Clinical characteristics of Taiwanese children with congenital adrenal hyperplasia caused by 21-hydroxylase deficiency in the pre-screening era.

BACKGROUND/PURPOSE: Data about the clinical manifestations of congenital adrenal hyperplasia caused by 21-hydroxylase deficiency (21-OHD) are lacking in Taiwan. Therefore, this study analyzed the clinical features of 21-OHD in Taiwanese children to improve the diagnosis of this disorder, and to provide background information regarding the ongoing neonatal screening program for 21-OHD in Taiwan. METHODS: Eighty children with 21-OHD, 39 with the salt-wasting (SW) type and 41 with the simple-virilizing (SV) type, were evaluated by a review of their medical records. Their clinical symptoms and signs, laboratory findings, and genetic mutations were analyzed. RESULTS: The most frequent features in 21-OHD patients were hyperpigmentation and signs of androgen excess. Clinical manifestations related to hyponatremia such as poor feeding, poor weight gain, and dehydration were noted most frequently in patients with SW-type 21-OHD. Five patients had low serum cortisol with elevated plasma adrenocorticotropic hormone levels, and 22 patients had elevated dehydroepiandrosterone sulfate levels. All had elevated blood levels of 17-hydroxyprogesterone, androstenedione and testosterone. Hyponatremia and hyperkalemia were detected in 29 patients with SW-type 21-OHD. In terms of molecular diagnosis, mutations at IVS2-12A/C --> G and gene deletion were the most frequent mutations detected in SW-type 21-OHD, while I172N and mutation at IVS2-12A/C --> G were most frequent in SV type. CONCLUSION: Taiwanese children with 21-OHD have characteristic clinical findings such as hyperpigmentation, androgen excess, and failure to thrive. There is a good correlation between genotype and pheno-type. Laboratory tests, including serum 17-hydroxyprogesterone, androstenedione, and testosterone levels are more sensitive than serum cortisol or dehydroepiandrosterone sulfate levels for diagnosing 21-OHD in prepubertal children.

Effect of growth hormone therapy on adult height of children with Turner syndrome.

BACKGROUND/PURPOSE: Short stature is a common manifestation of Turner syndrome. The purpose of this study was to evaluate the effect of growth hormone (GH) therapy alone on the adult height of children with Turner syndrome. METHODS: From 1987 to 2006, 21 Turner syndrome patients who had been treated with GH for >2 years and had reached adult height were enrolled in the study. The dosage of GH was 0.33 mg/kg/week. Estrogen replacement therapy was prescribed at the age of 15.6+/-0.9 years, if indicated. The patients had been followed-up until they reached their adult height. During the same period, 28 Turner syndrome patients who were not treated with growth-promoting agents were enrolled for comparison. Mann-Whitney U test and Wilcoxon signed rank test were used for comparison. RESULTS: Twenty-one patients in the study group started GH therapy at the age of 11.5+/-1.8 years. The duration of GH therapy was 4.0+/-1.5 years. The growth rate before treatment was 3.8+/-0.7 cm/year, which increased to 7.1+/-1.4, 5.4+/-1.4 and 4.7+/-0.9 cm/year during the first 3 years of GH therapy, respectively. Patients who received GH reached an adult height of 150.0+/-5.1 cm, which was significantly higher than the 144.7+/-5.9 cm of the control group (p<0.05). The adult height of the study group was 6.3+/-3.3 cm taller than their projected adult height upon enrolment. No major adverse events were detected during GH therapy. CONCLUSION: GH alone is safe and effective for the promotion of growth in children with Turner syndrome in Taiwan.

Evaluation of beta-cell function in diabetic Taiwanese children using a 6-min glucagon test.

This study evaluates the effects of glucagon 30 mug/kg (maximal 1 mg) on beta-cell function in children by C-peptide determined before and 6 min after intravenous administration. From 1990 to 2005, 118 Taiwanese children with newly diagnosed diabetes mellitus (98 children with type 1 and 20 children with type 2) and 29 normal Taiwanese children were enrolled in this study. Fasting and 6-min post-glucagon C-peptide levels were analyzed. In the pre-pubertal group, the median fasting serum C-peptide levels were 0.2 and 0.8 nmol/l in type 1 diabetes and normal children, respectively. These levels rose to 0.3 and 1.9 nmol/l after glucagon stimulation. In the pubertal group, the median fasting serum C-peptide levels were 0.3, 1.0 and 0.9 nmol/l in type 1 diabetes, type 2 diabetes and normal children, respectively. They rose to 0.4, 2.5 and 2.7 nmol/l after glucagon stimulation. Both fasting and post-glucagon C-peptide levels in type 1 diabetes patients were significantly lower than those of normal children and children with type 2 diabetes. The optimal cut-off values to distinguish type 1 diabetes patients from those with type 2 as determined by the receiving operating characteristic curve were 0.7 and 1.1 nmol/l, respectively. The sensitivities of both C-peptide values were 93%. The post-glucagon C-peptide level was more powerful in distinguishing type 1 diabetes from type 2 diabetes with higher specificity (95% vs. 85%). The 6-min glucagon test is valuable in assessing beta-cell function in children and can help pediatricians in the differential diagnoses of diabetes mellitus in children.

