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Objectives: To evaluate bone mineral density (BMD) and body composition in prepubertal and adolescent patients with the classical form of 21-hydroxylase deficiency., Material and Method: The authors measured height, weight and used dual energy x-ray absorptiometry (DEXA) to evaluate lumbar spine, whole body BMD and body composition in 10 prepubertal and adolescent patients with the classical form of 21-hydroxylase deficiency. Serum hormone concentrations (17-hydroxyprogesterone, dehydroepiandrosterone sulfate) were also measured. Results were compared with those of age- and sex-matched controls., Results: Seven patients were adolescent (4 girls and 3 boys; age range, 9.0-19.6 years) and three patients were prepubertal. (2 girls and 1 boy; age range, 6.5-8.6 years). There were no significant differences in age, height z-score, weight z-score and body mass index between the patients with congenital adrenal hyperplasia (CAH) and controls. DEXA showed no differences between each group in whole body BMD, but showed significantly elevated areal regional BMD at the lumbar spine (L1-L4) in CAH patients. However four of the 10 CAH patients and 6 of the 10 controls had osteopenia. The BMD z-score at the lumbar spine was significantly correlated with increasing weight z-score in both CAH patients and controls. When CAH patients with osteopenia were compared with those with normal BMD, there was a trend toward lower weight z-score, higher dose of glucocorticoids and longer duration of treatment among the osteopenic patients, but it did not reach statistical significance., Conclusion: Classical 21-hydroxylase deficiency patients treated with long-term glucocorticoids did not have impaired bone mineral density compared with healthy, age and sex-matched controls. However, the reference data for BMD in the Thai pediatric population is lacking and the number of studied participants was limited so we need further studies.

Background: Diagnosis of growth hormone deficiency (GHD) needs both clinical and biological aspects such as auxological data and GHprovocative tests, and active metabolites of GH including IGF-I and IGFBP-3. In GHD children, rhGH has been used worldwide with minimal serious side effects. The aims of the present study were to describe the experience in King Chulalongkorn Memorial Hospital regarding diagnosis and treatment with rhGH in GHD children., Material and Method: Clinical data of 173 short children was retrospectively reviewed. Two GH provocative tests used in the present study were insulin tolerance test (ITT) and clonidine test. To make the diagnosis of GHD, the children had to fail both GH provocative tests (peak GH < 10 ng/ml). Baseline clinical data, IGF-I, and IGFBP-3 were compared between the group with true positive test and the group with false positive test. Thirty-five children with GHD, who had been treated with rhGH, were evaluated in terms of growth response, changes of IGF-I SDS and the relationship between these parameters., Results: From the present study, ITT could diagnose GHD with true positive 57% and false positive 43% and clonidine could diagnose with true positive 67% and false positive 33%. Clinical data including chronological age, bone age, HtSDS, WtSDS, IGF-I SDS, and IGFBP-3 SDS were not different between the true positive and false positive group. rhGH with a mean dose of 29.3 +/- 4.6 microg/kg/day increased height velocity (HV) from 3.9 +/- 2.5 to 9.3 +/- 2.5, 8.1 +/- 1.5, 7.2 +/- 2.2, 6.8 +/- 2.2, 7.6 +/- 2.4, and 6.5 +/- 1.8 cm/yr after 6 months, 1, 2, 3, 4, and 5 years after treatment, respectively. This also improved HtSDS during treatment and brought the HtSDS into the target range after 3 years of treatment. At the end of the first year of treatment, the difference of IGF-I SDS (DeltaIGF-I SDS) > or = 1 could predict a good response (DeltaHtSDS > or = 0.5) with sensitivity of 88.9% and specificity of 60% respectively. At the end of the second year, DeltaIGF-I SDS > or = 1 could predict a good response with sensitivity and specificity of 100% and 29%, respectively., Conclusion: From the present study, the authors demonstrated the investigation and treatment practices of short children with GHD. The growth response is satisfactory even with a lower dose than suggested. In addition, measurement of IGF-I and IGFBP-3 cannot be used in diagnosing GHD but can predict the height outcome at least by the first 2 years of the treatment. However long-term outcome need to be clarified.

