Acute gonadotroph and somatotroph hormonal suppression after traumatic brain injury

Abstract

Hormonal dysfunction is a known consequence of moderate and severe traumatic brain injury (TBI). In this study we determined the incidence, time course, and clinical correlates of acute post-TBI gonadotroph and somatotroph dysfunction. Patients had daily measurement of serum luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone, estradiol, growth hormone, and insulin-like growth factor-1 (IGF-1) for up to 10 days post-injury. Values below the fifth percentile of a healthy cohort were considered abnormal, as were non-measurable growth hormone (GH) values. Outcome measures were frequency and time course of hormonal suppression, injury characteristics, and Glasgow Outcome Scale (GOS) score. The cohort consisted of 101 patients (82% males; mean age 35 years; Glasgow Coma Scale [GCS] score <or=8 in 87%). In men, 100% had at least one low testosterone value, and 93% of all values were low; in premenopausal women, 43% had at least one low estradiol value, and 39% of all values were low. Non-measurable GH levels occurred in 38% of patients, while low IGF-1 levels were observed in 77% of patients, but tended to normalize within 10 days. Multivariate analysis revealed associations of younger age with low FSH and low IGF-1, acute anemia with low IGF-1, and older age and higher body mass index (BMI) with low GH. Hormonal suppression was not predictive of GOS score. These results indicate that within 10 days of complicated mild, moderate, and severe TBI, testosterone suppression occurs in all men and estrogen suppression occurs in over 40% of women. Transient somatotroph suppression occurs in over 75% of patients. Although this acute neuroendocrine dysfunction may not be TBI-specific, low gonadal steroids, IGF-1, and GH may be important given their putative neuroprotective functions.

FIG. 1.

Daily mean (± standard deviation) gonadotropin and testosterone levels in male traumatic brain injury patients (n = 82). (A) Luteinizing hormone (LH). (B) Follicle-stimulating hormone (FSH). (C) Total testosterone (T).

FIG. 2.

Daily mean (± standard deviation) gonadotropin and estradiol levels in female traumatic brain injury patients (n = 19). (A) Luteinizing hormone (LH). (B) Follicle-stimulating hormone (FSH). (C) Estradiol (E₂).

FIG. 3.

Daily mean (± standard deviation) growth hormone (GH) and insulin-like growth factor-1 (IGF-1) levels in male and female traumatic brain injury patients (n = 101). (A) GH (n = 101). (B) IGF-1 (age 16–24 years; n = 34). (C) IGF-1 (age 25–39 years; n = 32). (D) IGF-1 (age 40–54 years; n = 19). (E) IGF-1 (age > 55 years; n = 16).