Low or Low-Normal Insulin-Like Growth Factor 1 After Traumatic Brain Injury: Interpretation and Implications

Growth hormone deficiency (GHD) is a prevalent consequence of traumatic brain injury (TBI) that can contribute to prolonged adverse symptoms and impaired quality of life. The overlap between symptoms of GHD and chronic TBI complicates the clinical picture, highlighting the need for precise diagnostic tools. Insulin-like growth factor 1 (IGF-1), a key mediator of growth hormone (GH) activity, is frequently utilized as a surrogate marker of GH status. However, IGF-1 levels may be normal in patients with confirmed GHD. Furthermore, low or low-normal IGF-1 is not specific to GHD, and provocative testing is required to confirm GHD in most patients with suspected deficiency. To provide a pragmatic clinical framework for interpreting IGF-1 z-score <0 in symptomatic patients after TBI, we reviewed the literature in the PubMed and PubMed Central databases addressing IGF-1 and GHD, differential diagnoses associated with low and low-normal IGF-1, and international guidelines on GH testing. Among TBI patients, GHD remains a leading cause of reduced IGF-1, but alternative diagnoses include malnutrition, chronic liver or kidney disease, poorly controlled diabetes mellitus, hypothyroidism, sepsis, and genetic conditions such as Laron syndrome. A systematic and evidence-based approach to IGF-1 interpretation is essential for distinguishing primary neuroendocrine dysfunction from secondary causes. The use of z-scores improves diagnostic precision by standardizing IGF-1 levels for age and sex. Our framework aids clinicians in integrating thorough neuroendocrine evaluation with broader medical assessments, clinical considerations, and comorbidities, thereby improving diagnostic accuracy and patient management. Future research should emphasize refined screening protocols for neuroendocrine dysfunction in TBI.