Treatment of true Precocious Puberty (PP) with GnRH agonist can improve final adult height by suppressing gonadotropin and sex hormone levels that delays the fusion of long bone epiphyseal growth plates. However, deprivation of estrogen may affect the acquisition of peak bone mass, especially in individuals with low calcium intake. Ten Thai girls with idiopathic true PP were evaluated for Bone Mineral Density (BMD) and body composition by DXA scanner (Hologic, Inc) before and after GnRH agonist therapy for 1 year. During treatment, all children were allowed to consume a normal diet without extra calcium supplementation. In addition, serum calcium, phosphate, alkaline phosphatase and osteocalcin were also measured. The results showed that GnRH agonist could improve predicted adult height from 149.4 +/- 5.4 to 153.6 +/- 6.8 cm (p < 0.001). Serum osteocalcin, representing the bone marker formation, decreased from 184.2 +/- 66.7 to 108.6 +/- 35.3 ng/mL (p = 0.012) However, the treatment had no negative effects on BMD lumbar spine and total BMD but increased percentage of fat mass from 25.7 +/- 5.2 to 31.6 +/- 5.5%. (p =0.007). In conclusion, treatment with GnRH agonist in Thai girls with true PP for 1 year can improve PAH without negative effects on BMD but a longer period of treatment needs to be studied.

Objectives: To determine the etiologies and associated endocrine disorders in children with central diabetes insipidus (DI)., Material and Method: The authors retrospectively reviewed the medical records of children with central DI, who were admitted at department of Pediatrics, King Chulalongkorn Memorial Hospital, between 2000 and 2004. Aims of this study were to identify the etiology of central DI in children and also described the anterior pituitary hormone insufficiencies which may occur., Results: Of the total 51 patients, 27 patients were males and 24 were females. Intracranial tumors produced DI in 36 children (70.6%), but 17 of these 36 children (47.22%) had DI before surgical removal of the tumors. Fifteen patients (29.4%) had DI from non-tumor causes, which include idiopathic in 2 patients (13.5%), terminal events in 4 patients (26.8%), central nervous system (CNS) infection in 5 patients (33.3%), CNS anomalies in 2 patients (13.5%), Kabuki syndrome in 1 patient (6.6%), head injury in 1 patient (6.6%). Anterior pituitary function was evaluated in all tumor group and 8 patients of non-tumor group. In intracranial tumor group, growth hormone deficiency (GHD) was documented in 14 from 22 patients (63.6%), secondary adrenal insufficiency in 13 from 20 patients (65%), central hypothyroid in 27 from 36 patients (75%), hyperprolactinemia in 5 from 8 patients (62.5%)., Conclusion: The most common etiology of central DI is intracranial tumor, and at least 50% of them have clinical features suggesting central DI before surgery. More than 60% have associated anterior pituitary hormone insufficiency.

Background: Precocious puberty is characterized by breast development in girls prior to 8 years old and may have acne, adult odor, growth spurt and menstruation. Conventionally, gonadotropin releasing hormone (GnRH) stimulation test is a gold standard for diagnosis of central precocious puberty but it is a time-comsuming procedure that is not practical on an out patient basis., Objective: To evaluate the basal luteinizing hormone (LH)/follicle stimulating hormone (FSH) ratio in diagnosis of central precocious puberty in order to save time and cost., Subjects and Method: The GnRH stimulation tests were performed on 51 girls with breast development before 8 years old. The 51 girls were divided into 2 groups, 24 girls with central precocious puberty (CPP) and 27 girls with premature thelarche (PT), and the clinical data and GnRH stimulation tests data were compared between the 2 groups. The authors also compared the clinical data and GnRH stimulation tests data between 13 girls with PT and 12 girls with thelarche variants (TV) who developed puberty approximately 1 year later as confirmed by GnRH stimulation test., Results: Girls with CPP had a large bone age and chronological age ratio and advancement of breast staging. Girls with TV had a greater level of basal luteinizing hormone (LH), peak LH and 120 min estradiol than girls with PT. Basal luteinizing hormone and follicle stimulating hormone (FSH) ratio greater than 0.2 can be used to diagnose CPP with 75 per cent sensitivity, 85 per cent specificity, 82 per cent positive predictive value (PPV) and 82 per cent negative predictive value (NPV)., Conclusion: Girls with CPP have a basal LH/FSH ratio greater than 0.2 and this can be used as a cut-off point for the diagnosis CPP.

