Improved glycemic control among Thai children and young adults with type 1 diabetes participating in the diabetes camp.

Diabetes Education Program, Faculty of Medicine Siriraj Hospital has provided summer camps for Thai children with type 1 diabetes since 1990. The objective of this study was to evaluate the effectiveness of the diabetes camp in glycemic control. Twenty male and forty-two female patients participated in the 5-day diabetes camp held in Karnchanaburi, Thailand in 2003. The mean age was 14.1 +/- 4.3 years and the mean duration of disease was 4.5 +/- 3.5 years. Fifty out of sixty-two patients returned for a 3-month-postcamp visit. The glycemic control improved significantly. The mean precamp and postcamp HbA1c levels were 10.0 +/- 3.1% and 9.0 +/- 2.6% (p = 0.008) respectively. The diabetes camp is a valuable program for patients to learn diabetes-self management skills, especially in countries where the diabetes education programs are not always available.

Intensive diabetes education program and multidisciplinary team approach in management of newly diagnosed type 1 diabetes mellitus: a greater patient benefit, experience at Siriraj Hospital.

It is accepted worldwide that an effective multidisciplinary management team is essential for providing comprehensive self-management training to type I diabetics and their families. Therefore, the authors developed an intensive multidisciplinary education team that included pediatric endocrinologists, a dietitian, a psychologist, nurses, scientists and volunteers in the Department of Pediatrics, Siriraj Hospital in August 1996. This study aimed to analyze twenty-four newly diagnosed diabetics who underwent this specified program and multidisciplinary team approach in comparison to twenty-eight diabetic patients who were diagnosed before the program and team were established in order to see whether the length of hospitalization had been reduced and to compare the readmission rates of recurrent DKA with previous patients. The results demonstrated that by using the intensive program and multidisciplinary team the average length of admission was reduced from 36.04 days to 17.63 days (p value = 0.03). The readmission rate in the first year after diagnosis was also reduced from 17.8 per cent to 4 per cent. Concerning diabetes control, the average HbA1c level showed significantly better control. Therefore, this study demonstrated a successful team and program for newly diagnosed Thai childhood and adolescent diabetics and also emphasized that a multidisciplinary team approach with an effectively intensive education program is important in helping diabetics and families cope with their emerging problems and receive the long-term benefits of effective self-care.

Persistent hyperinsulinemic hypoglycemia of infancy: experience at Siriraj Hospital.

BACKGROUND: Persistent hyperinsulinemic hypoglycemia of infancy (PHHI) is the most common cause of recurrent or persistent hypoglycemia in early childhood. Conventionally, pancreatectomy (Px) has often been recommended to control hypoglycemia. However, PHHI can be managed successfully by intensive medical treatment to avoid pancreatectomy. METHOD: Data from 10 infants (8M, 2F) with PHHI were retrospectively analyzed. RESULTS: Eight patients (80%) developed symptoms within 72 hours after birth (early-onset). Six patients (60%) underwent 85 per cent-95 per cent Px due to failure of medical treatment. Two patients who underwent less than 95 per cent Px required second Px (97% and 99%). One patient developed permanent diabetes mellitus and malabsorption. Hypoglycemia could be successfully managed by medication alone in four patients (40%). Of these, three patients had early-onset neonatal hypoglycemia. Medication could be discontinued in three patients (75%). Three of ten patients (30%) had delayed development. Pancreatectomies and/or the diagnosis of PHHI were made late for these patients. One of these three children also developed epilepsy. CONCLUSIONS: Patients with PHHI frequently require pancreatectomy which commonly results in long-term complications especially diabetes mellitus and malabsorption. Our data suggest that PHHI can be managed successfully with an intensive medical regimen even in patients with early-onset hypoglycemia. Although medical management is very laborious for the family and physician, it should be applied until euglycemia is accomplished. Moreover, the early diagnosis of PHHI and the successful hypoglycemic control are very necessary to prevent permanent neurologic sequelae.

Ambiguous genitalia: an overview of 22 years experience and the diagnostic approach in the Pediatric Department, Siriraj Hospital.

