BACKGROUND Combined pituitary hormone deficiency 3(CPHD3;OMIM:221750)is caused by mutations within the LHX3 gene(OMIM:600577),which located on the subtelomeric region of chromosome 9 at band 9q34.3,has seven coding ex...BACKGROUND Combined pituitary hormone deficiency 3(CPHD3;OMIM:221750)is caused by mutations within the LHX3 gene(OMIM:600577),which located on the subtelomeric region of chromosome 9 at band 9q34.3,has seven coding exons and six introns.LIM homeobox(LHX)3 protein is the key regulator of pituitary development in fetal life.CASE SUMMARY We have diagnosed and treate an 11-year-old boy with combined pituitary hormone deficiency(CPHD).The main clinical manifestations were pituitary hormone deficiency,hydrocele of the tunica vaginalis,pituitary dwarfism,gonadal dysplasia,micropenis,clonic convulsion,and mild facial dysmorphic features.We collected peripheral blood from the patient,the patient's older brother,as well as their parents,and sequenced them by using high-throughput whole-exosome sequencing,which was verified by Sanger sequencing.The results showed that there were two compound heterozygous variants of c.613G>C(p.V205L)and c.220T>C(p.C74R)in the LHX3 gene.c.613G>C(p.V205L)was inherited from his mother and c.220T>C(p.C74R)from his father.His brother also has both variants and symptoms.CONCLUSION This study reported ununreported genetic mutations of LHX3,and recorded the treatment process of the patients,providing data for the diagnosis and treatment of CPHD.展开更多
Background The proliferative activity and penetration into the hypothalamic structures in children craniopharyngiomas （CP） often make radical resection difficult. Therefore, complete resection of CP often results in...Background The proliferative activity and penetration into the hypothalamic structures in children craniopharyngiomas （CP） often make radical resection difficult. Therefore, complete resection of CP often results in permanent multiple pituitary hormone deficiency （MPHD）. This study aimed to elucidate the postoperative pituitary hormonal disturbances, and hormone replacement therapy （HRT） time and dosage in children with CP. Methods Twenty patients with growth retardation and CP after resection, comprising 14 boys and 6 girls, with a mean age of （10.63±3.18） years （Group A） and 10 male patients of group A aged 〉10 years （Group B） were entolled. Thirty age-, sex- and Tanner stage-matched normal children （control Group A）, and 44 male older children 〉10 years （control Group B） served as controls. The serum concentrations of insulin-like growth factor-1 （IGF-1）, growth hormone （GH）, free thyroxine （FT4）, thyroid-stimulating hormone （TSH）, adrenocorticortropic hormone （ACTH）, cortisol （COR）, follicle stimulating hormone （FSH）, luteinizing hormone （LH）, prolactin （PRL）, testosterone （T） and estradiol （E2） were measured in the CP patients after resection and in controls. The appropriate time and dosage of HRT were investigated. Linear correlation analysis was made between levothyroxine （L-T4） dosage and primary FT4 in CP patients after resection. Results All cases had MPHD. The serum peak GH, IGF-1, FT4 and COR levels of Group A were significantly lower than that of the control Group A. The serum IGF-1 concentration increased to the normal level after 3 months of rhGH therapy; the serum FSH, LH, and T levels were significantly decreased （P 〈0.001）; however, E2 and PRL were significantly increased （P 〈0.001） in Group B compared with the control Group B; 18 cases were found to have central diabetes insipidus （DI） by water deprivation test and MRI. There was a significant negative linear regression （r=-0.8, P 〈0.001） between L-T4 and primary FT4 in Group A patients with CP after resection, giving a regression equation of L-T4 dosage （μg·kg^-1·d^-1） = 3.5-0.2×FT4 （μg·kg^-1·d^-1）. The time and corresponding dosage of HRT for CP after resection were： rhGH started 1 year after resection and no recurrence of CP on MRI, when IGF-1 reached the normal range, the rhGH dosage was （0.13±0.04） U·kg-1·d-1; hydrocortisone （H-C） was started as soon as possible, and was kept in the lower normal range, at a dosage of （12.6±4.8） mg/m^2; levothyroxine started after H-C or at the same time to maintain FT4 in the higher normal range, at a dosage of （1.65±0.70） μg·kg^-1·d^-1; Minirin （DDAVP） was started as soon as possible, elicited no symptoms, and maintained normal electrolyte levels; the dosage was （0.16±0.04） mg/m^2. Conclusion Patients with CP after resection often displayed MPHD, and needed total HRT at appropriate time and dosage to improve the quality of life and normal growth.展开更多
