Between January 1981 and March 1994, neonatal screening for congenital hypothyroidism (CH) in Hokkaido prefecture, Japan, detected thirty-four cases of Down syndrome (DS) with thyroid dysfunction. Of these 34 infants, 14 were diagnosed as having CH and the rest had various degrees of transient thyroid dysfunction. The incidence of CH in DS is estimated to be 1 in 41, being about 100 times more frequent than in the general population. Nevertheless, the prevalence of thyroid dysfunction in infants with DS was lower than that previously described in older children with DS. Periodical examination of thyroid function in children with DS is therefore recommended.

View full abstract

We report the identification of a somatic mutation in the gene encoding the α subunit of the stimulatory G protein (Gsα) of adenylyl cyclase in an 8-year-old girl with a toxic thyroid nodule. She had symptoms and signs of thyrotwdcosis. The nodule was resected and found to be an adenoma. To clarify the molecular basis of this tumor, the presence of mutations at codon 201 and 227 in the Gsα gene was sought in deoxyribonucleic acid (DNA) extracted from the tumor and the patient's blood using polymerase chain reaction amplification (PCR). A G-to-A transition resulting in the replacement of Arg by His (Arg 201 to His) was found in exon 8 of one allele encoding Gsα. Because thyrocytes are programmed to proliferate in response to elevated 3', 5'-cyclic AMP (cAMP) levels, the activating Gsα mutation observed in this patient probably contributed to tumorgenic development. To our knowledge, this is the first case in which the activating Gsα mutation in a Japanese child with a toxic thyroid adenoma has been identified.

View full abstract

The purpose of this study was to examine the influence of the variation in bone age at the onset of the pubertal growth spurt (PGS) on pubertal height gain and on final height. The subjects were 26 boys and 28 girls who had been treated at the Department of Orthodontics, School of Dentistry, Tohoku University, and had reached their final heights. Each child had longitudinal growth record and several hand and wrist X-ray films.
A significant positive correlation between the bone age and height at the onset of PGS was recognized in boys (r=0.734, P<0.01, n=26) and girls (r=0.655, P<0.01, n=28). A significant negative correlation between the bone age at the onset of PGS and the pubertal height gain was recognized in boys (r=-0.732, P<0.01) and girls (r=-0.775, P<0.01). However, there was no significant correlation between final height and bone age at the onset of PGS.
We found that the rate of bone maturation during puberty negatively correlated with the bone age at the onset of PGS and although bone age at the onset of PGS was distributed over a wide range, bone age at PHV was concentrated around 13 years in boys and 11 years in girls.

View full abstract

Two boys with idiopathic growth hormone (GH) deficiency developed hemolysis at 2 months and 4 months, respectively, after the start of GH replacement therapy. The hemolysis was subclinical and was noticed on routine laboratory tests. Although there was no direct evidence for a causal relationship between the incident and GH therapy, no other couse was found in these 2 patients. There were no family histories suggesting hemolysis, although we did not perform tests among the family members of either patient. Despite the continuation of GH administration, the hemolysis was transient and no other adverse effects were observed during the subsequent 4 years. Such hemolytic episodes could easily be overlooked even on routine laboratory tests during GH treatment.

View full abstract

The bone mineral density (BMD) of 56 children with simple obesity (BMI>24 for males (n=34), >23 for females (n=22), aged from 6 to 16 years) was investigated using dual energy X-ray absorptiometry (DXA). The BMD of the whole skeleton, legs, pelvis, and lumbar spine (L2-4) was significantly increased in obese children compared with nonobese children (38 males and 42 females, aged from 4 to 17 years), while the arms showed no significant difference between the two groups. This regional inequality of the increased BMD in obese children wasprobably due to the physical stimulation of weight bearing.

View full abstract

We report a patient who had the complete androgen insensitivity syndrome (CAIS) associated with a novel point mutation in the ligand-binding domain of the androgen receptor (AR) gene.
The patient was 12 years old with complete female external genitalia, inguinal testes, and a 46, XY karyotype. In endocrine tests, basal serum levels of follicle stimulating hormone (FSH) and luteinizing hormone (LH) were elevated and the FSH and LH responses to luteinizing hormonereleasing hormone (LH-RH) administration were exaggerated. The basal testosterone level and response to human chorionic gonadotropin (HCG) were compatible with those of a normal boy.
The AR gene was examined and a single nucleotide exchange from G to T at position 7, 362 was detected, which resulted in the substitution of phenylalanine for valine at position 734. This amino acid is located on exon E within the ligand-binding domain of the AR. Screening for the G to T mutation at nucleotide position 7, 362 by allele-specific amplification of genomic deoxyribonucleic acid (DNA) did not reveal the mutant DNA in normal subjects. The valine residue at position 734 is highly conserved in the ligand-binding domains of the steroid receptor superfamily. Thus, this novel mutation of exon E (V734P) may be associated with the phenotype of CAIS.

View full abstract

Ovarian follicular cysts were diagnosed antenatally or postnatally by routine obstetric ultrasound scanning in 7 infants. In 5 of them the serum levels of estradiol (E₂), insulin-like growth factor-I (IGF-I), osteocalcin and other hormones were measured serially after birth for almost one year. The patients' growth and skeletal maturation were also assessed. The elevated serum E₂ levels (242-8, 300 pg/mL) in cases with ovarian cysts fell after cystectomy/cyst aspiration or conservative management, but their serum E₂ levels remained high compared with those of control infants for 1-5 months. The IGF-I and osteocalcin serum levels of some patients were also relatively high. Furthermore, a tendency to growth acceleration during early infancy and advancement of skeletal age were each observed in two patients.
Our present observations suggest that neonatal ovarian cysts associated with elevated serum E₂levels during early infancy may affect the statural growth and bone maturation of female infants.

View full abstract

A girl aged 10 years and 7months who was 168.9 cm tall was diagnosed as having familial tall stature and was treated with a combination of octreotide acetate (50 μg. sc injection three times daily) and Kaufmann therapy (Premarin 2.5 mg/day for 26 days a month with Provera 10 mg for the last 7 days with Premarin, cyclically) for 25 months to reduce final height. Serum insulin-like growth factor I (IGF-I) and the urinary growth hormone (GH) level decreased and serum gonadotropins were completely suppressed during the treatment. After discontinuation of the treatment, serum IGF-I, urinary GH, and gonadotropins returned to the pubertal level. Her height velocity decreased and bone age advanced from 11.4 years to 14 years during the 25-month treatment. When the treatment was discontinued at the chronological age of 12 years and 11 months, her bone age was 14 years and her height was 176.4 cm. She has almost stopped growing at 13 years and 11 months, and has reached a final height of 177.6 cm.
Since the patient grew only 7.9 cm during puberty, it can be concluded that the combination treatment was very effective in reduction of final height.

View full abstract