Congenital hypothyroidism following maternal I-131 therapy in unsuspected pregnancy.

The authors report a term infant with congenital hypothyroidism following maternal radioiodine (I-131) treatment for papillary thyroid cancer in unsuspected pregnancy. The woman received 150 millicuries (mCi) of I-131 during the second trimester of pregnancy. Antenatal care was done in the other hospital without the awareness of previous I-131 treatment during pregnancy. The child presented with congenital hypothyroidism and recurring attacks of postprandial bilious vomiting due to midgut malrotation and Ladd bands. This case reminds physicians of the importance of obtaining an accurate menstrual history and providing information on conception in fertile woman before receiving I-131 treatment.

The etiologies of adrenal insufficiency in 73 Thai children: 20 years experience.

BACKGROUND: Adrenal insufficiency (AI) is an event caused by an inadequate secretion or action of adrenal hormones. It can be classified as primary (1 degree) and secondary (2 degree). AI may result in severe morbidity and mortality when undiagnosed or ineffectively treated. OBJECTIVE: To determine the etiologies of AI in Thai children. MATERIAL AND METHOD: Data of children with AI presented to the authors' pediatric endocrine service between 1982 and 2002 (20 years) were retrospectively collected and analyzed. RESULTS: AI was diagnosed by clinical and laboratory data in 73 children (31 boys and 42 girls). Sixty-two (84.9%) patients had 1degree AI while 11 (15.1%) had 2 degree AI. The majority of patients with 1 degree AI (87.1%) were diagnosed with congenital adrenal hyperplasia (CAH). Other causes of 1 degree AI were uncommon such as ACTH unresponsiveness (4.8%) and no definite diagnosis (8.1%). Most children with 1 degree AI presented with hyperpigmentation. Causes of 2 degree AI were as follows: panhypopituitarism (63.6%), isolated ACTH deficiency (9.1%), and low birth weight (27.3%). CONCLUSION: In the present study, CAH was the most common cause of 1 degree AI while panhypopituitarism was the most common cause of 2 degree AI. Other causes of AI were quite uncommon. Definite causes of AI have not yet been identified in some children. Further clinical observation and special tests including molecular studies in these children are warranted for diagnostic and prognostic importance.

Treatment outcome of Graves' disease in Thai children.

BACKGROUND: Graves' disease is the most common cause of thyrotoxicosis in children. Treatment of Graves' disease consists of anti-thyroid drugs, radioactive iodide and thyroidectomy but the optimal treatment of GD in children is still controversial. OBJECTIVE: To review treatment outcome of Graves' disease in Thai children. MATERIAL AND METHOD: Retrospective review of 32 children with Graves' disease, diagnosed between Jan. 1994 and Dec. 2004, at the Division of Pediatric Endocrinology, Department of Pediatrics, Faculty of Medicine Siriraj Hospital, Mahidol University, Thailand was performed. RESULTS: All patients (median age 10.5 yrs, range 2.85-15 yrs) presented with goiter and increased serum T4 (median 18.4 mcg/dL, range 8.8-30 mcg/dL), serum T3 (median 443 ng/dL, range 206-800 ng/dL) and suppressed TSH levels (median 0.009 mU/L, range 0-0.18 mU/L). Anti-thyroglobulin and Anti-microsomal antibodies were positive in 70% and 82% respectively. All patients except two were initially treated with propylthiouracil (PTU). Two patients were initially treated with methimazole. Adverse reaction of PTU occurred in two patients (One girl had arthralgia, positive pANCA, nephritis and another girl had skin rash and arthralgia). Clinical course of 32 patients after treatment with anti-thyroid drugs mainly PTU for 3.4 (range 0.3-11.2) years is as follows: six (18.8%) underwent remission (cessation of PTU > 2 yrs), three (9.4%) relapsed, one (3.1%) underwent subtotal thyroidectomy, and seven (21.9%) had I131 treatment. All patients (6 of 7) who received I131 dose of 100 microCi/g of thyroid tissue required more than a single dose of I131 treatment. Further outcome in fifteen patients (46.9%) is yet to be followed. Among these patients PTU was just discontinued in four and eleven had never been off anti-thyroid drugs (four still had biochemical hyperthyroidism and seven were biochemically euthyroid). CONCLUSION: PTU was the most common first line therapy in the presented patients with Graves' disease. Remission rate was only 18.8% after an average 3.5 years of treatment with anti-thyroid drugs. I131 or thyroidectomy was used as second line therapy in the present study. They were offered to those who developed side effects, had poor compliance or failed medication. For those who received I131, higher dose (200 microCi/g of thyroid tissue) seemed to be more effective than the lower dose (100 microCi/g).

