AUTHOR AND EDITOR INFORMATION

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INTRODUCTION

Section 2 of 11  

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• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
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Background

The greatest challenge associated with endocrine complications in individuals with traumatic brain injury (TBI) is early recognition of these subtle problems. Endocrine complications can produce significant impact on the progress and outcome of TBI rehabilitation. Prompt diagnosis and treatment of endocrine complications following TBI facilitate the rehabilitation process of patients with TBI.

The release of pituitary hormones orchestrated by the neuropeptide signals from the hypothalamus provides a tight control of hormone-regulated homeostasis. The pituitary gland is protected well within the sella turcica of the sphenoid bone; however, the pituitary stalk, connected to the anterior pituitary and hypothalamus, is vulnerable to the effects of TBI, especially in patients with associated facial fractures, cranial nerve injuries, and dysautonomia.

Pathophysiology

Autopsy studies in fatal TBI cases demonstrate a fairly high prevalence of hypothalamic and pituitary abnormalities, including anterior lobe necrosis, posterior lobe hemorrhage, and traumatic lesions of the hypothalamic-pituitary stalk. Some variability is noted in studies. Anterior pituitary infarction occurred in 9-38% of patients, posterior pituitary hemorrhage occurred in 12-45% of cases, and traumatic lesions of the stalk occurred in 5-30%.

The traumatic rupture of the pituitary stalk results in anterior lobe infarction because of disruption of the portal blood supply between the hypothalamus and anterior pituitary. Ninety percent of the anterior lobe is nourished by the hypophyseal portal veins, which originate from and follow the pituitary stalk. An alternative explanation is that posttraumatic edema of the pituitary gland within the bony sella turcica compromises the portal blood supply, resulting in anterior lobe ischemia/necrosis. Both mechanisms may contribute to anterior lobe dysfunction following TBI.

Anterior hypothalamic trauma often is observed on postmortem studies and may be associated with pituitary hemorrhage or infarction related to TBI. Anterior pituitary hormones (eg, growth hormone [GH], thyrotropin, corticotropin, gonadotropins) are released by the neuropeptide-releasing hormones from the hypothalamus. The posterior pituitary hormones (eg, vasopressin, oxytocin) are produced by the hypothalamus and are carried by long axonal projections into the posterior pituitary; they are released later. The posterior lobe vascular supply is not affected by pituitary stalk trauma because it is supplied by the inferior hypophyseal arteries, which arise from the internal carotid artery below the level of the diaphragma sella. Infarction of the posterior lobe is, therefore, rare, and the mechanism of the development of diabetes insipidus (DI) is by denervation-losing neural integrity with the hypothalamus.

The most common endocrine complication after a TBI is syndrome of inappropriate antidiuretic hormone (SIADH). SIADH causes a dilutional hyponatremia secondary to inappropriate renal water conservation. Relatively less common post-TBI endocrinopathies include anterior hypopituitarism (AH), DI, cerebral salt wasting (CSW), and primary adrenal insufficiency (PAI). The most common endocrinopathies associated with hypopituitarism, in descending order, include hypogonadism, hypothyroidism, adrenal insufficiency, hyperprolactinemia, DI, and GH deficiency. Both CSW and PAI are peripheral causes of hyponatremia after a TBI. SIADH, AH, and DI have central endocrine etiologies.

Frequency

United States

In the United States, the annual incidence of TBI is 1.5-2 million people. Of that population, 70,000-90,000 persons sustain a chronic significant disabling condition. A retrospective study demonstrated that 4% of patients with TBI sustained an associated neuroendocrine disorder of the hypothalamic-pituitary axis. This condition is underdiagnosed, as 40-63% of fatal cases of TBI reveal postmortem pathologic findings of the hypothalamus/anterior pituitary.

Mortality/Morbidity

According to data from the Centers for Disease Control and Prevention, state surveillance projects report the annual rate for TBI to be 200 individuals per 100,000 people, with an estimated 52,000 fatalities annually. Estimates of prevalence suggest that a total of 2.5-6.5 million persons are living with the sequelae of TBI. These estimates may be inaccurate since these data are limited to hospitalized patients with TBI and prehospital fatalities from TBI.

Race

No known statistical racial predisposition exists in relation to TBI. Approximately 20% of TBI cases are related to violence, especially firearm violence. Young African-American males are exposed to violent acts with greater frequency than other populations, which may be reflected in a somewhat higher-than-average incidence of TBI.

