, Volume 18, Issue 4, pp 561–567 | Cite as

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

  • Aline P. Otto
  • Marcela M. França
  • Fernanda A. Correa
  • Everlayny F. Costalonga
  • Claudia C. Leite
  • Berenice B. Mendonca
  • Ivo J. P. Arnhold
  • Luciani R. S. Carvalho
  • Alexander A. L. Jorge



Children initially diagnosed with isolated GH deficiency (IGHD) have a variable rate to progress to combined pituitary hormone deficiency (CPHD) during follow-up.


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.

Patients and 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.


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).


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.


Isolated GH deficiency Follow-up studies Disease progression Combined pituitary hormone deficiency Kaplan–Meier estimate 



This work was supported by grants from Sao Paulo Research Foundation (FAPESP) (2013/03236-5) and from The National Council for Scientific and Technological Development (CNPq) (307922/2013-8 to I.J.P.A.; 305743/2011-2 to B.B.M.; 304678/2012-0 to A.A.L.J).

Conflict of interest

The authors declare there is no conflict of interest that could be perceived as influencing the impartiality of the research reported.


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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Aline P. Otto
    • 1
  • Marcela M. França
    • 1
  • Fernanda A. Correa
    • 1
  • Everlayny F. Costalonga
    • 1
  • Claudia C. Leite
    • 2
  • Berenice B. Mendonca
    • 1
  • Ivo J. P. Arnhold
    • 1
  • Luciani R. S. Carvalho
    • 1
  • Alexander A. L. Jorge
    • 3
  1. 1.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 EndocrinologiaUniversidade de Sao PauloSão PauloBrazil
  2. 2.Departamento de Radiologia, Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo (HC da FMUSP)Universidade de Sao PauloSão PauloBrazil
  3. 3.Unidade de Endocrinologia Genetica, Laboratorio de Endocrinologia Celular e Molecular LIM/25, Disciplina de Endocrinologia da Faculdade de MedicinaUniversidade de Sao PauloSão PauloBrazil

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