Does GnRH analog improve the final height in Thai girls with idiopathic central precocious puberty?

Ten Thai girls with idiopathic central precocious puberty (ICPP) were treated with gonadotrophin releasing hormone (GnRH) analog for a mean period of 1.5+/-0.4 years. The predicted adult height at the end of treatment was significantly higher than that at the start of treatment (158.2+/-7.9 vs 153.0+/-8.7 cm, p=0.009). In addition, treatment with GnRH analog could significantly regress the breast staging from 3.4+/-0.8 to 2.6+/-1.0 (p=0.04),but not the pubic hair staging. Five of them reached a final height which was not significantly higher than the predicted adult height before treatment (153.1+/-4.8 vs 150.7+/-1.0 cm, p=0.5). In conclusion, treatment with GnRH analog in Thai girls with ICPP can improve the predicted adult height and regress the breast staging. However, the improvement of final height is not promising.

Clinical and molecular characteristics of Thai patients with achondroplasia.

Achondroplasia is an autosomal dominant disorder characterized by disproportionately short stature, frontal bossing, rhizomelia, and trident hands. Most patients appear sporadically resulting from a de novo mutation associated with advanced paternal age. A glycine to arginine mutation at codon 380 (G380R) of the fibroblast growth factor receptor 3 gene (FGFR3) was found to be the most common cause of achondroplasia in various populations. We identified and clinically characterized 3 Thai patients with achondroplasia. In all of them, we also successfully identified the G380R mutation supporting the observation that this is the most common mutation in achondroplasia across different ethnic groups including Thai.

Establishing gas chromatography-mass spectrometry to diagnose organic acidemias in Thailand.

Disorders of organic acid metabolism are a group of disorders which has long been ignored by majority of Thai physicians. Part of this is due to lack of laboratories in Thailand to verify the diagnosis of the disorders. We have recently developed a technique to qualitatively analyze organic acids utilizing Gas Chromatography-Mass Spectrometry (GC-MS). Eight patients in four families were successfully identified as having organic acidemias (OA) by this method. Two families had methylmalonic acidemia, one had propionic acidemia, and the other had 3-methylcrotonyl CoA carboxylase deficiency. To our knowledge, this is the first laboratory in Thailand being able to use GC-MS to diagnose OA. Availability of a laboratory in Thailand and affordability of the test are expected to result in earlier diagnosis and identification of more cases of OA in Southeast Asian countries. Consequently, prompt and proper treatment can be anticipated which should lead to better prognosis for patients with this group of disorder.

A cost-benefit of gnRH stimulation test in diagnosis of central precocious puberty (CPP).

The GnRH stimulation test is the gold standard to diagnose central precocious puberty (CPP). Conventionally, we need at least 2 hours to finish the test which seems to be costly and time consuming. In this study, we described the pattern of LH and FSH levels during the GnRH test in 27 girls who presented with various degrees of precocious puberty. We found that the blood samples at 90 and 120 min after GnRH were not necessary. To save the cost of diagnosis, the basal LH/FSH ratio > 0.2, the 30 min LH/FSH ratio after GnRH > 0.9 and the peak LH/FSH ratio > 1.0 can be used to diagnose CPP with positive predictive values (PPV) of 87.3, 89.4 and 93.8 per cent respectively.

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.

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.

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.