Hypopituitarism following Severe Traumatic Brain Injury

Abstract

Although hypopituitarism is a known complication of traumatic head injury, it may be under-recognized due to its subtle clinical manifestations. To address this issue, we determine the prevalence of neuroendocrine abnormalities in patients rehabilitating from severe traumatic brain injury (Glasgow Coma Scale ≤ 8). 76 patients (mean age 39 ± 14 yr; range 18 - 65; 53 males and 23 females; BMI 25.8 ± 4.2 kg/m²; mean ± SD) with a severe traumatic brain injury, an average of 22 ± 10 months before this study (median, 20 months), underwent a series of standard endocrine tests, including TSH, free T4, T4, T3, prolactin, testosterone (males), estradiol (females), cortisol, ACTH, GH, and IGF‐I. All subjects also underwent GH response to GHRH + arginine. Growth hormone deficiency (GHD) was defined as a GH response < 9 µg/L to GHRH + arginine and was confirmed by ITT (< 3 µg/L). Pituitary deficiency was shown in 24 % of the patients (18/76). 8 % (n = 6) had GHD (GH-peak range [GHRH + arginine]: 2.8 - 6.3 µg/L; GH-peak range [ITT]: 1.5 - 2.2 µg/L; IGF‐I range: 62 - 174 µg/L). 17 % (n = 13) had hypogonadism (total testosterone < 9.5 nmol/L and low gonadotropins in 12 males; low estradiol, and low gonadotropins in 1 female). Total testosterone levels did not correlate with BMI or age. 2 males with hypogonadism also showed a mild hyperprolactinemia (33 and 41 ng/ml). 3 % (n = 2) patients had partial ACTH-deficiency (cortisol-peak [ITT] 392 and 417 nmol/L) and 3 % (n = 2) had TSH-deficiency. In summary, we have found hypopituitarism in one-fourth of patients with predominantly secondary hypogonadism and GHD. These findings strongly suggest that patients who suffer head trauma must routinely include neuroendocrine evaluations.

