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.

Impact on neonatal outcome and anthropometric growth in very low birth weight infants with histological chorioamnionitis.

BACKGROUND/PURPOSE: Chorioamnionitis (CAM) is one of the main causes of preterm labor. The specific aim of our study was to evaluate neonatal outcome and anthropometric growth at the corrected age of 2 years after exposure to an adverse intrauterine event of CAM in very low birth weight (VLBW, less than 1500 g) infants. METHODS: One hundred and nineteen VLBW infants had adequate placental histological data available for the study. Maternal and perinatal characteristics and neonatal morbidity were determined. The infants were followed up prospectively and their anthropometric growth was recorded in the neonatal follow-up clinic for 2 years. RESULTS: Histological CAM was evident in 64 cases (53.8%, CAM group). Patients with histological CAM delivered earlier (27.8 +/- 2.9 vs. 29.6 +/- 3.6 weeks, p = 0.003), and they had higher incidence of preterm premature rupture of membranes (PPROM, p less than 0.001) and longer ventilation days (p = 0.001). After adjusting for gestational age, sepsis (aOR, 3.355), bronchopulmonary dysplasia (aOR, 3.018) and mechanical ventilation (aOR, 4.094) had a higher incidence in the CAM group. At the corrected ages of 6, 12, 18 and 24 months, anthropometric measurements, including body weight, body height and head circumference, were similar for the study and control infants. CONCLUSION: Histological CAM was associated with a higher incidence of PPROM, sepsis, bronchopulmonary dysplasia, more mechanical ventilation and longer ventilation days. However, at the age of 2 years, CAM had no impact on anthropometric growth.

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.

Outcome of myasthenia gravis mothers and their infants.

BACKGROUND: The aim of this retrospective study was to assess neonatal outcomes of pregnant women with myasthenia gravis (MG). METHODS: Pregnant women with MG who were treated in our hospital over an 8-year period were enrolled. Data relating to the course of the mother's MG (including the anti-acetylcholine receptor antibody (anti-AchR) titer and drug dosage), delivery mode, delivery course, puerperium period, and neonatal outcomes were obtained from the medical records. RESULTS: Twelve women with MG had 13 pregnancies in our hospital from January 1997 to December 2005. None of the mothers needed intensive care. Two patients delivered vaginally, and ten delivered by cesarean section. Fourteen infants were born at an average gestational age of 37.2 +/- 2.0 weeks; their average birth weight was 2838.6 +/- 724.2 g. Two neonates (14.2%) had a congenital anomaly. Transitory neonatal myasthenia gravis (NMG) was diagnosed in one infant (7.1%). CONCLUSIONS: In our study, MG exacerbations occurred in 38.5% of the patients. Postpartum, all MG patients experienced deterioration except one patient who deteriorated in the first trimester with a concomitant upper airway tract infection. Only 1 of the 14 neonates developed transient NMG; the incidence of transient NMG was lower than that previously reported. There was no correlation between the occurrence of NMG and the maternal anti-AChR titer. The cesarean section rate was approximately 33%; this high rate of elective cesarean sections in these MG patients could have prevented the occurrence of some of the complications related to vaginal delivery.

Slipped capital femoral epiphysis as a complication of growth hormone therapy.

Slipped capital femoral epiphysis (SCFE) is a rare complication of growth hormone (GH) therapy. Here, we report three patients who developed SCFE during GH therapy. The first two patients had hypopituitarism and had started GH therapy at the age of 15 years 6 months and 13 years 9 months, respectively. SCFE developed 4 years and 1 year after GH therapy, respectively. The third patient had Prader-Willi syndrome with obesity and hypogonadism and began GH therapy at the age of 12 years and 11 months. SCFE developed 2 months after starting GH therapy. Pain over the hip joints or over the knees is an early sign of SCFE. Despite recommendation, none of the three patients continued GH therapy. A high index of suspicion during GH therapy in patients at high risk of SCFE is important for early diagnosis and appropriate management.

Generalized lymphangiomatosis presenting as cardiomegaly.

Lymphangioma refers to the local proliferation of well-differentiated lymphatic tissue. Generalized lymphangiomatosis is rare. We report a previously healthy 8-month-old infant who suffered from tachypnea with mild fever for 2 weeks. Imaging studies revealed a well-defined, large mass occupying the mediastinum, which presented as cardiomegaly. The disseminated mass extended to the thymus, lung, and spleen. Lymphangiomatosis was diagnosed by biopsy. Drainage of the pericardial fluid and total parenteral nutrition did not result in improvement of chylopericardium. Secondary hypogammaglobulinemia and septic shock developed sequentially. Surgical removal of the mediastinal mass and spleen were performed. Daily subcutaneous injection of interferon (IFN) alpha-2b was then given for 3 months. No recurrence was noted during 2 years of follow-up. IFN alpha-2b may be considered as an alternative for the treatment of generalized lymphangiomatosis.

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.

Urolithiasis and primary parathyroid adenoma: report of one case.

A 12-year-old girl was admitted to ward because of persistent left flank pain, vomiting, and hematuria. A stone was located at the ureteropelvic junction of the left kidney, as determined by means of abdominal sonography. Metabolic investigation for a renal stone revealed that she had hypercalcemia, hypophosphatemia, and hypercalciuria. Hyperparathyroidism was diagnosed based on the hypercalcemia and inappropriately elevated serum parathyroid hormone level. A parathyroid adenoma was successfully diagnosed by using thallium/technetium subtraction parathyroid scanning. Extracorporeal shock wave lithotripsy was performed to treat the renal stone, and the parathyroid adenoma was successfully removed. The patient's postoperative course was uneventful. This case is presented because urolithiasis and hyperparathyroidism are rare in children. Metabolic evaluation is mandatory in children with a renal stone. Further investigation for the hyperparathyroidism should be performed if hypercalcemia associated with hypercalciuria is documented.

Management of hemobilia with transarterial angiographic embolization: report of one case.

A nine-year-old girl who developed life threatening hemobilia after blunt abdominal trauma was successfully managed by embolization of the hepatic artery aneurysm. However, biliary fistula persisted and subcapsular liver abscess occurred after the endoscopic sphincterotomy and the placement of a nasobiliary drain for bile leakage. Debridement of the abscess and insertion of a drain tube eventually cured the event. The relevant literature is reviewed and the management of the hemobilia is discussed.