Vitamin D status and glucose homeostasis in obese children and adolescents living in the tropics.

BACKGROUND: Pediatric obesity continues to rise and has become a major health problem worldwide. Vitamin D deficiency has been increasing among obese non-Asian children and is associated with abnormal glucose homeostasis in obese adults. However, data on the vitamin D status and its association with glucose homeostasis in obese children residing in tropical Asian countries are unavailable. OBJECTIVE: To assess vitamin D status and glucose homeostasis in obese Thai children. PATIENTS AND METHODS: A total of 150 obese, and 29 healthy non-obese children and adolescents were enrolled. Weight, height, body mass index (BMI) and waist circumference were obtained. All obese children underwent an oral glucose tolerance test with glucose and insulin measurements. Plasma 25-hydroxyvitamin D (25-OHD) and calciotropic blood chemistries were measured in all participants. Insulin sensitivity indices were calculated from the measured glucose and insulin levels. RESULTS: Approximately 25% of the obese children and adolescents had impaired glucose tolerance, impaired fasting plasma glucose (FPG) and diabetes. Seventeen out of 150 (11.3%) obese children and 3 out of 29 (10.3%) non-obese children had vitamin D deficiency, which was defined as a 25-OHD level of <50 nmol l(-1). Glucose tolerance and insulin sensitivity indices were comparable between obese children with sufficient vitamin D and those with vitamin D deficiency. There were no relationships among serum 25-OHD; weight, height, and BMI standard deviation scores; insulin sensitivity indices; FPG and insulin; and 2-h plasma glucose and insulin levels. CONCLUSION: Vitamin D deficiency is not as prevalent in obese Thai children as in obese non-Asian children from high-latitude countries. Adiposity per se is unlikely to be a determinant of vitamin D status in these obese individuals. There was no association between vitamin D deficiency and abnormal glucose homeostasis.

Sexual maturation in Thai boys.

BACKGROUND: A worldwide secular trend towards earlier onset of puberty in girls has been noted during recent years. However, the data on sexual maturation of boys are relatively scarce and normative data of sexual maturation in Thai boys are still lacking. AIM: To determine the age of secondary sexual maturation in normal Thai boys. METHODS: Three hundred healthy urban boys aged 9-18 years were recruited during January 1997 to December 1999. Genital and pubic hair maturity staging was determined using the method of Marshall and Tanner. Testicular size was assessed by Prader orchidometer. Probit analysis was used to analyze the onset of puberty (gonadarche) and pubarche. RESULTS: Median (range) ages of the onset of puberty and pubarche were 10.8 (9.5-12) and 12.4 (10.9-13.9) years, respectively. CONCLUSION: The age of onset of genital development in boys living in Bangkok seems to be slightly earlier than that of boys in other countries. However, the onset of pubic hair development is comparable.

N-methyl-D-aspartate (NMDA) receptors mediate the release of gonadotropin-releasing hormone (GnRH) by NMDA in a hypothalamic GnRH neuronal cell line (GT1-1).

