Diabetes Insipidus Following TBI: Diagnosis and Management

Diabetes insipidus (DI) is a syndrome characterized by excretion of inappropriate amounts of dilute urine, which, if untreated, will lead to severe derangements in electrolyte and volume homeostasis. Among the several classes of this syndrome, the most common is central DI, which is characterized by a deficiency in the production of arginine vasopressin (AVP), otherwise known as antidiuretic hormone (ADH). AVP is produced in the supraoptic and paraventricular nuclei of the hypothalamus and stored in the posterior pituitary; its secretion is triggered by the hypothalamic osmoreceptors in response to elevated serum osmolality. Its site of action is the distal tubules and collecting ducts of the kidney, where it acts upon the V2 receptor to induce the translocation of aquaporin-2 water channels from storage in cytoplasmic vesicles to the apical membrane of the epithelial cells. These channels allow water to migrate according to its osmotic gradient, from nephron to bloodstream, thereby correcting an existing serum hyperosmolality and leaving a more concentrated urine in the process.

 

Central DI can be further classified as acquired, genetic, or idiopathic. Accounting for approximately 17 percent of all cases of acquired central DI is traumatic brain injury (TBI)¹.  TBI is a leading cause of morbidity and mortality in both pediatric and adult populations every year. According to CDC data collected from 2002 through 2006², annual emergency room visits for TBI in the United States tally 1.7 million, leading to 275,000 hospitalizations and 52,000 deaths. Diabetes insipidus secondary to post-TBI hypopituitarism has been recognized since 1921³. Studies conducted since then have found that central DI can be caused by damage at one or more of the sites involved in AVP production and secretion, including the hypothalamic osmoreceptors, the supraoptic or paraventricular nuclei, or the superior portion of the supraopticohypophyseal tract⁴. Interestingly, isolated damage below the level of the median eminence, including damage to the posterior pituitary, will lead only to transient DI, as AVP will still reach circulation by means of the portal capillaries of the median eminence⁵. Thus, depending upon the nature of the injury, DI can be temporary or permanent, and can range in degree from mild to severe. The overall prevalence of DI after TBI, taking into account both acute and chronic phases of injury, is reported in the literature to range from 1.7% - 26%⁴.

 

Certain studies have found that the development of DI seems to be directly correlated to the severity of the insult⁶, with independent risk factors including a Glasgow Coma Scale lower than or equal to 8, cerebral edema, a head Abbreviated Injury Score higher than 3, and penetrating mechanism of injury⁷. Others, however, have failed to demonstrate such a correlation^8,9. Interestingly, more cases of permanent DI have been reported after mild as opposed to severe TBI⁶. Regardless, DI in the TBI patient is associated with increased morbidity⁴, and in brain-dead patients, can endanger the viability of potential donor organs, largely as a result of organ hypoperfusion secondary to untreated or insufficiently treated hypovolemia¹⁰. Thus, all TBI patients, including those with mild injury who are expected to make full recovery, as well as those with non-survivable insults, should be closely monitored for the development of DI, and aggressively treated upon arrival at diagnosis.

 

Diabetes insipidus should be suspected in any TBI patient whose urine output is greater than 300 mL/hr for three consecutive hours. To establish whether the patient is undergoing a water or a solute diuresis, basic urine and serum studies should be sent (see below)⁴.

 

                                         Suggestive of solute diuresis:                      Suggestive of water diuresis:

Urine specific gravity                            1.009-1.035                                                     1.001-1.005

Urine osmolality                               250-320 mOsm/kg                                           50-150 mOsm/kg

Urine sodium                                       normal to high                                                   normal to low

Serum sodium                                      normal to low                                                    normal to high

Serum osmolality                            285-295 mOsm/kg                                                >295 mOsm/kg

 

Water diuresis in a TBI patient alone is highly suggestive of DI, although other diagnoses should be considered in the differential. These include chronic renal insufficiency, multiple myeloma, amyloidosis, sickle cell disease, the recovery phase of ATN, and perhaps most importantly, fluid overload, as the patient may have been administered large amounts of electrolyte-free fluid if recently operated upon. Although alternative diagnoses can generally be ruled out based upon a patient’s history, DI can be diagnosed with confidence if the patient’s serum sodium is greater than 150 mmol/L in the setting of polyuria >3L/day or >300 mL/hr for at least three hours⁴. Alternatively, an 8-hour water deprivation test can be performed, with a subsequent urine osmolality <600 mOsm/kg being sufficient for diagnosis⁴.

 

Treatment of central DI in the acute phase involves replacement of lost intravascular volume as well as AVP, along with close monitoring of serum osmolality and electrolytes. Below is an algorithmic approach to management, based largely upon a Vanderbilt University Medical Center Trauma and Surgical Critical Care Practice Management Guidelines protocol11, as well as recommendations from Chou et al., 2011⁴.

*D5W or ½ NS should be used for volume correction; no more than 50% of loss should be replaced over first 24 hours

*Serum sodium should not be allowed to fall by greater than 1 mEq/hr

 1.      Diabetes Insipidus. Library of the National Medical Society. 2008  http://www.medical-library.org/journals4a/diabetes_insipidus.htm

2.      Faul M, Xu L, Wald MM, Coronado VG. Traumatic brain injury in the United States: emergency department visits, hospitalizations, and deaths. Atlanta (GA): Centers for Disease Control and Prevention, National Center for Injury Prevention and Control; 2010.

3.      Rouvillois, H., L. Reverchon, et al. (1921). "L´esions traumatiques del’hypophyse dans les fractures de la base du crane." Bull Mem Soc Chirurg Paris 47: 685-689.
 
4.      Yi-Chun Chou, Tzu-Yuan Wang and Li-Wei Chou (2011). Diabetes Insipidus and Traumatic Brain Injury, Diabetes Insipidus, Prof. Kyuzi Kamoi (Ed.), ISBN: 978-953-307-367-5, InTech, Available from: http://www.intechopen.com/books/diabetes-insipidus/diabetes-insipidus-and-traumatic-brain-injury
 
5.      Rose, B., R. Narins, et al. (2001). "Clinical Physiology of Acid-Base and Electrolyte Disorders, 5th ed, ." 751-754.
 
6.      Tsagarakis, S., M. Tzanela, et al. (2005). "Diabetes insipidus, secondary hypoadrenalism and hypothyroidism after traumatic brain injury: clinical implications." Pituitary 8(3-4): 251-4.
 
7.      Hadjizacharia, P., E. O. Beale, et al. (2008). "Acute diabetes insipidus in severe head injury: a prospective study." J Am Coll Surg 207(4): 477-84.
 
8.      Agha, A., E. Thornton, et al. (2004). "Posterior pituitary dysfunction after traumatic brain injury." J Clin Endocrinol Metab 89(12): 5987-92.
 
9.      Lieberman, S. A., A. L. Oberoi, et al. (2001). "Prevalence of neuroendocrine dysfunction in patients recovering from traumatic brain injury." J Clin Endocrinol Metab 86(6):2752-6.
 
10.  Saner FH. Kavuk I. Lang H. Radtke A. Paul A. Broelsch CE. Organ protective management of the brain-dead donor. Eur J Med Res. 9(10):485-90, 2004 Oct .
 
11.  Vanderbilt University Medical Center Trauma and Surgical Critical Care Practice Management Guidelines, http://traumaburn.com/mdprotocolstyle.htm; http://traumaburn.com/Protocols/2007/2007DIABETESINSIPIDUSDxandMgtPMG.pdf

this post contributed by Dr. Hadyn Hollister