Intensive Care Med (1991) 17:25-29
IntensiveCare Medicine 9 Springer-Verlag 1991
E n d o c r i n e abnormalities in severe traumatic brain injury a cue to prognosis in severe craniocerebral trauma? J . M . H a c k l 1, M. G o t t a r d i s ~, Ch. W i e s e r 1, E. R u m p l 2, Ch. S t a d l e r 2, S. Schwarz ~ a n d R. M o n k a y o 3 Department of 1 Anaesthesia and General Intensive Care Medicine and 3 Institute for Experimental Pathology, University Hospital of Innsbruck and 2 Department of Neurology, General Hospital of Klagenfurt, Austria Received: 9 March 1990; accepted: 14 August 1990
Abstract. P a t i e n t s with severe craniocerebral t r a u m a ( s C C T ) d i s p l a y m e t a b o l i c a n d e n d o c r i n e changes. The q u e s t i o n is raised w h e t h e r h o r m o n a l p a t t e r n s give cues to the p r o g n o s i s o f o u t c o m e o r not. I n 21 p a t i e n t s the funct i o n o f the a d r e n o c o r t i c a l , g o n a d a l , t h y r o i d a n d h u m a n g r o w t h h o r m o n e ( h G H ) - i n s u l i n system was assessed. L H , F S H , T S H , p r o l a c t i n a n d h G H were s t i m u l a t e d . 3 groups o f p a t i e n t s were f o r m e d . G r o u p I: p a t i e n t s in acute phase w i t h a G l a s g o w C o m a Score (GCS) m o r e t h a n 6 (group I a ) a n d less t h a n 6 ( g r o u p I b ) . G r o u p II: p a t i e n t s in transition to t r a u m a t i c a p a l l i c s y n d r o m e (TAS). G r o u p III: p a t i e n t s w i t h full-blown or resolving TAS. T h e values o f g r o u p I a c o m p r i s e d low T3, T4 a n d testosterone, elevated insulin, n o r m a l h G H . G r o u p I b h a d h y p o t h y r o i d T3 a n d T4 a n d a n a t t e n u a t e d r e s p o n s e o f L H , T S H , p r o l a c t i n a n d h G H to s t i m u l a t i o n . G r o u p III: there was seen a n end o c r i n e n o r m a l i s a t i o n with elevated T4 a n d T B G a n d an altered response o f h G H a n d p r o l a c t i n to s t i m u l a t i o n . E n d o c r i n e a b n o r m a l i t i e s were n o t helpful in p r e d i c t i n g w h i c h course, either to b e t t e r or to worse, a given p a t i e n t w o u l d follow.
Key words: Severe c r a n i o c e r e b r a l t r a u m a - A d r e n a l syst e m - G o n a d a l system - T h y r o i d a l system g r o w t h h o r m o n e - I n s u l i n system
Human
Severe c r a n i o c e r e b r a l t r a u m a (sCCT) very o f t e n results in persistent defects a n d invalidity. I n m a n y p a t i e n t s the inc o m p l e t e recovery is due to a p r o l o n g e d course with meta b o l i c d e r a n g e m e n t s [1 - 7 ] . T h e m o s t c o m m o n m e t a b o l ic feature is the progressive loss o f n i t r o g e n resu!ting in c o n s i d e r a b l e loss o f weight, p o l y n e u r o p a t h y , peri~irthritis a n d l i a b i l i t y o f infections [1, 3, 8]. A d d i t i o n a l l y , a n y n o n specific b u t b r i e f l y stressing f a c t o r changes t h e s e r u m levels o f testosterone, T3, T4, cortisol, (nor-)epinephrine, g l u c a g o n , insulin a n d sex h o r m o n e s . Such c h a n g e s are f r e q u e n t l y o b s e r v e d in s C C T [ 3 - 5 , 9 - 2 1 ] . T h e a i m o f t h e present investigation was to delineate the changes o f h y p o t h a l a m i c , p i t u i t a r y a n d target g l a n d
h o r m o n e levels in each p h a s e after sCCT. We were m o s t interested to answer the q u e s t i o n w h e t h e r there are p h a s e d e p e n d e n t specifics o f e n d o c r i n e d y s r e g u l a t i o n a n d w h e t h e r there is a cue to p r o g n o s i s o f outcome. A s the pit u i t a r y g l a n d a n d its vascular s u p p l y is k n o w n to be very sensitive even to m i n o r h e a d t r a u m a , it was t e m p t i n g to l o o k for c o r r e l a t i o n s between its f u n c t i o n a l integrity a n d the overall severity o f t h e disease.
