Neuroendocrine dysfunction following mild TBI: When to screen for it

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Applied Evidence

Neuroendocrine dysfunction following mild TBI: When to screen for it

J Fam Pract. 2014 January;63(1):11-16

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References

1. Injury prevention & control: Traumatic brain injury national TBI estimates. Centers for Disease Control and Prevention Web site. Available at: http://www.cdc.gov/traumaticbraininjury/statistics.html. Accessed August 12, 2013.

2. Armed Forces Surveillance Center. DoD Worldwide Numbers for TBI. Defense and Veterans Brain Injury Centers Web site. Available at: www.dvbic.org/dod-worldwide-Numbers-tbi. Accessed August 12, 2013.

3. Department of Veterans Affairs, Department of Defense. VA/DoD clinical practice guideline for management of concussion/mild traumatic brain injury (mTBI). Available at: http://www.healthquality.va.gov/management_of_concussion_mtbi.asp. Published April 2009. Accessed August 12, 2013.

4. Ghigo E, Masel B, Aimaretti G, et al. Consensus guidelines on screening for hypopituitarism following traumatic brain injury. Brain Inj. 2005;19:711-724.

5. Krahulik D, Zapletalova J, Frysak Z, et al. Dysfunction of hypothalamic-hyperphysical axis after traumatic brain injury in adults. J Neurosurg. 2010;113:581-584.

6. Behan LA, Phillips J, Thompson CJ, et al. Neuroendocrine disorders after traumatic brain injury. J Neurol Neurosurg Psychiatry. 2008;79:753-759.

7. Tanriverdi F, Unluhizarci K, Kelestimur F. Pituitary function in subjects with mild traumatic brain injury: a review of literature and proposal of a screening strategy. Pituitary. 2010;13:146-153.

8. Bondanelli M, Ambrosio MR, Zatelli MC, et al. Hypopituitarism after traumatic brain injury. Eur J Endocrinol. 2005;152:679-691.

9. Wilkinson CW, Pagulayan KF, Petrie EC, et al. High prevalence of chronic pituitary and target-hormone abnormalities after blast related mild traumatic brain injury. Front Neurol. 2012;3:11.

10. Bondanelli M, Ambrosio MR, Cavazzini L, et al. Anterior pituitary function may predict functional and cognitive outcome in patients with traumatic brain injury undergoing rehabilitation. J Neurotrauma. 2007;24:1687-1697.

11. Benvenga S, Campenmi A, Ruggeri R, et al. Hypopituitarism secondary to head trauma. J Clin Endocrinol Metab. 2000;85:1353-1361.

12. Schneider H, Kreitschman-Andermahr I, Ghigo E, et al. Hypothalamopituitary dysfunction following traumatic brain injury and aneurysmal subarachnoid hemorrhage: a systematic review. JAMA. 2007;298:1429-1438.

13. Amar AP, Weiss MH. Pituitary anatomy and physiology. Neurosurg Clin N Am. 2003;14:11-23.

14. Tanriverdi F, Unluhizarci K, Kocyigit I, et al. Brief communication: Pituitary volume and function in competing and retired male boxers. Ann Intern Med. 2008;148:827-831.

15. Bondanelli M, De Marinis L, Ambrosio MR, et al. Occurrence of pituitary dysfunction following traumatic brain injury. J Neurotrauma. 2004;21:685-696.

16. Klose M, Watt T, Brennum J, et al. Posttraumatic hypopituitarism is associated with an unfavorable body composition and lipid profile, and decreased quality of life in 12 months after injury. J Clin Endocrinol Metab. 2007;92:3861-3868.

17. Aimeretti G, Ambrosio MR, Di Somma C, et al. Residual pituitary function after brain injury-induced hypopituitaryism: a prospective 12-month study. J Clin Endocrinol Metab. 2005;90:6085-6092.

18. Agha A, Phillips J, Thompson CJ. Hypopituitarism following traumatic brain injury. Br J Neurosurg. 2007;21:210-216.

19. Cohan P, Wang C, McArthur DL, et al. Acute secondary adrenal insufficiency after traumatic brain injury: a prospective study. Crit Care Med. 2005;33:2358-2366.

20. Rothman MS, Arciniegas DS, Filley CM, et al. The neuroendocrine effects of traumatic brain injury. J Neuropsychiatry Clin Neurosci. 2007;19:363-372.

21. Defense Centers of Excellence. Neuroendocrine screening post mild TBI clinical recommendation. Available at: http://www.dcoe.mil/Content/Navigation/Documents/DCoE_TBI_NED_Reference_Card.pdf. Published February 2012. Accessed August 12, 2013.

