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Research Letters |

Successful Treatment of Adult Cerebral Salt Wasting With Fludrocortisone FREE

Peter Lee, MBBS(Hons); Graham R. D. Jones, PhD; Jacqueline R. Center, MBBS, FRACP, PhD
Arch Intern Med. 2008;168(3):325-326. doi:10.1001/archinternmed.2007.126.
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Hyponatremia following cerebral trauma has commonly been attributed to the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). Cerebral salt wasting (CSW) can lead to a similar clinical picture, for which treatment is not well defined.

Report of a Case. A 75-year-old man presented with a 3-week history of worsening ataxia following blunt head trauma in a motor vehicle crash 1 month earlier. His history included uncomplicated type 2 diabetes mellitus and hypertension, managed with rosiglitazone, 4 mg/d, and ramipril, 2.5 mg/d. The patient was confused and had marked truncal ataxia. Central venous pressure was low at 3 mm Hg, indicating volume depletion. Euglycemia and normotension were maintained following the discontinuation of both rosiglitazone and ramipril therapies.

A computed tomographic scan of the brain demonstrated acute and chronic bilateral frontoparietal subdural hematomas measuring up to 22 mm in the maximum dimension, with shift of the septum pellucidum to the right by 5 mm and subfalcine herniation. Findings from serum biochemical analysis demonstrated a serum sodium level of 123 mEq/L (137-146 mEq/L) (milliequivalents per liter to millimoles per liter is a 1-to-1 conversion); an osmolality of 259 mOsm/kg (275-295 mOsm/kg) (milliosmoles per kilogram to millimoles per kilogram is a 1-to-1 conversion), a uric acid level of 0.34 mg/dL (4.2-8.4 mg/dL) (to convert to micromoles per liter, multiply by 59.485), a urinary sodium level of 236 mEq/L; and a urinary osmolality of 825 mOsm/kg. Hypothyroidism, hypoadrenalism, and liver and renal failure were excluded from serum biochemical analysis. Findings from serum biochemical analysis performed 1 month prior immediately following the motor vehicle crash were normal.

Bilateral burr holes were made for drainage, with subsequent reduction in size of bilateral hematomas. Hyponatremia was corrected with 3% hypertonic saline. Withdrawal of hypertonic saline 3 days later led to a decrease in serum sodium level to 120 mEq/L (Figure). Hypertonic saline was reintroduced to maintain a serum sodium level above 125 mEq/L. A repeated attempt to withdraw hypertonic saline 3 days later again led to a fall in serum sodium level with persistent inappropriate natriuresis (Figure). N-terminal pro-brain natriuretic peptide level was not elevated. Plasma renin activity and aldosterone concentration measured on day 6 were undetectable. Treatment with fludrocortisone was commenced initially at 0.2 mg/d and later reduced to 0.1 mg/d, and a rapid reduction in natriuresis and restoration of serum sodium level to the normal range was observed (Figure).

Place holder to copy figure label and caption
Figure.

Changes in serum and urinary sodium concentration with treatment. For serum sodium, milliequivalents per liter to millimoles per liter and, for pro-brain natriuretic peptide (pro-BNP), picograms per milliliter to nanograms per liter are 1-to-1 conversions.

Graphic Jump Location

Comment. Both CSW and SIADH are associated with hyponatremia, hypouricemia, and inappropriately high urinary sodium concentration and osmolality. The only distinguishing features are signs of volume depletion. It has been postulated that CSW is a centrally mediated process, possibly via secretion of natruretic peptides1 or disrupted sympathetic neural input to the proximal tubules.2 Serum N-terminal pro-brain natriuretic peptide level was not elevated in our case.

Scattered case reports in the pediatric population demonstrated suppressed plasma renin activity and plasma aldosterone concentration in CSW, while plasma aldosterone concentration usually remained normal or high in SIADH,3,4 although this is not a universal finding. While hyporeninemic hypoaldosteronism can be a manifestation of renal tubulopathy in type 2 diabetes, prior normal findings from serum biochemical analysis excluded it as a preexisting contributing complication in our patient.

