Practice Essentials
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. [1, 2, 3] 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 (panhypopituitarism). Endocrine complications following TBI are treated by medical management and usually do not require surgical intervention.
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.
Signs and symptoms of post–head injury endocrine complications
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.
Primary adrenal insufficiency (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 include the following:
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Slowed pulse
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Hypothermia
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Orthostatic hypotension
Dermatologic findings include the following:
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Pale, soft, waxy skin
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Hyperpigmentation
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Decreased axillary and pubic hair
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Areolar depigmentation
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Decreased male facial hair
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Decreased sweating and sebum secretion
Workup in post–head injury endocrine complications
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 (panhypopituitarism).
Serial hormone assays may be used to determine the secretory pattern and to assess the hypothalamic regulation of pituitary function. All patients with TBI should undergo a baseline hormone evaluation at the time of hospital or intensive care unit (ICU) discharge, as well as at 3 months and 12 months post-TBI.
Laboratory/clinical screening studies of pituitary function include the following:
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Growth hormone (GH) - Height, weight, and bone age (< 18 y)
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Insulinlike growth factor-I (IGF-I) (0900)
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Thyrotropin - Free thyroxine (T4) and triiodothyronine (T3) by radioimmunoassay (0900)
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Corticotropin - Serum cortisol (0900 h)
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Gonadotropins - Serum estradiol or testosterone (0900)
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Prolactin - Serum prolactin
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Antidiuretic hormone (ADH) - Serum/urine sodium, serum/urine osmolalities, and urine output
Management of post–head injury endocrine complications
Endocrine complications following TBI are treated by medical management and usually do not require surgical intervention.
From the endocrinologist's perspective, patients with vital endocrinopathies, such as diabetes insipidus, 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. Patients who are 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.
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 central nervous system (CNS) dysfunction, including quadriplegia, pseudobulbar palsy, seizures, coma, and death. Hepatic failure, hypokalemia, and malnutrition are risk factors for osmotic demyelination.
Patients with less serious symptoms of hyponatremia and dilute urine concentrations of less than 200 mmol/L usually require fluid retention and close monitoring. More serious symptoms of hyponatremia include urine concentrations of greater than 200 mmol/L.
The most common treatment for syndrome of inappropriate antidiuretic hormone (SIADH) is fluid restriction to less than 800 mL/d to induce a negative water balance.
Related Medscape Drugs & Diseases topics:
Classification and Complications of Traumatic Brain Injury
Head Trauma [Pediatrics: Cardiac Disease and Critical Care Medicine]
Head Trauma [Trauma]
Post Head Injury Autonomic Complications
Traumatic Brain Injury (TBI) - Definition, Epidemiology, Pathophysiology
Pathophysiology
Autopsy studies in fatal traumatic brain injury (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. [4] Some variability is noted in studies. Anterior pituitary infarction has been seen to occur in 9-38% of patients; posterior pituitary hemorrhage, in 12-45% of cases; and traumatic lesions of the stalk, in 5-30% of patients.
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], [5] 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. [6, 7, 8, 9, 10, 11]
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). [12, 13, 14, 15, 16, 17, 18, 19] The most common endocrinopathies associated with hypopituitarism, in descending order, include hypogonadism, hypothyroidism, adrenal insufficiency, hyperprolactinemia, DI, and GH deficiency. [20] CSW and PAI are peripheral causes of hyponatremia after a TBI. SIADH, AH, and DI have central endocrine etiologies.
A study by Izzy et al indicated that endocrine complications can be associated with traumatic brain injuries (TBIs) of any severity. Patients with mild TBI and those with moderate to severe TBI both showed an increased risk for diabetes, with the hazard ratio (HR) for each group being 1.9. Diabetes risk was particularly high in persons aged 18-40 years, the HR being 4.6 in persons with mild TBI. Moreover, the risk for mortality was increased in patients with post-TBI adrenal insufficiency, the HR for those with moderate to severe TBI being 6.2. [21]
A study by Giuliano et al found that at 1-year follow-up, eight out of 23 patients (34.8%) with complicated mild TBI demonstrated GH deficiency, while in a second group, followed up at 5 years or longer postinjury, 12 out of 25 patients (48.0%) with complicated mild TBI showed GH deficiency. The study also found that the patients with GH deficiency, particularly those in the group followed up at 1 year, more frequently demonstrated visceral adiposity and an adverse metabolic profile than did patients who were not GH deficient. The investigators suggested that patients who have suffered complicated mild TBI be assessed for GH deficiency even several years postinjury. [22]
Epidemiology
Frequency
United States
In the United States, the annual incidence of traumatic brain injury (TBI) is 1.5-2 million people. [23] 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, [24, 25] as demonstrated by evidence that 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 incidence of traumatic brain injury (TBI) to be 200 individuals per 100,000 people, with an estimated 52,000 fatalities each year. 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, because these data are limited to hospitalized patients with TBI and to prehospital fatalities from TBI.
Race
No known statistical racial predisposition exists in relation to traumatic brain injury (TBI). Approximately 20% of TBI cases are related to violence, especially firearm violence. In general, young African-American males are exposed to violent acts more frequently than other populations are, which may be reflected in a somewhat higher-than-average incidence of TBI in this group.
Sex
The male-to-female ratio for the incidence of traumatic brain injury (TBI) is greater than 2:1. The incidence of neuroendocrine complications following TBI is directly proportional to this ratio.
Age
The populations at greatest risk for traumatic brain injury are young people aged 15-24 years and individuals older than 75 years. Children aged 5 years or younger also are at risk. [5]
A study by Ortiz et al, using data drawn from the Arizona Health Care Cost Containment System (AHCCCS), indicated that children who sustain a TBI have approximately three times the risk of being subsequently diagnosed with a central endocrinopathy than do members of the general population. [26]
A study by Dassa et al indicated that permanent pituitary dysfunction can result from severe childhood TBI, with GH deficiency and central precocious puberty capable of appearing a number of years post-TBI. [27]
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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.
Tables
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. |
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