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. 2025 Oct 16;110(11):e3673-e3684.
doi: 10.1210/clinem/dgaf156.

Adult Growth Hormone Deficiency, Replacement Therapy, and Outcomes in Long-Term Childhood Cancer Survivors

Tomoko Yoshida  1 , Jessica L Baedke  1 , Huiqi Wang  1 , Yan Chen  1 , Christine Yu  1   2 , Carmen L Wilson  1 , Daniel A Mulrooney  1   3 , Stephanie B Dixon  1   3 , I Chan Huang  1 , Tara M Brinkman  1   4 , Kevin R Krull  4 , Sogol Mostoufi-Moab  5   6 , José Miguel Martínez  7 , Kirsten K Ness  1 , Melissa M Hudson  1   3 , Yutaka Yasui  1 , Angela Delaney  1   2
Affiliations

Adult Growth Hormone Deficiency, Replacement Therapy, and Outcomes in Long-Term Childhood Cancer Survivors

Tomoko Yoshida et al. J Clin Endocrinol Metab. .

Abstract

Context: The consequences of untreated adult growth hormone deficiency (aGHD) among childhood cancer survivors are not well defined. The lack of evidence and socioeconomic factors may contribute to underutilization of growth hormone therapy (GHT) among survivors with aGHD.

Objectives: This work aimed to examine the association of GHT use with socioeconomic factors and to assess the effect of untreated aGHD in survivors using insulin-like growth factor-1 (IGF1) as a marker of GH action.

Methods: A total of 3902 five-year survivors of childhood cancer aged 18 years and older were included. The associations between GHT use and socioeconomic factors (health insurance coverage, income, area deprivation index), and associations between IGF1 levels and prevalences of adverse physical, neurocognitive, and psychosocial outcomes were assessed cross-sectionally by multivariable logistic regression adjusting for potential confounders.

Results: Among 354 survivors with severe aGHD, 9.0% were on GHT. Socioeconomic disadvantages were independently associated with less use of GHT (eg, odds ratio [OR] of GHT use 0.27; 95% CI, 0.08-0.84 for annual household income <$40 000 vs ≥$80 000). The low IGF1 group (z score ≤ -2) experienced significantly higher prevalences of various adverse outcomes compared to the normal IGF1 group (z score >0), including various neurocognitive impairment (eg, verbal reasoning [OR 2.79; 95% CI, 1.95-3.98]), diminished health-related quality of life (eg, physical functioning [1.97; 1.35-2.86]), abnormal glucose metabolism (1.82; 1.21-2.71), and abnormal fat percentage (3.16; 1.98-5.26).

Conclusion: Untreated aGHD potentially contributes to multidimensional adverse outcomes, and GHT may provide health benefits among survivors, though socioeconomic disadvantage may limit their access to GHT.

Keywords: IGF-1; childhood cancer survivors; growth hormone deficiency; health disparities; health insurance; recombinant human growth hormone.

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Conflict of interest statement

Disclosure Statement

The authors declare no competing interests.

Figures

Figure 1.
Figure 1.. Study participants
A, Demographic/socioeconomic analysis; B, IGF1 analysis. The shaded square in A shows individuals with severe aGHD, who were included in the socioeconomic analysis. Abbreviations: aGHD, adult growth hormone deficiency; GHT, growth hormone therapy; IGF1, insulin-like growth factor-1; SJLIFE, St. Jude Lifetime Cohort Study.
Figure 2.
Figure 2.. Insulin-like growth factor-1 (IGF1) levels and prevalence of adverse outcomes.
Associations between IGF1 levels and prevalence of outcomes were assessed in 3899 survivors. The dots and error bars show adjusted odds ratios (ORs) and 95% CIs for the risk of having each outcome. The black square and triangle indicate IGF1 z score category of low (≤−2) and low-normal (>−2 to ≤0), respectively. The black circle and broken line represent the null reference association (OR = 1, normal IGF1, z score >0). P-trend indicates the P value from the trend test, treating 3 IGF1 z score categories as an ordinal variable to examine the dose-dependent relationship. All analyses were adjusted for potential confounders (sex, race/ethnicity, age at cancer diagnosis, years since cancer diagnosis, tumor in the hypothalamic-pituitary [HP] region, HP radiation dose, use of growth hormone therapy in childhood, hypogonadism, hypothyroidism, adrenal insufficiency). Analyses exclusive of neurocognitive outcomes were also adjusted for educational attainment, annual household income, health insurance coverage, and area deprivation index.
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