Journal of Rehabilitation Medicine 51-4inkOmslag | Page 36

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observed both hypo- and hyper-function of the thyroid,
adrenal and somatotrophic axes (17, 18). It can be
speculated why both hypo- and hyper-function of the
pituitary occurs, but it might be related to different
reactions to stress and changes in body weight. Most
previous studies observed pituitary hypofunction in
one or multiple axes (1, 2), but only a few studies re-
ported hyperfunction of the adrenal axis (30), thyroid
axis (31) and somatotrophic axis (30).
Low gonadotrophins had a significant negative as-
sociation with GOSE, but not with BNIS or RLAS-R.
This finding is in agreement with the results of several
previous studies reporting on the impact of multiple
hormone dysfunctions, including the gonadotrophic
axis, such as studies of patients with aSAH (32–34)
and patients with both TBI and aSAH (35), all reporting
worse outcome, as measured by GOS. One previous
study by Marina et al. (30) also used GOSE and ob-
served a negative impact of low gonadotrophins in
patients with TBI. Thus, even though study samples
and design differ and previous studies assessed out-
come with GOS, the findings regarding an association
between gonadal hormone insufficiencies and worse
global outcome are concordant. One previous study
on TBI by Bondanelli et al. (29) reported a negative
impact specifically of gonadotrophin disturbances on
cognitive/behavioural function, with outcome mea-
sured with Disability Rating Scale (DRS) and with
RLAS. These findings are also in agreement with
ours regarding global outcome, while we observed
no association with cognitive function according to
RLAS-R or BNIS. This discrepancy may have several
causes, including that our study also used data from
patients with aSAH.
No signs of an impact of either abnormal thyroid or
cortisol level were found. BNIS, RLSA-R and GOSE
were lower in the subgroup with high thyroid levels
at group comparison, but when multivariate analysis
was made, no independent association was seen. Thus,
although frequent, neither high nor low T4 or cortisol
levels were associated with worse cognitive or global
outcome at 12 months. This finding is in contrast to
studies demonstrating that hypothyroidism and hy-
perthyroidism, as well as low or high glucocorticoid
levels (36) may have a negative impact on cognitive
function (37), but in line with a study by Schneider
et al. (35) of TBI and aSAH, who found no impact of
corticotropic dysfunction on GOS. The discrepancies
observed in the studies might be caused by differences
in study cohorts, differences in methods of hormonal
analyses, as well as interpretation of these and the
degree of hormonal abnormality.
Regarding the somatotrophic axis, high IGF-I had a
significant negative association with RLAS-R, but no
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association with BNIS. The cause of increased levels
of IGF-I as well as of other hormones, as frequently
observed in our study, but not often reported in other
studies is not clear. Factors at play may include somatic
stress reactions as well as complex interactions bet-
ween the pituitary hormones, as suggested previously
(31). Notably, we observed no association between low
IGF-I levels and GOSE, which agrees with findings
by Schneider et al. (35) in the study of TBI and aSAH,
who observed no impact of somatotrophic dysfunction
on GOS.
However, it should be pointed out that an IGF-I level
within normal reference range does not exclude GH
deficiency, since 30% of patients with GH deficiency
have IGF-I levels within the normal reference range
(38). Thus, there is a risk for underestimation of growth
hormone deficiency in our study.
Prolactin levels were low in too few patients to al-
low any conclusion. High prolactin levels were more
frequent and were associated with lower performance
according to RLAS-R and GOSE. This is in agreement
with a study by Marina et al. (30), who reported lower
GOSE in patients with TBI and elevated stress hormo-
nes (prolactin, IGF-I and cortisol).
The analyses of associations between multiple low
hormone /values and outcome were hampered by
the low frequency of multiple hormone deviations in
individual patients at any of the 4 test-points. Thus,
our finding of no significant associations between
multiple low or high hormones and outcome measured
with BNIS, RLAS-R or GOSE at 12 months after the
event must be interpreted with caution. Even though
our results are in line with a study of patients by Ba-
visetty et al. (39), who found no association between
pituitary dysfunction (somatotrophic, gonadotrophic,
thyreotrophic, corticotrophic, posterior pituitary axes)
and GOSE after TBI, it is reasonable to assume that
multiple pituitary dysfunction would have more impact
on clinical outcome than isolated pituitary dysfunction,
as also indicated in some previous studies.
Our data suggest that global measures, such as
GOSE, may be more sensitive to an impact of pituitary
dysfunction than specific cognitive measure, such as
BNIS. One may speculate that this reflects that not
only cognitive function, but also other, e.g. emotional,
motor or musculoskeletal functions, are also disturbed
by pituitary dysfunction and impact on the global
outcome according to GOSE. We believe that further
studies are warranted to elucidate this, to increase
our understanding of the clinical impact of pituitary
dysfunction, and to learn whether there is any reason
to intervene in terms of substitution therapy outside
established treatment criteria in order to enhance re-
covery after TBI or aSAH.