Key words

Severe traumatic brain injury - hypopituitarism

References

• 1 Abs R. Update on the diagnosis of GH deficiency in adults.  Eur J Endocrinol. 2003;  148 (Suppl 2) S3-S8
• 2 Agha A, Rogers B, Mylotte D, Taleb F, Tormey W, Phillips J, Thompson C J. Neuroendocrine dysfunction in the acute phase of traumatic brain injury.  Clin Endocrinol (Oxf). 2004 c;  60 584-591
• 3 Agha A, Rogers B, Sherlock M, O'Kelly P, Tormey W, Phillips J, Thompson C J. Anterior pituitary dysfunction in survivors of traumatic brain injury.  J Clin Endocrinol Metab. 2004 a;  89 4929-4936
• 4 Agha A, Sherlock M, Phillips J, Tormey W, Thompson C J. The natural history of post-traumatic neurohypophysial dysfunction.  Eur J Endocrinol. 2005;  152 371-377
• 5 Agha A, Thornton E, O'Kelly P, Tormey W, Phillips J, Thompson C J. Posterior pituitary dysfunction after traumatic brain injury.  J Clin Endocrinol Metab. 2004 b;  89 5987-5992
• 6 Aimaretti G, Ambrosio M R, Benvenga S, Borretta G, De Marinis L, De Menis E, Di Somma C, Faustini-Fustini M, Grottoli S, Gasco V, Gasperi M, Logoluso F, Scaroni C, Giordano G, Ghigo E. Hypopituitarism and growth hormone deficiency (GHD) after traumatic brain injury (TBI).  Growth Horm IGF Res. 2004;  14 (Suppl A) S114-S117
• 7 Bengtsson B A, Brummer R J, Bosaeus I. Growth hormone and body composition.  Horm Res. 1990;  33 19-24
• 8 Benvenga S, Campenni A, Ruggeri R M, Trimarchi F. Clinical review 113: hypopituitarism secondary to head trauma.  J Clin Endocrinol Metab. 2000;  85 1353-1361
• 9 Benvenga S, Lo Giudice F, Campenni A, Longo M, Trimarchi F. Post-traumatic selective hypogonadotropic hypogonadism.  J Endocrinol Invest. 1997;  20 675-680
• 10 Bondanelli M, De Marinis L, Ambrosio M R, Monesi M, Valle D, Zatelli M C, Fusco A, Bianchi A, Farneti M, degli Uberti E C. Occurrence of pituitary dysfunction following traumatic brain injury.  J Neurotrauma. 2004;  21 685-696
• 11 Breed S T, Flanagan S R, Watson K R. 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
• 12 Clifton G L, Grossman R G, Makela M E, Miner M E, Handel S, Sadhu V. Neurological course and correlated computerized tomography findings after severe closed head injury.  J Neurosurg. 1980;  52 611-624
• 13 Coiro V, Volpi R, Cataldo S, Capretti L, Caffarri G, Pilla S, Chiodera P. Dopaminergic and cholinergic involvement in the inhibitory effect of dexamethasone on the TSH response to TRH.  J Investig Med. 2000;  48 133-136
• 14 Edwards O M, Clark J D. Post-traumatic hypopituitarism. Six cases and a review of the literature.  Medicine (Baltimore). 1986;  65 281-290
• 15 Goni M J, Monreal M, Goni F, Sopena M, Gil M J, Moncada E, Salvador J. 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
• 16 Growth Hormone Research Society . 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
• 17 Herrmann B L, Berg C, Vogel E, Nowak T, Renzing-Koehler K, Mann K, Saller B. 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
• 18 Jean-Bay E. The biobehavioral correlates of post-traumatic brain injury depression.  J Neurosci Nurs. 2000;  32 169-176
• 19 Johannsson G, Marin P, Lonn L, Ottosson M, Stenlof K, Bjorntorp P, Sjostrom L, Bengtsson B A. 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
• 20 Kelly D F, Gonzalo I T, 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
• 21 Lieberman S A, Oberoi A L, Gilkison C R, Masel B E, Urban R J. Prevalence of neuroendocrine dysfunction in patients recovering from traumatic brain injury.  J Clin Endocrinol Metab. 2001;  86 2752-2756
• 22 Marshall L F, Marshall S B, Klauber M R, Van Berkum Clark M, Eisenberg H, Jane J A, Luerssen T G, Marmarou A, Foulkes M A. The diagnosis of head injury requires a classification based on computed axial tomography.  J Neurotrauma. 1992;  9 (Suppl 1) S287-S292
• 23 Masel B E. Rehabilitation and hypopituitarism after traumatic brain injury.  Growth Horm IGF Res. 2004;  14 (Suppl A) S108-S113
• 24 Mazaux J M, Richer E. Rehabilitation after traumatic brain injury in adults.  Disabil Rehabil. 1998;  20 435-447
• 25 Muller E E. Neural control of somatotropic function.  Physiol Rev. 1987;  67 962-1053
• 26 Radetti G, Bernasconi S, Bozzola M, Volta C, Tonini G, Gentili L, Rigon F. 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
• 27 Rees P. Hypopituitarism after head injury.  Lancet. 2001;  358 1812
• 28 Richard I, Rome J, Lemene B, Louis F, Perrouin-Verbe B, Mathe J F. Post-traumatic endocrine deficits: analysis of a series of 93 severe traumatic brain injuries.  Ann Readapt Med Phys. 2001;  44 19-25
• 29 Seidell J C, Visscher T L. Body weight and weight change and their health implications for the elderly.  Eur J Clin Nutr. 2000;  54 (Suppl 3) S33-S39
• 30 Valenta L J, De Feo D R. Post-traumatic hypopituitarism due to a hypothalamic lesion.  Am J Med. 1980;  68 614-617
• 31 Webster J B, Bell K R. Primary adrenal insufficiency following traumatic brain injury: a case report and review of the literature.  Arch Phys Med Rehabil. 1997;  78 314-318