Material and methods A total of 21 patients with sCCT were submitted to a fixed plan of investigation)There were 16 males and 5 females with a mean age of 30.5 (I5-52) years. No patient was known to be hormonally diseased prior to sCCT. A control group was composed of 9 healthy males with a mean age of 28 years. The patients were grouped according to neurologic syndromes: Group I: Patients with acutely raised intracranial pressure on day 2 - 5 after trauma. This group was subdivided as follows: Group Ia: Patients with a midbrain syndrome (MBS) II or III according to Gerstenbrand and Luecking [21] and with a Glasgow Coma Score (GCS) [5] higher than 6. Group Ib: Patients with a MBS IV or bulbar brain syndrome (BBS) I [21] and a GCS less than 6. Group II: Patients in transition to the traumatic apallic syndrome (TAS) according to Gerstenbrand and Avenarius [1, 5, 21] after resolution of increased intracranial pressure displaying a prolonged midbrain syndrome with features of a hypersympathetic vegetative regulation such as tachycardia, exaggerated catabolism and sweating. They were investigated on day 7 - 10 after trauma. Group III: Patients with full-blown TAS [5, 2/], characterized by the typical symptoms of coma vigile (i.e. they were awake but not aware), exaggerated catabolism and hypersympathetie regulation of metabolism [3, 8] or patients with resolving TAS. This group was divided with regard to the time course of clinical improvement: Group .gila: Patients with an apallic syndrome lasting less than 60 days and hence tendency to improve. Group IIIb: Patients with prolonged TAS, i.e. outlasting 60 days. All patients were treated in the intensive care unit with only minor variations in their treatment protocols including corticosteroid treatment for increased intracranial pressure. Endocrine studies were done in patients and controls under identical circumstances. In 11 patients the investigations were done only once, in the other patients in the mean 3.6 (2- 5) times. Before endocrine stimulation basic values were obtained for cortisol, dehydroepiandosterone-
26
J.M. Hackl et al.: Endocrine abnormalities in brain injury
Table 1. Mean values and standard deviation of adrenal hormones of control group and patients groups. Cortisol (~tg/1), 17-OHP (17-hydroxy-progesterone, Ixg/I), Cpd-S (11-desoxycortisol, ~tg/l) and DHEA-S (dehydroepiandrosterone-sulphate, lxg/1). Controls = control group with 9 men, group Ia = 9 sCCT patients with a MBS II and III (10 inquiries), group Ib = 8 sCCT patients with a MBS IV or a BBS (8 inquiries), group II = 7 patients with a transition stage to TAS (8 inquiries), group IIIa = 3 patients in a full-blown TAS, duration of therapy 60 days (16 inquiries)
Cortisol 17-OHP Cpd-S DHEA-S
Controls
Group Ia
Group Ib
Group II
Group IIIa
Group IIIb
153.0 • 28.0 0.7 • 0.2 1.9 • 1.0 1849 • 162
55.0 • 2.0* 0.7 • 1.2 1.3 4- 0.4 831 +__353
146.0 • 58.0 1.7 -2_1.2 19.7 • 17.2"* 609 • 320
103.0 +_28.0 2.2 4- 0.4 2.1 4- 1.9 272 • 67**
157.0 • 32.0 0.6 • 0.1 0.6 4- 0.1 383 • 44"*
145.5 • 13.0 1.1 • 0.1 1.1 • 0.3 785 4- 197*
* p
IntensiveCare Medicine 9 Springer-Verlag 1991
E n d o c r i n e abnormalities in severe traumatic brain injury a cue to prognosis in severe craniocerebral trauma? J . M . H a c k l 1, M. G o t t a r d i s ~, Ch. W i e s e r 1, E. R u m p l 2, Ch. S t a d l e r 2, S. Schwarz ~ a n d R. M o n k a y o 3 Department of 1 Anaesthesia and General Intensive Care Medicine and 3 Institute for Experimental Pathology, University Hospital of Innsbruck and 2 Department of Neurology, General Hospital of Klagenfurt, Austria Received: 9 March 1990; accepted: 14 August 1990
