Cerebral salt wasting syndrome in a child with central diabetes insipidus following surgery for recurrent craniopharyngioma: A case report

Introduction

Craniopharyngiomas constitute 6%–9% of brain tumors in children. ¹ Surgical treatment in these cases can produce disorders related to water and sodium. ¹ Two of them are central diabetes insipidus (CDI) and cerebral salt wasting syndrome (CSWS). ¹ The combination of CDI and CSWS in children is associated with high mortality, ² and its management includes fluid therapy according to urinary losses, plasma sodium levels, and balance of fluids. ³ Fludrocortisone is useful in children with CSWS who do not respond to fluid management.^1,4–7 In the case of adult and pediatric patients with the combination of CDI and CSWS, the usefulness of cortisone acetate, ² hydrocortisone, ² and ibuprofen ⁸ has also been reported.

The reason for this case report is to describe the effectiveness of the use of fludrocortisone in a pediatric patient with the combination of CDI and CSWS and to review the literature.

Case

A 6 years and 3 months old male patient was diagnosed with craniopharyngioma. Six months later he had a partial resection surgery and a ventriculoperitoneal shunt system was placed. Hypopituitarism (diabetes insipidus, central hypothyroidism, and central adrenal insufficiency) occurred after this surgery, for which he received hormone replacement therapy with desmopressin 10 µg intranasally every 12 h, levothyroxine 50 µg PO every 24 h from Monday to Saturday and 75 µg on Sundays, and hydrocortisone 5 mg PO every 8 h. One month later (when the patient was 6 years and 10 months old), he presented to the emergency department with left amaurosis and sporadic frontal headache, was diagnosed with recurrent craniopharyngioma and underwent complete resection surgery.

Information about mannitol use during the second surgery could not be obtained. After this surgery, he received vasopressin at a dose of 0.06–1.54 mIU/kg/h instead of desmopressin and hydrocortisone at a stress dose of 15 mg IV every 6 h (50.8 mg/m²/day). On the day after surgery (second day), hydrocortisone was reduced to 7.5 mg IV every 8 h (19 mg/m²/day), and on the subsequent day, it was reduced again to 5 mg IV every 8 h (12.7 mg/m²/day). In the first 2 days after the procedure, the patient had episodes of mild polyuria and normal serum sodium. However, toward the end of the third day, he was showing several episodes of hyponatremia despite replacement with parenteral 3% NaCl (total sodium administration was equivalent to 10 mEq/kg/day).

On the fourth day, marked polyuria (6.91 mL/kg/day) progressively appeared. However, there were no signs of dehydration on the clinical exam, and vital functions through the day were: heart rate 63–64 beats/min, respiratory rate 24–25 breaths/min, blood pressure 100/58–102/52 mmHg, and body temperature 36.0°C–36.3°C. Due to this, blood studies were performed on the same day: glucose 83 mg/dL (reference range: 70–100), Na 127–130 mEq/L (reference range: 135–147 mEq/L), K 4.14 mEq/L (reference range: 3.4–4.7 mEq/L), Cl 97 mEq/L (reference range: 95–108 mEq/L), urea 6.4 mg/dL (reference range: 15–36 mEq/L), creatinine 0.31 mg/dL (reference range: 0.4–0.7 mEq/L), and calculated serum osmolarity 265.8 mOsm/kg. Simultaneous random urine showed: Na 206 mEq/L, K 15.23 mEq/L, Cl 202 mEq/L, urea 160.5 mg/dL, creatinine 10.94 mg/dL, and calculated urine osmolarity 471.2 mOsm/kg. Random urine normal values were not available since results should be interpreted in conjunction with serum results. These measurements were made when the patient was receiving an intravenous sodium amount equivalent to 10 mEq/kg/day. With these results, the diagnosis of CSWS combined with diabetes insipidus was proposed. On the fifth day, the administration of fludrocortisone was started at 50 µg PO every 24 h. On the sixth day, the patient improved his serum sodium levels and urinary flow.

On the eighth day, the use of desmopressin was resumed at 10 µg intranasally every 12 h, and on the ninth day, the route of administration of hydrocortisone was changed from intravenous to oral route. On the eleventh day, random urine sodium levels remained <120 mEq/L (Na 85 mEq/L), so it was decided to suspend the use of fludrocortisone. That same day, a decreased free T4 level was obtained in a hormonal profile (Table 1), so the dose of levothyroxine was then increased to 50 µg from Monday to Wednesday and 75 µg from Thursday to Sunday. On the twenty-second day of hospitalization, the patient was discharged and scheduled for outpatient follow-up. Serum and random urine sodium controls, as well as urinary flow and total daily fluid intake, are found in more detail in Figure 1.

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Table 1.

Post-surgery hormonal profile results.

Laboratory tests	Results	Units	Reference range
TSH	0.011	µIU/mL	0.57–4.13
Free T4	0.592	ng/dL	0.96–1.86
ACTH (8 am)	6.14	pg/mL	5.00–63.0
Cortisol (8 am)	<1.0	µg/dL	4.46–22.7
Prolactin	<0.5	ng/mL	<20
IGF-1	26.4	ng/mL	63–279

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Figure 1.

Urine output, serum sodium, urinary sodium, and fluid intake of the patient over the 2 weeks after the surgery.

