The role of prostacyclin (PGI2) and thromboxane A2 (TXA2) in pathogenesis of dengue hemorrhagic fever (DHF).

In previous studies it has been demonstrated that the levels of plasma 6 keto-prostaglandin F1 alpha (6-K-PGF1), the stable metabolite of PGI2 were elevated in DHF patients during shock. In this study it is hypothesized that excessive PGI2 production plays a very important role in developing serious clinical manifestations of dengue shock syndrome (DSS) patients. In addition, an attempt was made to determine whether TXA2 has any significant role in such patients. Plasma 6-K-PGF1 and thromboxane B2 (TXB2), the stable metabolites of TXA2 were determined in 43 normal healthy children (NC) and 54 DHF patients without shock (DHF-N) and 33 DHF patients with shock (DHF-S). Subjects aged between 2 and 14 years. Plasma 6-K-PGF1 and TXB2 were measured by radioimmunoassay and the ratio of TXB2/6-K-PGF1 were also calculated. In 43 NC the values of plasma TXB2, 6-K-PGF1 and TXB2/6-K-PGF1 ratio were (mean +/- SE) 372.3 +/- 17.1, 150.1 +/- 2.4 and 2.52 +/- 0.12 pg/ml, respectively. In 54 DHF-N patients the corresponding values were 409.1 +/- 16.0, 278.4 +/- 11.6 and 1.54 +/- 0.06 pg/ml; whereas those in 33 DHF-S patients were 254.3 +/- 26.2, 349.1 +/- 20.5 and 0.757 +/- 0.073 pg/ml, respectively. Plasma 6-K-PGF1 levels of DHF-N and DHF-S patients were significantly greater than those in normal children (p < 0.001, p < 0.01 respectively). The plasma 6-K-PGF1 levels seem to be greater in DHF-S patients than in the DHF-N patients, however the difference in values were not statistically significant (p > 0.05). These findings indicate that plasma PGI2 level is significantly increased in DHF particularly during shock. Plasma TXB2 levels of DHF-N had no significant statistical difference from those of NC (p > 0.05); however, those in DHF-S patients were significantly lowered (p < 0.001) than those of NC and DHF-N patients. The findings suggest the important role of TXA2 to compensate for excessive PGI2 secretion in DHF patients. The failure or inadequate TXA2 production may eventually lead to shock. The ratios were significantly reduced in both DHF-N and DHF-S patients when compared to those of NC (p < 0.001 both). The ratio in DHF-S patients was also significantly lowered than that in DHF-N patients (p < 0.001). It is suggested that the imbalance between TXA2 and PGI2 production exists during DHF infection. The more reduction of plasma TXA2/PGI2 ratio leads to more overt and serious clinical manifestations of the disease.

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.

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.

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)

Screening for congenital hypothyroidism in Thailand: has its time come?

The incidence of congenital hypothyroidism at Ramathibodi Hospital was approximately 1:2,486-1:3,843 livebirths, comparable to those found in other industrialized countries. The screening program utilizing TSH measured by a kit manufactured in Thailand was accurate and cost-benefit. It is time to organize TSH screening at least in a university hospital in Thailand to prevent the social burden of raising mentally-handicapped children.