of DKA. HLA DR3 is the most important genetic marker in IDDM. HLA DR4 alone was not significantly increased in IDDm, but is combination with DR3 and DR4 was important genetic marker in Thai IDDM. However there was no relationship between HLA DR3 and/or HLA DR4 and DKA. However further investigation should be done to clarify the etiologic factor of Thai IDDM.