Background: Many children with brain tumors have abnormalities in water and sodium homeostasis, such as diabetes insipidus (DI), the syndrome of inappropriate antidiuretic hormone secretion (SIADH) and cerebral salt wasting syndrome (CSW), either pre-operatively or post-operatively. But little data have been published on the incidence, time of onset and clinical course of water and sodium disorders in children with brain tumors., Objectives: To characterize the water and sodium disorders in children undergoing surgical treatment for brain tumors., Patients and Method: The medical records of children with brain tumors admitted for surgery at King Chulalongkorn Memorial Hospital from January 1997 to December 2002 were retrospectively reviewed., Results: There were 79 patients, 46 males and 33 females included in this study. Water and sodium disorders occurred in 36 patients (45.57%), 23 patients had DI, 12 patients had SIADH and 1 patient had cerebral salt wasting syndrome (CSW). Nine of the 36 patients had pre-operative onset of water and sodium disorders (8 DI and 1 SIADH). The development of DI and SIADH was associated with the location of the brain tumors. Patients with sellar and suprasellar tumors had the highest incidence of DI (75.86%). Patients with tumors of the cerebral hemispheres had the highest incidence of SIADH (44.44%). Onset of post-operative DI ranged from 2 to 19 hours (mean 9.68 hours) and most patients developed SIADH within 24 hours post-operatively., Conclusions: DI and SIADH are common problems in children with brain tumors, especially after surgical treatment and the onset usually occurs within 24 hours after surgery. Patients with sellar and suprasellar tumors are more likely to have DI, patients with tumors of cerebral hemispheres and posterior fossa tumors are more likely to have SIADH.

Gonadotropin releasing hormone (GnRH) agonist has been used worldwide for the treatment of central precocious puberty. However, the results on final adult height (FAH) are discrepant in various studies especially in girls with normal early puberty. Fourteen girls with normal early puberty who were treated with depot GnRH agonists 3.75 mg intramuscular (i.m.) monthly for a mean period of 1.5 +/- 0.4 yr were retrospectively studied. The chronological age and bone age at the beginning of treatment were 9.9 +/- 0.7 yr and 12.6 +/- 0.9 yr, respectively. When the treatment was stopped, all the girls were followed-up until they reached their final adult heights. The results showed that the mean FAH was 154.0 +/- 6.9 cm, which was not significantly different from the predicted adult height (PAH) at start of treatment, 153.1 +/- 6.2 m. All the girls were divided into 2 groups. Group A was girls who had FAH-PAH at the start of treatment > or = 1.5 cm and group B, FAH-PAH at the start of treatment < 1.5 cm. The authors found that only the duration of treatment was different between these 2 groups, 1.7 +/- 0.3 yr in group A and 1.3 +/- 0.3 yr in group B (p = 0.015). In conclusion, GnRH agonist cannot improve the final height outcome in girls with normal early puberty. However, a longer period of treatment may improve the height prognosis.

The structure of insulin-like growth factor (IGF), especially IGF-I, and its receptor is similar to that of insulin. Therefore, the changes of IGFs and IGF-binding proteins may be related to glucose homeostasis in children with insulin dependent diabetes mellitus (IDDM). Sixty-three fasting blood samples of 21 children with IDDM attending 3 consecutive diabetic clinics were studied. The HbA1c progressively decreased from the 1st to the 3rd visit. IGF-I levels, both total and free forms, were not significantly different from that of control. IGFBP-3 levels in 3 visits (3406+/-305, 3376+/-252, and 2406+/-247 ng/mL) were significantly lower than that of control (5020+/-415 ng/mL) with the p value of 0.007, 0.002, and < 0.001 respectively. IGFBP-1 levels in the 1st and 2nd visits (102.1+/-12.9 and 114.1+/-14.5 ng/mL) were significantly higher than that of control (60.1+/-15.2 ng/mL) with the p value of 0.03 and 0.01 respectively, but not in the 3rd visit. IGF-I level had a positive correlation with IGFBP-3 (R=0.56, p=0.01) and free IGF-I (R=0.53, p=0.01). Free IGF-I had a negative correlation with IGFBP-1 (R=-0.64, p=0.01). IGF-II at the 15 visit had a negative correlation with HbA1c (R=-0.49, p=0.047). The authors found no correlations between IGF-I, IGFBP-3, free IGF-I, IGFBP-1 and HbA1c in the study. The patients' height SDS followed the genetic height potential. It was, therefore, postulated that a near normal free IGF-I level in diabetic children resulted from a balance of interaction between IGFBP-1 and IGFBP-3 to total IGF-I in order to keep the normal metabolic status as much as possible.

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.

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.

We have demonstrated the usefulness of the multiplex PCR to directly detect the dystrophin gene mutation. Prenatal diagnosis and confirmation of clinical diagnosis of DMD/BMD via non invasive technique are now possible. Nine DMD and one BMD patients were tested. Five DMD patients demonstrated deletion. Thus, this multiplex PCR could detect deletion in approximately 50 per cent of DMD/BMD Thai patients. Eighty per cent of the deletions were in the distal part, whereas, 20 per cent were in the proximal part. We are planning to establish other molecular techniques such as linkage analysis, cDNA hybridization and immunostaining of dystrophin protein to improve a mode of diagnosis and management of DMD/BMD patients in the Thai community.