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

Eur J Endocrinol. 2016 May;174(5):669-79. doi: 10.1530/EJE-15-1203. Epub 2016 Feb 17.

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-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.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Age Factors
  • Child
  • Congenital Hypothyroidism / epidemiology
  • Disease Progression*
  • Female
  • Follow-Up Studies
  • Gonadotropins / deficiency*
  • Human Growth Hormone / deficiency*
  • Humans
  • Hypopituitarism / epidemiology*
  • Hypothyroidism
  • Male
  • Pituitary Hormones / deficiency*
  • Sex Factors
  • Thyrotropin / deficiency

Substances

  • Gonadotropins
  • Pituitary Hormones
  • Human Growth Hormone
  • Thyrotropin

Supplementary concepts

  • Combined Pituitary Hormone Deficiency