Etiology and glycemic control among Thai children and adolescents with diabetes mellitus.

BACKGROUND: There is little data on etiology and metabolic control in children and adolescents with diabetes in developing countries. OBJECTIVE: Determine the etiology of diabetes in Thai youths and to evaluate their glycemic control. MATERIAL AND METHOD: The authors retrospectively reviewed the case records of 157 patients seen at the Department of Pediatrics, Siriraj Hospital between 2003 and 2004. RESULT: Type 1 diabetes (T1D) comprised 83%, type 2 diabetes (T2D) 13%, and other types 4%. GAD65 and IA-2 antibodies were positive in 63% and 61% of T1D patients, and 0% and 9% of T2D patients, respectively. There were an increasing number of new cases, both T1D and T2D, during the study period compared with a previous study conducted at the hospital. Mean HbA1c in T1D and T2D were 8.9 +/- 2.1% and 6.2 +/- 1.80%, respectively (p < 0.001). CONCLUSION: Based on the present study, glycemic control appeared to be more satisfactory in T2D patients than those with T1D. Glycemic control among T1D patients was comparable to others in developed countries.

Leptin level in Thai children and adolescents: Relation to BMI and sexes.

Objective: The prevalence of obesity is rapidly increasing worldwide, including Thai children. Serum leptin is demonstrated largely that it increased in the dynamic phase in childhood –onset obesity. To our knowledge, there was no data of leptin measurement in this age group of our population. Methods: Therefore, we measured serum leptin by an immunoradiometric assay in sample from 208 obese and non-obese healthy children aged 2-18 years old. Its relationship to body mass index (BMI), ages and sexes were analyzed. Results: The mean serum leptin concentration in obese children was 35.06 + 17.31 ng/ml compared with 14.70 + 8.93 ng/ml in the non - obese children (p < 0.001). The obese female had significant higher level than in obese male group (43.26 + 16.82 vs. 30.34 + 15.85 ng/ml; p < 0.001), but they were not different in the non - obese group. The results showed that serum leptin correlated with BMI (r = 0.71; p < 0.001) and with % weight for height (%wt for ht) (r = 0.60, p < 0.001), respectively. Leptin levels in both sexes compared to age were also demonstrated. We did not find leptin deficiency or leptin resistance in all obese cases. Conclusion: In summary, leptin level in Thai children were increased according to BMI, % wt for ht and sexes as demonstrated in other ethnic groups. However, there is neither leptin deficiency nor leptin resistance demonstrated in this study.

Thailand diabetes registry project: type of diabetes, glycemic control and prevalence of microvascular complications in children and adolescents with diabetes.

OBJECTIVE: To determine the etiology, glycemic control and prevalence of microvascular complications in Thai diabetic patients who were diagnosed at the age of less than 18 years and who attended diabetes clinics in university or tertiary care hospitals. MATERIAL AND METHOD: A cross-sectional, multi-center, hospital-based diabetes registry was carried out from diabetes clinics of 11 tertiary centers. Demographic data including laboratory results and microvascular complications were recorded. RESULTS: Two-hundred-and-fifty out of the 9419 (2.66%) diabetic patients were diagnosed before the age of 18 years, 78% had Type 1 diabetes (T1DM), 18.4% had Type2 diabetes (T2DM) and 3.6% had other types of diabetes. Mean +/- SD HbAlc of T1DM was 9.3 +/- 2.5, T2DM was 9.7 +/- 2.6 and other types of diabetes were 8.6 +/- 4%. The majority of patients had poor glycemic control according to ADA and WHO guidelines. The percentage of patients who had diabetes for more than 5 years but had not been screened for nephropathy and retinopathy were 57.7% and 16% in T1DM and were 46.4% and 14.2% in T2DM respectively. A significant correlation between microvacular complications (nephropathy and retinopathy) and duration of disease was found in T1DM (p < 0.001). CONCLUSION: The majority of Thai children and adolescents with diabetes had TIDM and unsatisfactory glycemic control. Screening for microvascular complications was under international standard. The national strategic plan for management of this disease especially in this age group should be urgently implemented.