Abstract. P a t i e n t s with severe craniocerebral t r a u m a ( s C C T ) d i s p l a y m e t a b o l i c a n d e n d o c r i n e changes. The q u e s t i o n is raised w h e t h e r h o r m o n a l p a t t e r n s give cues to the p r o g n o s i s o f o u t c o m e o r not. I n 21 p a t i e n t s the funct i o n o f the a d r e n o c o r t i c a l , g o n a d a l , t h y r o i d a n d h u m a n g r o w t h h o r m o n e ( h G H ) - i n s u l i n system was assessed. L H , F S H , T S H , p r o l a c t i n a n d h G H were s t i m u l a t e d . 3 groups o f p a t i e n t s were f o r m e d . G r o u p I: p a t i e n t s in acute phase w i t h a G l a s g o w C o m a Score (GCS) m o r e t h a n 6 (group I a ) a n d less t h a n 6 ( g r o u p I b ) . G r o u p II: p a t i e n t s in transition to t r a u m a t i c a p a l l i c s y n d r o m e (TAS). G r o u p III: p a t i e n t s w i t h full-blown or resolving TAS. T h e values o f g r o u p I a c o m p r i s e d low T3, T4 a n d testosterone, elevated insulin, n o r m a l h G H . G r o u p I b h a d h y p o t h y r o i d T3 a n d T4 a n d a n a t t e n u a t e d r e s p o n s e o f L H , T S H , p r o l a c t i n a n d h G H to s t i m u l a t i o n . G r o u p III: there was seen a n end o c r i n e n o r m a l i s a t i o n with elevated T4 a n d T B G a n d an altered response o f h G H a n d p r o l a c t i n to s t i m u l a t i o n . E n d o c r i n e a b n o r m a l i t i e s were n o t helpful in p r e d i c t i n g w h i c h course, either to b e t t e r or to worse, a given p a t i e n t w o u l d follow.
Key words: Severe c r a n i o c e r e b r a l t r a u m a - A d r e n a l syst e m - G o n a d a l system - T h y r o i d a l system g r o w t h h o r m o n e - I n s u l i n system
Human
Severe c r a n i o c e r e b r a l t r a u m a (sCCT) very o f t e n results in persistent defects a n d invalidity. I n m a n y p a t i e n t s the inc o m p l e t e recovery is due to a p r o l o n g e d course with meta b o l i c d e r a n g e m e n t s [1 - 7 ] . T h e m o s t c o m m o n m e t a b o l ic feature is the progressive loss o f n i t r o g e n resu!ting in c o n s i d e r a b l e loss o f weight, p o l y n e u r o p a t h y , peri~irthritis a n d l i a b i l i t y o f infections [1, 3, 8]. A d d i t i o n a l l y , a n y n o n specific b u t b r i e f l y stressing f a c t o r changes t h e s e r u m levels o f testosterone, T3, T4, cortisol, (nor-)epinephrine, g l u c a g o n , insulin a n d sex h o r m o n e s . Such c h a n g e s are f r e q u e n t l y o b s e r v e d in s C C T [ 3 - 5 , 9 - 2 1 ] . T h e a i m o f t h e present investigation was to delineate the changes o f h y p o t h a l a m i c , p i t u i t a r y a n d target g l a n d
h o r m o n e levels in each p h a s e after sCCT. We were m o s t interested to answer the q u e s t i o n w h e t h e r there are p h a s e d e p e n d e n t specifics o f e n d o c r i n e d y s r e g u l a t i o n a n d w h e t h e r there is a cue to p r o g n o s i s o f outcome. A s the pit u i t a r y g l a n d a n d its vascular s u p p l y is k n o w n to be very sensitive even to m i n o r h e a d t r a u m a , it was t e m p t i n g to l o o k for c o r r e l a t i o n s between its f u n c t i o n a l integrity a n d the overall severity o f t h e disease.
