MKSAP: 74-year-old woman with fatigue, anorexia, and weight loss

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A 74-year-old woman is evaluated for a 2-month history of fatigue, anorexia, and a 6-kg (13.2-lb) weight loss. She was treated with chemotherapy for ovarian cancer 6 months ago. She also has hypertension managed with hydrochlorothiazide.

On physical examination, temperature is 36.2 °C (97.2 °F), blood pressure is 132/75 mm Hg without postural changes, pulse rate is 86/min without postural changes, and respiration rate is 14/min. BMI is 23. There are no neurologic findings. Estimated central venous pressure is less than 5 cm H2O. Cardiac and pulmonary examinations are normal. There is no peripheral edema.

Laboratory studies:

Blood urea nitrogen 5 mg/dL (1.8 mmol/L)
Serum creatinine 0.4 mg/dL (35.4 µmol/L)
Sodium 128 mEq/L (128 mmol/L)
Potassium 3.8 mEq/L (3.8 mmol/L)
Chloride 90 mEq/L (90 mmol/L)
Bicarbonate 25 mEq/L (25 mmol/L)
Glucose 60 mg/dL (3.3 mmol/L)
Osmolality 266 mosm/kg H2O
Cortisol (8 AM) 20 µg/dL (552 nmol/L) (normal range, 5-25 µg/dL [138-690 nmol/L])
Thyroid-stimulating hormone 1.3 µU/mL (1.3 mU/L)
Urine studies:
Osmolality 50 mosm/kg H2O (normal range, 300-900 mosm/kg H2O)
Potassium 15 mEq/L (15 mmol/L) (normal range for women, 17-164 mEq/L [17-164 mmol/L])
Sodium 12 mEq/L (12 mmol/L) (normal range for women, 15-267 mEq/L [15-267 mmol/L])

Which of the following is the most likely cause of this patient’s hyponatremia?

A: Hypovolemia
B: Low solute intake
C: Measurement error (pseudohyponatremia)
D: Primary adrenal insufficiency

MKSAP Answer and Critique

The correct answer is B: Low solute intake.

This patient has hypotonic hyponatremia due to low solute intake. Her history of anorexia and weight loss, in conjunction with clinical euvolemia and both low plasma and low urine osmolality and sodium, supports this diagnosis. Because some solute excretion by the kidney is required for urinary water excretion, this patient’s low solute intake is limiting her ability to excrete free water, leading to hypotonic hyponatremia as her water intake exceeds her ability to excrete urinary water.

The absence of physical examination findings suggesting hypovolemia, including postural changes in blood pressure and pulse, decreases the likelihood of hypovolemic hyponatremia in this patient. In patients with hypovolemia, urine osmolality typically exceeds 400 mosm/kg H2O, which reflects increased tubular water resorption under the influence of antidiuretic hormone.

Pseudohyponatremia is characterized by a low serum sodium concentration due to measurement in a falsely large volume; an interfering substance displaces the liquid component of the sample, similar to ice cubes in a pitcher. The most common space-occupying substances are lipids and paraproteins. Measured plasma osmolality is normal in pseudohyponatremia and cannot be accounted for by increases in other solutes such as glucose, urea, or alcohols. The low measured plasma osmolality and the absence of an osmolal gap are consistent with hypotonic hyponatremia and exclude the diagnosis of pseudohyponatremia.

Hyponatremia is found in most patients with primary adrenal insufficiency, reflecting both mineralocorticoid deficiency and increased vasopressin secretion caused by cortisol deficiency. The absence of hypotension, hypovolemia, hyperkalemia, and a relatively high morning serum cortisol level does not support a diagnosis of primary adrenal insufficiency.

Key Point

  • Low solute intake can cause hypotonic hyponatremia.

This content is excerpted from MKSAP 16 with permission from the American College of Physicians (ACP). Use is restricted in the same manner as that defined in the MKSAP 16 Digital license agreement. This material should never be used as a substitute for clinical judgment and does not represent an official position of ACP. All content is licensed to on an “AS IS” basis without any warranty of any nature. The publisher, ACP, shall not be liable for any damage or loss of any kind arising out of or resulting from use of content, regardless of whether such liability is based in tort, contract or otherwise.


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