Hypopituitarism following traumatic brain injury: prevalence is affected by the use of different dynamic tests and different normal values

Abstract

Objective: Traumatic brain injury (TBI) has emerged as an important cause of hypopituitarism. However, considerable variations in the prevalence of hypopituitarism are reported. These can partly be explained by severity of trauma and timing of hormonal evaluation, but may also be dependent on endocrine tests and criteria used for diagnosis of hypopituitarism. Methods: Systematic review of studies reporting prevalence of hypopituitarism in adults R1 year after TBI focusing on used (dynamic) tests and biochemical criteria. Results: We included data from 14 studies with a total of 931 patients. There was considerable variation in definition of hypopituitarism. Overall, reported prevalences of severe GH deficiency varied between 2 and 39%. Prevalences were 8-20% using the GHRH-arginine test (cutoff !9 mg/l), 11-39% using the glucagon test (cutoff 1-5 mg/l), 2% using the GHRH test (no cutoff), and 15-18% using the insulin tolerance test (ITT; cutoff !3 mg/l). Overall, the reported prevalence of secondary adrenal insufficiency had a broad range from 0 to 60%. This prevalence was 0-60% with basal cortisol (cutoff !220 or !440 nmol/l), 7-19% using the ACTH test, and 5% with the ITT as first test (cutoff !500 or !550 nmol/l). Secondary hypothyroidism was present in 0-19% (free thyroxine) or 5-15% (thyroid-releasing hormone stimulation). Secondary hypogonadism was present in 0-29%. Conclusion: The reported variations in the prevalence rates of hypopituitarism after TBI are in part caused by differences in definitions, endocrine assessments of hypopituitarism, and confounding factors. These methodological issues prohibit simple generalizations of results of original studies on TBI-associated hypopituitarism in the perspective of meta-analyses or reviews.

The Case of Hypopituitarism in Traumatic Brain Injury

“…Trauma severity varied considerably among the studies (Table 1). In general, a lower prevalence of posttraumatic hypopituitarism tended to be recorded in studies recruiting less severely injured patients (Kokshoorn et al, 2011;van der Eerden et al, 2010), and indicators of increased trauma severity was also suggested to be associated with development of hypopituitarism by some (Bavisetty et al, 2008;Bondanelli et al, 2004;Kelly et al, 2000;Klose et al, 2007a;Schneider et al, 2008), while not by others (Agha et al, 2004;Aimaretti et al, 2005;Leal-Cerro et al, 2005). In 22 TBI patients Kelly et al (Kelly et al, 2000) identified injury severity in terms of an initial Glasgow Coma Scale score (GCS) of less than 10, diffuse brain swelling and hypoxia/hypotension as risk factors of posttraumatic hypopituitarism.…”

“…Other surrogate measures of trauma severity have been suggested to predict post-TBI hypopituitarism, including increased intracranial pressure (Klose et al, 2007a), diffuse axonal injury and basal skull fractures (Schneider et al, 2008). Recently, Kokshoorn et al (Kokshoorn et al, 2010) questioned the considerable variation of the reported prevalence, and assessed the impact of methodological differences among the present studies. They confirmed that part of the variation indeed seemed to be caused by differences in study design, diagnostic procedures, and other confounding factors such as BMI, prohibiting simple generalization from the original studies.…”

“…They confirmed that part of the variation indeed seemed to be caused by differences in study design, diagnostic procedures, and other confounding factors such as BMI, prohibiting simple generalization from the original studies. In general, a lower prevalence of posttraumatic hypopituitarism tended to be recorded in studies using the ITT for the evaluation of the GH reserve (Kelly et al, 2000;Klose et al, 2007a;Kokshoorn et al, 2011), and in the studies using confirmatory tests (Agha et al, 2004;Klose et al, 2007a;LealCerro et al, 2005;van der Eerden et al, 2010). Table 2 a-d illustrates the relationship between diagnostic stringency and reported prevalence of GH, ACTH, LH/FSH and TSH deficiencies.…”

“…Over the last 10 years, the field has received increased attention and chronic anterior pituitary hormone deficiency has been reported with a prevalence ranging from 1% and up to 83% (Table 1). The results from most studies have suggested that persistent posttraumatic hypopituitarism might be a more common complication in TBI than previously believed, although some studies have failed to show such high occurrence rates (Kokshoorn et al, 2011;van der Eerden et al, 2010). The diversity of the reported prevalences of chronic anterior pituitary hormone deficiency is likely to be explained by differences in study populations, study designs, and diagnostic procedures.…”

Serum insulin‐like growth factor‐I levels are associated with improved white matter recovery after traumatic brain injury

“…One potential factor is post‐traumatic hypopituitarism, which can be produced by TBI and can influence brain repair 13, 14, 15. Studies using gold standard dynamic testing have reported a prevalence of the most common endocrinopathy, growth hormone (GH) deficiency (GHD), of 2.7 to 11.8% in patients >1 year after TBI 14, 16, 17.…”