Previous studies demonstrated that an excitatory amino acid analog, N-methyl-D-aspartate (NMDA), stimulates GnRH secretion in the rat, prepubertal primate, and ovine fetus at the hypothalamic level. It is not known if this stimulatory effect of NMDA is mediated directly on the GnRH neurosecretory neuron. A hypothalamic GnRH neuronal cell line (GT1-1) provided a useful model system to study the effect of NMDA on GnRH release by both superfusion and static incubation techniques. Studies with GT1-1 cells indicate that GnRH neurons exhibit spontaneous autorhythmicity and function intrinsically as a neuronal oscillator for the synchronous discharge of GnRH pulses. In static incubation studies, 10(-4) and 10(-3) M NMDA increased GnRH release, whereas 10(-6), 10(-5), and 10(-2) M NMDA had no effect. A competitive NMDA receptor antagonist, AP-5 (10(-4)-10(-2) M), and a noncompetitive NMDA receptor antagonist, MK-801 (10(-12)-10(-5) M), inhibited the action of NMDA. Superfusion of GT1-1 cells after a 90-min control period followed by either continuous NMDA or intermittent NMDA (10(-4) and 10(-3) M) for 90 min increased GnRH pulse amplitude by 100-400%, but had no effect on the interpulse interval (17 min by Cluster); 10(-6), 10(-5), and 10(-2) M NMDA had no effect on either pulse amplitude or interpulse interval. MK-801 (10(-5) M) attenuated the stimulatory effect of NMDA on GnRH pulse amplitude. Incubation in glycine-free and high magnesium medium abolished the action of NMDA on GnRH release. Hybridization analysis of GT1-1 mRNA with an NMDA R1 receptor cDNA showed that this pure neuronal cell line expressed NMDA receptor transcripts observed as a 4.2-kilobase band. The results demonstrate that NMDA stimulates GnRH neurons directly to secrete GnRH through their NMDA receptors by increasing pulse amplitude without affecting pulse frequency.

Nitric oxide synthesized by gonadotropin-releasing hormone neurons is a mediator of N-methyl-D-aspartate (NMDA)-induced GnRH secretion.

N-Methyl-D-aspartate (NMDA) directly stimulates gonadotropin-releasing hormone (GnRH) neurons to secrete GnRH. It is not known if this stimulatory effect of NMDA is mediated by NO. Northern blot analysis of the immortalized hypothalamic GnRH neuronal cells (GT1-1) mRNA with a neuronal NOS cDNA revealed this clonal cell line expressed neuronal NOS transcripts as a single 10.5-kb band. Immunoblot analysis of GT1-1 proteins with anti-neuronal NOS serum showed that the GT1-1 cells contain neuronal NOS. GT1-1 cells were used to study the effects of NO and NMDA on GnRH release. L-Arginine (10(-2) M), a precursor of NO enhances basal GnRH secretion. Both oxyhemoglobin (Hb)(10(-6)-10(-4) M), a NO scavenger and N omega-nitro-L-arginine (NNA)(10(-3),10(-2) M), a NOS inhibitor and inactivator block basal as well as NMDA-induced GnRH release. Sodium nitroprusside (SNP) (10(-4), 10(-3) M), a NO donor stimulates GnRH release, an effect inhibited by Hb. Incubation of GT1-1 cells in Ca(2+)-free medium abolished the stimulatory effect of NMDA on GnRH release. In contrast, incubation in medium with increasing concentrations of Ca2+ enhances basal GnRH release as well as augments NMDA-mediated GnRH release. The results demonstrate that L-arginine-NO pathway is functional in the GT1-1 cells and an increase in intracellular Ca2+ [Ca2+]i following NMDA receptor activation activates NOS to generate NO. We conclude that endogenous NO mediates, at least in part, basal as well as NMDA-stimulated GnRH release and may play a role as an intercellular messenger in synchronizing pulsatile GnRH release.

The luteinizing hormone-releasing hormone-secreting hypothalamic hamartoma is a congenital malformation: natural history.