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Due to the range of symptoms related to the combinations of possible hormonal derangements, NED can be an elusive diagnosis and may have a deleterious effect on individuals who sustain TBI.¹² For example, an undiagnosed GH deficiency—which can result in increased abdominal fat mass and decreased lean muscle mass as well as impaired cardiac function, dyslipidemia, and insulin resistance—makes it more difficult for an affected individual either to recover from additional injuries or to maintain fitness. Considering NED may avoid a delay in diagnosis and improve prognosis.^7,8,20

Findings leading to recommendations on diagnosis

Primary care providers, military and civilian alike, can benefit from the findings andSymptoms of NED include fatigue, insomnia, impaired cognition, memory loss, difficulty concentrating, and emotional and mood disturbances. recommendations of an expert panel assembled by the Defense Centers of Excellence (DCoE) for Psychological Health and Traumatic Brain Injury to address NED in mTBI. The panel that convened in December 2010 included experts representing the military services, the Department of Veterans Affairs, DCoE, and civilian sectors. Based on the group’s recommendations combined with literature review findings, the DCoE developed a clinical recommendation to encourage primary care providers to consider screening for NED in patients with persistent symptoms following mTBI.²¹ Key findings and issues identified by the group included the following:
• The most frequent mechanism of injury in the military deployed population is blast-induced TBI. Such injury could occur in the civilian population at construction blast sites or in factories producing or using highly flammable substances.
• The prevalence of any anterior pituitary hormone deficiency is as high as 30% to hormone deficiency is as high as 30% to 80% at 24 to 36 months post injury.
• The prevalence of posterior pituitary hormone deficiency is as high as 4% to 7% at 12 months post injury.
• The anterior pituitary hormones most frequently affected in survivors of TBI are ACTH, gonadotropin, prolactin, and GH.
• In 2004 Agha et al,²² reported >28% of survivors of TBI had at least one anterior pituitary hormone deficiency.
• According to research by Agha et al²³ in 2005, >20% of survivors of TBI developed DI; those who developed DI, either acutely or permanently, were more likely to have sustained a severe TBI.
• The development of pituitary dysfunction is independent of the severity of TBI.
• In 2005, civilian guidelines⁴ recommended screening for pituitary dysfunction in all patients who sustained a moderate to severe TBI.
• In 2010, civilian guidelines⁷ recommended screening for pituitary dysfunction in patients who sustained a mild TBI.

When to screen for NED after TBI

Given the complexities described—including the similarity of NED to other post-mTBI medical diagnoses and such concomitant disorders as a sleep disorder, memory difficulties, depression, PTSD, and PCS24—consider NED in the primary care setting following confirmed TBI of any severity level when symptoms suggestive of NED persist for >3 months following injury or appear up to 36 months later.^7,8,12,20

Screen for NED with confirmed TBI of any severity level if suggestive symptoms persist for >3 months or appear up to 36 months following injury.Order a lab evaluation of blood levels for cortisol (drawn at 8 am), LH, FSH, PRL, insulin-like growth factor-1, TSH, free thyroxine-4, and testosterone for men (8 am) and estradiol for women (8 am). With frankly abnormal lab results or with borderline results and strong clinical suspicion for NED, refer for further endocrinology workup (FIGURE).²¹ Earlier diagnosis of NED results in more rapid improvement of symptoms and an improved prognosis.^7,8,20 Postinjury screening for NED should be one component of a thorough clinical evaluation by a qualified provider, and not used in isolation for clinical decision making. NED screening should not be routinely ordered during the early stages of mTBI, defined as <3 months postinjury.

Provider awareness and willingness to include NED screening in a timely manner, and to refer to specialty services as indicated for symptoms that may be sleep related or psychiatric in nature, may increase the opportunities for early treatment, better rehabilitation outcomes, and better overall quality of life.

Looking ahead

While the DCoE expert group made recommendations on screening for NED in the military combat population, they also acknowledged that NED diagnosis and treatment would benefit from additional areas of research:
• the effect of GH replacement (for GH-deficient patients or as prophylaxis for all TBI patients) on rehabilitation response and quality of life
• the role of multiple TBIs on long-term cognition and possible premature aging
• the role of NED over time
• biomarkers for diagnosis
• factors affecting resiliency
• resiliency in the context of increased or decreased susceptibility to the development of an acute clinical syndrome, as well as susceptibility in developing the spectrum of consequences of TBI.