MON-451 Growth Hormone Deficiency (GHD) over 4 Years after Mild Traumatic Brain Injury (mTBI) in Deployed Veterans: Interim Review

Introduction: mTBI is associated with anterior pituitary hormone dysfunction. The potential long-term effect of this injury on pituitary function in Veterans is not clear. Methods: We present an interim report of our 4-year longitudinal prospective pilot study of pituitary function in Veterans diagnosed with mTBI. Of the 34 mTBI Veterans enrolled, we have tested 28 of them (4 female, 24 male; mean±SD age and BMI, 31.1±7.0 years and 30.2±6.2, respectively) for baseline pituitary hormone levels and cortisol response to ACTH. In 22 subjects growth hormone response to glucagon stimulation (GST) was tested at baseline. The same baseline data were obtained for 15 age-, sex-, deployment- and BMI-matched control subjects without mTBI (2 female,13 male; mean±SD age and BMI 33.9±6.8 years and 32.7±7.2, respectively). Follow-up testing has been done for 18 mTBI subjects in Year 1, 13 subjects in Year 2, 8 subjects in Year 3 and 3 subjects in Year 4. GH cutoffs of <1ng/mL for patients with a BMI≥25, and ≤ 3 ng/mL for a BMI < 25 were used for the diagnosis of GHD. Results: GHD was present in 9% (2/22) at baseline, 22% (4/18) at Year 1, 8% (1/13) at Year 2, 22% (2/9) at Year 3, and 0% (0/3) at Year 4. GHD did not occur in the same subject in subsequent years, and it appeared to recover within a year. The peak GST GH level for all subjects at each year trended downward from baseline to Years 1, 2, 3, and 4: (ng/mL, mean±SD) 7.6±7.7; 7.5±13.0; 3.5±3.3; 4.4±4.3; 1.9±0.9, respectively. Secondary hypogonadism occurred in 11%, 6%, 8% of subjects at baseline, Year 1 and Year 2, respectively; none has been found in Years 3 and 4. There are no subjects identified with hypothyroidism or overt adrenal insufficiency at baseline or over 4 years. Unexpectedly, GHD was detected in 27% (4/15) of control subjects. The mean±SD BMI of 39.4±7.8 for these subjects was higher than the BMI values for GH sufficient (GHS) control subjects (30.2±5.2), mTBI patients with GHD (29.6±4.6) and GHS (30.9±6.2). Secondary hypogonadism was present in 14%, and there were no cases of hypothyroidism or adrenal insufficiency. Conclusions: GHD occurs in patients with mTBI at up to 3 years of observation using the stricter GH cutoff criterion with a BMI ≥25. Because each patient with GHD in a particular year was unique, the cumulative occurrence of GHD thus far is 41% (9/22) over 4 years. The highest prevalence was in Year 2. Each subject appeared to recover from GHD in one year. Attrition of subjects has decreased the later year numbers; a more complete review will be possible when the remaining subject testing is completed. The detection of GHD in the non-mTBI control group suggests there may be additional factors in deployment itself that can put military personnel at risk. BMI as a confounding factor with the GST or any GH testing cannot be excluded. Identification of GHD and hypogonadism in Veterans with mTBI will provide treatment opportunities to enhance their recovery.