Development of additional pituitary hormone deficiencies in pediatric patients originally diagnosed with isolated growth hormone deficiency due to organic causes

Christopher J. Child, Werner F. Blum, Cheri Deal, Alan G. Zimmermann, Charmian A. Quigley, Stenvert L S Drop, Gordon B. Cutler, Ronald (Ron) Rosenfeld

Research output: Contribution to journalArticle

9 Citations (Scopus)

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). Design: Data were analysed for 716 growth hormone-treated children with organic IGHD, who were growth hormone-naive 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.

Original languageEnglish (US)
Pages (from-to)669-679
Number of pages11
JournalEuropean Journal of Endocrinology
Volume174
Issue number5
DOIs
StatePublished - May 1 2016

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Pituitary Dwarfism
Pituitary Hormones
Pediatrics
Growth Hormone
Neuroendocrinology
Mutation
Hypothyroidism
Gonadotropins
Genes
Neoplasms
Logistic Models
Regression Analysis
Research Personnel
Insulin

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Development of additional pituitary hormone deficiencies in pediatric patients originally diagnosed with isolated growth hormone deficiency due to organic causes. / Child, Christopher J.; Blum, Werner F.; Deal, Cheri; Zimmermann, Alan G.; Quigley, Charmian A.; Drop, Stenvert L S; Cutler, Gordon B.; Rosenfeld, Ronald (Ron).

In: European Journal of Endocrinology, Vol. 174, No. 5, 01.05.2016, p. 669-679.

Research output: Contribution to journalArticle

Child, Christopher J. ; Blum, Werner F. ; Deal, Cheri ; Zimmermann, Alan G. ; Quigley, Charmian A. ; Drop, Stenvert L S ; Cutler, Gordon B. ; Rosenfeld, Ronald (Ron). / Development of additional pituitary hormone deficiencies in pediatric patients originally diagnosed with isolated growth hormone deficiency due to organic causes. In: European Journal of Endocrinology. 2016 ; Vol. 174, No. 5. pp. 669-679.
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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). Design: Data were analysed for 716 growth hormone-treated children with organic IGHD, who were growth hormone-naive 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.",
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AU - Child, Christopher J.

AU - Blum, Werner F.

AU - Deal, Cheri

AU - Zimmermann, Alan G.

AU - Quigley, Charmian A.

AU - Drop, Stenvert L S

AU - Cutler, Gordon B.

AU - Rosenfeld, Ronald (Ron)

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N2 - 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). Design: Data were analysed for 716 growth hormone-treated children with organic IGHD, who were growth hormone-naive 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.

AB - 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). Design: Data were analysed for 716 growth hormone-treated children with organic IGHD, who were growth hormone-naive 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.

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