Internal Medicine Correlations and Clinical Scenarios (CCS) USMLE Step 3

CASE 6: Syndrome of Inappropriate Secretion of Antidiuretic Hormone

Setting: ED

CC: “My husband has been really confused.”

VS: BP:112/76 mm Hg; P: 98 beats/minute; T: 99°F; R: 22 breaths/minute

HPI: A 58-year-old man with lung cancer diagnosed several weeks ago is admitted to the ED. He has been undergoing a staging evaluation and has not started therapy. He is brought in by his wife because he has been increasingly confused over the past 2 days.

PMHX:

Image Tobacco smoking for 30 years, quit 5 years ago

Image Hypertension

Medications:

Image Amlodipine

If CCS describes “Acute mental status changes of unclear etiology,” order naloxone, dextrose, and thiamine first. Acute confusion, like hypotension and dyspnea, is a reason to initiate therapy before PE.

PE:

Image General: visibly agitated and confused

Image Neurological: lethargic, confused, only able to state his name; examination incomplete secondary to inability to follow commands

Image Cardiovascular: normal

Image Abdomen: normal

Initial Orders:

Image CHEM-20

Image Oximeter

Image Calcium

Image Head CT

Which of these will not cause confusion?

a. Hyponatremia

b. Hypernatremia

c. Hyperkalemia

d. Hypercalcemia

e. Hypoxia

Answer c. Hyperkalemia

Potassium disorders do not cause altered mental status. Potassium disorders lead to cardiac conduction abnormalities by altering the resting membrane potential. Altered mental status and confusion are caused by:

• Any sodium or glucose disorder

• High calcium

• Hypoxia

• Anatomic abnormalities of the brain

• Intoxication

• Liver or renal failure

These are also the same things that cause seizures.

The worst form of confusion is a seizure!

Resting membrane potential is strongly based on ungated potassium channels.

If a patient can speak, but does not know his name, it is a psychiatric problem.

Advance the case the smallest amount of time to get the first test results. On CCS, you do not have to do anything to get the reports of tests as long as you advance the clock. There is no difference between the “On” and “In” types of time advance. If it is 9 a.m., it is the same to say advance “IN 15 minutes” or “ON 9:15 a.m.”

Report:

Image CHEM-20: sodium 112 mEq/L; BUN 8 g/dL; creatinine 0.7 mg/dL

Image Oximeter: 97% on room air

Image Calcium: 9.2 mg/dL (normal)

Image Head CT: no metastases

Sodium kills with seizures.

Volume status is the key to diagnosing sodium disorders.

• High volume: CHF, cirrhotic, nephrotic

• Low volume: diuretics, Addison disease

• Normal: syndrome of inappropriate secretion of antidiuretic hormone (SIADH), pseudohyponatremia, psychogenic polydipsia

Depolarization is based on the rapid influx of sodium.

PE:

Image Extremities: no edema, no dehydration

Image Neurological: lethargic, stuporous

You will never lose points on CCS by examining a patient too much.

Orders:

Image 3% hypertonic saline

Image Conivaptan IV

Image Repeat chemistry

Image Urine sodium, urine osmolarity

Image Uric acid level

Image Transfer patient to ICU

With hyponatremia, a healthy person would make:

• Maximally dilute urine (lowest possible osmolarity)

• Minimum urine sodium (<10 mEq/L)

Laboratory tests are always done first (before other procedures) on CCS. If a test (urine sodium) and a treatment (hypertonic saline) are ordered simultaneously, the test is always done first.

Low sodium level alters the depolarization of neural tissue.

What is the mechanism of conivaptan?

a. It resets the hypothalamic osmostat.

b. It is a V1-receptor antagonist.

c. It is a V2-receptor antagonist.

d. It is a V2-receptor stimulant.

e. It inhibits the posterior pituitary release of antidiuretic hormone (ADH).

Answer c. It is a V2-receptor antagonist.

Conivaptan and tolvaptan are peripheral V2-receptor antagonists. They inhibit the effect of ADH on the collecting duct. They inhibit permeability of the collecting duct so it cannot reabsorb water.

Normal minimum urine osmolarity: 50 mOsm

The distal convoluted tubule (DCT) is the site of the minimum osmolarity of urine.

Move the clock forward 30 to 60 minutes and reexamine the neurologic system and recheck the sodium level.

Report:

Image Urine sodium 64 mEq/L (high)

Image Urine osmolarity 480 mOsm/kg

Orders:

Image CHEM-7

Each aquaporin passes 1,000,000 water molecules/second reabsorbing back into the body.

Conivaptan prevents placement of aquaporins in the collecting duct.

Advance the clock 1 to 2 hours at a time for the first 12 hours in severe hyponatremia. Severity in hyponatremia is based on the symptoms, not the number.

Severe Hyponatremia = Seizures, Coma, or Profound Confusion

Report:

Image Sodium 114 mEq/L after 2 hours of treatment

Image Uric acid level low (diluted by excess free water)

Increase sodium level by 6 to 12 points over 12 hours in patients with severe hyponatremia.

The sodium content of NS is 154 mEq/L, while this patient has a sodium level of 112 or 114 mEq/L. What will be the effect of giving NS to this person?

a. Too rapid an increase in serum sodium

b. Too slow an increase in serum sodium

c. No effect

d. Decrease in serum sodium

Answer d. Decrease in serum sodium

NS drops serum sodium levels in SIADH. This is one of the hardest things to understand about the disorder. It has to do with osmolarity. The osmolarity of NS is less than the patient’s urine. NS osmolarity is 308 mOsm/kg (Na 154 mOsm/kg + chloride [Cl] 154 mOsm/kg). The urine osmolarity of this patient is 480 mOsm/kg. This means that NS is actually more dilute than the patient’s urine. Although the sodium level of NS is greater than that in the patient’s serum, the patient’s urine is more dilute. Each liter of NS will give net free water compared with the patient’s urine, and the serum sodium level will drop.

If you give a diuretic such as furosemide with the NS, you will improve the patient’s serum sodium level. This is because loop diuretics will decrease the urine osmolarity.

Never give NS alone in SIADH! It makes it worse!

Furosemide drops urine osmolarity so net free water is lost.

After 4 hours, the serum sodium level rises to 117 mEq/L. Symptoms start to improve and the patient is less confused.

What happens when the sodium level is brought up too rapidly?

a. Monocular blindness

b. Central pontine demyelinization

c. Cerebral edema

d. Transverse myelitis

Answer b. Central pontine demyelinization

Remember to keep the rate of the rise of the sodium level slow. If a low sodium level is brought up too fast, there is central pontine myelinolysis, or osmotic demyelinization syndrome. This syndrome is delayed several days after the correction of the sodium. It looks like a brainstem stroke with dysarthria, dysphagia, diplopia, and mental status changes.

Increase the sodium 12 to 18 points over the first 24 to 48 hours. Once sodium is on the rise, there is no benefit to elevating it rapidly. For the long term, this patient has an uncorrectable cause of SIADH with his lung cancer. The patient will need either demeclocycline or tolvaptan to prevent a recurrence of symptomatic hyponatremia.

Demeclocycline and tolvaptan

• Inhibit ADH effect on the collecting duct



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