Material and methods A total of 21 patients with sCCT were submitted to a fixed plan of investigation)There were 16 males and 5 females with a mean age of 30.5 (I5-52) years. No patient was known to be hormonally diseased prior to sCCT. A control group was composed of 9 healthy males with a mean age of 28 years. The patients were grouped according to neurologic syndromes: Group I: Patients with acutely raised intracranial pressure on day 2 - 5 after trauma. This group was subdivided as follows: Group Ia: Patients with a midbrain syndrome (MBS) II or III according to Gerstenbrand and Luecking [21] and with a Glasgow Coma Score (GCS) [5] higher than 6. Group Ib: Patients with a MBS IV or bulbar brain syndrome (BBS) I [21] and a GCS less than 6. Group II: Patients in transition to the traumatic apallic syndrome (TAS) according to Gerstenbrand and Avenarius [1, 5, 21] after resolution of increased intracranial pressure displaying a prolonged midbrain syndrome with features of a hypersympathetic vegetative regulation such as tachycardia, exaggerated catabolism and sweating. They were investigated on day 7 - 10 after trauma. Group III: Patients with full-blown TAS [5, 2/], characterized by the typical symptoms of coma vigile (i.e. they were awake but not aware), exaggerated catabolism and hypersympathetie regulation of metabolism [3, 8] or patients with resolving TAS. This group was divided with regard to the time course of clinical improvement: Group .gila: Patients with an apallic syndrome lasting less than 60 days and hence tendency to improve. Group IIIb: Patients with prolonged TAS, i.e. outlasting 60 days. All patients were treated in the intensive care unit with only minor variations in their treatment protocols including corticosteroid treatment for increased intracranial pressure. Endocrine studies were done in patients and controls under identical circumstances. In 11 patients the investigations were done only once, in the other patients in the mean 3.6 (2- 5) times. Before endocrine stimulation basic values were obtained for cortisol, dehydroepiandosterone-
26
J.M. Hackl et al.: Endocrine abnormalities in brain injury
Table 1. Mean values and standard deviation of adrenal hormones of control group and patients groups. Cortisol (~tg/1), 17-OHP (17-hydroxy-progesterone, Ixg/I), Cpd-S (11-desoxycortisol, ~tg/l) and DHEA-S (dehydroepiandrosterone-sulphate, lxg/1). Controls = control group with 9 men, group Ia = 9 sCCT patients with a MBS II and III (10 inquiries), group Ib = 8 sCCT patients with a MBS IV or a BBS (8 inquiries), group II = 7 patients with a transition stage to TAS (8 inquiries), group IIIa = 3 patients in a full-blown TAS, duration of therapy 60 days (16 inquiries)
Cortisol 17-OHP Cpd-S DHEA-S
Controls
Group Ia
Group Ib
Group II
Group IIIa
Group IIIb
153.0 • 28.0 0.7 • 0.2 1.9 • 1.0 1849 • 162
55.0 • 2.0* 0.7 • 1.2 1.3 4- 0.4 831 +__353
146.0 • 58.0 1.7 -2_1.2 19.7 • 17.2"* 609 • 320
103.0 +_28.0 2.2 4- 0.4 2.1 4- 1.9 272 • 67**
157.0 • 32.0 0.6 • 0.1 0.6 4- 0.1 383 • 44"*
145.5 • 13.0 1.1 • 0.1 1.1 • 0.3 785 4- 197*
* p
