Skip to main content
SpringerLink
Log in

Growth hormone deficiency after mild combat-related traumatic brain injury

  • Published:
Pituitary Aims and scope Submit manuscript

Abstract

Objective

Traumatic brain injury (TBI) has been recognized as a cause of growth hormone deficiency (GHD) in civilians. However, comparable data are sparse in veterans who incurred TBI during combat. Our objective was to determine the prevalence of GHD in veterans with a history of combat-related TBI, and its association with cognitive and psychosocial dysfunction.

Design

Single center prospective study.

Patients

Twenty male veterans with mild TBI incurred during combat 8–72 months prior to enrollment.

Measurements

GHD was defined by a GH peak <3 μg/L during glucagon stimulation test. Differences in neuropsychological, emotional, and quality of life of the GHD Veterans were described using Cohen’s d. Large effect sizes were considered meaningful.

Results

Mean age was 33.7 years (SD 7.8) and all subjects had normal thyroid hormone and cortisol levels. Five (25 %) exhibited a subnormal response to glucagon. Sixteen participants (80 %) provided sufficient effort for valid neuropsychological assessment (12 GH-sufficient, 4 GHD). There were large effect size differences in self-monitoring during memory testing (d = 1.46) and inhibitory control (d = 0.92), with worse performances in the GHD group. While fatigue and post-traumatic stress disorder were comparable, the GHD group reported more depression (d = 0.80) and lower quality of life (d = 0.64).

Conclusions

Our study found a 25 % prevalence of GHD in veterans with mild TBI as shown by glucagon stimulation. The neuropsychological findings raise the possibility that GHD has adverse effects on executive abilities and mood. Further studies are needed to determine whether GH replacement is an effective treatment in these patients.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Hoge CW (2008) Re: Psychiatric diagnoses in historic and contemporary military cohorts: combat deployment and the healthy warrior effect. Am J Epidemiol 168(9):1095–1096 (author reply 1096–1098)

  2. Himanen L, Portin R, Tenovuo O, Taiminen T, Koponen S, Hiekkanen H, Helenius H (2009) Attention and depressive symptoms in chronic phase after traumatic brain injury. Brain Inj 23(3):220–227

    Article  PubMed  Google Scholar 

  3. Strandberg T (2009) Adults with acquired traumatic brain injury: a theoretical analysis from a social recognition perspective. Soc Work Health Care 48(2):169–191

    Article  PubMed  Google Scholar 

  4. Terrio H, Brenner LA, Ivins BJ, Cho JM, Helmick K, Schwab K, Scally K, Bretthauer R, Warden D (2009) Traumatic brain injury screening: preliminary findings in a US Army Brigade Combat Team. J Head Trauma Rehabil 24(1):14–23

    Article  PubMed  Google Scholar 

  5. Bavisetty S, McArthur DL, Dusick JR, Wang C, Cohan P, Boscardin WJ, Swerdloff R, Levin H, Chang DJ, Muizelaar JP et al. (2008) Chronic hypopituitarism after traumatic brain injury: risk assessment and relationship to outcome. Neurosurgery 62(5):1080–1093 (discussion 1093–1084)

  6. Kelly DF, McArthur DL, Levin H, Swimmer S, Dusick JR, Cohan P, Wang C, Swerdloff R (2006) Neurobehavioral and quality of life changes associated with growth hormone insufficiency after complicated mild, moderate, or severe traumatic brain injury. J Neurotrauma 23(6):928–942

    Article  PubMed  Google Scholar 

  7. Leon-Carrion J, Leal-Cerro A, Cabezas FM, Atutxa AM, Gomez SG, Cordero JM, Moreno AS, Ferrari MD, Dominguez-Morales MR (2007) Cognitive deterioration due to GH deficiency in patients with traumatic brain injury: a preliminary report. Brain Inj 21(8):871–875

    Article  CAS  PubMed  Google Scholar 

  8. Lieberman SA, Oberoi AL, Gilkison CR, Masel BE, Urban RJ (2001) Prevalence of neuroendocrine dysfunction in patients recovering from traumatic brain injury. J Clin Endocrinol Metab 86(6):2752–2756

    CAS  PubMed  Google Scholar 

  9. VA/DoD (2009) Clinical practice guideline for management of concussion/mild traumatic brain injury. J Rehabil Res Dev 46(6):CP1–68

  10. Gomez JM, Espadero RM, Escobar-Jimenez F, Hawkins F, Pico A, Herrera-Pombo JL, Vilardell E, Duran A, Mesa J, Faure E et al (2002) Growth hormone release after glucagon as a reliable test of growth hormone assessment in adults. Clin Endocrinol 56(3):329–334

    Article  CAS  Google Scholar 

  11. Koltowska-Haggstrom M, Hennessy S, Mattsson AF, Monson JP, Kind P (2005) Quality of life assessment of growth hormone deficiency in adults (QoL-AGHDA): comparison of normative reference data for the general population of England and Wales with results for adult hypopituitary patients with growth hormone deficiency. Horm Res 64(1):46–54