Discussion

The surgical treatment and radiotherapy used in cases of craniopharyngioma can produce various endocrine alterations. ¹ The incidence of disorders related to water and sodium in children undergoing surgeries of the sellar and suprasellar area is 40%–72%. ¹ Hyponatremia occurring after pituitary surgery is common and may be due to inadequate fluid administration, hypocortisolism, hypothyroidism, Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH), overuse of desmopressin for the management of diabetes insipidus, and CSWS. ¹ CDI and CSWS are characterized by polyuria. ¹ However, SIADH is characterized by oliguria. ¹

CSWS was first described by Peters in 1950 in three patients who had hyponatremia, renal sodium loss, and dehydration without hypothalamic, pituitary, or adrenal gland problems but with Central Nervous System (CNS) disorders. ⁴ Nowadays it is known that in CSWS there is an osmotic diuresis caused by increased excretion of sodium in the urine, which leads to sodium depletion and signs of hypovolemia (rapid reduction in body weight, arterial hypotension, tachycardia, and dry mucous membranes). ⁸

It is known that CSWS can occur secondary to any CNS damage such as subarachnoid hemorrhages, brain surgeries, infections, brain trauma, brain tumors, hydrocephalus, and cerebrovascular events.^1,4 Cases of CSWS secondary to posterior reversible encephalopathy syndrome, ⁹ Kawasaki disease, ¹⁰ and Wernicke encephalopathy ¹¹ have also been reported. CSWS is thought to result from increased levels of natriuretic peptides, especially brain natriuretic peptides, or due to poor sympathetic outflow to kidneys. ¹ Thus, kidneys are unable to maintain sodium leading to reduction in extracellular volume (ECV). ¹² However, reduced ECV induces a higher stimulus for Antidiuretic Hormone (ADH) secretion than osmolality, so the patient remains hyponatremic despite the hypoosmolality. ¹²

The best-known diagnostic criteria for CSWS in children are those proposed by Jimenez et al., which include: high urinary sodium excretion (>120 mEq/L) and urine osmolarity (>300 mOsm/kg) despite the presence of polyuria (>3 mL/kg/h), hyponatremia (<130 mEq/L), and a negative 24-h fluid balance.^1,4,13 However, Jimenez et al. suggested that a negative fluid balance might not be necessary because the fluid can be replaced promptly, thus preventing the onset of volume depletion. ¹³ They also report a series of patients with a negative fluid balance but without clinically significant signs (e.g., orthostatic hypotension, tachycardia, sunken eyes, and dry mucous membranes). ¹³ On the fourth day of hospitalization, the patient in this report presented a urine sodium level >120 mEq/L (206 mEq/L) and urine osmolarity >300 mOsm/kg (471.2 mOsm/kg) despite having polyuria and serum sodium <130 mEq/L (127 mEq/L). Besides, he did not have signs of dehydration.

There are several differential diagnoses for hyponatremia after pituitary surgery in the patient of the present report. SIADH could be a possible explanation; however, it is not characterized by polyuria, ¹ and the patient of the present report had polyuria. Hypothyroidism and adrenal insufficiency can lead to hyponatremia because they are associated with SIADH ¹⁴ ; thus, they would not explain polyuria. Possible mannitol use during surgery could explain hyponatremia and polyuria. ¹⁵ Still, its effect does not last longer than 24 h, ¹⁵ and polyuria in the patient in the present report appeared on the fourth day after surgery. Excessive water intake could also be a differential diagnosis for hyponatremia ¹⁴ ; however, the day polyuria appeared in the patient of this report, the total fluid intake was only 89.06 mL/kg/day. Thus, together with the biochemical findings explained above, the patient was diagnosed with CSWS.

Low IGF-1 values were not considered a sufficient diagnostic criterion for Growth Hormone (GH) deficiency, but follow-up and further testing are required to confirm this possibility. Information about follow-up could not be obtained, which is a limitation of this report.

Treatment of CSWS initially consists of compensating for fluid deficiency with isotonic (0.9% NaCl) or hypertonic (3% NaCl) serum. ⁴ Oral sodium supplementation is also used. ⁵ Fludrocortisone 0.05–0.2 mg/day is useful in normalizing sodium levels in pediatric patients with CSWS who present hyponatremia despite receiving isotonic or hypertonic serum or receiving even large amounts of oral sodium supplements.^1,4–7 The child of the present report successfully responded to fludrocortisone treatment.

The combination of CDI and CSWS is a challenge for medical management as it is associated with high mortality. ² In one series it has been reported that of 16 pediatric patients, 13 died, and 3 survived in a vegetative state. ³ Treatment of CSWS in these cases also includes parenteral fluid replacement based on urinary losses, plasma sodium levels, and fluid balance. ³ About other pharmacological alternatives in these cases, a report that included adults and children described the usefulness of using cortisone acetate 25–50 mg every 12 h and hydrocortisone 100 mg every 12 h. ² Another report that included only pediatric patients described the effectiveness of ibuprofen in reducing polyuria and total urinary sodium excretion, without evidence of side effects on cardiovascular function or glomerular filtration rate. ⁸ Ibuprofen has an anti-natriuretic effect and regulates the Na-K-2Cl cotransporter in the loop of Henle. ⁸

This case highlights the importance of evaluating the criteria for diagnosis of CSWS in the context of each individual patient to avoid underdiagnosis. Treatment and evolution of pediatric patients with CSWS as one of this report can help build the foundation for subsequent systematic reviews or trials.

Conclusion

In pediatric patients with CDI following surgery for cranial tumors, an episode of CSWS may occur. The timely identification of CSWS in these cases is important to reduce the mortality associated with the combination of CDI and CSWS. Likewise, it should be remembered that to date useful pharmacological alternatives have been described in those cases that do not show an adequate response to management based solely on fluid and sodium replacement.