Thailand diabetes registry project: prevalence of diabetic retinopathy and associated factors in type 1 diabetes mellitus.

OBJECTIVE: To determine the prevalence and factors associated with Diabetic Retinopathy (DR) of type 1 diabetes mellitus in Thailand. MATERIAL AND METHOD: A cross-sectional, multicenter hospital-based study was carried out from April to December 2003. Diabetic patients in diabetic clinics of 11 tertiary centers were registered. Retinopathy was evaluated by the ophthalmologists. RESULTS: Seven thousand one hundred and ni neteen diabetic patients received retinal examination. The number of patients with type 1 diabetes was 347. The prevalence of DR in type 1 diabetes was 21.6% (75). This consisted of Non-Proliferative DR (NPDR) 10.9% (38) and Proliferative DR (PDR) 10.7%. Patients with DR were significantly older, predominantly female, longer duration ofdiabetes, had higher BMI, systolic Blood Pressure (BP), diastolic BP serum creatinine, and TriGlycerides (TG) levels than those without DR. Both groups ofpatients were not different in term ofplasma glucose and glycosylated hemoglobin levels. Although the patients with DR had a higher percentage of overt proteinuria than those without DR, there was no difference in percentage of patients with positive microalbuminuria in both groups. This may be explained by limitation of data (only 16% had results of microalbuminuria and 19% had results of proteinuria). After adjusted for duration of diabetes, serum creatinine and smoking status, factors (adjusted odds ratio [95% confidence interval]) associated with DR were duration of diabetes 5-9.9 years (4.0 [1.49-10.91]), 10-14.9 years (6.86 [2.45-19.20]), 15-19.9 years (21.13 [7.22-61.78]), > or =20 years (22.15 [7.32-66.99]) when compared with duration of diabetes less than 5 years, serum creatinine >2 mg/dl (6.0 [2.09-17.22]) when compared with creatinine less than 2 mg/dl. From the presented model, age, gender, systolic BP >140 mmHg, diastolic BP >90 mmHg, serum TG and smoking status were not factors associated with DR. CONCLUSION: Diabetic retinopathy affects about one fifth of type 1 diabetic patients in our study. The authors found the factors associated with DR in type 1 DM were duration of diabetes and serum creatinine. Regular screening for DR and more aggressive management of metabolic factors should be done to reduce the prevalence ofDR.

Thailand diabetes registry (TDR) project: clinical status and long term vascular complications in diabetic patients.

OBJECTIVE: The primary objectives of the Thailand Diabetes Registry project were to identify the characteristics of Thai diabetic patients in tertiary care medical centers and to determine the extent of long term diabetic complications. The secondary objective aimed at building up and strengthening clinical research network among Thai experts in diabetes mellitus and collection of baseline data for future follow-up study. MATERIAL AND METHOD: A cross-sectional, multi-center, hospital-based diabetes registry was carried out from diabetes clinics of 11 tertiary centers. Demographic data, clinical status of diabetes and its complications were collected and analyzed for the prevalence of complications and risk factors. RESULTS: Nine-thousand-four-hundred-and-nineteen patients were registered for the project and 94.6% were type 2 diabetes. Mean +/- SD of age was 59.4 +/- 13.5 and duration of diabetes was and 10 +/- 7.6 years. Only 38.2% of the subjects achieved glycemic control of FPG under 130 mg/dl in only 30.7% had an HbA lc of less than 7%. The overall prevalence of dyslipidemia found in this population was 73.3%, hypertension was 63.3% and obesity (BMI >25 kg/m2) was 52.6%. Diabetic nephropathy was the most common complication accounting for 43.9% followed by retinopathy 30.7%, IHD 8.1% and cerebrovascular disease 4.4%. CONCLUSION: The prevalence of dyslipidemia and hypertension were high in this population, which may be associated with the high prevalence of diabetic complications. The unsatisfactory control of metabolic status may be due to aging and long duration of diabetic patients in this registry.

Preliminary data of insulin glargine use among Thai adolescents and young adults with type 1 diabetes mellitus treated at Siriraj Hospital.