The LHRH-secreting hypothalamic hamartoma (HH), a congenital malformation consisting of a heterotopic mass of nervous tissue that contains LHRH neurosecretory neurons attached to the tuber cinereum or the floor of the third ventricle, can cause true or central precocious puberty (TPP). We have suggested that it functions as an ectopic LHRH pulse generator independent of the central nervous system inhibitory mechanism that normally restrains the hypothalamic LHRH pulse generator. TPP associated with a hamartoma has all of the hormonal hallmarks of puberty, including a pubertal pattern of pulsatile LH and a pubertal plasma LH response to LHRH administration. Little is known about the natural history of HH. We present long term data on 10 children (5 females and 5 males) with TPP due to HH. Physical signs of puberty were observed at a mean age of 2.2 +/- 1.6 yr (range, 0.5-5.1). Two of 10 had a pedunculated mass, and 8 of 10 had a sessile mass. The hamartoma varied in diameter from 4-25 mm and did not change with time (3.5-8.7 yr). Four patients have a seizure disorder, 3 with gelastic seizures (1 with mental retardation) and 1 with tonic-clonic seizures. The shape of the hamartoma, sessile or pedunculated, did not correlate with the occurrence of seizures. At presentation with sexual precocity, the mean height SD for chronological age was +3.5 +/- 0.4, the mean height SD for bone age was -1.9 +/- 0.4, and the mean bone age SD for chronological age was +6.8 +/- 0.7. Baseline data were comparable to those of 10 females with idiopathic TPP. Nine of 10 HH patients and all idiopathic TPP patients were treated with a LHRH agonist. The response to therapy was excellent in both groups and indistinguishable. Nine of 10 HH children attend school regularly and, aside from those with seizures, have no neurological handicap. While surgical resection of the hamartoma has been recommended, it carries an increased risk of morbidity and mortality and, if removal is incomplete, does not arrest the sexual precocity. In our experience, LHRH agonist therapy for TPP due to HH is the preferable approach.

Deletion of amino acids Asp487-Ser488-Phe489 in human cytochrome P450c17 causes severe 17 alpha-hydroxylase deficiency.

17 alpha-Hydroxylase deficiency blocks the biosynthesis of cortisol and sex steroids, resulting in mineralocorticoid excess, hypertension, sexual infantilism, and female phenotype in both genetic sexes. The disease is caused by mutations in the gene encoding cytochrome P450c17, which is the single enzyme that mediates both 17 alpha-hydroxylase and 17,20-lyase activities. We report a 14-yr-old patient from Thailand with a classical clinical presentation of this rare disorder. Analysis of her P450c17 gene by polymerase chain reaction amplification and sequencing showed a nine-base deletion, eliminating codons 487-489 (Asp-Ser-Phe) near the carboxy-terminus of P450c17. This deletion creates a BclI site in the mutant DNA, permitting accurate demonstration that the patient was homozygous for this lesion, whereas one parent and two siblings were heterozygous. By use of site-directed mutagenesis, we created a vector that could express this mutated form of P450c17 when transfected into non-steroidogenic COS-1 cells. Such transfected cells produced immunodetectable P450c17 protein, but had no 17 alpha-hydroxylase or 17,20-lyase activity, whereas cells similarly transfected with a vector expressing normal human P450c17 could 17 alpha-hydroxylate either pregnenolone or progesterone and convert 17 alpha-hydroxypregnenolone to dehydroepiandrosterone, showing the presence of both activities. This is the first report of the molecular genetic basis of 17 alpha-hydroxylase deficiency in a Southeast Asian patient.

Endemic cretinism in Thailand: a multidisciplinary survey.

Endemic cretinism has been classified into neurological and myxedematous types. Profound mental deficiency, deaf-mutism and cerebral diplegia are predominantly found in the former. The latter have been described as less mentally retarded but with severe growth retardation and myxedematous features. The pathogenesis of different clinical types of endemic cretinism is still unclear. Recently, a unifying hypothesis suggested that iodine deficiency, severe enough to cause maternal and fetal hypothyroxinemia, results in neurological defects in all cretins. We conducted the present study in northern Thailand to determine the validity of this hypothesis in another geographical area. The study consisted of a multidisciplinary survey on 112 endemic cretins aged 2-66 years in Nan. They were categorized clinically into three types of endemic cretins, neurological (n = 57), myxedematous (n = 19) and mixed form (n = 36). The subjects were generally short and the majority had severe mental retardation (mean intellectual quotient (I.Q.) 30.8 +/- 8.8), psychomotor defect and profound sensorineural hearing loss. The I.Q. score and proportion of cretins with sensorineural hearing loss and psychomotor defect were similar among the three types of cretins. The most frequent neurological abnormalities were spasticity, hyper-reflexia, the presence of primitive reflexes and gait disturbance. These abnormalities were distributed equally among the three types of endemic cretins. Delayed skeletal maturation and abnormal epiphysis were also present in all types of cretins. However, myxedematous cretins were shorter (P < 0.01), having more myxedematous features (P < 0.05 to P < 0.001) and less sexual maturation (P < 0.05). Thyroid volume was lower in cretins with hypothyroidism (P < 0.01). In conclusion, our findings support the hypothesis that neurological features are present in all types of cretins, and are the consequence of maternal and fetal hypothyroxinemia due to severe iodine deficiency. The clinical manifestations of the cretins were subsequently modified by the length and severity of postnatal iodine deficiency and hypothyroidism.

