Projects

Predicting Growth Hormone Deficiency in Traumatic Brain Injury

THE PROBLEM

A potential devastating sequela of traumatic brain injury (TBI) is post-traumatic hypopituitarism.  The incidence of hypopituitary dysfunction following TBI is 15-68% with higher risk in severe TBI2. The most common pituitary abnormality is growth hormone deficiency (GHD) (approximately 15.7%) either in isolation or in conjunction with hypogonadism, adrenal failure, hypothyroidism or diabetes insipidus3,4. Symptoms of GHD include fatigue, impairment of attention and memory, decreased muscle mass and strength, visceral obesity, decreased quality of life, dyslipidemia, premature atherosclerosis and osteoporosis5.  Many of these symptoms overlap with those that occur following brain injury, making the clinical diagnosis of GHD very difficult in patients with TBI.  Treating GHD in patients with TBI has been shown to improve quality of life6, motor speed7, information-processing speed7, executive function6,7 and memory6,7 suggesting treating GHD in patients with TBI is an important component of  improving the patient’s function and health.  Current recommendations suggest all complicated mild TBI and moderate-severe TBI patients with persistent symptoms be tested for GHD at 12 months post injury8.  However, the gold standard for diagnosing GHD is a glucagon stimulation test (GST) or insulin tolerance test (ITT) which is resource intensive, expensive and in limited availability. Alternatively, some European sites use the Quality of Life in Adult Growth Hormone Deficiency Assessment (Qol-AGHDA) to screen for growth hormone testing9,10 using greater than 11/35 as a cut-off (higher signifies worse score), but this is in patients suspected of GHD due to other causes, not TBI. However, no study has investigated the patient characteristics, and outcome measures that would predict GHD in patients with TBI due to all causes.

STUDY HYPOTHESES AND OBJECTIVES

We hypothesize severity of injury, mechanism of injury, depressive symptoms, fatigue, poor executive function and poor quality of life scores will be predict GHD deficiency in patients with TBI.  The primary objective of this study is to develop a clinical prediction tool based on patient characteristics, relevant clinical and functional symptoms established by questionnaires to predict GHD in patients with TBI.

METHODS

For this prospective observational cohort pilot study, 100 patients presenting to the Calgary Brain Injury Program from September 2018-February 2020 who meet the inclusion/exclusion criteria will be asked to participate.  Inclusion criteria includes patients between the ages of 18-65 years, sustained a complicated mild (loss of consciousness or post-traumatic amnesia for greater than 30 minutes), moderate or severe TBI and have persistent symptoms 12 months post-injury.  Baseline patient characteristics and neurological examination will be collected.  Patients will be asked to complete a battery of questionnaires including Fatigue Severity Score, Qol,-AGHDA, patient health questionnaire – 9 (PHQ-9 for depression), Hospital General Anxiety Disorder -7 (GAD-7) and frontal assessment battery (FAB-executive cognitive function).   Once baseline assessment is completed patients will then participate in either GST or ITT to determine GHD.

Descriptive statistics will be applied to patient characteristics. Mann-Whitney U test will be administered to compare group means (GHD vs. no GHD). Area under the curve (AUC) will be calculated using receiver operator curve analysis (ROC) will be performed to evaluate diagnostic threshold of all questionnaires (FSS, Qol-AGHDA, PHQ-9, HAD-7 and FAB).

TIMELINES

MSI Foundation Grant in March 2018.

CO-INVESTIGATORS

• Kline, Gregory
• Li Pi Shan, Rodney
• McGovern, Christine Helen
• Grant, Christopher