Sex

The male-to-female ratio is greater than 2:1. The incidence of neuroendocrine complications following TBI is directly proportional to the male-to-female ratio.

Age

The populations at greatest risk for TBI are young people aged 15-24 years and individuals older than 75 years. Children aged 5 years and younger also are at risk.

CLINICAL

Section 3 of 11  

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History

Approximately 30-50% of patients who survive post TBI demonstrate endocrine complications. Most post-TBI endocrinopathies do not have typical specific history patterns.

• DI is an exception, as it does have a specific history. DI most commonly is associated with severe TBI and basilar skull fractures with cranial nerve involvement, craniofacial trauma, and postcardiopulmonary arrest. Delayed onset of DI is associated with a poor prognosis due to hypothalamic involvement causing permanent DI. Acute DI following a mild-to-moderate TBI indicates a posterior pituitary lesion with only a temporary antidiuretic hormone (ADH) deficiency.
• AH also has a specific history. AH usually is associated with moderate-to-severe TBI. With improvement of emergency care and neurosurgical care for these patients, there are more survivors demonstrating AH. AH may present weeks to months after the TBI, typically in the acute or chronic rehabilitation phase. Any patient with unexplained malaise or a setback with regard to functional status should be examined and tested for AH or the other post-TBI endocrinopathies. In summary, risk factors for AH include relatively serious TBI (Glasgow Coma Scale score <10), diffuse brain swelling, and hypotensive or hypoxic episode.
• SIADH is the most common TBI-associated neuroendocrinopathy causing hyponatremia. The incidence is reportedly as high as 33%.
• CSW is a less common cause of hyponatremia in the post-TBI population. These patients are dehydrated and lose weight.
• PAI is rare and presents with superimposed psychiatric symptoms of depression, confusion, and apathy. PAI is associated with fatigue, weakness, anorexia, and weight loss. These problems may present insidiously over a prolonged period. The acute presentation of PAI includes nausea, vomiting, and hypertension.

Physical

• Physical examination findings may be obscured by the altered cognitive status of patients who are post-TBI.
• Common post-TBI findings, such as lethargy, fatigue, and slowed mental processing time, also are associated with endocrine complications.
• In extreme cases, hyponatremia can cause seizures, confusion, and coma.
• PAI may present with acute psychiatric problems, such as psychosis, depression, apathy, or a schizophrenialike syndrome.
• General physical examination findings may include myxedematous, addisonian-appearing, or slowed mentation.
• Vital signs
• • Slowed pulse
  • Hypothermia
  • Orthostatic hypotension
• Dermatologic findings
• • Pale, soft, waxy skin
  • Hyperpigmentation
  • Decreased axillary and pubic hair
  • Areolar depigmentation
  • Decreased male facial hair
  • Decreased sweating and sebum secretion
• Neurologic findings
• • Mental status changes (eg, lethargy, confusion, slowed mentation)
  • Muscle weakness (may be proximal due to endocrine myopathy)
  • Hyporeflexia or areflexia
  • Hypotonia

Causes

The following paragraphs cover the most common post-TBI endocrine complications.