Persistent hyperinsulinemic hypoglycemia of infancy: long-term outcome following subtotal pancreatectomy.

BACKGROUND: Persistent hyperinsulinemic hypoglycemia of infancy (PHHI) is the most common cause of persistent hypoglycemia in infants. The current standard treatment is subtotal pancreatectomy (Px). However, the long-term outcome following surgery needs further attention. METHODS: We analyzed 10 children (7 M, 3 F) with PHHI who underwent partial (65-80%) and subtotal (81-95%) Px. Follow-up ranged from 2 to 9.4 yr (mean = 4.2 yr). We divided them into 2 groups based upon the age at onset of hypoglycemia: early (< 1 mo) and late (> or = 1 mo). RESULTS: The seven patients in the early-onset group underwent 85-95% Px between ages of 18 d and 3 mo. Three of them initially treated by 85-90% Px had persistent hypoglycemia postoperatively. Two out of three required a 2nd operation with 95% Px for controlling hypoglycemia, though both still had persistent hypoglycemia and required medication to control blood glucose. The remaining four had 95% Px and had maintained euglycemia postoperatively. One patient developed diabetes 6 yr after surgery. Six of seven patients had delayed development and subnormal IQ. Three patients of the late-onset group (3 mo, 6 mo and 4 yr) underwent partial Px (80%, 65% and 65%, respectively) and maintained euglycemia postoperatively. Despite 65% Px, one developed diabetes 3 yr after surgery. CONCLUSIONS: These results suggest that children with early-onset hypoglycemia have more severe hyperinsulinism than those with late-onset hypoglycemia. The former require 95% Px for maintaining euglycemia, but long-term complications with diabetes may be common. In contrast, the latter require lower percentage Px which may reduce the incidence of diabetes in the future.

Plasma prostacyclin (PGI2) in dengue hemorrhagic fever.

Dengue hemorrhagic fever (DHF) is an epidemic viral disease. The exact mechanism attributable to platelet and vascular dysfunctions is still obscure. Plasma 6-keto-PGF1a (6KPGF1), the stable metabolite of PGI2 was determined in 60 DHF patients and in 11 non-DHF (NDHF) patients with fever of over 38.5 degrees C to compare with that of 33 normal children (NC) in the same age group (2-15 years). Among 60 DHF patients, 32 had blood obtained during impending shock, whereas blood samples of the remainder were taken during normotension. Their plasma 6 KPGF1 values (mean +/- SE) were 201.06 +/- 12.42 and 132.87 +/- 13.08 pg/ml respectively. All patients had serology positive for acute dengue viral infection. The plasma 6 KPGF1 (mean +/- SE) of 33 NC and 11 - NDHF subjects were 149.82 +/- 4.93 and 108.69 +/- 14.53 respectively. The plasma 6KPGF1 levels of 32 DHF patients with impending shock were significantly higher than those of 28 normotensive DHF patients (p less than 0.005), 33 NC (p less than 0.005) and 11 - NDHF patients (p less than 0.005). However the levels in 28 normotensive DHF patients are not statistically different from the values of 33 NC and 11 - NDHF patients. It is concluded that there is a tendency of excessive PGI2 production in DHF patients during hypotensive crisis.

Prolactin (PRL) release in normal and growth hormone deficient children after oral metoclopramide.

