Hypopituitarism following severe traumatic brain injury

Abstract

Although hypopituitarism is a known complication of head injury and subarachnoid hemorrhage (SAH), it may be underrecognized due to its subtle clinical manifestations. To address this issue, we determine the prevalence of neuroendocrine abnormalities in patients rehabilitating from severe traumatic brain injury (Glasgow Coma Scale ≤8). 76 patients (mean age 39±14 yr; range 18–65; 53 males and 23 females; BMI 25.8±4.2kg/m2; mean±SD) with a severe traumatic brain injury an average of 22±10 months before study (median, 20 months) underwent a series of standard endocrine tests, including TSH, free T4, T4, T3, prolactin, testosterone (males), estradiol (females) cortisol, ACTH, GH, IGF-I, IGFBP-3. All subjects also underwent GH response to GHRH+arginine test and LH/FSH to GnRH. In 70% of patients (n=53), Cortisol/ACTH response to CRH and TSH response to TRH were determined. Growth hormone deficiency (GHD) was defined as a GH response <9µg/L to GHRH+arginine and was affirmed by ITT (<3µg/L). Pituitary deficiency was shown in 24% of the patients (18/76). 8% (n=6) had GHD (GH-peak range [GHRH+ARG]: 2.8–6.3µg/L; GH-peak range [ITT]: 1.5–2.2µg/L; IGF-I range: 62–174µg/L). 14% (n=11) had hypogonadism (total testosterone <9.5 nmol/L, low free testosterone index and low gonadotropins in 10 males; low estradiol, low gonadotropins and secondary amenorrhoe in 1 female). Total testosterone levels did not correlate with BMI or age. 4% (n=3) males with hypogonadism showed also a mild hyperprolactinemia (33, 37 and 41 ng/ml). 3% (n=2) patients had partial ACTH-deficiency (cortisol-peak [ITT] 392 and 417 nmol/L) and 4% (n=3) had TSH-deficiency. In summary, we have found hypopituitarism in one-fourth of patients with predominantly hypogonadism and GHD. These findings strongly suggest that patients who suffer head trauma must routinely include neuroendocrine evaluations.