• Syndrome of inappropriate antidiuretic hormone
• • SIADH is the most common neuroendocrine complication following TBI, with a reported incidence as high as 33%. In the TBI rehabilitation setting, SIADH is the most common cause of hyponatremia.
  • Hyponatremia often is seen in the rehabilitation setting among survivors of either traumatic or nontraumatic brain injury (eg, hemorrhagic stroke, brain tumors, CNS infections). This problem is associated most often with SIADH. Approximately 30% of patients of neurosurgery demonstrate SIADH. SIADH also can be induced by medications such as carbamazepine, major tranquilizers, and antidepressants.
  • Hyponatremia can cause several problems, including cerebral ischemia (by volume depletion), lassitude, seizures, confusion, and coma.
  • SIADH causes renal water conservation with a secondary hyponatremia because of dilution. In patients who are not dehydrated or using diuretics, the laboratory diagnosis is based upon a urine osmolality greater than serum osmolality. The serum osmolality in patients with SIADH is less than 280 osm/kg, serum sodium less than 135 mEq/L, and urine sodium greater than 25 mEq/L.
  • The treatment in most cases is fluid restriction and, in unusual situations, IV hypertonic saline.
• Cerebral salt wasting
• • Although most cases of hyponatremia due to brain injury are caused by SIADH, a less common etiology is CSW syndrome. Peters et al first described CSW in 1950. CSW is caused by impaired renal tubular function, resulting in the inability of the kidneys to conserve salt. The etiology may be attributable to direct neural influence on renal tubular function. Salt wasting with volume depletion is the hallmark of this syndrome. Clinically, patients manifesting CSW are dehydrated, lose weight, have orthostatic hypotension, and demonstrate a negative fluid balance. In cases of CSW and SIADH, the laboratory values often are the same for serum/urine osmolalities and electrolytes; however, elevated serum blood urea nitrogen (BUN), serum potassium, and serum protein concentration also are supportive of the diagnosis of CSW. Additionally, serum uric acid is normal in those with CSW and low in those with SIADH.
  • Treatment of this type of hyponatremia with associated dehydration consists of replacement of both fluids and salt, which is best managed by IV normal saline or, in rare cases, IV hypertonic saline. Rehydration significantly reduces the risk of cerebral ischemia or cerebrovascular accident.
• Diabetes insipidus
• • DI is rare, with an estimated 1 case per 100,000 hospital admissions. Posttraumatic DI occurs in 2-16% of all cases. The most common etiologies of posttraumatic DI include severe closed head injury, frequently with basilar skull fractures; craniofacial trauma; thoracic injury; postcardiopulmonary arrest; and intraventricular hemorrhage in neonatal patients. DI frequently is associated with cranial nerve injuries. The usual onset is 5-10 days following trauma.
  • Characteristic features of DI include polyuria, low urine osmolality, high serum osmolality, normal serum glucose, and normal-to-elevated serum sodium. Urine output usually is greater than 90 mL/kg/d, with a specific gravity less than 1.010 and an osmolality of 50-200 mOsm.
• Anterior hypopituitarism
• • AH, or panhypopituitarism, is not as rare a complication following a closed head injury, usually following moderate-to-severe craniocerebral trauma. With improvements in emergency and acute neurosurgical care for patients with head injuries, more severely involved patients are surviving than ever before. This subset of patients is most susceptible to development of AH. The mechanism of development of AH in patients with severe head injuries is that the major blood supply to the anterior lobe of the pituitary gland is interrupted because of trauma to the unprotected stalk connecting the anterior pituitary to the median eminence of the hypothalamus.
  • Additionally, the hypothalamus secretes releasing and inhibitory hormones into the portal or stalk circulation for controlling release of the anterior pituitary hormones. Although the pituitary gland is protected well by the bony sella turcica, the pituitary stalk is not covered by dura mater and lies in the subarachnoid space. Severe craniocerebral injury may traumatize the stalk directly, or an anterior lobe infarction can occur due to impaired portal system circulation secondary to shock and cerebral edema.
  • The arterial blood supply of the posterior lobe of the pituitary comes directly from the inferior hypophyseal arteries branching from the internal carotid arteries. The posterior pituitary hormones are secreted by the hypothalamus.
  • Autopsy studies of 100 patients who died from craniocerebral trauma demonstrated pituitary lesions in approximately 60% of the group studied. Of those subjects with pituitary lesions, 59 demonstrated capsular hemorrhage, 42 demonstrated posterior lobe hemorrhages, and 22 revealed anterior lobe ischemic necrosis. Most patients (20 of 22) with anterior lobe ischemic necrosis died within the first 7 days following injury because of the severity of the craniocerebral trauma associated with shock and severe cerebral edema. Clinical anterior hypopituitarism is so rare in association with closed head injuries because most of these patients do not survive secondary to the severity of their injuries. This clinical syndrome presents itself only when two thirds of the anterior pituitary has been destroyed.
  • The syndrome of AH may manifest an insidious onset, weeks to months after the original closed head injury. The patient may become progressively lethargic or anorexic and may demonstrate hypothermia, bradycardia, or hypotension with hyponatremia. These symptoms result in a significant setback if they occur during the acute phase of rehabilitation of the patient who has sustained a closed head injury. Any unexplained onset of malaise and generally decreased vital signs with associated stagnation of rehabilitation progress in a patient following closed head injury should prompt the clinician to suspect the presence of AH.