Studies were done to determine plasma PRL in response to oral MC 0.2 mg/kg in 17 normal children (NC), 12 males and 5 females aged between 4.7-12.8 years and in 26 idiopathic growth hormone deficient children (IGHD), 15 M, 11 F, between 1.5-14.7 years old. Peak serum GH levels above 10 ng/ml after clonidine test and during insulin induced hypoglycemia were used to distinguish these 2 groups. None of the subjects had secondary sex characteristics. Adrenocortical and thyroid disorders were excluded. The subjects were fasted overnight. Blood samples for PRL determination were obtained at 0, 60, 90, 120 min after oral MC. In 17 NC the basal serum PRL values ranged from 0 to 19.2 ng/ml with the mean +/- SE of 7.24 +/- 1.7 ng/ml. The peak serum PRL response to MC ranges were from 33 to 127 ng/ml with the mean +/- SD and +/- SE of 64.45 +/- 24.22 and +/- 5.88 ng/ml respectively giving the cut point-2SD value of 16.01 ng/ml. Among 26I GHD, only 2 patients (7.69%) being all male, had peak PRL response to MC below 16.01 ng/ml, whereas, the rest (92.31%) had peak PRL levels above it. It is concluded that oral MC 0.2 mg/kg is the potent PRL stimulator in children, which can be safely used to test pituitary PRL secretion effectively. The majority (92.31%) of idiopathic GH deficient children had adequate serum PRL response to oral MC, whilst 7.69 per cent disclosed inadequate response which might indicate different etiologies.

Slipped capital femoral epiphysis in Ramathibodi Hospital.

Slipped capital femoral epiphysis is rare in Asiatic Indonesian-Malays. Seven cases (9 hips) of this condition in Ramathibodi Hospital including five boys (average age, 12.5 years) and two girls (average age, 13 years) were reviewed. Most of the cases (4 out of 7) were acute on chronic and mild slips. No endocrine disorder was observed in all cases. All of the patients had a body weight above the mean of the normal population, four of which were obese. For the treatment, a single screw fixation including one case with cancellous and six cases with cannulated type were used. In the follow-up of average 2.5 years, six cases had satisfactory results. Avascular necrosis occurred in one case with mild and chronic slips in which a cancellous screw was used. It is concluded that obesity is the important factor related to the etiology in this study and probably is the same in other developing countries. The effect of a cancellous screw causing avascular necrosis is still questionable.

Gonadotropin-releasing hormone testing in premature thelarche.

Premature thelarche (PT) is characterized by isolated breast development in girls prior to 8 years of age. In addition, there is neither growth spurt nor advanced bone age. It has been suggested that luteinizing hormone (LH) response to gonadotropin-releasing hormone (GnRH) alone is adequate to distinguish central precocious puberty from PT. However, LH response to GnRH is greater in infancy than that in childhood. Therefore, gonadotropin response to GnRH in girls with isolated premature breast development in different age group was studied. Thirty-six girls with isolated PT (aged 0.25-8 years) were evaluated. They were classified into 2 groups; aged < 4 years (group A: mean age 1.57 +/- 0.87 years, n = 13) and > or = 4 years (group B: mean age 6.97 +/- 0.94 years, n = 23). Initial evaluation included X-ray bone age, pelvic sonography and GnRH testing. Patients were followed for at least 1 year to confirm that no patient had progression into puberty. Bone ages in both groups were within mean +/- 2 SD in all patients. Pelvic sonography was performed in all patients which revealed no abnormality of ovaries and uterus. Pubertal response to GnRH stimulation is characterized by peak LH of > 20 IU/L or delta LH of > 15 IU/L which is generally greater than peak follicle stimulating hormone (FSH) or delta FSH, respectively. Mean peak LH and delta LH in group A were 13.0 +/- 6.06 and 11.4 +/- 5.92 IU/L whereas those in the group B were 8.5 +/- 4.10 and 6.3 +/- 3.49 IU/L. Therefore, LH response to GnRH in group A was significantly higher than that in group B (p < 0.05). In addition, the mean peak FSH and delta FSH in group A were 120.5 +/- 45.87 and 109.9 +/- 42.09 IU/L whereas those in the group B were 48.7 +/- 24.05 and 39.9 +/- 23.69 IU/L. Therefore, FSH response to GnRH in group A was significantly greater than that in group B (p < 0.001). LH response to GnRH alone can distinguish prepuberty from puberty in girls > 4 years of age. However, in prepubertal young girls with PT aged < 4 years, pubertal LH response can occur, i.e. peak LH > 20 IU/L. Hence, the greater FSH response to GnRH than that of LH would confirm the diagnosis of premature thelarche in this group. Therefore, the evaluation of FSH response to GnRH is beneficial to distinguish puberty from prepuberty in young girls.

