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Pituitary dysfunction and relation to cognitive and global outcome after traumatic brain injury or aneurysmal subarachnoid haemorrhage

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posted on 2024-09-02, 18:16 authored by Anna Tölli

Traumatic brain injury (TBI) and aneurysmal subarachnoid haemorrhage (aSAH) are leading causes of deaths and may cause permanent physical, cognitive, behavioural, and psychosocial disabilities limiting daily activities in survivors. One potential complication of TBI and aSAH is deficient secretion of one or more pituitary hormones. The prevalence of pituitary dysfunction (PiD) following TBI or aSAH varies significantly among published studies. The aims of this thesis were to increase knowledge about PiD after TBI and aSAH and to explore the clinical impact of such dysfunction on cognitive and global outcome after TBI and aSAH. For this purpose, a cohort of 84 adult patients with moderate to severe TBI and 46 with aSAH was followed with repeated assessments of pituitary function and global and cognitive function up to 12 months post-event. Of the baseline cohort, 56 patients with TBI and 35 with aSAH were assessed at all-time points.

Paper I reports findings in the acute stage when hypocortisolism was seen in 12% of patients with TBI and 14% with aSAH and thyroid deficiency was seen in 17% of patients with TBI and 20% with aSAH. We found no relations between hormonal levels and injury variables and no marker of increased risk for pituitary deficiency. Paper II reports findings during the first year after the event. Perturbations in pituitary function were most frequent early after the event but continued to occur until 12 months post-event. The most frequent was hypogonadotrope hypogonadism observed in 27% of patients with TBI and 41% with aSAH at 6 months, and in 21% of patients with TBI and 23% with aSAH at 12 months. Thyroid deficiency was seen in the acute stage in 24% of patients with TBI and 23% with aSAH, in 7% of patients with TBI and 3% with aSAH at 3 months, in 4% of patients with TBI and 3% with aSAH at 6 months, and in 0% of patient with TBI and 6% with aSAH at 12 months. Adrenal deficiency was seen in the acute stage in 11% of patients with TBI and 15% with aSAH, in 6% patients with TBI and 0% with aSAH at three months, in 2% patients with TBI and 3% with aSAH at six months and in 4% patients with TBI and none with aSAH at 12 months. Low levels of insulin-like growth factor 1 (IGF-I), a marker for growth hormone activity, were seen in 17% of patients with TBI and 12% with aSAH at 6 months and in 14% of patients with TBI and 3% with aSAH at 12 months. In total, 7 out of 91 patients required hormonal replacement (4 testosterone, 1 growth hormone, 2 hydrocortisone). No relations were seen between hormonal levels and injury variables.

In Paper III we compared the time course of cognitive and global recovery in the two diagnostic groups and explored the relations between acute injury severity markers and clinical outcome. Cognitive function was still impaired in 63% of patients with TBI and 76% with aSAH at 3 months but improved significantly between all-time points in both groups except from 6 to 12 months after TBI. The proportion of patients with cognitive impairments was not significantly different between groups at any time point. At 12 months, 62% patients with TBI and 63% with aSAH had good outcome according to the Glasgow Outcome Scale Extended (GOSE), 64% of patients with TBI and 41% with aSAH had good cognitive function according to the Barrow Neurological Institute Screen for Higher Cerebral Functions (BNIS), and 55% of patients with TBI and 40% with aSAH had good cognitive functioning according to Rancho Los Amigos Cognitive Scale-Revised (RLAS-R). Cognitive function according to BNIS correlated with cognitive/behavioural function according to the RLAS-R and with global outcome according to the GOSE. Acute Glasgow Coma Scale (GCS) scores were associated with cognitive function according to the BNIS T-scores after TBI but not after aSAH. BNIS T-scores after aSAH were not related to Hunt and Hess scores or to Fisher scores. In Paper IV we explored associations between pituitary dysfunction and clinical outcome at 12 months after TBI and aneurysmal SAH. Controlling for baseline variables, low levels of gonadal hormones were associated with lower GOSE score (b = −0.804, p = 0.033), high levels of prolactin were associated with lower RLAS-R scores (b = −1.418, p = 0.034), and high levels of IGF-I were associated with lower RLAS-R scores (b = −1.784, p = 0.002) and lower GOSE scores (b = −1.491, p = 0.006). Thus, pituitary dysfunction during the first year after TBI and aSAH might impact on clinical outcome at 12 months.

In conclusion, these studies demonstrate that PiD occurs from the acute phase until 12 months after TBI and aSAH. The study supports the need for systematic follow-up of pituitary function after moderate or severe TBI or aSAH even though only a few patients need replacement hormonal therapy. The study could not identify a marker of increased risk for pituitary dysfunction. Cognitive improvements after aSAH and TBI showed similarities and correlate with global function. GCS scores were associated with outcome after TBI but not after aSAH. Pituitary dysfunction during the first year after TBI and aSAH might impact on clinical outcome at 12 months, and further studies are needed to fully clarify the clinical importance and optimal management of pituitary dysfunction after TBI and aSAH.

List of scientific papers

I. Pituitary Function in the Acute Phase of Traumatic Brain Injury and Subarachnoid Hemorrhage. Tölli, A., Borg, J., Bellander, B-M., Höybye, Ch. International Journal of Clinical Medicine. 2015. 06(06): p. 411-422.
https://doi.org/10.4236/ijcm.2015.66054

II. Pituitary function within the first year after traumatic brain injury or subarachnoid haemorrhage. Tölli, A., Borg, J., Bellander, B-M., Johansson, F., Höybye, Ch. J Endocrinol Invest. 2017. 40(2): p. 193-205.
https://doi.org/10.1007/s40618-016-0546-1

III. The effect of time on cognitive impairments after non-traumatic Subarachnoid Haemorrhage and after Traumatic Brain Injury. Tölli, A., Höybye, Ch., Bellander, B-M., Johansson, F., Borg, J.
https://doi.org/10.1080/02699052.2018.1497203

IV. Impact of pituitary dysfunction on cognitive and global outcome after Traumatic Brain Injury and aneurysmal Subarachnoid Haemorrhage. Tölli, A., Höybye, Ch., Bellander, B-M., Borg, J. [Submitted]

History

Defence date

2018-10-12

Department

  • Department of Clinical Sciences, Danderyd Hospital

Publisher/Institution

Karolinska Institutet

Main supervisor

Borg, Jörgen

Co-supervisors

Höybye, Charlotte; Bellander, Bo-Michael

Publication year

2018

Thesis type

  • Doctoral thesis

ISBN

978-91-7831-099-9

Number of supporting papers

4

Language

  • eng

Original publication date

2018-09-19

Author name in thesis

Tölli, Anna

Original department name

Department of Clinical Sciences, Danderyd Hospital

Place of publication

Stockholm

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