What are the Endocrine causes of hyponatremia following Traumatic brain injury ?

Original Case by Taylor et al

Review by Dr. Om J Lakhani (Endocrinologist)

A 44-year-old male with no substantial medical history was injured falling off his road bike at 25 mph and sustained a traumatic brain injury resulting in a marked expressive dysphasia. CT brain demonstrated a small left subdural haematoma, left temporal contusion and right petrous temporal bone fracture. He did not require surgical intervention. Forty eight hours after injury he developed a lower motor neurone facial weakness secondary to the temporal bone fracture, therefore dexamethasone was commenced.

Q Define traumatic brain injury ?

TBI is a non-degenerative, non-congenital insult to the brain from an external mechanical force causing temporary or permanent neurological dysfunction, which may result in impairment of cognitive, physical and psychosocial functions

Q What are the Endocrine problems associated with traumatic brain injury ?

  1. Post traumatic hypopituitarism (PTHP)
  2. Diabetes Insipidus
  3. Hyponatremia (SIADH , Cerebral salt wasting)

Q Which are the risk factors associated with Pituitary dysfunction after traumatic brain injury ?

  • Diffuse axonal injury
  • Fracture of skull base
  • Older age

Q Does the severity of GCS (Glasgow common scale) associated with pituitary dysfunction ?

  • Yes
  • Lower post resuscitation GCS is associated with more severe pituitary dysfunction

Q Which inflammatory mediator is related involvement leads to SIADH in TBI ?

  • IL6 increases release of Vasopressin
  • It leads to SIADH after TBI

Q Which type of forces damage the Hypothalamic pituitary unit ?

  • Shearing forces tend to cause damage to midline structure- more likely to be involved in Hypothalamic pituitary damage

Q What type of skull fracture can cause direct pituitary damage ?

  • Basal skull fractures

Q Which pituitary hormones increase and which reduce after an acute traumatic event ?

  • ACTH, GH, Prolactin – increase
  • FSH/LH and TSH- reduce

Q When does diabetes insipidus occur in Acute TBI ?

  • It generally manifests on day 5-10
  • It is often transient

Q In what period after brain injury does post traumatic hypopituitarism occur ?

  • Time period is variable from 1 months to 23 years
  • In 75% of patients it occurs within the first year
  • 35% cases within first 3 months

Q What type of damage predominantly leads to PTHP ?

  1. Vascular damage
  2. Shearing axonal injuries

Q Which part of the blood system of pituitary is most vulnerable to damage ?

  • The damage most predominantly occurs in the long hypophyseal portal system that goes through the sellar diaphragm
  • This part is most vulnerable to mechanical damage

Q Describe the percentage of various hormonal injuries following PTHP ?

  1. GHD – 30%
  2. Gonadotropin deficiency – 28%
  3. ACTH Deficiency – 18%
  4. Thyrotropin deficiency – 18%
  5. Diabetes insipidus- 2.7 %
  6. Hyperprolactinemia- 0-12%
  7. Hypoprolactinemia- also reported

Q When should pituitary evaluation be done after TBI ?

  • Generally done 3- 6 months after head injury

On Day 5 of admission his sodium level fell.

Q What are the causes of Hyponatremia following Traumatic brain injury ?

  1. SIADH
  2. Cerebral salt wasting
  3. Central Adrenal insufficiency

Q What are the Diagnostic criteria for SIADH ?

  1. Serum osmolality <280 mom/kg
  2. Urine osmolality >100 mom/kg
  3. Urinary sodium >30 meq/l
  4. Euvoluemic patient
  5. Adrenal insufficiency and hypothyroidism ruled out
  6. Low uric acid
  7. No acid base balance
  8. Normal potassium

Q Describe the management of SIADH ?

  • The management of SIADH deals mainly with management of Hyponatremia.
  • Before correction of hyponatremia you need to answer following questions :
    • How Rapidly did the hyponatremia develop ?
    • How severe is the hyponatremia ?
    • Is the patient symptomatic ?
  • In most cases of asymptomatic chronic , mild to moderate hyponatremia, free fluid restriction is mainstay of treatment.

Initially attributed to SIADH, his sodium continued to fall rapidly despite fluid restriction and slow sodium tablets. Baseline paired serum and urine osmolality were 265 and 595 respectively with urine sodium of 191 mmol/L. He was referred to endocrinology who suspected a diagnosis of CSW on the basis of failure of resolution with fluid restriction, low JVP and high urine output.


Q What are the essential features of Cerebral salt wasting ?