Combined raw cornstarch and nifedipine as an additional treatment in persistent hyperinsulinemic hypoglycemia of infancy.

This study reports the result of treatment with the combination of raw cornstarch and nifedipine in two infants affected with hyperinsulinemic hypoglycemia of variable severity. The first infant developed hypoglycemia during early neonatal period and required subtotal pancreatectomy. She still developed hypoglycemia after her second operation. The second infant developed hypoglycemia at the age of 7 months. Raw cornstarch and nifedipine efficiently normalized both infants' blood glucose levels. Although they still need frequent feedings, no hypoglycemic episode was reported except when they were sick. Their growth and development were markedly improved after initiation of treatment.

Insulin-like growth factor-I (IGF-I) screening for the diagnosis of growth hormone (GH) deficiency.

Growth hormone deficiency (GHD) is a common cause of growth retardation in children and adolescents. Gold standard for the diagnosis of GHD is based upon two standard growth hormone (GH) provocative tests demonstrating a peak serum GH of less than 7 ng/mL. These tests, besides requiring multiple blood samplings, are time-consuming and costly. GH primarily mediates its growth-promoting effect through insulin-like growth factor-I (IGF-I). Hence, basal serum IGF-I level reflects GH status. We studied 47 prepubertal children with or without short stature. Aged ranged between 4.3 and 15.6 years. They were divided into 2 groups based upon 2 standard GH provocative tests. Seventeen Children were classified as having GHD. The remaining 30 were non-GHD. Basal serum IGF-I was obtained before GH testing. The means +/- SE (range) of serum IGF-I concentration were 44.26 +/- 3.19 (19.10-75.63) ng/mL in GHD and 118.42 +/- 10.03 (60.65-235.91) ng/mL in non-GHD which were significantly different (P < 0.001). 88.2 per cent of GHD had serum IGF-I concentration less than 60 ng/mL whereas 100 per cent of non-GHD had serum IGF-I greater than 60 ng/mL. There was no correlation between serum IGF-I and either bone age or chronologic age in children with GHD. These data indicate that serum IGF-I level is a useful screening test to exclude GHD with high sensitivity. We suggest that if serum IGF-I is less than 80 ng/mL in prepubertal children, GH provocative tests should be performed to diagnose GHD. If serum IGF-I is greater than 80 ng/mL, growth rate monitoring is recommended. If growth rate is decreased despite normal IGF-I, GH provocative tests should be obtained to rule out GHD.

Congenital complete absence of GH, TSH and PRL in infants: a consequence of Pit-1 gene deletion.