  • The endocrine workup for AH includes serum hormonal assays (eg, cortisol (0900), testosterone, triiodothyronine (T3), thyroxine (T4), thyrotropin, follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estrogen (females). Insulinlike growth factor-I (IGF-I) is a screening assay for GH deficiency. Advance provocative GH testing may be necessary to confirm this diagnosis. Also perform a CBC count and serum electrolyte evaluation.
  • Treatment involves multiple hormonal replacement therapy and monitoring of serum levels along with the clinical response of the patient. The patient usually responds with improved vital signs, improved constitutional symptoms, and increased endurance for participation and progress in the rehabilitation program. The hormonal replacement therapy usually is required long term.
• Primary adrenal insufficiency
• • PAI usually presents with psychiatric symptoms of depression, confusion, and apathy.
  • Additional features include self-mutilation, paranoia, psychosis, and schizophrenic behaviors.
  • The mechanism of the psychiatric presentation is related to factors such as hypoglycemia, elevated exogenous endorphins, and axonal conduction changes.
  • Progressive deficiency of glucocorticoid and mineralocorticoid hormonal activity leads to progressive generalized weakness, hypotension, fatigue, anorexia/nausea, and hyperpigmentation. Diagnosis of PAI is difficult in the patients with TBI because these particular symptoms may be ascribed to the TBI itself.
  • The most common cause of PAI is autoimmune or idiopathic adrenalitis (in 65-84% of cases). The next most common etiology is adrenal parenchymal destruction secondary to tuberculosis, sarcoidosis, malignancy, acute sepsis (including systemic fungal infections), and acquired immunodeficiency syndrome (AIDS).
  • Acute adrenal crisis may result from bilateral adrenal hemorrhage from trauma, sepsis, surgery, or acute burns. If this problem is unrecognized, acute adrenal crisis may lead to acute shock and death. Adrenal failure usually is permanent in patients who survive the acute phase of the adrenal crisis.
  • Several rare hereditary syndromes are associated with PAI, such as familial glucocorticoid insufficiency, adrenoleukodystrophy, and adrenomyeloneuropathy. PAI results from deficiency of both glucocorticoid and mineralocorticoid hormonal activity, combined with a reduction of feedback to the anterior pituitary gland. The cortisol deficiency results in excessive secretion of corticotropin from the anterior pituitary gland and excessive secretion of corticotropin-releasing hormone from the hypothalamus.
  • The presentation of PAI may be acute, characterized by nausea, vomiting, and hypertension. Alternatively, this clinical entity may present insidiously with slow development of nonspecific symptoms over a prolonged period. The most common features include fatigue, weakness, anorexia, and weight loss. Additional findings include hyponatremia, hyperkalemia, skin hyperpigmentation, and gastric motility impairment, leading to complete gastric stasis.
  • Physiatrists must be aware of PAI, even though it is rare, because the presentation of adrenal insufficiency can be similar to the presentation of TBI. The symptoms limiting rehabilitation of patients following TBI can be attributed to the brain injury itself or to deconditioning secondary to prolonged bedrest. Treatment of this underlying problem by mineralocorticoid and glucocorticoid replacement therapy can result in a significant improvement of rehabilitation progress and outcome.
• Other post-TBI endocrine complications
• • Early puberty is defined as secondary sexual development in females younger than 8 years and in males younger than 9 years. Precocious puberty can occur in children with head injuries because of inappropriate secretion of gonadotropin-releasing hormone (GRH), resulting in subsequent release from the anterior pituitary of both LH and FSH. These hormones cause the early onset of puberty from the increasing levels of gonadal steroids and gametogenesis.
  • Hypogonadism also can occur following head trauma. In one study, approximately one third of the female patients who had head injuries (ie, 26 of 78) experienced temporary amenorrhea, usually not longer than 3 months. This phenomenon is secondary to hypothalamic dysfunction, resulting in absent or decreased secretion of GRH.
  • In male patients following head injury, both gonadotropin and testosterone levels are low immediately posttrauma. Later, in response to exogenous GRH, the anterior pituitary responds with release of high levels of LH and FSH, which is typical of hypothalamic dysfunction. At 3-6 months after the head injury, 5 of 21 male patients demonstrated persistently low serum testosterone levels. Depending upon the clinical situation, consider appropriate testosterone replacement therapy.
• Summary
• • Approximately 30-50% of patients with moderate-to-severe head injury demonstrate endocrine complications. These problems may not present in a classic textbook fashion in those who are severely impaired following TBI. The only clue to determining endocrine complications may be an unexplained failure to progress or a setback in the TBI rehabilitation program.
  • The most common endocrine abnormality is SIADH, followed by DI.
  • SIADH is also the most common cause of hyponatremia; however, other causes include fluid overload or extracellular fluid depletion from GI or renal loss of sodium.
  • Criteria for diagnosis of SIADH include low serum osmolality, hyponatremia, and inappropriately concentrated urine with urine sodium of greater than 25 mEq/L.
  • Hyponatremia that remains unresponsive to standard treatment for SIADH should point the clinician to other causes of hyponatremia.
  • Another clue to recognizing adrenal insufficiency is hyperkalemia associated with the hyponatremia secondary to a loss of mineralocorticoid activity at the kidney, causing urine sodium loss, impaired excretion of potassium, and hydrogen ion retention.
  • Azotemia also may be associated with adrenal insufficiency.

