Hyponatremia secondary to the syndrome of inappropriate secretion of antidiuretic hormone (SIADH): therapeutic decision-making in real-life cases

Abstract

Despite being the most common electrolyte disturbance encountered in clinical practice, the diagnosis and treatment of hyponatremia (defined as a serum sodium concentration <135 mmol/L) remains far from optimal. This is extremely troubling because not only is hyponatremia associated with increased morbidity, length of hospital stay and hospital resource use, but it has also been shown to be associated with increased mortality. The reasons for this poor management may partly lie in the heterogeneous nature of the disorder; hyponatremia presents with a variety of possible etiologies, differing symptomology and fluid volume status, thereby making its diagnosis potentially complex. In addition, a general lack of awareness of the clinical impact of the disorder, a fear of adverse outcomes through overcorrection of sodium levels, and a lack of effective targeted treatments until recent years, may all have contributed to a reticence to actively treat cases of hyponatremia. There is therefore a clear unmet need to further educate physicians on the pathophysiology, diagnosis and management of this important condition. Through the use of a variety of real-world cases of patients with hyponatremia secondary to the syndrome of inappropriate secretion of antidiuretic hormone-a condition that accounts for approximately one-third of all cases of hyponatremia-this supplement aims to provide a comprehensive overview of the challenges faced in diagnosing and managing hyponatremia. These cases will also help to illustrate how some of the limitations of traditional therapies may be overcome with the use of vasopressin receptor antagonists.

Keywords: AVP; SIADH; hyponatremia; syndrome of inappropriate secretion of antidiuretic hormone; vasopressin.

Figure 1:

Possible relationships between hyponatremia and mortality [8]. The figure illustrates possible scenarios to explain the relationship between hyponatremia and mortality. In one scenario, hyponatremia and mortality are both caused by severe underlying disease. In another scenario, hyponatremia directly results in mortality (e.g. hyponatremia leading to cerebral edema in acute hyponatremia and the osmotic demyelination syndrome when chronic hyponatremia is corrected too rapidly). In the final scenario, hyponatremia indirectly contributes to mortality by causing organ dysfunction. Adapted from Hoorn and Zietse [8].

Figure 2:

Case 1: treatment response and patient progress. SIADH, syndrome of inappropriate secretion of antidiuretic hormone.

Figure 3:

Diagnostic algorithm for hyponatremia. BUN, blood urea nitrogen; CHF, chronic heart failure; SIADH, syndrome of inappropriate secretion of antidiuretic hormone; TSH, thyroid-stimulating hormone.

Figure 4:

Case 2: magnetic resonance imaging suggesting a recurrence of his known anaplastic oligoastrocytoma and intracerebral bleeding.

Figure 5:

Case 2: treatment response and patient progress. ICU, intensive care unit.

Figure 6:

Case 3: pneumonia diagnosed via chest X-ray.

Figure 7:

Case 4: results of CT scans. CT scan taken at (A) initial presentation and (B) after 3 months’ therapy with etoposide and carboplatin.

Figure 8:

Case 4: serum [Na⁺] response to treatment.

Figure 9:

Patterns of plasma vasopressin levels where compared with plasma sodium levels in patients with SIADH [15]. Type A is characterized by unregulated secretion of vasopressin, type B by elevated basal secretion of vasopressin despite normal regulation by osmolality, type C by a ‘reset osmostat’ and type D by undetectable vasopressin. The shaded area represents normal values of plasma vasopressin. Adapted from Ellison and Berl [15].

Figure 10:

Case 4: response to tolvaptan therapy. Effect of tolvaptan before and after administration on (A) diuresis (average value between Day 1 and 7 following tolvaptan; statistical analysis conducted using Student's t-test), (B) urinary osmolality and (C) urinary [Na⁺].

Figure 11:

Case 5: treatment summary, serial serum [Na⁺] measurements, and patient progress.

Figure 12:

Estimated probability of need for long-term treatment of SIADH depending on underlying etiology [68]. Adapted from Verbalis [68].