The patient was the first child of a short mother (140 cm) born at term with a birthweight of 2,700 g. On arrival, she was 1 4/12-year-old, weighed 4,150 g and 47 cm long. Her bone age was at the 6 month-old level. Endocrine investigation revealed undetectable plasma growth hormone (GH), thyrotropin (TSH) and prolactin (PRL) levels. CT scan of ovaries revealed bilateral ovarian agenesis in spite of normal, 46 XX karyotype. MRI of the brain did not demonstrate intracranial tumor or congenital malformation. Peak plasma GH level after oral clonidine provocation, insulin induced hypoglycemia, and I.V. GH-RF stimulation were 0.6, 0, and 0 ng/ml respectively. Peak plasma TSH response after I.V. TRH stimulation was 0.04 microU/ml. The patient could not secrete PRL at any time after insulin induced hypoglycemia, TRH and metoclopramide stimulations. On the other hand the child had elevated basal plasma cortisol (38 micrograms/dl at 8.00 AM) and raised 24 hr urinary 17 OHCS excretion (50 mg/1 g Cr against normal value of 3 mg/1 g Cr) without evidence of Cushing syndrome probably indicate partial glucocorticoid resistance. Peak plasma cortisol responses after intravenous metoclopramide and insulin induced hypoglycemia were 46 and 42.9 micrograms/dl respectively. Dexamethasone administration reduced plasma cortisol to 2.9 micrograms/dl. The child had also elevated basal plasma FSH (36 microU/ml) and LH (5 microU/ml) with further elevation to the peak of 123 and 99 microU/ml respectively after LHRH stimulation. All evidence suggested the diagnosis of congenital complete absence of GH, TSH, and PRL which is characteristic of Pit-1-gene deletion.(ABSTRACT TRUNCATED AT 250 WORDS)

Thyroid function in healthy Thai neonates.

OBJECTIVES: To construct a normative data for serum thyroxine (T4), free T4 (FT4), triiodothyronine (T3) and thyrotropin (TSH) in Thai neonates. STUDY DESIGN: A cross-sectional study of 275 healthy full-term neonates was conducted. Blood samples were obtained from umbilical cords of the neonates and from heel pads of infants aged 1-30 days. Hormone measurements included serum T4, FT4, T3 and TSH. RESULTS: Mean serum T4 and FT4 levels rapidly increased after delivery to the maximum level at 1-3 days of age. Thereafter, they declined to a steady state level within 2-4 weeks. Mean serum T3 level was very low at birth. The concentration increased 3-5 times and reached a steady state levels within 1 week. In contrast, mean serum TSH declined from birth and the level at 1-3 days of age was slightly less than that of the cord blood. It changed little after 3 days of age. Previous studies have shown a transient TSH surge in the first 24-48 hour of life. TSH surge was not apparent in our study because samples were not obtained from infants < 24 hours old. Therefore, if TSH is measured for screening of congenital hypothyroidism, samples should be obtained from umbilical cord or infants aged > 48 hours. CONCLUSIONS: This study provides the normative data for thyroid function tests in Thai full-term neonates. These data are useful for detection and verification of hypothyroidism in a screening program for congenital hypothyroidism.

Five-year thyrotropin screening for congenital hypothyroidism in Ramathibodi Hospital.

OBJECTIVES: To detect newborns with congenital hypothyroidism (CH) and to treat the affected infants as early as possible. STUDY DESIGN: Cord blood thyrotropin (TSH) screening for CH in Ramathibodi Hospital began in 1993. From October 1993 to December 1998, 35,390 neonates were screened. The infants with elevated TSH level of greater than 30 mU/L were recalled for verification of CH. Confirmation tests included total thyroxine, free thyroxine and TSH level. Thyroid scan and uptake were performed in some affected infants. RESULTS: Twelve infants with CH were detected resulting in an incidence of one in 2,949 live-births. All affected infants were asymptomatic at birth. Of 12 infants with CH, one premature neonate had a delayed TSH elevation and was diagnosed as having primary hypothyroidism at 2 months of age. The recall rate for validation of CH based on a cut-off value at serum TSH level of greater than 30 mU/L is 1.1 per cent. If the cut-off value of serum TSH level was raised to greater than 40 mU/L, the recall rate would decrease to 0.43 per cent. None of the affected infants had cord blood TSH level of less than 50 mU/L except one premature patient. Therefore, beginning in January 1997, the cut-off value of TSH was raised to 40 mU/L or greater. Pitfalls in this program include incomplete blood-specimen collection and incomplete follow-up. To strengthen the program, improvements were made in the follow-up system from 1996 onward. Therefore, the coverage for blood-specimen collection progressively increased from 84 per cent in 1994 to 96 per cent in 1998. Simultaneously, the patients' return after recalls also increased from 38 per cent to 100 per cent. CONCLUSIONS: The incidence of CH in Ramathibodi Hospital is approximately 1:3,000 live-births. The optimal cord blood TSH level for recall is 40 mU/L or greater. The intensification of follow-up strategy resulted in better response to recall and earlier treatment in the affected infants.