DIFFERENTIALS

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Other Problems to be Considered

Syndrome of inappropriate antidiuretic hormone
Diabetes insipidus
Cerebral salt wasting
Postneurosurgery
Tumor
SIADH can be induced by medications (eg, carbamazepine, major tranquilizers, antidepressants).
Phenytoin and chlorpromazine inhibit release of ADH.
Lithium may block the action of ADH peripherally at the kidney.

Diabetes insipidus
Hypothalamic (post-TBI) versus peripheral (nephrogenic) DI
Familial - X-linked recessive or autosomal dominant DI
Acquired DI - TBI, postneurosurgery, tumors, granulomatous, infections, vascular disorders, circulating antibodies to vasopressin, autoimmunity, and idiopathic

Cerebral salt wasting
Hypothalamic/nephrogenic DI
Syndrome of inappropriate antidiuretic hormone
Primary adrenal insufficiency

Anterior hypopituitarism
Postneurosurgery
Tumors
Vascular (postpartum)
Infections
Granulomatous disease
Idiopathic.

Primary adrenal insufficiency
Autoimmune (idiopathic adrenalitis)
Tuberculosis
Sarcoidosis
Malignancy
Acute sepsis (including systemic fungal infections)
Acquired immune deficiency syndrome

WORKUP

Section 5 of 11  

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Lab Studies

• The hallmark of endocrine disorders is an abnormal serum level of either a particular hormone or the entire spectrum of associated hormones, such as in anterior hypopituitarism or panhypopituitarism.
• • Serial hormonal assays may be used to determine the secretory pattern and to assess the hypothalamic regulation of pituitary function. All TBI patients should undergo baseline hormonal evaluations at the time of hospital or ICU discharge, at 3 months, and at 12 months post TBI. The endocrinologist's workup may include provocative testing. Confirmatory testing of GH deficiency is by assay of IGF-I. A low level of IGF-I in the absence of malnutrition is indicative of severe GH deficiency; however, aging or other factors (eg, liver disease, chronic renal disease, obesity, diabetes mellitus) can also cause a low level of IGF-I.
  • Careful clinical assessment of patients who have sustained TBI and who develop unexplained lethargy, generalized weakness, or anorexia should include an endocrine evaluation. Endocrine problems interfere with progress of rehabilitation and are detrimental to the rehabilitation outcome if not recognized and treated promptly.
• Laboratory/clinical screening studies of pituitary function
• • GH - Height, weight, and bone age ( <18 y)
  • IIGF-I (0900)
  • Thyrotropin - Free T4 and T3 by radioimmunoassay (0900)
  • Corticotropin - Serum cortisol (0900 h)
  • Gonadotropins - Serum estradiol or testosterone (0900)
  • Prolactin - Serum prolactin
  • ADH - Serum/urine sodium, serum/urine osmolalities, and urine output

Imaging Studies

• Cranial MRI provides the most specific cross-sectional views of the hypothalamus and pituitary gland. The diagnosis and treatment of endocrine complications following TBI are based upon both clinical findings and laboratory studies of overall pituitary hormonal regulation and of each individual endocrine gland.

TREATMENT

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Surgical Intervention

Endocrine complications following TBI are treated by medical management and usually do not require surgical intervention.

Consultations

Endocrinology subspecialty consultation may be needed following TBI in patients who demonstrate subtle findings of underlying endocrine abnormalities evidenced by a slowdown or complete halt in the progression of a TBI rehabilitation program. This group of patients includes those who have a growth delay (eg, pediatric patients) or unexplained constitutional symptoms of lethargy/poor appetite following TBI and young female patients with amenorrhea following TBI.