The effects of gonadotropin releasing hormone analogue therapy on girls with gonadotropin-dependent precocious puberty.

BACKGROUND/PURPOSE: It has been reported that gonadotropin releasing hormone analogue (GnRHa) therapy can improve the adult height of patients with gonadotropin-dependent precocious puberty. The purpose of this study was to evaluate the effect of GnRHa on the adult height of girls with gonadotropin-dependent precocious puberty and the adverse effects of such therapy. METHODS: Between 1989 and 2006, 11 girls with gonadotropin-dependent precocious puberty who had been treated with GnRHa and reached their adult height were enrolled in the present study. Follow-up studies of bone age, pelvic sonography and GnRH test were done regularly during the period of treatment. All patients had bone mineral density examined at least 2 years after completion of GnRHa therapy. RESULTS: GnRHa therapy was initiated at the age of 8.0 +/- 1.5 years. The predicted adult height immediately before GnRHa therapy was 146.7 +/- 4.8 cm (-2.3 +/- 0.9 standard deviation [SD]). The duration of GnRHa therapy was 4.7 +/- 1.8 years. The adult height of the patients was 156.3 +/- 4.3 cm (-0.6 +/- 0.8 SD), which is similar to their target height of 157.0 +/- 4.5 cm (-0.5 +/- 0.8 SD). The uterine sizes and gonadotropin responses to GnRH stimulation were well suppressed during treatment. Menstruation resumed 9.2 +/- 5.9 months after the discontinuation of treatment in these patients. Forty-five percent of patients had lumbar bone mineral density less than 1 SD below that of normal young Taiwanese adults in the Taipei region. CONCLUSION: GnRHa therapy can improve the adult height of patients with gonadotropin-dependent precocious puberty. However, 45% of patients had decreased bone accretion during therapy.

Long-term outcome of hormonal status in Taiwanese children with Hashimoto's thyroiditis.

UNLABELLED: The objective of this prospective study was to evaluate both thyroid function in children with Hashimoto's thyroiditis and the necessity of lifetime thyroxine replacement therapy. A total of 47 patients with goiter and positive thyroid auto-antibodies participated in the study. Serum thyroxine and thyrotropin levels and titers of thyroid auto-antibodies were checked regularly throughout the follow-up period. At the beginning of the study, 25 patients were diagnosed as euthyroid, but at the end of the study, 22 patients initially diagnosed with euthyroidism remained euthyroid, while eight patients with subclinical hypothyroidism and three patients with overt hypothyroidism had become euthyroid. Thus, of the 22 patients with thyroid dysfunction at diagnosis, subclinical or overt, 11 became euthyroid during the follow-up period. The effect of thyroxine treatment on thyroid auto-antibody titers was not significant. CONCLUSION: Our data shows that Hashimoto's thyroiditis in children has a benign course and that thyroid function in one half of the patients with thyroid dysfunction at diagnosis reverts to normal. Careful follow-up of thyroid function is important in order to determine the necessity and timing of thyroxine replacement therapy.

Adult height of patients with classical congenital adrenal hyperplasia.

BACKGROUND AND PURPOSE: Data on factors that affect the final height of patients with classical congenital adrenal hyperplasia (CAH) are limited. This study investigated the factors that can affect height outcome of patients with classical CAH. METHODS: A retrospective study of 44 patients (16 males, 28 females) with classical CAH who had attained the adult height without gonadotropin-releasing hormone analog therapy was conducted. Adult height standard deviation scores (AHSDS) and target height standard deviation scores (THSDS) were determined. The impact of type, gender, control of disease activity or occurrence of precocious puberty on height was analyzed. RESULTS: The difference between AHSDS and THSDS of the 44 patients was -0.7 +/- 1.0 and was greatest in simple-virilizing males (-1.1 standard deviation score [SDS]). However, no significant differences in height outcomes were identified between genders and types. The differences between AHSDS and THSDS of patients with good control of disease activity or normal puberty were -0.3 SDS and -0.4 SDS, respectively, which were better height outcomes than those of the other groups (p < 0.05). CONCLUSIONS: Classical CAH can lead to reduced adult height. Good control of disease activity and the prevention of the occurrence of precocious puberty is important to achieving normal adult height outcome.