Elevated serum cholesterol levels in Bangkok children and adolescents.

Hypercholesterolemia is a major cardiovascular risk factor. This study aimed to assess serum total cholesterol (TC) levels of children and adolescents living in Bangkok, Thailand. During 1995-1997, nonfasting blood samples were obtained from 570 healthy school children and adolescents aged 9-18 years. The mean TC levels ranged from 143-180 mg/dl in males and from 145-202 mg/dl in females. The prevalences of hypercholesterolemia (TC > or = 200 mg/dl) were 12.2 per cent and 20.3 per cent in males and females, respectively. Twenty-eight per cent of males and 26.9 per cent of females had borderline values (TC 170-199 mg/dl). TC inversely correlated with age (r = -0.16, P < 0.01) in males. The findings indicate that notable percentage of these children had elevated cholesterol levels and warrant additional study concerning risk factors and tracking of lipoprotein levels from childhood into adulthood.

Effects of maternal iodine supplementation during pregnancy and lactation on iodine status and neonatal thyroid-stimulating hormone.

OBJECTIVE: To determine the iodine status in pregnant and lactating women, as well as neonatal thyroid-stimulating hormone (TSH) concentration. STUDY DESIGN: Pregnant women cared at our hospital, the University Hospital in Bangkok, had routinely received 200 µg iodine tablet daily since October 2010. Urinary iodine concentrations (UICs) of 1508 pregnant and 87 lactating women and 76 offspring and breast milk iodine concentration (BMIC) (n=57) were measured. Cord serum TSH levels from hypothyroidism screening were analyzed. RESULT: Median UIC levels of pregnant and lactating women were 170.6 and 138.0 µg l(-1), respectively. Median BMIC and infants' UIC at 2-month postpartum in iodine-supplemented group were higher than the respective values of non-supplemented group. Median cord serum TSH level obtained before iodine supplementation (n=8332) was higher than that obtained after supplementation (n=5181; 7.3 vs 5.2 mU l(-1)). CONCLUSION: Maternal iodine supplementation improved iodine nutrition in their breast-fed offspring. A trend toward declining in cord serum TSH values after iodine supplementation indicates improvement of iodine status during pregnancy.

Decreased cortisol response to insulin induced hypoglycaemia in asthmatics treated with inhaled fluticasone propionate.

AIMS: To assess adrenal function in asthmatic children treated with inhaled fluticasone propionate for up to 16 weeks. METHODS: Children with asthma and bronchial hyperresponsiveness to inhaled methacholine were treated with inhaled fluticasone 250-750 microg/day via Volumatic spacer. The insulin tolerance test (ITT) was performed to assess adrenal function. RESULTS: Eighteen asthmatic patients (10 boys, 8 girls), aged 7-17 years received inhaled fluticasone therapy at a median dose of 477 microg/m2 per day for 5-16 weeks. Adrenal suppression, defined as 60 minute serum cortisol less than 500 nmol/l, was found in 9 of 18 children. Following the ITT, the median basal and 60 minute serum cortisol concentrations of the suppressed group were 135.0 and 350.0 nmol/l, respectively; the corresponding values for the unsuppressed group were 242.2 and 564.7 nmol/l. Repeat ITT in the suppressed group 2-3 months after discontinuation of fluticasone revealed that all patients had a 60 minute serum cortisol greater than 500 nmol/l. CONCLUSION: After therapy for asthma with inhaled fluticasone at approximately 500 microg daily for up to 16 weeks, half the children had evidence of adrenal suppression.