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2
3
4
5
Hypopituitarism after TBI: history
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o Simmonds - 1914 description of hypophyseal cachexia (Simmond‘s disease)
o Cyran - 1918 oreport on traumatic hypophyseal cachexia o Escamilla and Lisser - 1942 o Edwards and Clark - 1986 o Benvenga et al - 2000
Simmonds M. Dtsch Med Wochenschr. 1914;40:322. Cyran E. Dtsch Med Wochenschr. 1918;44:1261. Escamilla RF, Lisser H. J Clin Endocrinol. 1942;2:65. Edwards OM, Clark JDA. Medicine. 1986;65:281. Benvenga S et al. J Clin Endocrinol Metab. 2000;85:1353.
epidemiology
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in Germany 300.000 to 500.000 cases of TBI/year 30.000 deaths per year 50%–75% traffic accidents
costs: data from the USA
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$38 billion /year for severe TBI
12% hospital costs
88% secondary costs (rehabilitation…)
cost/patient: $0.8-1.8 million
age of TBI patients
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40 35 incidence (%)
30 25
n=218
20 15 10
5 0 0-10 11-19 20-29 30-39 40-49 50-59 >60
age (years)
Benvenga S et al. J Clin Endocrinol Metab. 2000;85:1353. The Endocrine Society.
time between accident and diagnosis
10
80
Pats with TBI and pituitary insufficiency
70 60 50 40 30
n=202
20 10
0
<1 1-2 2-3 3-4 4-5 5-6 6-7 7-8 8-10 11-19 >20
years
Benvenga S et al. J Clin Endocrinol Metab. 2000;85:1353. The Endocrine Society.
Dr. Etzrodt‘s Case: Neurol Rehabil 2005 (4):247-8
since 1996 anemia of unknown origin
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tiredness childlessness
march 2004
clinical deterioration muscle pain hypothermia apathy june 2004
paleness androgenic hair missing lateral eye brows missing
loss of libido, erectile dysfunction
Dr. Etzrodt‘s Case: Neurol Rehabil 2005 (4):247-8
since 1996 anemia of unknown origin
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tiredness childlessness
march 2004
clinical deterioration muscle pain hypothermia apathy june 2004
paleness androgenic hair missing lateral eye brows missing
loss of libido, erectile dysfunction
Dr. Etzrodt‘s Case: Neurol Rehabil 2005 (4):247-8
endocrinological substitution Cortisone 12.5-12.5-12.5 mg
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Levothyroxine 0.1 mg/d Testosterone 50 mg/d GH 0-0-0-0.3 mg
prevalence of hypopituitarism after TBI: Data of two recent Studies
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• hypopituitarism in TBI occurs more often than expected
• diagnosis often not sucpected from clinical course • the symptoms of hypopituitarism resemble those of other residual defects not related to hormonal insufficiency after TBI
1. Kelly DF, Gaw Gonzalo IT, Cohan P, Berman N, Swerdloff R, Wang C. Hypopituitarism following traumatic brain injury and aneurysmal subarachnoid hemorrhage: a preliminary report. J Neurosurg. 2000;93:743-752.
2. Lieberman SA, Oberoi AL, Gilkison CR, Masel BE, Urban RJ. Prevalence of neuroendocrine dysfunction in patients recovering from traumatic brain injury. J Clin Endocrinol Metab. 2001;86:2752-2756. 3. Carroll PV, Christ ER, Bengtsson BÅ, et al. Growth hormone deficiency in adulthood and the effects of growth hormone replacement: a review. J Clin Endocrinol Metab. 1998:83:382-395.
16th annual Conference of Neurotrauma Gwalior 17-19 August 2007
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hypopituitarism after traumatic brain injury and SAH – neuroendocrine data from the acute phase in 71 patients
O. Ganslandt, J. Kreutzer, M. Buchfelder
Dept. of Neurosurgery, University Erlangen – Nuremberg, Germany Chair: Prof. Dr. med. M. Buchfelder
BASIC ENDOCRINE DIAGNOSTIC – ACUTE PHASE SHT/SAH
Author Tanriverdi 2006
Schneider 2006
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Data 0-24 h + 12 mon
3+12 mon
n
GH
Tes
ACTH/Cor
fT3/fT4/TSH
Prl
>2 axes
DI
52 78
38% 10%
8% 21%
19% 9%
6% 3%
-
10% 36%
-
Leal-Cerro 2005
Agha 2005
>12 mon
>12 mon
170
102
6%
11%
17%
12%
6%
13%
6%
1%
12%
25%
28%
2%
7%
Agha 2004
Aimaretti 2004
12. d
3 mon
50
100
18%
21%
80%
17%
16%
8%
2%
5%
52%
-
35%
22%
4%
Bock 2004
Bondanelli 2004
7. d
12 -64 mon
27
50
4%
14%
83%
14%
26%
0%
52%
10%
8%
30%
27%
0%
Dimopoulou 2004
Popovic 2004
22. d
12 mon
34
67
9%
30%
24%
9%
24%
7%
15%
22%
4%
53%
51%
4%
Schneider 2003
Liebermann 2001
3 mon
13 mon
26
70
12%
15%
48%
2%
19%
7%
22%
-
88%
69%
-
Kelly 2002
26 mon
22
18%
23%
5%
5%
-
36%
-
STUDY DESIGN
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71 patients (36 SAH, 35 TBI)
32 female (61% SAH), 39 male (74% TBI) age in years: mean 53,6, median 53
TBI: mean 54,4 median 60 SAH: mean 52,7 median 50
10 patients (benign trauma w/o TBI)
in cooperation with dept. of emergency medicine, Univ. Hospital Erlangen
STUDY DESIGN – anterior + posterior pituitary-function
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(super)acute phase (2-12 hrs) basal level: PRL, Cortisol, ACTH, LH, FSH, OES,TES, fT3, fT4, TSH, GH und IGF-1 actual median 3 hrs acute phase (1-5 day) in/outtake, e‘lytes, serum/urine-osmolality/day osmotherapy?
