MKSAP Quiz: 1-year history of weight gain, fatigue, easy bruising
A 48-year-old woman who works the night shift presents with a one-year history of gaining 25 pounds, as well as fatigue, easy bruising, and difficulty remembering things. Medical history is significant for hypertension, type 2 diabetes, and menopausal hot flushes. After medication review and physical exam, what is the most appropriate next step in evaluation?
A 48-year-old woman is evaluated for a 1-year history of 11.3-kg (25-lb) weight gain, fatigue, easy bruising, and difficulty remembering things. She works the night shift at a hotel reception desk. Medical history is significant for hypertension, type 2 diabetes mellitus, and menopausal hot flushes. Medications are lisinopril, estradiol, aspirin, and metformin.
On physical examination, blood pressure is 142/88 mm Hg. Other vital signs are normal. BMI is 34. The patient has central obesity, and a dorsocervical fat pad is present. There are no abdominal striae, no proximal muscle weakness, and no supraclavicular fat pads.
Which of the following is the most appropriate next step in evaluation of this patient?
A. 1-mg overnight dexamethasone suppression test
B. 24-Hour urine free cortisol measurement
C. Late night salivary cortisol measurement
D. Morning serum total cortisol measurement
MKSAP Answer and Critique
The correct answer is B. 24-Hour urine free cortisol measurement. This content is available to MKSAP 18 subscribers as Question 42 in the Endocrinology and Metabolism section. More information about MKSAP is available online.
This patient should be screened for Cushing syndrome, and the best screening test in this patient is measurement of 24-hour urine free cortisol to quantify total daily cortisol secretion. Biochemical testing is used to establish the diagnosis of Cushing syndrome. It is critical that the biochemical diagnosis is firmly established prior to any imaging studies due to the relatively high prevalence of clinically insignificant pituitary and adrenal masses. Initial tests include the 1-mg overnight dexamethasone suppression test, 24-hour urine free cortisol, and late-night salivary cortisol. While the 1-mg overnight dexamethasone test and the late-night salivary cortisol test may be more convenient, they are likely to be less accurate in this patient because of her shift work and estrogen use. Measurement of 24-hour urine free cortisol is not impacted by estrogen therapy or sleeping patterns. A threefold or greater increase over normal values is diagnostic of Cushing syndrome if compatible clinical features are present (centripetal obesity, facial plethora, abnormal fat deposition in the supraclavicular or dorsocervical areas, and wide violaceous striae); if this increase is present, test results should be repeated to confirm the abnormal result.
The 1-mg overnight dexamethasone suppression test is also not reliable in this patient because it relies on serum cortisol measurement.
The late night salivary cortisol test is not a reliable screening test in this patient because she works a night shift and therefore her diurnal cortisol secretion will be reversed.
Measurement of morning serum cortisol is unreliable as a screening test for Cushing syndrome because normal secretion of cortisol is pulsatile and the normal range is broad. Hence, there is considerable overlap between serum cortisol levels seen in normal people, those with Cushing syndrome, and those with hypercortisolism due to psychological or medical stressors.
In addition, serum cortisol measurement is unreliable in this patient as she is on oral estrogen, which leads to an increase in cortisol binding proteins and subsequent elevation of serum total cortisol levels without impacting free cortisol levels.
Key Point
- The 24-hour urine free cortisol test for Cushing syndrome is not impacted by either estrogen therapy or sleeping patterns.