Abnormality of the DAX-1 gene accounts for many instances of congenital adrenal hypoplasia. In the present study, we performed molecular genetic analysis of DAX-1 in 4 unrelated Japanese patients with adrenal hypoplasia congenita and hypogonadotropic hypogonadism. A double-point mutation for V126M and W171X was identified in 1 family and a complex de novo insertion-deletion mutation was identified in a second. The DAX-1 gene was entirely deleted in a 3rd patient as well as in a 4th with the additional feature of glycerol kinase deficiency.

SummaryPrevious study showed that congenital isolated TSH deficiency in Japan is resulted exclusively from a G-A transition at nucleotide 145 in exone 2 of the TSH/3-subunit gene. All reported cases were from the inbred in Shikoku Island. We describe here a 10-year-old boy with hereditary TSH deficiency in the same area. The patient was born with a weight of 3,225 g to non-consanguineous parents. Evaluation at age 2 months revealed typical manifestations of cretinism without goiter. Serum T4, T3, and TSH values were 2.53 ~g/dl, 107 ng/dl, and 0.5 t~U/ml, respectively. A TRH stimulation test showed no increment of serum TSH value. Other anterior pituitary hormone levels were all within the normal range. Two oligonucleotide primers Tla and Tlb were synthesized according to the sequence data. Amplified 169 bp nucleotides in exon 2 of the TSH/3 gene with this primer set were digested with MaeI. Both the phenotypically normal brother and normal controls showed only the 169 bp fragment, whereas the proband showed 140 and 29 bp fragments and both parents showed three fragments; 169, 140, and 29 bp. These results were consistent with the point mutation of TSH/3 gene in Japanese patients with congenital isolated TSH deficiency. Our PCR method with MaeI digestion contributes to the rapid detection of the homozygous patient and the heterozygous carrier. Key Wordscongenital isolated thyroid-stimulating hormone deficiency, hypothyroidism, thyroid-stimulating hormone p chain, polymerase chain reaction (PCR) Received November 5, 1991 ; Accepted November 25, 1991. 313 314 R. MORI et al.

Males with classical 3β-hydroxysteroid dehydrogenase (3β-HSD) deficiency manifest appropriate secondary sexual maturation with an elevation in serum testosterone levels at pubertal age. To define the origin of serum testosterone, we evaluated a male patient with classical 3β-HSD who showed pubertal development. High values of testosterone and a ratio of Δ⁵ to Δ⁴ steroids in the spermatic vein indicated direct production of considerable amounts of testosterone and a persistent defect of 3β-HSD activity in the gonad. Immunohistochemical analysis showed distinct immunoreactivity in the Leydig cells of the patient. The patient was homozygous for a nonsense mutation in the type-II 3β-HSD gene. We propose that gonadal type-I 3β-HSD could be expressed by gonadotropin stimulation at pubertal age, and Δ⁴-steroid precursors would convert to testosterone.

We describe a 3-year-old Japanese boy with growth retardation and on empty sella turcica. He was born uneventfully by vertex delivery, birth weight 2 ,890 g, length 50 cm. At the age of 3 11/12, his height was 86.7 cm (-3.3 standard deviation (SD)) and the carpal bone age was moderately delayed. Peak values of serum growth hormone and the other pituitary hormone levels by conventional stimulation tests were all within the normal range. The serum insulin-like growth factor I (IGF-I) was 29.9 ng/mL. The mean value of urinary growth hormone (GH) was 42 pg/mg Cr. Magnetic resonance imaging (MRI) showed an extremely thin and downward compressed anterior pituitary lobe with a normal pituitary stalk and posterior lobe. The skull roentgenogram showed a sella turcica of normal size. The etiology of the empty sella in the patient remained obscure. The shape of the pituitary gland in the patient is different from that due to intrinsic embryological defect in the pituitary development, indicating that an extrinsic factor might have caused the empty sella. Primary empty sella syndrome (ESS) as seen in this patient due to extrinsic factors is an important category in idiopathic GH deficiency other than perinatal injury. Careful follow up in his case is necessary to elucidate the relationship between pituitary function and empty sella.