  • Low circulating volume
  • Low serum sodium
  • Sodium loss in urine

Q What are the theories for pathophysiology of this disorder ?

Two theories

  • Due to BNP increases urine sodium loss and suppresses renin (more likely theory)
  • Due to reduced central sympathetic outflow prevents activation for RAS in state of hypovoluemia loss of Sodium in urine

Q Which is more common SIADH or CSW ?

  • SIADH is more common

Q When is CSW generally seen after neurosurgical procedure ?

  • Generally seen 10 days after neurosurgical procedure

Q What are the CF of CSW  ?

  • Hyponatremia à cerebral edema à altered sensorium
  • Dehydration
  • Polyuria

Q What are the diagnostic criteria for CSW  ?

  • In patient with CNS disorder
  • Serum sodium <135
  • Urine osmolality >100
  • Urine sodium >40
  • Reduced serum uric acid
  • Clinical evidence of hypovolaemia

Q Which is the most important feature to distinguish SIADH and CSW  ?

  • It is the status of circulating volume – which is low in CSW

Q What are the essential points to differentiate Cerebral salt wasting from SIADH ?

  • CSW: With Infusion of fluids there is improvement in hyponatremia and reduction in urine osmolality
  • SIADH- Infusion of fluid à no improvement in hyponatremia and urine remains concentratedà this is because ADH is not suppressed

Urine output assessment was challenging to interpret initially due to extreme confusion, and agitation preventing catheterisation but his urine output was in excess of 3 L a day at this point despite a 1.5 L fluid restriction. During this time the patient recalls having excessive thirst and a craving for the salt tablets, which he later found unpalatable.

Despite hypertonic saline (1.8% saline) being commenced, his sodium continued to fall, with increased cerebral oedema and worsening confusion. This combination necessitated admission to intensive care with a sodium nadir of 116 mmol/L. A graph of his serum sodium, urine sodium and daily intravenous sodium is shown in Fig. 1.


Q Why is differentiating CSW and SIADH important from treatment point of view ?

  • Because treatment is opposite
  • SIADH – there is need for fluid restriction
  • CSW- there is need for fluid infusion and not restriction
  • Doing the opposite in both the condition can worsen each of the condition

Q What type of fluid is generally given in CSW ?

  • Generally isotonic fluid
  • This is not the case in SIADH where isotonic fluid will worsen the patient

Q Which Pharmacological agent is used in treatment of Cerebral Salt wasting ?

  • Fludrocortisone

Infusion of 5% saline (>950 mEq of sodium required in first 24 h in ITU) restored serum sodium to low normal levels within 72 h (sodium 134 mmol/L). During his intensive care admission he also required inotropic support which further highlights the extent of his volume depletion. Following the stabilisation of his sodium levels he was stepped back down to the neurosurgical high dependency unit. However, his urinary sodium remained persistently elevated peaking at 254 mmol/L, (urine osmolality 710 mmol/kg) serum sodium fell to 125 mmol/L despite hypertonic saline and he required substantial volume replacement (equivalent of more than 4 L/day of 1.8% saline). Urine output remained persistently high between 3 and 5 L a day over this time.

Fludrocortisone was therefore introduced at 75 µg bd and ultimately increased to 150 µg bd, which resulted in a substantial (threefold) fall in requirements for hypertonic saline that was still required for another 7 days. His sodium remained stable around 130 mmol/L on fludrocortisone alone and he was discharged home 25 days post injury. Fludrocortisone was continued for the next four months.

The dexamethasone initiated at 48 hours was continued for a 1-week course. As a baseline cortisol taken 24 h post the final dexamethasone was 94 nmol/L, he was maintained on hydrocortisone 10 mg bd which was continued until after discharge. A post discharge short synacthen test was normal and hydrocortisone was then stopped.

It took four months to wean him off the fludrocortisone without the occurrence of rebound hyponatraemia suggestive of on-going, albeit mild, CSW. Intriguingly, the attempt in the week after he developed peripheral oedema on fludrocortisone was successful and he has remained stable off fludrocortisone for three months.

Learning points

  1. Post-traumatic hypopituitarism, Diabetes Insipidus, SIADH and Cerebral salt wasting are important Endocrine disorders following traumatic brain injury
  2. Treatment of SIADH and Cerebral salt wasting is different, hence it is important to differentiate the two conditions in patients who present with hyponatremia following TBI
  3. Isotonic fluids with or without fludrocortisone is the treatment of choice in patients with CSW.



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