Fludrocortisone has been used to prevent ischemia in patients with subarachnoid hemorrhage,5 but its use in other cerebral pathologic conditions is poorly studied.3,4,6 Hyponatremia not responding to fluid restriction should raise the concern of undiagnosed CSW, which may be supported by excessive natriuresis and suppressed plasma renin activity and plasma aldosterone concentration. The lack of sustained response to hypertonic saline led to our empirical trial of fludrocortisone, which was later supported by the results of suppressed plasma renin activity and plasma aldosterone concentration. Early administration of fludrocortisone may alleviate the need of hypertonic saline infusion and shorten hospital stay.

In conclusion, we describe the biochemical changes in a case of CSW and its successful response to fludrocortisone therapy. Although the mechanism of inappropriate hyporeninemic hypoaldosteronism in CSW remains uncertain, and it may not be universal in all cases of CSW, the current case indicates that fludrocortisone therapy may be of benefit in selected adult patients with CSW and refractory hyponatremia.

ARTICLE INFORMATION

Correspondence: Dr Lee, Department of Endocrinology, St Vincent's Hospital, 390 Victoria St, Darlinghurst NSW 2010, Australia (pcylee@gmail.com).

Author Contributions:Study concept and design: Lee and Center. Acquisition of data: Lee and Jones. Analysis and interpretation of data: Lee, Jones, and Center. Drafting of the manuscript: Lee. Critical revision of the manuscript for important intellectual content: Lee, Jones, and Center. Administrative, technical, and material support: Lee and Jones. Study supervision: Center.

Financial Disclosure: None reported.

Berendes  EWalter  MCullen  P  et al.  Secretion of brain natriuretic peptide in patients with aneurysmal subarachnoid haemorrhage. Lancet 1997;349 (9047) 245- 249
PubMed Link to Article
Palmer  BF Hyponatremia in patients with central nervous system disease: SIADH versus CSW. Trends Endocrinol Metab 2003;14 (4) 182- 187
PubMed Link to Article
Kappy  MSGanong  CA Cerebral salt wasting in children: the role of atrial natriuretic hormone. Adv Pediatr 1996;43(4)271- 308
PubMed
Taplin  CECowell  CTSilink  MAmbler  GR Fludrocortisone therapy in cerebral salt wasting. Pediatrics 2006;118 (6) e1904- e1908
PubMed Link to Article
Hasan  DLindsay  KWWijdicks  EF  et al.  Effect of fludrocortisone acetate in patients with subarachnoid hemorrhage. Stroke 1989;20 (9) 1156- 1161
PubMed Link to Article
Ishikawa  SESaito  TKaneko  KOkada  KKuzuya  T Hyponatremia responsive to fludrocortisone acetate in elderly patients after head injury. Ann Intern Med 1987;106 (2) 187- 191
PubMed Link to Article

Figures

Place holder to copy figure label and caption
Figure.

Changes in serum and urinary sodium concentration with treatment. For serum sodium, milliequivalents per liter to millimoles per liter and, for pro-brain natriuretic peptide (pro-BNP), picograms per milliliter to nanograms per liter are 1-to-1 conversions.

Graphic Jump Location

Tables

References

Berendes  EWalter  MCullen  P  et al.  Secretion of brain natriuretic peptide in patients with aneurysmal subarachnoid haemorrhage. Lancet 1997;349 (9047) 245- 249
PubMed Link to Article
Palmer  BF Hyponatremia in patients with central nervous system disease: SIADH versus CSW. Trends Endocrinol Metab 2003;14 (4) 182- 187
PubMed Link to Article
Kappy  MSGanong  CA Cerebral salt wasting in children: the role of atrial natriuretic hormone. Adv Pediatr 1996;43(4)271- 308
PubMed
Taplin  CECowell  CTSilink  MAmbler  GR Fludrocortisone therapy in cerebral salt wasting. Pediatrics 2006;118 (6) e1904- e1908
PubMed Link to Article
Hasan  DLindsay  KWWijdicks  EF  et al.  Effect of fludrocortisone acetate in patients with subarachnoid hemorrhage. Stroke 1989;20 (9) 1156- 1161
PubMed Link to Article
Ishikawa  SESaito  TKaneko  KOkada  KKuzuya  T Hyponatremia responsive to fludrocortisone acetate in elderly patients after head injury. Ann Intern Med 1987;106 (2) 187- 191
PubMed Link to Article

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