文摘BACKGROUND Combined pituitary hormone deficiency 3(CPHD3;OMIM:221750)is caused by mutations within the LHX3 gene(OMIM:600577),which located on the subtelomeric region of chromosome 9 at band 9q34.3,has seven coding exons and six introns.LIM homeobox(LHX)3 protein is the key regulator of pituitary development in fetal life.CASE SUMMARY We have diagnosed and treate an 11-year-old boy with combined pituitary hormone deficiency(CPHD).The main clinical manifestations were pituitary hormone deficiency,hydrocele of the tunica vaginalis,pituitary dwarfism,gonadal dysplasia,micropenis,clonic convulsion,and mild facial dysmorphic features.We collected peripheral blood from the patient,the patient's older brother,as well as their parents,and sequenced them by using high-throughput whole-exosome sequencing,which was verified by Sanger sequencing.The results showed that there were two compound heterozygous variants of c.613G>C(p.V205L)and c.220T>C(p.C74R)in the LHX3 gene.c.613G>C(p.V205L)was inherited from his mother and c.220T>C(p.C74R)from his father.His brother also has both variants and symptoms.CONCLUSION This study reported ununreported genetic mutations of LHX3,and recorded the treatment process of the patients,providing data for the diagnosis and treatment of CPHD.
文摘Background The proliferative activity and penetration into the hypothalamic structures in children craniopharyngiomas （CP） often make radical resection difficult. Therefore, complete resection of CP often results in permanent multiple pituitary hormone deficiency （MPHD）. This study aimed to elucidate the postoperative pituitary hormonal disturbances, and hormone replacement therapy （HRT） time and dosage in children with CP. Methods Twenty patients with growth retardation and CP after resection, comprising 14 boys and 6 girls, with a mean age of （10.63±3.18） years （Group A） and 10 male patients of group A aged 〉10 years （Group B） were entolled. Thirty age-, sex- and Tanner stage-matched normal children （control Group A）, and 44 male older children 〉10 years （control Group B） served as controls. The serum concentrations of insulin-like growth factor-1 （IGF-1）, growth hormone （GH）, free thyroxine （FT4）, thyroid-stimulating hormone （TSH）, adrenocorticortropic hormone （ACTH）, cortisol （COR）, follicle stimulating hormone （FSH）, luteinizing hormone （LH）, prolactin （PRL）, testosterone （T） and estradiol （E2） were measured in the CP patients after resection and in controls. The appropriate time and dosage of HRT were investigated. Linear correlation analysis was made between levothyroxine （L-T4） dosage and primary FT4 in CP patients after resection. Results All cases had MPHD. The serum peak GH, IGF-1, FT4 and COR levels of Group A were significantly lower than that of the control Group A. The serum IGF-1 concentration increased to the normal level after 3 months of rhGH therapy; the serum FSH, LH, and T levels were significantly decreased （P 〈0.001）; however, E2 and PRL were significantly increased （P 〈0.001） in Group B compared with the control Group B; 18 cases were found to have central diabetes insipidus （DI） by water deprivation test and MRI. There was a significant negative linear regression （r=-0.8, P 〈0.001） between L-T4 and primary FT4 in Group A patients with CP after resection, giving a regression equation of L-T4 dosage （μg·kg^-1·d^-1） = 3.5-0.2×FT4 （μg·kg^-1·d^-1）. The time and corresponding dosage of HRT for CP after resection were： rhGH started 1 year after resection and no recurrence of CP on MRI, when IGF-1 reached the normal range, the rhGH dosage was （0.13±0.04） U·kg-1·d-1; hydrocortisone （H-C） was started as soon as possible, and was kept in the lower normal range, at a dosage of （12.6±4.8） mg/m^2; levothyroxine started after H-C or at the same time to maintain FT4 in the higher normal range, at a dosage of （1.65±0.70） μg·kg^-1·d^-1; Minirin （DDAVP） was started as soon as possible, elicited no symptoms, and maintained normal electrolyte levels; the dosage was （0.16±0.04） mg/m^2. Conclusion Patients with CP after resection often displayed MPHD, and needed total HRT at appropriate time and dosage to improve the quality of life and normal growth.
