BACKGROUND Noonan syndrome(NS)is an autosomal dominant,multisystem disorder with a prevalence of 1 in 1000-2500.Multiple etiologies have been proposed for short stature in NS,including resistance to growth hormone(GH)...BACKGROUND Noonan syndrome(NS)is an autosomal dominant,multisystem disorder with a prevalence of 1 in 1000-2500.Multiple etiologies have been proposed for short stature in NS,including resistance to growth hormone(GH)and GH deficiency(GHD).Irrespective of the presence of GHD,NS is a Food and Drug Administration-approved indication for recombinant-GH therapy.Few case reports of combined anterior pituitary hormone deficiency(CPHD)in NS have been reported.AIM To describe the clinico-biochemical characteristics of NS with CPHD and to assess the response to recombinant GH therapy.METHODS An ambispective case-control study was conducted to compare the clinicohormonal profile and response to recombinant-GH in pediatric patients with NS and CPHD and pediatric patients with NS but without CPHD.RESULTS Five children with NS and CPHD were compared to 6 patients with NS but without CPHD.The most common anterior pituitary hormone involvement in combination with GHD was adrenocorticotrophic hormone deficiency causing hypocortisolemia(n=3,60%),followed by hypogonadotropic hypogonadism and secondary hypothyroidism(n=1 each).Pituitary hypoplasia was seen in the magnetic resonance imaging of all patients with CPHD.Patients with NS and CPHD had lower standard deviation scores of height(-4.18 vs-2.52,P=0.009),bodyweight,and body mass index but a slightly better first year response to recombinant GH(9.2 vs 5.5,P=0.06).There were no differences in dysmorphisms and other anomalies between the two groups.Patients with NS and CPHD had a similar response to GH as patients with CPHD but without NS.One patient with NS and CPHD developed hypocortisolism after GH initiation.CONCLUSION Hypoplasia of the pituitary and GHD with involvement of other pituitary hormones may be seen in NS and may determine response to recombinant GH therapy.展开更多
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
文摘BACKGROUND Noonan syndrome(NS)is an autosomal dominant,multisystem disorder with a prevalence of 1 in 1000-2500.Multiple etiologies have been proposed for short stature in NS,including resistance to growth hormone(GH)and GH deficiency(GHD).Irrespective of the presence of GHD,NS is a Food and Drug Administration-approved indication for recombinant-GH therapy.Few case reports of combined anterior pituitary hormone deficiency(CPHD)in NS have been reported.AIM To describe the clinico-biochemical characteristics of NS with CPHD and to assess the response to recombinant GH therapy.METHODS An ambispective case-control study was conducted to compare the clinicohormonal profile and response to recombinant-GH in pediatric patients with NS and CPHD and pediatric patients with NS but without CPHD.RESULTS Five children with NS and CPHD were compared to 6 patients with NS but without CPHD.The most common anterior pituitary hormone involvement in combination with GHD was adrenocorticotrophic hormone deficiency causing hypocortisolemia(n=3,60%),followed by hypogonadotropic hypogonadism and secondary hypothyroidism(n=1 each).Pituitary hypoplasia was seen in the magnetic resonance imaging of all patients with CPHD.Patients with NS and CPHD had lower standard deviation scores of height(-4.18 vs-2.52,P=0.009),bodyweight,and body mass index but a slightly better first year response to recombinant GH(9.2 vs 5.5,P=0.06).There were no differences in dysmorphisms and other anomalies between the two groups.Patients with NS and CPHD had a similar response to GH as patients with CPHD but without NS.One patient with NS and CPHD developed hypocortisolism after GH initiation.CONCLUSION Hypoplasia of the pituitary and GHD with involvement of other pituitary hormones may be seen in NS and may determine response to recombinant GH therapy.
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.
