title: Pituitary stalk interruption syndrome in 58 Chinese patients: clinical features and genetic analysis.
abstract: OBJECTIVE
  Pituitary stalk interruption syndrome (PSIS) is rare and its clinical features and pathogenesis are poorly understood. This study characterized the clinical and genetic features of PSIS in Chinese patients.
  
  
  METHODS
  Clinical data of 58 patients with PSIS and 46 patients with GH deficiency but a normal pituitary stalk (NPS) were retrospectively analysed. HESX1, LHX4, OTX2 and SOX3 polymorphisms were screened in 33 PSIS patients, and GH1 and GHRHR in 4 NPS patients.
  
  
  RESULTS
  Deficiency of GH was 100% in both PSIS and NPS groups. Other deficiency rates for PSIS and NPS groups were as follows: ACTH, 77·6% and 23·9%; TSH, 43·1% and 10·9%; LH/FSH, 94·2% and 47·4%; and combined pituitary hormone, 93·1% and 41·3% respectively. In PSIS and NPS patients, the percentages of anterior pituitary hypoplasia were 98·3% and 54·3%, pituitary stalk abnormality were 100% and 0%, and ectopic neurohypophysis were 91·4% and 0%. A novel heterozygous sequence variant (c.142A>T, p.T48S) was found in HESX1 in one PSIS patient, 3 polymorphisms (c.63T>C, p.G21G; c.450C>T, p.N150N; and c.983A>G, p.N328S) in LHX4 in 7, 1 and 31 PSIS patients, respectively, and a hemizygous polymorphism (c.157G>C, p.V53L) in SOX3 in one PSIS patient. No OTX2 abnormality was detected in PSIS patients, and no GH1 or GHRHR polymorphisms in NPS patients.
  
  
  CONCLUSIONS
  Compared with NPS, PSIS patients had more severe anterior pituitary hormone deficiency, lower anterior pituitary hormone secretion and higher probability of abnormal pituitary morphology. HESX1, LHX4 and SOX3 polymorphisms may be associated with PSIS.
authors.affiliation: Department of Endocrinology, Chinese PLA General Hospital, Beijing, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Yang
authors.forename: Qing-hua
authors.initials: QH
authors.lastname: Guo
authors.forename: Bao-an
authors.initials: BA
authors.lastname: Wang
authors.forename: Jing-tao
authors.initials: JT
authors.lastname: Dou
authors.forename: Zhao-hui
authors.initials: ZH
authors.lastname: Lv
authors.forename: Jian-ming
authors.initials: JM
authors.lastname: Ba
authors.forename: Ju-Ming
authors.initials: JM
authors.lastname: Lu
authors.forename: Chang-yu
authors.initials: CY
authors.lastname: Pan
authors.forename: Yi-ming
authors.initials: YM
authors.lastname: Mu
mesh_terms: D000293:Adolescent; D000595:Amino Acid Sequence; D044466:Asian People / Q000235:genetics; D002648:Child; D002681:China; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D013006:Growth Hormone / Q000172:deficiency / Q000235:genetics; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D060850:LIM-Homeodomain Proteins / Q000235:genetics; D008297:Male; D008969:Molecular Sequence Data; D051857:Otx Transcription Factors / Q000235:genetics; D010900:Pituitary Diseases / Q000208:ethnology / Q000235:genetics*; D010902:Pituitary Gland / Q000473:pathology*; D011110:Polymorphism, Genetic; D018013:Receptors, Neuropeptide / Q000235:genetics; D018017:Receptors, Pituitary Hormone-Regulating Hormone / Q000235:genetics; D012189:Retrospective Studies; D055748:SOXB1 Transcription Factors / Q000235:genetics; D017386:Sequence Homology, Amino Acid; D013577:Syndrome; D014157:Transcription Factors / Q000235:genetics; D055815:Young Adult
chemical_list: C489736:HESX1 protein, human; D018398:Homeodomain Proteins; C486362:LHX4 protein, human; D060850:LIM-Homeodomain Proteins; C497659:OTX2 protein, human; D051857:Otx Transcription Factors; D018013:Receptors, Neuropeptide; D018017:Receptors, Pituitary Hormone-Regulating Hormone; C527785:SOX3 protein, human; D055748:SOXB1 Transcription Factors; D014157:Transcription Factors; D013006:Growth Hormone; C048250:somatotropin releasing hormone receptor