    Article  PubMed  Google Scholar 

  12. Cohen J (1992) A power primer. Psychol Bull 112(1):155–159

    Article  CAS  PubMed  Google Scholar 

  13. Agha A, Rogers B, Sherlock M, O’Kelly P, Tormey W, Phillips J, Thompson CJ (2004) Anterior pituitary dysfunction in survivors of traumatic brain injury. J Clin Endocrinol Metab 89(10):4929–4936

    Article  CAS  PubMed  Google Scholar 

  14. Aimaretti G, Ambrosio MR, Di Somma C, Gasperi M, Cannavo S, Scaroni C, Fusco A, Del Monte P, De Menis E, Faustini-Fustini M et al (2005) Residual pituitary function after brain injury-induced hypopituitarism: a prospective 12-month study. J Clin Endocrinol Metab 90(11):6085–6092

    Article  CAS  PubMed  Google Scholar 

  15. Herrmann BL, Rehder J, Kahlke S, Wiedemayer H, Doerfler A, Ischebeck W, Laumer R, Forsting M, Stolke D, Mann K (2006) Hypopituitarism following severe traumatic brain injury. Exp Clin Endocrinol Diabetes 114(6):316–321

    Article  CAS  PubMed  Google Scholar 

  16. Kelly DF, Chaloner C, Evans D, Mathews A, Cohan P, Wang C, Swerdloff R, Sim MS, Lee J, Wright MJ et al (2014) Prevalence of pituitary hormone dysfunction, metabolic syndrome, and impaired quality of life in retired professional football players: a prospective study. J Neurotrauma 31(13):1161–1171

    Article  PubMed  Google Scholar 

  17. Klose M, Juul A, Poulsgaard L, Kosteljanetz M, Brennum J, Feldt-Rasmussen U (2007) Prevalence and predictive factors of post-traumatic hypopituitarism. Clin Endocrinol 67(2):193–201

    Article  CAS  Google Scholar 

  18. Ulfarsson T, Arnar Gudnason G, Rosen T, Blomstrand C, Sunnerhagen KS, Lundgren-Nilsson A, Nilsson M (2013) Pituitary function and functional outcome in adults after severe traumatic brain injury: the long-term perspective. J Neurotrauma 30(4):271–280

  19. Klose M, Stochholm K, Janukonyte J, Lehman Christensen L, Frystyk J, Andersen M, Laurberg P, Christiansen JS, Feldt-Rasmussen U (2014) Prevalence of posttraumatic growth hormone deficiency is highly dependent on the diagnostic set-up: results from The Danish National Study on Posttraumatic Hypopituitarism. J Clin Endocrinol Metab 99(1):101–110

  20. Munoz A, Urban R (2013) Neuroendocrine consequences of traumatic brain injury. Curr Opin Endocrinol Diabetes Obes 20(4):354–358

    CAS  PubMed  Google Scholar 

  21. Bondanelli M, De Marinis L, Ambrosio MR, Monesi M, Valle D, Zatelli MC, Fusco A, Bianchi A, Farneti M (2004) degli Uberti EC: occurrence of pituitary dysfunction following traumatic brain injury. J Neurotrauma 21(6):685–696

    Article  PubMed  Google Scholar 

  22. Ghigo E, Masel B, Aimaretti G, Leon-Carrion J, Casanueva FF, Dominguez-Morales MR, Elovic E, Perrone K, Stalla G, Thompson C et al (2005) Consensus guidelines on screening for hypopituitarism following traumatic brain injury. Brain Inj 19(9):711–724

    Article  CAS  PubMed  Google Scholar 

  23. Ho KK (2007) Consensus guidelines for the diagnosis and treatment of adults with GH deficiency II: a statement of the GH Research Society in association with the European Society for Pediatric Endocrinology, Lawson Wilkins Society, European Society of Endocrinology, Japan Endocrine Society, and Endocrine Society of Australia. Eur J Endocrinol Eur Federation Endocr Soc 157(6):695–700

    Article  CAS  Google Scholar 

  24. Conceicao FL, Fisker S, Andersen M, Kaal A, Jorgensen JO, Vaisman M, Christiansen JS (2003) Evaluation of growth hormone stimulation tests in cured acromegalic patients. Growth Horm IGF Res 13(6):347–352

    Article  CAS  PubMed  Google Scholar 

  25. Yuen KC, Biller BM, Katznelson L, Rhoads SA, Gurel MH, Chu O, Corazzini V, Spiller K, Gordon MB, Salvatori R et al (2013) Clinical characteristics, timing of peak responses and safety aspects of two dosing regimens of the glucagon stimulation test in evaluating growth hormone and cortisol secretion in adults. Pituitary 16(2):220–230

    Article  CAS  PubMed  Google Scholar 

  26. Cernak I, Noble-Haeusslein LJ (2010) Traumatic brain injury: an overview of pathobiology with emphasis on military populations. J Cereb Blood Flow Metab 30(2):255–266

