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As many as 20–55% of patients with a history of traumatic brain injury
(TBI) experience chronic endocrine dysfunction, leading to impaired
quality of life, impeded rehabilitation efforts, and lowered life expec-
tancy. Endocrine dysfunction after TBI is thought to result from accel-
eration-deceleration forces to the brain within the skull, creating enduring
hypothalamic and pituitary neuropathology, and subsequent hypotha-
lamic-pituitary (HP)-axis dysfunction. These experiments were designed
to test the hypothesis that a single diffuse TBI results in chronic dys-
function of corticosterone (CORT), a glucocorticoid released in response
to stress, with evidence of structural damage to the HP-axis. We used a
rodent model (adult, male Sprague-Dawley rats) of diffuse TBI induced
by midline fluid percussion (mFP). At 2 months post-injury, circulating
levels of CORT were evaluated at rest, under restraint stress and in
response to dexamethasone, a synthetic glucocorticoid commonly used to
test HP-axis regulation. Further, we assessed changes in injury-induced
neuron morphology (Golgi stain) and neuropathology (silver stain) in the
paraventricular nucleus (PVN) of the hypothalamus. Resting plasma
CORT levels were decreased by
*
60% at 2 months post-injury, con-
comitant with altered complexity of neuron processes in the PVN over
time. Results provide evidence that a single moderate diffuse TBI leads to
hormonal and structural changes, as it pertains to the HP-adrenal axis,
that can contribute to the persistence of endocrine dysfunction. Future
experiments aim to evaluate additional HP-related hormones and ana-
tomical pathology that will support mFP-induced diffuse TBI as a model
of TBI-induced chronic endocrine dysfunction.
Supported, in part by: ADHS14-00003606, Phoenix VA Health
Care System, NIH R03 NS-077098, NIH R01 NS-065052, Science
Foundation Arizona, PCH Mission Support Funds
Keywords: Corticosterone, Diffuse TBI, Neuron morphology, En-
docrine Dysfunction
A7-02
A PROSPECTIVE EVALUATION OF NEURO-ENDOCRINE
AND NUTRITION ABNORMALITIES FOLLOWING SEVERE
TRAUMATIC BRAIN INJURY IN ADULT PATIENTS
Dana Vanino
, Phillip Choi, Emily Lamm, YueFang Chang, Lori
Shutter, David Okonkwo, Ava Puccio
University of Pittsburgh, Neurosurgery, Pittsburgh, USA
Neuro-endocrine dysfunction after traumatic brain injury (TBI) has
previously been reported to occur in 15–90% of patients in small patient
series. In this study, we evaluate the prevalence of acute neuro-endocrine
and nutrition dysfunction following severe TBI in a large single-center,
prospective cohort. Neurological outcome was measured by the Glasgow
Outcome Scale (GOS) score at 6-month and 12-month post-TBI. Over a 6
year period (2009–2014) endocrine and nutrition data was collected for
234 patients (mean age 42.9
–
18.1 years, 77.4% male, initial Glasgow
Coma Scale score
£
8, Injury Severity Scale 27.6
–
11.5). T3, total pro-
tein, albumin and testosterone (male only) were predominantly low in
61.5%, 72.2%, 59.4%, and 97.1%, respectively. Random serum cortisol
and prolactin were predominantly elevated in 86.9% and 56.3%, re-
spectively. 6 month post-TBI GOS revealed that 26.6% of patients had a
good outcome (GOS 4–5) and 73.4% of patients had a poor outcome
(GOS 1–3). 12 month GOS resulted in 27.1% good outcome and 72.9%
poor outcome. When comparing change between first and last mea-
surement with 6 month GOS, total protein and albumin were significant
(p 0.008 and 0.013, respectively). At 12 months, total protein and free T3
were significant (p 0.002 and 0.015, respectively). Spearman correlation
between outcome and last measured value were significant at 6 month
GOS in total protein (p
<
0.0001), albumin (p
<
0.001) and cortisol (p
0.075), and 12 month GOS in total protein (p
<
0.0001) and albumin
(p
<
0.001). Our results are consistent with previous literature demon-
strating that neuro-endocrine and nutrition abnormalities are frequent
after severe TBI, and are associated with poor outcome. These findings
further support that neuro-endocrine disturbances may be important
clinical targets in the management of severe TBI.
