title: Frequent development of combined pituitary hormone deficiency in patients initially diagnosed as isolated growth hormone deficiency: a long term follow-up of patients from a single center.
abstract: BACKGROUND
  Children initially diagnosed with isolated GH deficiency (IGHD) have a variable rate to progress to combined pituitary hormone deficiency (CPHD) during follow-up.
  
  
  OBJECTIVE
  To evaluate the development of CPHD in a group of childhood-onset IGHD followed at a single tertiary center over a long period of time.
  
  
  METHODS
  We retrospectively analyzed data from 83 patients initially diagnosed as IGHD with a mean follow-up of 15.2 years. The Kaplan-Meier method and Cox regression analysis was used to estimate the temporal progression and to identify risk factors to development of CPHD over time.
  
  
  RESULTS
  From 83 patients initially with IGHD, 37 (45%) developed CPHD after a median time of follow up of 5.4 years (range from 1.2 to 21 years). LH and FSH deficiencies were the most common pituitary hormone (38%) deficiencies developed followed by TSH (31%), ACTH (12%) and ADH deficiency (5%). ADH deficiency (3.1 ± 1 years from GHD diagnosis) presented earlier and ACTH deficiency (9.3 ± 3.5 years) presented later during follow up compared to LH/FSH (8.3 ± 4 years) and TSH (7.5 ± 5.6 years) deficiencies. In a Cox regression model, pituitary stalk abnormalities was the strongest risk factor for the development of CPHD (hazard ratio of 3.28; p = 0.002).
  
  
  CONCLUSIONS
  Our study indicated a high frequency of development of CPHD in patients initially diagnosed as IGHD at childhood. Half of our patients with IGHD developed the second hormone deficiency after 5 years of diagnosis, reinforcing the need for lifelong monitoring of pituitary function in these patients.
authors.affiliation: Unidade de Endocrinologia do Desenvolvimento, Laboratorio de Hormonios e Genetica Molecular LIM/42 do Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo (HC da FMUSP), Disciplina de Endocrinologia, Universidade de Sao Paulo, São Paulo, 05403-900, Brazil.
authors.forename: Aline P
authors.initials: AP
authors.lastname: Otto
authors.forename: Marcela M
authors.initials: MM
authors.lastname: França
authors.forename: Fernanda A
authors.initials: FA
authors.lastname: Correa
authors.forename: Everlayny F
authors.initials: EF
authors.lastname: Costalonga
authors.forename: Claudia C
authors.initials: CC
authors.lastname: Leite
authors.forename: Berenice B
authors.initials: BB
authors.lastname: Mendonca
authors.forename: Ivo J P
authors.initials: IJ
authors.lastname: Arnhold
authors.forename: Luciani R S
authors.initials: LR
authors.lastname: Carvalho
authors.forename: Alexander A L
authors.initials: AA
authors.lastname: Jorge
mesh_terms: D000293:Adolescent; D000324:Adrenocorticotropic Hormone / Q000172:deficiency*; D000328:Adult; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D018450:Disease Progression; D004393:Dwarfism, Pituitary / Q000453:epidemiology*; D005260:Female; D005640:Follicle Stimulating Hormone / Q000172:deficiency*; D005500:Follow-Up Studies; D019382:Human Growth Hormone / Q000172:deficiency*; D006801:Humans; D007018:Hypopituitarism / Q000453:epidemiology* / Q000473:pathology; D007031:Hypothalamus / Q000473:pathology; D053208:Kaplan-Meier Estimate; D008137:Longitudinal Studies; D007986:Luteinizing Hormone / Q000172:deficiency*; D008279:Magnetic Resonance Imaging; D008297:Male; D010902:Pituitary Gland / Q000473:pathology; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D013972:Thyrotropin / Q000172:deficiency*; D013997:Time Factors; D014667:Vasopressins / Q000172:deficiency*; D055815:Young Adult
chemical_list: D014667:Vasopressins; D019382:Human Growth Hormone; D000324:Adrenocorticotropic Hormone; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D013972:Thyrotropin