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Alternatively, the HPA axis hypofunction might arise from several mechanisms, including chronic inflammation with elevated TNF- levels, a regulatory T cells response with increased IL-10 and transforming growth factor (TGF)-, heightened oxidative and nitrosative stress pathways, notably elevated nitric oxide (NO) production, and infection-related factors like LPS tolerance and viral infections affecting the HPA axis (see Table 2) [79]

10.1271/bbb1961.41.1547 134 HuangW.WangY.HuangZ.WangX.ChenL.ZhangY.et al (2018)

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Other Considerations Complexity is inherent to the identification of patients who might benefit the most from mecasermin treatment as access to testing required for the definitive diagnosis of SPIGFD (e.g., GH antibody testing, genetic testing, or a clear test to assess IGF-1 response to GH [an IGF-1 generation test]) is limited in many Canadian jurisdictions

doi: 10.1016/S0891-5849(03)00184-9