    Article  PubMed Central  PubMed  Google Scholar 

  27. Goldstein LE, Fisher AM, Tagge CA, Zhang XL, Velisek L, Sullivan JA, Upreti C, Kracht JM, Ericsson M, Wojnarowicz MW et al (2012) Chronic traumatic encephalopathy in blast-exposed military veterans and a blast neurotrauma mouse model. Sci Transl Med 4(134):134ra160

  28. Baxter D, Sharp DJ, Feeney C, Papadopoulou D, Ham TE, Jilka S, Hellyer PJ, Patel MC, Bennett AN, Mistlin A et al (2013) Pituitary dysfunction after blast traumatic brain injury: the UK BIOSAP study. Ann Neurol 74(4):527–536

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  29. Wilkinson CW, Pagulayan KF, Petrie EC, Mayer CL, Colasurdo EA, Shofer JB, Hart KL, Hoff D, Tarabochia MA, Peskind ER (2012) High prevalence of chronic pituitary and target-organ hormone abnormalities after blast-related mild traumatic brain injury. Front Neurol 3:11

    Article  PubMed Central  PubMed  Google Scholar 

  30. van Liempt S, Vermetten E, Lentjes E, Arends J, Westenberg H (2011) Decreased nocturnal growth hormone secretion and sleep fragmentation in combat-related posttraumatic stress disorder; potential predictors of impaired memory consolidation. Psychoneuroendocrinology 36(9):1361–1369

    Article  PubMed  Google Scholar 

  31. de Kloet CS, Vermetten E, Rademaker AR, Geuze E, Westenberg HG (2012) Neuroendocrine and immune responses to a cognitive stress challenge in veterans with and without PTSD. Eur J Psychotraumatol 3

  32. Reimunde P, Quintana A, Castanon B, Casteleiro N, Vilarnovo Z, Otero A, Devesa A, Otero-Cepeda XL, Devesa J (2011) Effects of growth hormone (GH) replacement and cognitive rehabilitation in patients with cognitive disorders after traumatic brain injury. Brain Inj 25(1):65–73

    Article  CAS  PubMed  Google Scholar 

  33. High WM Jr., Briones-Galang M, Clark JA, Gilkison C, Mossberg KA, Zgaljardic DJ, Masel BE, Urban RJ (2010) Effect of growth hormone replacement therapy on cognition after traumatic brain injury. J Neurotrauma 27(9):1565–1575

  34. Moreau OK, Cortet-Rudelli C, Yollin E, Merlen E, Daveluy W, Rousseaux M (2013) Growth hormone replacement therapy in patients with traumatic brain injury. J Neurotrauma 30(11):998–1006

    Article  PubMed  Google Scholar 

  35. Toogood A, Brabant G, Maiter D, Jonsson B, Feldt-Rasmussen U, Koltowska-Haggstrom M, Rasmussen AK, Buchfelder M, Saller B, Biller BM (2012) Similar clinical features among patients with severe adult growth hormone deficiency diagnosed with insulin tolerance test or arginine or glucagon stimulation tests. Endocr Pract Off J Am College Endocrinol Am Assoc Clin Endocrinol 18(3):325–334

    Google Scholar 

Download references

Acknowledgments

The study was funded by an Investigator Initiated Study grant from Novo Nordisk Inc. During this study, LSP was also supported by NIH awards DK066204 and UL1 RR025008, VA award HSR&D IIR 07-138, and a Cystic Fibrosis Foundation award PHILLI12A0. The funding sources played no role in the design and conduct of the study, analysis and interpretation of the data, and preparation of the manuscript. We thank Mari Hart, RN, MSN and Gordana Pajkovic, CRC (research staff). The contents of this manuscript do not represent the views of the Department of Veterans Affairs or the United States Government. Portions of this work were presented at the annual meeting of the Endocrine Society that took place in Houston, TX in June 2012.

Conflict of interest

The authors declare that there is no duality of interest associated with this manuscript.

Author information

Authors and Affiliations

  1. Atlanta Veteran Affairs Medical Center, The Emory Clinic, Emory University, 1365 B Clifton Rd, Atlanta, GA, 30322, USA

    Adriana G. Ioachimescu, Benjamin M. Hampstead, Anna Moore, Elizabeth Burgess & Lawrence S. Phillips

  2. Division of Endocrinology, Department of Medicine, Emory University, Atlanta, GA, USA

    Adriana G. Ioachimescu, Elizabeth Burgess & Lawrence S. Phillips

  3. Department of Neurosurgery, Emory University, Atlanta, GA, USA

    Adriana G. Ioachimescu

  4. Department of Rehabilitation Medicine, Emory University, Atlanta, GA, USA

    Benjamin M. Hampstead & Anna Moore

Authors
  1. Adriana G. Ioachimescu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Benjamin M. Hampstead
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Anna Moore
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Elizabeth Burgess
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Lawrence S. Phillips
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Adriana G. Ioachimescu.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ioachimescu, A.G., Hampstead, B.M., Moore, A. et al. Growth hormone deficiency after mild combat-related traumatic brain injury. Pituitary 18, 535–541 (2015). https://doi.org/10.1007/s11102-014-0606-5

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11102-014-0606-5

Keywords

Search

Navigation