title: Development of additional pituitary hormone deficiencies in pediatric patients originally diagnosed with isolated growth hormone deficiency due to organic causes.
abstract: OBJECTIVE
  To determine characteristics of children initially diagnosed with isolated growth hormone deficiency (IGHD) of organic aetiology, who later developed multiple pituitary hormone deficiencies (MPHD).
  
  
  METHODS
  Data were analysed for 716 growth hormone-treated children with organic IGHD, who were growth hormone-naïve at baseline in the multinational, observational Genetics and Neuroendocrinology of Short Stature International Study.
  
  
  METHODS
  Development of MPHD was ascertained from investigator-provided diagnoses, adverse events and concomitant medications. Analyses were performed for all patients and separately for those who developed MPHD within 4.5 years or had >3.5 years follow-up and continued to have IGHD (4-year cohort).
  
  
  RESULTS
  MPHD developed in 71/716 (9.9%) children overall, and in 60/290 (20.7%) in the 4-year cohort. The most frequent additional deficiencies were thyroid-stimulating hormone (47 patients) and gonadotropins (23 patients). Compared with those who remained with IGHD, children who developed MPHD had more severe GHD at study entry, significantly lower baseline insulin-like growth factor1, peak stimulated growth hormone, and more frequent diagnosis of intracranial tumour or mutation of gene(s) controlling hypothalamic-pituitary development and/or function. Multivariate logistic regression analyses identified female gender, longer follow-up, higher baseline age and lower peak stimulated growth hormone as predictors of MPHD development.
  
  
  CONCLUSIONS
  MPHD is more likely to develop in patients with severe organic IGHD, especially those with history of intracranial tumour or mutation of gene(s) controlling hypothalamic-pituitary development and/or function. Older baseline age, female gender and longer follow-up duration were also associated with higher incidence of MPHD. Long-term monitoring of pituitary function is recommended, irrespective of the aetiology of GHD.
authors.affiliation: Lilly Research LaboratoriesErl Wood Manor, Windlesham, Surrey, UK cjc@lilly.com.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Child
authors.affiliation: University of GiessenGiessen, Germany.
authors.forename: Werner F
authors.initials: WF
authors.lastname: Blum
authors.affiliation: University of Montreal and CHU Ste-JustineMontreal, Quebec, Canada.
authors.forename: Cheri
authors.initials: C
authors.lastname: Deal
authors.affiliation: Lilly Research LaboratoriesIndianapolis, Indiana, USA.
authors.forename: Alan G
authors.initials: AG
authors.lastname: Zimmermann
authors.affiliation: Sydney Children's HospitalRandwick, New South Wales, Australia.
authors.forename: Charmian A
authors.initials: CA
authors.lastname: Quigley
authors.affiliation: Department of PediatricsErasmus Medical Centre, Sophia Children's Hospital, Rotterdam, The Netherlands.
authors.forename: Stenvert L S
authors.initials: SL
authors.lastname: Drop
authors.affiliation: Gordon Cutler Consultancy LLCDeltaville, Virginia, USA.
authors.forename: Gordon B
authors.initials: GB
authors.lastname: Cutler
authors.affiliation: Department of PediatricsOregon Health and Science University, Portland, Oregon, USA.
authors.forename: Ron G
authors.initials: RG
authors.lastname: Rosenfeld
mesh_terms: D000293:Adolescent; D000367:Age Factors; D002648:Child; D003409:Congenital Hypothyroidism / Q000453:epidemiology; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006062:Gonadotropins / Q000172:deficiency*; D019382:Human Growth Hormone / Q000172:deficiency*; D006801:Humans; D007018:Hypopituitarism / Q000453:epidemiology*; D007037:Hypothyroidism; D008297:Male; D010907:Pituitary Hormones / Q000172:deficiency*; D012737:Sex Factors; D013972:Thyrotropin / Q000172:deficiency
chemical_list: D006062:Gonadotropins; D010907:Pituitary Hormones; D019382:Human Growth Hormone; D013972:Thyrotropin