Jing-Sheng Lee

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

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.

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.

HLA-DQB1 Codon 57 and IDDM in Chinese Living in Taiwan

OBJECTIVE To study the human leukocyte antigen (HLA)-DQB1 genetic background in the Chinese population in Taiwan and its association with the low incidence of insulin-dependent diabetes mellitus (IDDM) in this population. RESEARCH DESIGN AND METHODS Forty-eight IDDM patients and 59 nondiabetic unrelated control subjects were recruited from the population in Taiwan. HLA-DQB1 exon 2 was enzymatically amplified by polymerase chain reaction. HLA-DQBl alleles were diagnosed by dot blotting and hybridization with 16 sequence-specific oligonucleotide probes. RESULTS DQB1*0201 and DQB1*0302 alleles were more frequent and DQB1*0301 and DQB1*0601 were less frequent in Chinese with IDDM than in control subjects. Genotypes for homozygous non-aspartic acid residue (NA/NA) at position 57 were positively associated with IDDM at a relative risk of 4.34 (P < 0.001), and those for homozygous aspartic acid (A/A) were negatively associatedwith IDDM at a relative risk of 0.14 (P < 0.001). Among the NA/A heterozygotes, only DQB1*0201/ DQB1*0303 was significantly increased in IDDM subjects. CONCLUSIONS The amino acid residue at position 57 of HLA-DQ β3-chain is significantly associated with the development or prevention of IDDM in Chinese subjects living in Taiwan. Other genetic and environmental factors may also play important roles in pathogenesis of IDDM.

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.

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.

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.

Thyroid disease in Chinese children with IDDM.

From the Department of Internal Medicine, Meimai Central Hospital, Akashi; and the Department of Laboratory Medicine, Tokushima University School of Medicine, Tokushima, Japan. Address correspondence to Yasuhiro Tahara, MD, PHD, Department of Internal Medicine, Meimai Central Hospital, Matsugaoka 4-1-32, Akashi, 673 Japan. FPG, fasting plasma glucose; HPLC, highperformance liquid chromatography; N1DDM, non-insulin-dependent diabetes mellitus; ID DM, insulin-dependent diabetes mellitus.

Growth retardation as the initial manifestation of intracranial tumors: report of two cases

Two boys (9 years and 14 years old) were brought to visit our pediatric endocrine clinic with the chief complaint of short stature. Because of growth retardation, they were admitted for further evaluation. Physical examinations, including neurological examinations, were unremarkable but the laboratory examination confirmed the diagnosis of hypopituitarism in both patients. Skull radiography examinations showed some calcifications at suprasellar regions in the case 1 but negative findings in case 2. Furthermore, computed tomography (CT) of the head of case 2 performed at an outside hospital half a year before was reported to be normal, so case 2 fits the conventional diagnosis of idiopathic hypopituitarism. However, magnetic resonance image (MRI) study of the head disclosed that both of them are victims of an intracranial tumor, craniopharyngioma and germ cell tumors respectively. After surgical intervention, followed by radiotherapy, both patients were stable without any neurological deficit. Our experience confirmed that an MRI study of sellar region is warranted in search of the etiology of hypopituitarism.

Thyroid Function in Normal Neonates and Infants

This study was undertaken to determine the thyroid function of normal healthy Chinese neonates and infants from birth to 2 years of age. Our results showed that mean serum thyrotropin (TSH) levels decreased steeply in the first 3 days of life. Mean serum thyroxine (T4) concentration was high in the first 7 days of life and it decreased to the level of normal preschool children at 6-9 months of age. On the other hand, there was a tendency for mean serum triiodothyronine (T3) level to increase with age. It is hoped that the establishment of the ranges of the thyroid function study in normal Chinese neonates and infants can help to avoid misdiagnosis and inappropriate therapy of thyroid disorders during this period of life.