The newborn with abnormal genital development presents a difficult diagnostic and treatment challenge for the pediatrician providing care. It is important that a definitive diagnosis be determined as quickly as possible so that the appropriate treatment plan can be established to minimize medical, psychological and social complications. The purpose of this study was to provide an extensive review of the clinical characteristics of a patient cohort with ambiguous genitalia, from 22 years' experience in the Division of Endocrinology and Metabolism, Department of Pediatrics, Siriraj Hospital, and to classify them into diagnostic categories. Moreover, a cascade of diagnostic tools in approaching sexual ambiguity in the authors' institution, starting with history and physical examination and leading to further radiographic and laboratory investigations is demonstrated and can be adopted as a guideline for the clinical management of these disorders. From 1979 to 2001, care was provided to a total of 109 patients with ambiguous genitalia, of whom 104 patients were reviewed. Among these individuals, 52 patients (50.0%) belonged to the diagnosis of female pseudohermaphroditism, 5 patients (4.8%) were in the true hermaphroditism group and the remaining 47 patients (45.2%) were in the male pseudohermaphroditism group. All female pseudohermaphrodites carried a diagnosis of congenital adrenal hyperplasia (CAH) and were reared as girls. 21 hydroxylase deficiency CAH accounted for all except one (98%) in this group. Among the 47 male pseudohermaphrodites, 9 (19.1%) had dysgenetic male pseudohermaphroditism, 7 (14.9%) had either testosterone biosynthetic defects or hCG unresponsiveness, 22 (46.8%) had either androgen insensitivity syndrome or 5 alpha-reductase deficiency, 4 (8.5%) had ambiguous genitalia in a 46,XY male associated with multiple anomalies and 5 (10.6%) had an unidentifiable cause. Sex reassignment occurred, not uncommonly, in 4 cases of female pseudohermaphrodites (7.7%) and at least 2 cases (3.9%) in the combined group of male pseudohermaphrodites and true hermaphrodites. The scope of the ambiguous genitalia problem is definitely not minor. An inappropriate approach to this problem poses an undue risk to the integrity of the physical and psychosexual health in the future for these children.

Diabetes insipidus in Thai children.

The medical record of 43 patients who presented with diabetes insipidus (DI) at Endocrine Unit, Department of Pediatric, Siriraj Hospital during 1986-1995 were retrospectively reviewed in order to determine the causes of diabetes insipidus in Thai children. The results demonstrated male to female ratio of 1.9:1, mean age of 6.1 (4 years. Patients had central diabetes insipidus of 90.7% and remaining 9.3% had nephrogenic diabetes insipidus (P<0.05). The causes of central DI were hematology and oncology disease (28.2%), brain tumor (25.6%), post CNS infection (10.25%) and indiopathic cause (35.8%). Hematology and oncology disease included Langerhan cell histiocytosis (23%), non-Hodgkin lymphoma (2.5%), ALL (2.5%). Brain tumor included germinoma (15%), craniopharygioma (7.5%), astrocytoma (2.5). The results of morning urine and serum osmolarity ratio showed less than 2 in 88% of cases. The remaining 12% had the ratio more than 2 and all patients of this group had organic causes of central DI. A water deprivation test did not demonstrate a difference between organic and non organic causes of central DI. The most common hormone insuffiencies after stimulation test were growth hormone and ACTH. In summary, children who present with central DI need investigations including complete physical examination and investigations for hemato-oncology disease. If there is no hematologic causes, a CT or MRI brain is a further investigation. An anterior pituitary function evaluation is also necessary foe further management.

Studies of GH gene defects in familial Isolated Growth Hormone Deficiency (IGHD).

One family with isolated GH deficiency (IGHD) was Studied. To determine GHI gene deletions, PCR and Southern blot analyses were used. None of the possible deletions were found in the subjects but the GH1 gene mutation was found. The family consisted of parents (both 140 cm) and their three children with isolated GHD. The daughter and two sons were first seen between 2.9 and 5.3 years of age when their HtSDSs were -2.2 to -3.6, and peak GHs were 0.9 to 4.0 mg/ml. The GH1 gene change was found in G-->A substitution at +28 in the intervening sequence or intron 3 (IVS3+28 G-->A). This change is a dominant-negative mutation which has never occurred in any reports in any reports in Thailand and we were the first group to report here. The segregation which and expression studies of the IVS3+28 G-->A variant are underway to confirm whether it is a new dominant-negative mutation that causes GHD by perturbing mRNA splicing.

Improving height velocity in boys with constitutional delayed growth and puberty (CDGP) by using oral testosterone undecanoate.