Physiological changes of adrenal androgens in childhood.

BACKGROUND AND PURPOSE: To investigate the change in serum dehydroepiandrosterone sulfate (DHEAS) and androstenedione concentrations during childhood and to clarify the relationship between adrenarche and gonadarche. METHODS: A cross-sectional study of 577 healthy children (297 boys and 280 girls), with ages ranging from 5 days to 12 years was conducted. After complete physical examination and recording of any sign of puberty, blood samples were drawn for the determination of serum DHEAS and androstenedione concentrations. For comparison, blood samples were also drawn from 39 normal adults, 23 men and 16 women. RESULTS: In both genders, the DHEAS and androstenedione levels at birth were 3.0 +/- 1.3 mumol/L and 4.1 +/- 2.3 nmol/L, respectively. They fell rapidly within 6 months, and were maintained at a low level until 6 years of age. After the age of 6, the levels of both adrenal androgens were significantly increased (p < 0.05). Adrenarche occurred at the age of 7.7 +/- 1.1 years in boys and at the age of 7.7 +/- 1.0 years in girls. Gonadarche occurred at the age of 11.2 +/- 0.8 years in boys (n = 33) and at the age of 10.3 +/- 0.8 years in girls (n = 46). The onset of adrenarche occurred about 2 to 3 years earlier than the onset of puberty (p < 0.001). CONCLUSIONS: Serum levels of adrenal androgens change dramatically during childhood. Serum concentration of DHEAS is a good marker for adrenal androgens production because gonadal androgens may interfere with serum concentration of androstenedione. For Taiwanese children, the onset of adrenarche occurred between the ages of 6 and 8 years, which was 2 to 3 years earlier than the onset of puberty.

Clinical characteristics and management of acute suppurative thyroiditis in children.

BACKGROUND: Acute suppurative thyroiditis is an uncommon disease in children. This paper describes the clinical characteristics and management of children with acute suppurative thyroiditis treated during a 15-year period at National Taiwan University Hospital. PATIENTS AND METHODS: From 1985 to 2000, acute suppurative thyroiditis was diagnosed in 11 previously healthy children (6 boys, 5 girls) at the Department of Pediatrics. Their mean age at diagnosis was 6.4 +/- 4.4 years. Leukocyte count, acute-phase reactants, thyroid function, and thyroid autoantibodies were assessed. Samples were taken by thyroid needle aspiration for cytology study and pus culture. Underlying pyriform sinus fistula (PSF) was demonstrated by barium esophagogram. RESULTS: Leukocytosis was noted in six cases (55%) and acute-phase reactants were elevated in eight cases (73%). Neither thyroid autoantibodies nor thyroid dysfunction was detected in any of the patients. Barium esophagogram detected PSF in eight of 10 patients examined. Five (45%) patients had recurrent suppurative thyroiditis before surgery. Cytology and pus cultures were available for 10 patients. Polymorphonuclear cells were the main findings in the smear from thyroid aspirates. Twenty-two organisms were isolated from six patients (60%). Streptococcus species (45%) and anaerobic organisms (41%) were the most common pathogens isolated. Mixed infection was detected in five of six children who had a causative microorganism identified. The microorganisms were all sensitive to amoxicillin-clavulanate. CONCLUSION: PSF plays a role in the pathogenesis of acute suppurative thyroiditis in children. Streptococcus species are the most common pathogens in acute suppurative thyroiditis. Our results suggest that amoxicillin-clavulanate is the drug of choice for the treatment of this disease.

Expression of zebrafish cyp11a1 as a maternal transcript and in yolk syncytial layer.

Cyp11a1 (P450scc, cholesterol side-chain cleavage enzyme) is the first enzyme for the synthesis of all steroid hormones. The regulation of steroid synthesis has been extensively investigated, except during embryogenesis. To study steroidogenesis in embryos, we have isolated the zebrafish cyp11a1 gene, which consists of 11 exons. Reverse transcription-polymerase chain reaction analysis indicates that zebrafish cyp11a1 is expressed temporally in two waves during embryonic stages and when sexual differentiation begins. It is expressed in adult brain, testicular Leydig cells, and the granulosa/theca layer of the ovary. In addition, zebrafish cyp11a1 is expressed in oocytes, and is inherited as a maternal transcript in early embryos. Throughout zebrafish epiboly and segmentation stages, cyp11a1 is expressed in the yolk syncytial layer. At 36 h post fertilization, cyp11a1 transcript is located ventral to the third somite, where the primordial interrenal gland is located. In summary, zebrafish cyp11a1 is expressed in the cytoplasm of oocytes, as a maternal transcript, and in yolk syncytial layer during early embryogenesis.