MKSAP Quiz: 3-year history of fatigue

A 36-year-old woman is evaluated for a 3-year history of fatigue that worsens after activity and does not improve with rest. She also notes intermittent diffuse myalgia and arthralgia, constipation, dizziness, headaches, urinary urgency, memory problems, and paresthesias. Following a physical exam and lab studies, what is the most appropriate diagnostic test to perform next?


A 36-year-old woman is evaluated for a 3-year history of fatigue that worsens after activity and does not improve with rest. She also notes intermittent diffuse myalgia and arthralgia, constipation, dizziness, headaches, urinary urgency, memory problems, and paresthesias. Her musculoskeletal symptoms, dizziness, and headache worsen in the upright position and improve when she lies back down. She has almost entirely eliminated social activities. Medical history is significant for episodic migraine and irritable bowel syndrome. Medications are sumatriptan, polyethylene glycol, and hyoscyamine.

On physical examination, vital signs are normal. BMI is 24. Neck circumference is 36 cm (14 in). The remainder of the examination is normal.

Laboratory studies obtained 6 months ago showed a normal complete blood count, electrolyte levels, kidney function test results, liver chemistry test results, fasting glucose level, serum creatine kinase level, and serum thyroid-stimulating hormone level.

Which of the following is the most appropriate diagnostic test to perform next?

A. Antinuclear antibody assay
B. Polysomnography
C. Serum cortisol level measurement
D. No further testing is recommended


MKSAP Answer and Critique

The correct answer is D. No further testing is recommended. This content is available to MKSAP 18 subscribers as Question 12 in the General Internal Medicine section. More information about MKSAP is available online.

No further diagnostic testing is required in this patient. She meets the diagnostic criteria for systemic exertion intolerance disease (SEID), which are fatigue of at least 6 months' duration accompanied by substantial reduction in preillness activities, postexertional malaise, unrefreshing sleep, and either cognitive impairment or orthostatic intolerance. Although the pathophysiology of SEID remains unclear, the phenomenon of central sensitization (the pathophysiologic dysregulation of the thalamus, hypothalamus, and amygdala) is gaining acceptance as a potential cause of SEID as well as of other highly prevalent comorbid conditions, including fibromyalgia, mood disturbances, irritable bowel syndrome, and interstitial cystitis.

This patient's history, examination, and previous diagnostic test results point to central sensitization, as demonstrated by the constellation of such symptoms as diffuse arthralgia and myalgia, chronic fatigue, bowel and bladder irritability, chronic headaches, brain fog, paresthesias, and unrefreshing sleep. In patients with SEID, the history and physical examination should guide the choice of diagnostic tests. It is reasonable to obtain a complete blood count, creatine kinase (for myalgia), electrolyte panel, thyroid-stimulating hormone level, fasting glucose level, and kidney and liver chemistry tests; however, unnecessary laboratory, imaging, and invasive studies should be avoided because most patients will have unrevealing findings, which provide no lasting reassurance to patients. In this case, the diagnostic evaluation should be limited unless there is compelling new information to warrant further testing.

Antinuclear antibody testing is an effective screening tool for systemic lupus erythematosus; however, myalgia, arthralgia, and fatigue are insufficient reasons to test for antinuclear antibodies unless accompanied by objective findings of systemic lupus erythematosus.

Patients at moderate to high risk for obstructive sleep apnea should undergo further testing, including a home sleep study or polysomnography. On the basis of this patient's presentation (female, young, normal BMI and neck circumference, lack of daytime sleepiness), she is considered to be at low risk for obstructive sleep apnea, and further sleep testing is not warranted.

Serum cortisol testing is unnecessary in this patient who is not manifesting findings that are suggestive of adrenal failure or insufficiency, such as hypotension, tachycardia, hyponatremia, and hyperkalemia.

Key Point

  • In patients with fatigue without a clear cause, it is reasonable to obtain a complete blood count, electrolyte panel, thyroid-stimulating hormone level, fasting glucose level, and kidney and liver chemistry tests; unnecessary laboratory, imaging, and invasive studies should be avoided.