longitudinal phase (3-4 months + 12-13 months) basal level + insulin-induced hypoglycemia
or
GHRH-Arginin+CRH (in case of seizure during acute phase))
STUDY DESIGN – METHODS/ASSAYS
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DPC Immulite 2000 Control GH/IGF-1 Immulite + supersensitive assay
cooperation, Med.Klinik – Innenstadt, München Lab Dr. Bidlingmaier
ACTH-level protease-inhibitor Trasylol, early separation,
ice/fridge
STUDY DESIGN – GRADING
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SAB
Diffuse TBI
Marshall et al, Journal of Neurotrauma, 1992
GCS, WFNS-Score, Hunt&Hess, Fisher
ms 2
ms 1
normal CT
SHT
midline shift 0-5mm, basal cisterns present, no mixed density lesion >25ml
GCS, Marshall
ms 4
ms 3
midline shift 0-5mm, basal cisterns Score compressed, no mixed density lesion >25ml
midline shift >5mm, no mixed density lesion >25ml Longitudinal/Outcome
ms 4 Karnofsky surgery SF-12 Index,
RF > 25 ml GOS, (EDH, SDH, contusion)
ms 5
no surgery
STUDY DESIGN – GRADING
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SAH 36 Patients:
H&H 1: 13,9% H&H 2: 25,0% H&H 3: 25,0% H&H 4: 22,2% H&H 5: 13,9% (mean GCS 15) (mean GCS 14,2) (mean GCS 11,1) (mean GCS 7,3) (mean GCS 5)
STUDY DESIGN – GRADING
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TBI 35 Patiens:
MS 1: MS 2: MS 3: MS 4: MS 5: MS 6: 11,4% 51,4% 11,4% 2,9% 17,1% 2,9% (mean GCS 14,8) (mean GCS 13,3) (mean GCS 7,5) (GCS 8) (mean GCS 6,5) (GCS 13)
RESULTS – ACUTE PHASE TBI/SAH
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pathological findings in one hypothalamicpituitary axis 67/71 patients (94%) pathological findings in two or more hypothalamic-pituitary axes 57/71 patients (80%)
BASIC ENDOCRINE DIAGNOSTIC – ACUTE PHASE SHT/SAH
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no correlation with GCS
hyperprolactinemia 25/71 patients (35%)
SAB: 50% of all cases TBI: 20% of all cases
BASIC ENDOCRINE DIAGNOSTIC – ACUTE PHASE SHT/SAH
basal cortisol level – acute phase SAH/TBI
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<10 µg/dl: 11%
basal cortisol level >25 µg/dl 44/71 patients (62%)
SAB: 50% of all cases SHT: 50% of all cases
BASIC ENDOCRINE DIAGNOSTIC – ACUTE PHASE SHT/SAH
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testosterone-level <2,8 ng/ml 9/40 males (22%) GH-level > 5,0 ng/ml 9/71 patients (12,7%)
IGF-1 ??
BASIC ENDOCRINE DIAGNOSTIC – ACUTE PHASE SHT/SAH
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IGF-1ng/ml – adapted for gender & age
IGF-1 level – acute phase SAH/TBI
IGF-1 reflects the pulsatile GH-secretion no correlation with GCS integrated over the days
IGF-1 adapted for gender & age too low 39/71 Patienten(55%)
SAH: 58% of all cases TBI: 51% of all cases
ACUTE PHASE TBI/SAH - CONCLUSION
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pathological findings in two or more hypothalamic-pituitary axes: 80% hyperprolactinemia in 72% of SAH-patients
cause? hemorrhage localisation? pituitary stalk? stress?
hypogonadism in males: 22%
IGF-1 level too low: 55%
cause? lab/assay-bias? acute mismatch IGF-1/IGFBP-3 ratio?
ACUTE PHASE TBI/SAH - CONCLUSION
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prospective value? probably not
value for detection of etiology and prevalence of pituitary disorders? probably yes 10 patients (trauma w/o TBI)
hyperprolactinemia 6/10 patients
IGF-1 level too low 8/10 patients
4.Expert-Meeting: Hypophyseninsuffizienz nach SHT und SAB 01.- 02.12.2006, Hamburg
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PROSPEKTIVE-LONGITUDINALE STUDIE DER HYPOPHYSENFUNKTIONEN NACH SHT UND SAB
Kooperationen und Partner: Dr. med. M. Bidlingmaier (Med. Klinik-Innenstadt, München) Dr. med A. Olk (Klinik für Unfallchirurgie, Erlangen) Prof. Dr. med D. Hennig (Klinik für Unfallchirurgie, Erlangen)
Neurochirurgische Klinik, Universität Erlangen - Nürnberg Direktor: Prof. Dr. med. M. Buchfelder
BASIC ENDOCRINE DIAGNOSTIC – ACUTE PHASE SHT/SAH
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basal ACTH-level >50 pg/dl 30/59 patients (51%) NA=12 Cortisol + ACTH elevated 23/37 Patients (62%) Cortisol + ACTH + PRL elevated 10/37 Patients (27%)