Keywords: traumatic brain injury, pituitary function, hormone de-
ficiency, nutrition, neuro-endocrine
A7-03
ENDOCRINE DYSFUNCTION AND PITUITARY AUTO-
IMMUNITY IN CRITICAL AND NEUROCRITICAL ILLNESS
Anna Teresa Mazzeo
1
, Carlotta Giolitti
1
, Silvia Grottoli
2
, Federica
Guaraldi
2
, Simone Caccia
1
, Mattia Zanin
1
, Chiara Martinet
1
, Fabio
Settanni
1
, Alessandro Berton
2
, Maria Angela Medugno
1
, Lara
Muratore
1
, Manuela Lucchiari
1
, Giulio Mengozzi
1
, Simona Cavallo
1
,
Ezio Ghigo
2
, Luciana Mascia
1
1
University of Torino, Anesthesia and Intensive Care, Torino, Italy
2
University of Torino, Endocrinology, Torino, Italy
Critical illness induces an activation of neuroendocrine system possibly
related to inflammatory response. Aim of this study was to investigate
the occurrence of neuroendocrine dysfunction in patients admitted to
ICU for sepsis, traumatic brain injury (TBI), subarachnoid hemorrhage
(SAH), and in a group of patients evolving to brain death (BD).
Methods:
Post-hoc analysis of prospectively collected data. Blood
samples were collected for determination of TSH, fT3, fT4, ACTH,
cortisol, prolactin, GH, IGF-I, and copeptin (at day 1, 2, 3 in sepsis,
TBI, SAH, and at the time of BD diagnosis). Antipituitary antibodies
(APA) were evaluated by an optimized IFI method on cryostat section
of monkey pituitary gland. Cytokine analysis was performed with
Bioplex technology. Comparison between groups was performed with
ANOVA and post hoc analysis.
Results:
113 patients (36 septic, 25 TBI, 21 SAH, 31 BD) were
studied. There was an high prevalence of endocrine dysfunction with
specific profiles: septic patients showed the highest level of copeptin
and the lowest of cortisol, FT3 and FT4. We observed in TBI an ap-
propriate activation of cortisol axis, high copeptin and IL6 and central
hypothyroidism and in BD very low copeptin due to diabetes insipidus
and severe inflammatory response. IL6 level in the four groups were,
respectively: 491
–
1434, 257
–
263, 183
–
315, 829
–
1269, and APA
were detected in 0, 40, 14, and 16%, respectively.
Conclusions:
Pituitary gland is a target of autoimmunity only in
neurocritical illnesses. The neuroendocrine dysfunction related to the
inflammatory reaction exibited a specific profile in the different crit-
ical illnesses. For the first time we have shown the presence of APA
within 24 hours of acute brain injury, possibly interpreted as a marker
of early inflammation after TBI.
Keywords: neurocritical care, critical care, endocrine dysfunction,
pituitary antibodies, sepsis, inflammation
A8 Poster Session II - Group A: Regeneration &
Plasticity
A8-01
PHARMACOLOGICAL MANIPULATION OF MTOR ACTIV-
ITY TO MODULATE MALADAPTIVE INTRASPINAL PLAS-
TICITY AND AUTONOMIC DYSREFLEXIA
Khalid Eldahan, Jenna VanRooyen, Samirkumar Patel,
Alexander
Rabchevsky
University of Kentucky, Dept. Physiology & Spinal Cord/Brain Injury
Research Center (SCoBIRC), Lexington, USA
A-38