A 68-year-old woman is brought to the emergency department due to worsening lethargy. Her family states that the patient has had headache and nausea for the past several days, and today she was confused and lethargic. Medical history is significant for seizure disorder, hypertension, type 2 diabetes mellitus, and bipolar disorder, for which she is on a number of medications. Vital signs are within normal limits. On physical examination, the patient is somnolent and responds to painful stimuli only. Mucous membranes are moist and jugular venous pressure is normal. The lungs are clear to auscultation and heart sounds are normal. There is no extremity edema. Laboratory evaluation reveals severe hyponatremia with a serum sodium of 118 mEq/L; blood urea nitrogen and serum creatinine are within normal limits. Serum osmolality is low and urine osmolality is high. Which of the following medications is the most likely cause of this patient's condition?
Syndrome of inappropriate antidiuretic hormone (SIADH) | |
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ADH = antidiuretic hormone; JVD = jugular venous distension; SSRIs = selective serotonin reuptake inhibitors. | |
This patient has symptomatic hyponatremia (eg, somnolence, lethargy) and her laboratory studies (eg, low serum osmolality, high urine osmolality) are consistent with the syndrome of inappropriate antidiuretic hormone secretion (SIADH). Antidiuretic hormone (ADH) is released by the hypothalamus and posterior pituitary and stimulates the renal collecting ducts to reabsorb water into the systemic circulation. Patients with excessive ADH activity (ie, SIADH) typically have the following manifestations:
Serum sodium and osmolality decrease, leading to hypotonic hyponatremia.
Urinary water excretion decreases, increasing urine osmolality and creating a concentrated urine.
Clinical euvolemia, which is reflected by an absence of edema, lung crackles, and jugular venous distention (signs of hypervolemia) along with absence of dry mucous membranes and elevated blood urea nitrogen (BUN) and creatinine (signs of hypovolemia).
In this case, the patient's SIADH is likely due to carbamazepine, an antiepileptic drug that induces ADH production and increases renal sensitivity to ADH. Other medications associated with SIADH include antidepressants (eg, selective serotonin reuptake inhibitors and tricyclic antidepressants), certain antidiabetic drugs (eg, chlorpropamide), and recreational drugs (eg, MDMA [ie, ecstasy]).
(Choice A) Canagliflozin is a diabetic medication that inhibits sodium-glucose cotransporter 2 in the renal proximal tubule, increasing urinary glucose excretion. Canagliflozin is linked to urinary tract infections and hypotension, but not SIADH.
(Choices C and E) Furosemide and spironolactone are often used in combination to treat severe heart failure. Furosemide reduces sodium reabsorption in the loop of Henle, increasing sodium and water excretion. Spironolactone blocks the mineralocorticoid receptor, which increases sodium excretion and potassium reabsorption. Both diuretics can induce hyponatremia; however, patients are typically also hypovolemic (eg, with dry mucous membranes and elevated BUN and creatinine). This patient's euvolemia and normal BUN and creatinine are more consistent with SIADH.
(Choice D) Lithium can cause ADH resistance in the renal collecting ducts, resulting in nephrogenic diabetes insipidus. In this condition, water cannot be reabsorbed; urine osmolality is low (dilute urine) and serum sodium and osmolality increase. This patient has an opposite picture (high urine osmolality, low serum sodium and osmolality), indicating SIADH.
Educational objective:
The syndrome of inappropriate antidiuretic hormone (SIADH) presents with hypotonic hyponatremia (ie, low serum osmolality and serum sodium), concentrated urine (ie, high urine osmolality), and euvolemia. Carbamazepine can cause SIADH by increasing antidiuretic hormone (ADH) secretion and renal sensitivity to ADH.