Insulin glargine is a new long-acting insulin analog with a duration of action of 24 hours and can be given once a day as the only basal insulin combined with short or rapid-acting insulin as bolus insulin for each meal. The goals of this study were to evaluate short term result of treatment with insulin glargine compared to NPH and to determine the initial dosage of insulin glargine in Thai adolescents with type 1 diabetes. We reviewed charts of 10 adolescents (median age 20.8 years, range 12.3-22.7 years) with type 1 diabetes who had received insulin glargine for > or = 4 months (median 16.5 months, range 4-25 months). Before switching to insulin glargine, all patients received NPH. Seventy percent of subjects had improvement of HbA1c from 10.4% (range 8.2-12.6) to 8% (range 6.7-10.6). The total amount of insulin dosage was significantly decreased from 1.2 (range 0.9-2.4) to 0.9 (range 0.4-1.5) units/kg/day as well as the percentage of basal insulin which was decreased from 70% (range 67-81) to 47% (range 38-56) of the total daily insulin. Insulin glargine did not cause severe hypoglycemia in this study. Conclusion: Insulin glargine is another promising therapy for adolescents with type 1 diabetes. We recommend the starting total daily insulin dosage to be decreased to 70-80% of previous dosage. Insulin glargine should be started at 50% of the new total daily insulin dosage.

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.

Clinical pictures of type 2 diabetes in Thai children and adolescents is highly related to features of metabolic syndrome.

Prevalence of type 2 diabetes (T2DM) in children and adolescents has increased, parallelled to the increased prevalence of obesity around the world. The objectives of this study are (1) to identify the clinical presenting features of T2DM in Thai children and adolescents, and (2) to identify evidence of feature of metabolic syndrome in these affected. We analyzed 26 T2DM patients who were treated by Pediatric endocrinologists in our hospital. The study showed that their mean ages (+/- SD) at diagnosis was 12.1 +/- 2.3 years, all were obese and 96% had acanthosis nigricans. Fifty three percents (53%) presented with clinical signs and symptoms which included DKA (19.2%), clinical triad of polyuria, polydipsia and weight loss (15.4%), only polyuria, polydipsia (11.5%) and abnormal menstruation (7%). The rest of 46.2% had no clinical symptoms. The initial fasting or random plasma glucose found above diagnostic range in 84.5%, the rest of 15.5% were diagnosed by using oral glucose tolerance test. Dyslipidemia was found in 75%. Fifteen percents had no family history. Eighty percents had three or more than three features of metabolic syndrome. In conclusions, clinical picture of type 2 diabetes in Thai youth varied from asymptomatic to severe illness (DKA). Almost all had clinical features of metabolic syndrome. Childhood obesity has become epidemic in our population. Such clinical picture should alert all pediatricians to be aware of chronic diseases and for making an early diagnosis and preventing long-term complications in the future.

Obese adolescent girls with polycystic ovary syndrome (PCOS) have more severe insulin resistance measured by HOMA-IR score than obese girls without PCOS.

The prevalence of obesity in Thai children is increasing. These individuals are at increased risks of metabolic syndrome that includes insulin resistance, type 2 diabetes mellitus (T2DM), polycystic ovary syndrome (PCOS), dyslipidemia and hypertension. PCOS has been known to be associated with insulin resistance. OBJECTIVES: To compare the insulin sensitivity between obese adolescent girls with PCOS and those without PCOS. MATERIAL AND METHOD: We reviewed demographic and hormonal data of 6 obese adolescent girls with PCOS and compared with 6 age, weight and BMI-matched non-PCOS controls. Each subject underwent an oral glucose tolerance test. RESULTS: Homeostasis model assessment of insulin resistance score (HOMA-IR score) in obese adolescent girls with PCOS was significantly higher than in girls without PCOS with median and range as follows (16.5 [3.8, 21.8] vs. 4.1 [3.3, 6.9], p = 0.04). Our study demonstrates that obese adolescent girls with PCOS have more severe insulin resistance measured by HOMA-IR score than girls without PCOS independent of the degree of obesity. Since insulin resistance is a metabolic precursor of future cardiovascular diseases, obese adolescent girls with PCOS might be at greater risk of developing cardiovascular disease in later adulthood than their non-PCOS counterparts.

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.

The epidemiology of type 1 diabetes in Thai children.

The incidence of type 1 diabetes in children aged 0-15 years in Thailand was reported to be as low as 0.2/100,000/year in 1984-1985. This survey from 1991 to 1995 by the same investigators using the same questionnaires distributed to hospitals in every province demonstrated increasing numbers. In Bangkok, the capital city, a survey was done by using the capture-recapture method, and found a significant incidence of 1.65/100,000/yr. This number is equal to the incidence in other countries in Asia. This result might be effectively considered as an exact incidence rate during this decade.

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.