A previously well 40-year-old Indonesian male presented with transient loss of consciousness following a fall-from-standing height while working as a sailor aboard a ship. He sustained traumatic brain injury (TBI) with subarachnoid and subdural hemorrhages and multiple facial fractures with raised serum creatine kinase 1014 U/L (NR <210U/L). His initial Glasgow coma scale score was 14. His injuries were managed conservatively. His initial serum sodium concentration was 140 mmol/L with normal renal panel and serum potassium 3.8 mmol/L. Full blood count and liver function test were unremarkable. Intravenous (IV) 0.9% sodium chloride (NaCl) infusion 2L/day was given for the first 3 days of admission in view of the significantly raised creatine kinase worrisome for early-onset rhabdomyolysis. However, serum sodium progressively fell to 125 mmol/L, and he was referred to the Endocrinology service on day 8 of admission (D8). His vital signs were stable with no hypotension or tachycardia (heart rate 81 beats/min, blood pressure 133/87 mmHg). He was clinically euvolemic with moist mucous membranes, clear lung fields on auscultation, and no peripheral oedema. Investigations revealed hypo-osmolar hyponatremia with markedly elevated urine sodium (144 mmol/L) and urine osmolality (1,045 mOsm/kg). His renal and thyroid function were normal and peak serum cortisol was normal (611 nmol/L) after a 1mcg ACTH-stimulation test. The clinical impression was SIADH from TBI. Intravenous sodium chloride drip was stopped, and he was restricted to 750 ml of fluid per day and given additional sodium chloride tablets (up to 272 mmol/day). Urine sodium concentration was persistently high even after saline infusion drip was discontinued (Figure 1).
Despite strict fluid restriction, his serum sodium continued to downtrend to 121 mmol/L (Figure 1). Urine sodium concentration (132-164 mmol/L) and urine osmolality (569-613 mOsm/kg) remained significantly raised. Differential diagnoses for the etiology of his refractory hyponatremia included (a) mild central hypocortisolism post-TBI, (b) SIADH, and (c) CSW. Although initial peak cortisol response to 1-mcg ACTH stimulation test exceeded 500 nmol/L with normal ACTH levels, this did not rule out acute central hypocortisolism precipitated by the recent TBI due to preserved adrenal tissue to external ACTH stimulation during acute pituitary injury. Thus, an insulin tolerance test was performed to assess the hypothalamic-pituitary-adrenal axis. He received 0.35 u/kg of regular insulin and achieved symptomatic hypoglycemia (plasma glucose 2.4 mmol/L) with a peak cortisol level of 502 nmol/L. The test was stopped prior to achieving the target of plasma glucose <2.2 mmol/L because the patient could not tolerate the hypoglycemia symptoms. In view of borderline cortisol response and the declining sodium concentrations, a trial of IV hydrocortisone replacement was started, but this did not result in an improvement of hyponatremia. The hyponatremia did not fulfill the criteria for CSW because he was clinically euvolemic with normal serum urea and creatinine and he did not have polyuria. Intravenous fluid administration worsened the hyponatremia. Fractional excretion of uric acid (FeUA) performed on D22 of admission was low at 9.29% (<11%) when patient was euvolemic was suggestive although not specific for SIADH. A repeat FeUA on D27 admission was still low at 7.98%.
Despite fluid restriction, high load of sodium chloride tablets and hydrocortisone, serum sodium fell further to 119 mmol/L with persistently raised urine sodium (110 mmol/L) and urine osmolality (844 mOsm/kg) and the patient reported worsening vertiginous giddiness associated with nausea. His renal function remained normal without potassium or magnesium derangement throughout the admission. In view of symptomatic hyponatremia, he was given 150 ml of IV 3% NaCl which transiently raised serum sodium level to 122 mmol/L. However, serum sodium level decreased to 119 mmol/L the next day (D22). Sodium chloride tablets were increased to 24 tablets daily and a decision was made for trial of oral fludrocortisone 0.05 mg (D22). This led to significant improvement in serum sodium to 127 mmol/L with a mild decrease in urine sodium from 155 to 139 mmol/L (D23) although the rise may not be attributed solely to fludrocortisone, in view of the relatively minor decrease in urine sodium concentration, and the subsequent rise in urine sodium concentration (200 mmol/L on D29). The usage of sodium chloride tablets and persistence of fluid restriction also contributed to the improvement in hyponatremia. Oral fludrocortisone was served every other day (0.05 mg) with gradual improvement in serum sodium (131 mmol/L on D25). After low dose fludrocortisone was started, there was also successful tapering of oral sodium chloride tablets down to 12 tablets a day, with further tapering till it was stopped 6 weeks later. He was discharged well on D29. A week later at the Endocrine clinic, his serum sodium normalized (138 mmol/L) while on lower doses of sodium chloride tablets, low dose hydrocortisone, and fludrocortisone 0.05 mg every other day. Fludrocortisone and hydrocortisone were stopped. His sodium level remained normal (142 mmol/L) without any medications 6 weeks after discharge. During this prolonged hospital stay for hyponatremia, the patient in case 1 expressed his concern that the symptomatic dizziness from hyponatremia would persist and affect his ability to work. He was relieved that both his symptoms and hyponatremia resolved completely. He was able to resume work subsequently.