Prevalence of Anterior Pituitary Dysfunction in Patients following Traumatic Brain Injury in a German Multi-centre Screening Program

Abstract

Introduction: We determined the prevalence of anterior pituitary dysfunction in a multi-centre screening program across five German endocrine centres in patients rehabilitating from TBI (GCS<13).

Patients & Methods: 246 patients (39±14 yrs; 133 males, 12±8 months after TBI) underwent a series of baseline endocrine tests with central assessment of TSH, free T4, prolactin, LH, FSH, testosterone (m), estradiol (f), cortisol, GH, and IGF-I. If IGF-I was <−2 SDS dynamic testing was performed. GHD was defined according to BMI-dependent cut-off values for GH response to GHRH+arginine of <4.2, <8.0 and <11.5 ng/ml in obese, overweight and lean subjects, respectively, or <3 micro g/l in ITT. Hypocortisolism was suggested when basal cortisol was <200 nmol/l and confirmed by ITT (peak<500 nmol/l).

Results: In TBI patients some degree of impaired pituitary function was shown in 21% (n=52/246). Total, multiple and isolated deficits were present in 1%, 2% and 18%, respectively. 19% had an IGF-I of <−1 SDS, 9% of <−2 SDS. In 5% GHD was confirmed. 9% had hypogonadism. 4% had hypocortisolism and 1% of patients had confirmed ACTH-deficiency. 12% had TSH-deficiency.

Summary: In summary, in this large series carried out on an unselected group of TBI survivors we have found hypopituitarism in every fifth patient with predominantly secondary hypogonadism and hypothyreosis. Regarding somatotrope insufficiency IGF-I is decreased in 50% of GHD patients.

Conclusion: These findings strongly suggest that patients who suffer head trauma should routinely undergo endocrine evaluation.

Key words

hypopituitarism - insufficiencies - GH adrenal gland - hormones - cerebrovascular disease - neuropathy