From the endocrinologist's perspective, patients with vital endocrinopathies such as DI, secondary adrenal failure, and secondary hypothyroidism should be promptly treated with hormone replacement therapy (HRT). Secondary hypogonadism and severe GH deficiency should be considered later, after replacement of other deficits and after retesting. Those severely involved in a persistent vegetative state would not likely benefit from HRT for secondary hypogonadism or GH deficiency. GH replacement therapy outcomes include increased muscle mass/exercise tolerance and improved quality of life/sense of wellness. Additionally, post-TBI patients functioning at a very low level who are also institutionalized should receive HRT only for vital endocrine hormones, including hydrocortisone, vasopressin, and T4. All patients with moderate-to-severe TBI should receive a baseline pituitary hormonal deficiency evaluation, especially if they were hospitalized for at least 1 day post TBI.

Other Treatment

Electrolyte therapy for patients with hyponatremia following TBI

• Hyponatremia is a decrease of serum sodium concentration of less than 136 mmol/L. Dilutional hyponatremia (ie, SIADH) secondary to water retention is the most common form.
• Hypotonic hyponatremia also results from water retention with essentially normal sodium stores. Most of the symptoms of hyponatremia are attributable to sequelae of CNS dysfunction, such as headaches, nausea, muscle cramping, lethargy, restlessness, disorientation, and depressed deep tendon reflexes.
• The slowly developing hyponatremia results in progressive cerebral edema and milder symptoms due to brain adaptation, with these patients experiencing minimal symptomatology. On the other hand, if the hyponatremia is characterized by a rapid onset, intracranial hypertension causes the more dangerous complications referred to above, especially in the more susceptible patient with brain injury. (See Image 1.)
• Aggressive treatment of hyponatremia, even by fluid restriction, can cause osmotic demyelination, a rare and serious complication. Brain shrinkage triggers pontine and extrapontine neuronal demyelination, causing disabling CNS dysfunction, including quadriplegia, pseudobulbar palsy, seizures, coma, and death. Hepatic failure, hypokalemia, and malnutrition are risk factors for osmotic demyelination.
• Management of hyponatremia
• • Patients with less serious symptoms of hyponatremia and dilute urine concentrations less than 200 mmol/L usually require fluid retention and close monitoring. More serious symptoms of hyponatremia include urine concentrations greater than 200 mmol/L.
  • The insensate fluid loss contributes to hyponatremia, assisted by both dermal and respiratory losses. Associated endocrinopathies (eg, hypothyroidism, adrenal failure) develop slowly. Hypothyroidism can masquerade as SIADH.
  • The correction of hyponatremia is no more than 8 mmol/L per day.
  • The initial correction is 1-2 mmol/L/h for several hours in patients with severe symptoms of hyponatremia (see table below). Indications to stop the rapid correction of hyponatremia include the need to control life-threatening complications, moderation of other symptoms, and serum sodium concentrations of 125-130 mmol/L.
  • The most common treatment for SIADH is fluid restriction to less than 800 mL/d to induce a negative water balance. If necessary, loop diuretics may be instituted by causing excretion of electrolyte-free water. If this treatment fails, use 600-1200 mg of demeclocycline to cause nephrogenic DI. Assessment of renal function is necessary as the condition is nephrotoxic, especially in patients with cirrhosis.

    Formulas for Use in Managing Hyponatremia and Characteristics of Infusates

    Formula*		Clinical Use
    Change in serum Na+ =	infusate Na+ — serum Na+ —————————— total body water +1	Estimate the effect of 1 L on any infusate serum Na+
    Change in serum Na+ =	(infusate Na+ + infusate K+ )—serum Na+ ———————————————— total body water +1	Estimate the effect of 1 L of any infusate containing Na+ and K+ on serum Na+
    Infusate	Infusate Na+	Extracellular—Fluid Distribution
    	mmol/L	%
    5% sodium chloride in water	855	100†
    3% sodium chloride in water	515	100†
    0.9% sodium chloride in water	154	100
    Ringer lactate solution	130	97
    0.45% sodium chloride in water	77	73
    0.2% sodium chloride in 5% dextrose in water	34	55
    5% dextrose in water	0	40

    *The number in formula 1 is a simplification of the expression (infusate Na^+—serum Na⁺) X 1 liter, with the value yielded by the equation in mmol/L. The estimated total body water (in liters) is calculated as a fraction of body weight. The fraction is 0.6 in children; 0.6 and 0.5 in nonelderly men and women, respectively; and 0.5 and 0.45 in elderly men and women, respectively.
    †In addition to its complete distribution in the extracellular compartment, this infusate induces osmotic removal of water from the intracellular compartment.