Treatment with oral testosterone undecanoate (40 mg daily) in 9 boys diagnosed as having constitutional delayed growth and puberty (CDGP) was studied. The mean chronological age was 12.1+ 1.7 years and the mean duration of treatment was 0.7+ 0.3 year. The height velocity was increased from 3.9+ 2.1 cm per year before treatment up to 8.1+ 2.3 cm per year treatment (p=0.003). However, the predicted adult height was not different between pre and post treatment. Eighty-nine percent of children reached the pubertal testicular size after treatment. Therefore, oral testosterone undecanoate was proved to be effective to improve height velocity but the predicted adult height in CDGP boys.

Serum IGF-I, IGF-II and IGFBP-3 levels in children with isolated growth hormone deficiencies and panhypopituitarism.

Serum IGF-I,IGF-II and IGFBP-3 levels were measured by radio-immunometric assay in 24 children, 16 with isolated growth hormone deficiencies (GHD) and 8 with panhypopituitarism. AII serum parameters were significantly lower in panhypopituitarism than in isolated GHD. Serum IGF-I levels were lower than the normal range in 50 percent of the patients. However, 66.7 percent of isolated GHD children older than 10 years had serum IGF-I levels lower than the normal range. AII isolated GHD children had serum IGFBP-3 levels lower than the 50th percentile or mean of normal range. Combined IGF-I and IGF-II levels had no more advantage than IGF-L levels in the diagnosis of isolated GHD. Serum IGFII levels were lower than normal range in 87.5 percent. In conclusion, serum IGFBP-3 measurement is useful than IGF-I in all age groups. Low serum IGF-II levels and panhypopituitarism were demonstrated in this study.

Molecular studies in growth hormone gene deletions in patients with isolated growth hormone deficiency.

Human GH deficiency (GHD) occurs in 1 in 4,000-10,000, and up to 30 percent of cases have an affected first degree relative suggesting many cases may be familial. To determine the GHD cases cased by GH gene defects we analyzed the GH genes of 90 consecutive cases. Genomic DNAs were used for PCR amplification of 2.7 kb fragments containing subjects’ GH gene; these PCR products were subjects to determine GH gene deletions. PCR products of 1900 and 1919 bp were obtained. By using the combination of restriction enzymes BglI, 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 by either PCR or Southern blot analysis.

Three years of growth hormone therapy in children with growth hormone deficiency.

The objects is to study the long-term therapeutic effect of recombinant DNA hGH by administration of biosynthetic hGH for 2 ½ - 3 years to 12 children with growth hormone (GH) deficiency, consisted of 7 males, 5 females; whose ages ranged from 3 years 4 months to 17 years old. All patients fulfilled the criteria of GH deficiency namely; growth rate less than 7 ng/ml after clonidine and dopa-propranolol stimulation test. Ten patients had idiopathic GH deficiency. Two had hypopituitarism as a result of brain tumors and cranial surgery. The growth rate was observed over a pretreatment period of 12 months. The patients received 0.1 µ/kg of recombinant DNA hGH subcutaneously 6 days per week. In males with GH-deficiency, pre-treatment mean height was 2.6 cm per year. The mean height increment at 6th, 12th, 24th, 30th, and 36th month of treatment were 6, 11.2, 14.1, 17.6, 20.6 and 23.4 cm respectively. The females had mean height increment during pre-treatment period of 2.2 cm per year. The mean height increment on 6th, 12th, 18th, 24th, and 30th month of treatment were 4.7, 7.8, 10.3, 14.2 and 14.4 cm respectively. All patients have a significant satisfactory response to recombinant DNA hGH in term of height increment. There was no report of either side effect or complication. Every patient has had improved sense of physical, mental and psycho-social well-being.

Optimized nuclear techniques and thyroid function studies in the newborn in iodine-deficient areas of Thailand.

Cord blood samples, as sera (n=4,753) and dried blood spots (n=855) obtained from subjects in iodinedeficient districts in northern Thailand, were studied for T4 and TSH. The methodology was optimized by the used of NETRIA bilk reagents and in-house methods were developed to adapt them for cost reduction, convenience and precision/accuracy. The biochemical findings with cut-off values at < 3 µg/dl for T4 and >50 mIU/L for TSH as confirmed by <1ng/dl for FT47 showed 16 cases (0.34%) of neonatal chemical hypothyroidism (NCH) varying from 0.18 to 1.59 percent of 4,753 cases. Out of the total 4,753 cases, 1.45 percent (n=96) could benefit from thyroxine administration. In this research project, the screening indicated a mild to moderate degree of IDD severity. The findings are useful for epidemiological monitoring and for advocacy of the IDD prevention and control programme.