References

• 1 Edwards OM, Clark JD. Post-traumatic hypopituitarism. Six cases and a review of the literature.  Medicine (Baltimore). 1986;  65 281-290
• 2 Benvenga S, Campenni A, Ruggeri RM. et al . Clinical review 113: Hypopituitarism secondary to head trauma.  J Clin Endocrinol Metab. 2000;  85 1353-1361
• 3 Breed ST, Flanagan SR, Watson KR. The relationship between age and the self-report of health symptoms in persons with traumatic brain injury.  Arch Phys Med Rehabil. 2004;  85 S61-S67
• 4 Masel BE. Rehabilitation and hypopituitarism after traumatic brain injury.  Growth Horm IGF Res. 2004;  14 ((Suppl A)) S108-S113
• 5 Agha A, Sherlock M, Phillips J. et al . The natural history of post-traumatic neurohypophysial dysfunction.  Eur J Endocrinol. 2005;  152 371-377
• 6 Rees P. Hypopituitarism after head injury.  Lancet. 2001;  358 1812
• 7 Valenta LJ, De Feo DR. Post-traumatic hypopituitarism due to a hypothalamic lesion.  Am J Med. 1980;  68 614-617
• 8 Benvenga S, Lo Giudice F, Campenni A. et al . Post-traumatic selective hypogonadotropic hypogonadism.  J Endocrinol Invest. 1997;  20 675-680
• 9 Lieberman SA, Oberoi AL, Gilkison CR. et al . Prevalence of neuroendocrine dysfunction in patients recovering from traumatic brain injury.  J Clin Endocrinol Metab. 2001;  86 2752-2756
• 10 Kelly DF, Gonzalo IT, Cohan P. et al . Hypopituitarism following traumatic brain injury and aneurysmal subarachnoid hemorrhage: a preliminary report.  J Neurosurg. 2000;  93 743-752
• 11 Richard I, Rome J, Lemene B. et al . Post-traumatic endocrine deficits: analysis of a series of 93 severe traumatic brain injuries.  Ann Readapt Med Phys. 2001;  44 19-25
• 12 Agha A, Rogers B, Sherlock M. et al . Anterior pituitary dysfunction in survivors of traumatic brain injury.  J Clin Endocrinol Metab. 2004;  89 4929-4936
• 13 Agha A, Thornton E, O’Kelly P. et al . Posterior pituitary dysfunction after traumatic brain injury.  J Clin Endocrinol Metab. 2004;  89 5987-5992
• 14 Bondanelli M, De Marinis L, Ambrosio MR. et al . Occurrence of pituitary dysfunction following traumatic brain injury.  J Neurotrauma. 2004;  21 685-696
• 15 Clifton GL, Grossman RG, Makela ME. et al . Neurological course and correlated computerized tomography findings after severe closed head injury.  J Neurosurg. 1980;  52 611-624
• 16 Marshall LF, Marshall SB, Klauber MR. et al . The diagnosis of head injury requires a classification based on computed axial tomography.  J Neurotrauma. 1992;  9 ((Suppl 1)) S287-S292
• 17 Consensus guidelines for the diagnosis and treatment of adults with growth hormone deficiency: summary statement of the Growth Hormone Research Society Workshop on Adult Growth Hormone Deficiency.  J Clin Endocrinol Metab. 1998;  83 379-381
• 18 Agha A, Rogers B, Mylotte D. et al . Neuroendocrine dysfunction in the acute phase of traumatic brain injury.  Clin Endocrinol (Oxf). 2004;  60 584-591
• 19 Aimaretti G, Ambrosio MR, Benvenga S. et al . Hypopituitarism and growth hormone deficiency (GHD) after traumatic brain injury (TBI).  Growth Horm IGF Res. 2004;  14 ((Suppl A)) S114-S117
• 20 Muller EE. Neural control of somatotropic function.  Physiol Rev. 1987;  67 962-1053
• 21 Goni MJ, Monreal M, Goni F. et al . Effects of cholinergic blockade on nocturnal thyrotropin and growth hormone (GH) secretion in type I diabetes mellitus: further evidence supporting somatostatin's involvement in GH suppression.  Metabolism. 1997;  46 1305-1311
• 22 Abs R. Update on the diagnosis of GH deficiency in adults.  Eur J Endocrinol. 2003;  148 ((Suppl 2)) S3-S8
• 23 Bengtsson BA, Brummer RJ, Bosaeus I. Growth hormone and body composition.  Horm Res. 1990;  33 19-24
• 24 Johannsson G, Marin P, Lonn L. et al . Growth hormone treatment of abdominally obese men reduces abdominal fat mass, improves glucose and lipoprotein metabolism, and reduces diastolic blood pressure.  J Clin Endocrinol Metab. 1997;  82 727-734
• 25 Herrmann BL, Berg C, Vogel E. et al . Effects of a combination of recombinant human growth hormone with metformin on glucose metabolism and body composition in patients with metabolic syndrome.  Horm Metab Res. 2004;  36 54-61
• 26 Seidell JC, Visscher TL. Body weight and weight change and their health implications for the elderly.  Eur J Clin Nutr. 2000;  54 ((Suppl 3)) S33-S39
• 27 Mazaux JM, Richer E. Rehabilitation after traumatic brain injury in adults.  Disabil Rehabil. 1998;  20 435-447
• 28 Jean-Bay E. The biobehavioral correlates of post-traumatic brain injury depression.  J Neurosci Nurs. 2000;  32 169-176
• 29 Webster JB, Bell KR. Primary adrenal insufficiency following traumatic brain injury: a case report and review of the literature.  Arch Phys Med Rehabil. 1997;  78 314-318
• 30 Radetti G, Bernasconi S, Bozzola M. et al . Pyridostigmine and metoclopramide do not restore the TSH response to TRH inhibited by L-thyroxine treatment in children with goiter.  J Endocrinol Invest. 2000;  23 744-747
• 31 Coiro V, Volpi R, Cataldo S. et al . Dopaminergic and cholinergic involvement in the inhibitory effect of dexamethasone on the TSH response to TRH.  J Investig Med. 2000;  48 133-136
• 32 Ghigo E. et al . Consensus guidelines on screening for hypopituitarism following traumatic brain injury.  Brain Inj. 2005;  19 ((9)) 711-724
• 33 Aimaretti G, Corneli G, Rovere S. et al . Insulin-like growth factor I levels and the diagnosis of adult growth hormone deficiency.  Horm Res. 2004;  62 ((Suppl 1)) 26-33 , Review.
• 34 Aimaretti G. Usefulness of IGF-I assay for the diagnosis of GH deficiency in adults.  J Endocrinol Invest. 1998;  21 ((8)) 506-511
• 35 Elmlinger MW, Kühnel W, Weber M. et al . Reference ranges for two automated chemiluminescent assays for serum insulin-like growth factor I (IGF-I) and IGF-binding protein 3 (IGFBP-3).  Clinical Chemistry and Laboratory Medicine. 2004;  42 ((6)) 654-664
• 36 Leal-Cerro A, Flores JM, Rincon M. et al . Prevalence of hypopituitarism and growth hormone deficiency in adults long-term after severe traumatic brain injury.  Clin Endocrinol (Oxf). 2005;  62 525-532
• 37 Weeke J, Hansen AP, Lundbaek K. The inhibition by somatostatin of the thyrotropin response to thyrotropin-releasing hormone in normal subjects.  Scand J Clin Lab Invest. 1974;  33 101-103
• 38 Teasdale G, Jennett B. Assessment of coma and impaired consciousness. A practical scale.  Lancet. 1974;  2 81-84
• 39 Herrmann BL. et al . Hypopituitarism following severe traumatic brain injury.  Exp Clin Endocrinol Diabetes. 2006;  114 ((6)) 316-321
• 40 Schneider HJ. et al . Hypothalamopituitary Dysfunftion following traumatic brain injury and aneurysmal subarachnoid hemorrhage.  JAMA. 2007;  298 ((12)) 1429-1438
• 41 Schneider HJ. et al . Prevalence of anterior pituitary insufficiency 3 and 12 months after traumatic brain injury.  Eur J Endocrinol. ;  154 ((2)) 259-265

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