MEDICATION

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The goals of pharmacotherapy are to reduce morbidity and prevent complications.

Drug Category: Hormone replacements

As most endocrinopathies following TBI are due to failure at the anterior pituitary level, treatment involves hormonal replacement. Individual hormonal replacement also is indicated, depending upon the specific endocrine gland involved. Posterior pituitary failure also is treated by replacement therapy.

Drug Category: Antibiotics

Tetracycline antibiotics are used to treat Rocky Mountain spotted fever, typhus fever, psittacosis, relapsing fever, chancroid, and gram-negative microorganism infections (depending upon specific culture/sensitivity results).

Drug Category: Diuretics

Inhibits resorption of sodium and chloride in both the proximal and distal tubules and the loop of Henle.

FOLLOW-UP

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Further Inpatient Care

• The clinical response of the patient after treatment has been instituted is the most important factor in determining the necessity of additional treatment. Follow-up endocrine studies (ie, hormonal levels) are necessary at least weekly until homeostasis has been achieved. Serum electrolytes, BUN, and creatinine levels need to be assessed at least daily until normalized, then these levels should be monitored at routine intervals.

Further Outpatient Care

• The outpatient follow-up care of these patients is individualized, depending upon the endocrine problem under treatment and the patient's metabolic stability.

In/Out Patient Meds

• As stated previously, medication management consists primarily of hormone replacement until both clinical response and normal serum levels have been achieved. In most cases, the HRT continues on a long-term outpatient basis. Most inpatients with associated electrolyte disorders usually are stabilized by intravenous electrolyte therapy before hospital discharge, and no further medication management is necessary.

Deterrence

• No deterrence/prevention program exists for endocrine complications following TBI. Early recognition of these problems through a high index of suspicion, close monitoring of serum electrolyte balance, and prompt corrective treatment minimizes any negative impact these complications have on the rehabilitation outcome.

Complications

• The most significant complication is failure to recognize these treatable endocrine complications, ultimately prolonging the rehabilitation program and decreasing the patient's functional outcome following TBI.
• Osmotic demyelination of the CNS, caused by an excessively rapid correction of hyponatremia with IV hypertonic saline, is an unusual but serious and, sometimes, lethal complication of TBI.

Prognosis

• The prognosis for the patient with endocrine complications following TBI is good to excellent, assuming these sometimes-subtle problems are diagnosed and treated promptly. Failure to recognize and treat these problems negatively affects the rehabilitation progress and, eventually, the long-term functional outcome.

Patient Education

• Depending on the level of patient cognitive impairment, the patient and caregivers/guardians are advised to be aware of any changes exhibited by the patients, such as unexplained patient lethargy, decreased tolerance to activity, or cold intolerance. These particular problems require immediate notification of the attending physician. The patient should undergo physician reevaluation and, if necessary, an endocrine workup. Rapid corrective hormonal replacement therapy then can be initiated and monitored at a follow-up session with the treating physician.
• For excellent patient education resources, visit eMedicine's Endocrine System Center. Also, see eMedicine's patient education article Anatomy of the Endocrine System.

MISCELLANEOUS

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Medical/Legal Pitfalls

• The most significant medical/legal pitfall is delayed diagnosis or failure to diagnose neuroendocrine abnormalities following TBI, especially in a patient with severe cognitive impairment. Should this problem remain untreated, the rehabilitation progress and eventual outcome may be compromised significantly. Nonreversible loss of function would be costly both in terms of patient care needs and, more importantly, the patient's quality of life.

MULTIMEDIA

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Media file 1:  Effects of hyponatremia on the brain and adaptive responses. Within minutes after the development of hypotonicity, water gain causes swelling of the brain and a decrease in osmolality of the brain. Partial restoration of brain volume occurs within a few hours as a result of cellular loss of electrolytes (rapid adaptation). The normalization of brain volume is completed within several days through loss of organic osmolytes from brain cells (slow adaptation). Low osmolality in the brain persists despite the normalization of brain volume. Proper correction of hypotonicity reestablishes normal osmolality without risking damage to the brain. Overly aggressive correction of hyponatremia can lead to irreversible brain damage.
	View Full Size Image
Media type:  Image

REFERENCES

Section 11 of 11

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Article Last Updated: Mar 16, 2006