A 35-year-old woman comes to the office due to fatigue and difficulty lifting heavy objects over the last several months. She has gained approximately 9.1 kg (20 lb) during the past year. The patient also reports easy bruising with minimal trauma. Medical history is unremarkable, and her only medication is a combined estrogen/progestin oral contraceptive. She does not use tobacco, alcohol, or illicit drugs. The patient lives with her boyfriend and has no children. She is employed as a secretary at a dental office.
Blood pressure is 160/100 mm Hg and pulse is 80/min. BMI is 29 kg/m². Examination shows facial plethora and excessive fat deposition in the supraclavicular and posterior neck regions. Skin examination shows excessive terminal hair on the face and lower abdomen.
Laboratory results are as follows:
Which of the following tests is the best next step in establishing this patient's diagnosis?

Question

A 35-year-old woman comes to the office due to fatigue and difficulty lifting heavy objects over the last several months. She has gained approximately 9.1 kg (20 lb) during the past year. The patient also reports easy bruising with minimal trauma. Medical history is unremarkable, and her only medication is a combined estrogen/progestin oral contraceptive. She does not use tobacco, alcohol, or illicit drugs. The patient lives with her boyfriend and has no children. She is employed as a secretary at a dental office.
Blood pressure is 160/100 mm Hg and pulse is 80/min. BMI is 29 kg/m². Examination shows facial plethora and excessive fat deposition in the supraclavicular and posterior neck regions. Skin examination shows excessive terminal hair on the face and lower abdomen.
Laboratory results are as follows:

Which of the following tests is the best next step in establishing this patient's diagnosis?

Quizplus · Accepted Answer

11ec193a_97b9_3e93_853d_59d0273e533c_MD0002_00 This patient's clinical presentation (weight gain, hypertension, hirsutism, hypokalemia, hyperglycemia, facial plethora, proximal weakness, easy bruising) is strongly suggestive of Cushing syndrome, which is likely endogenous as she is not taking any glucocorticoid medications. Diagnosis of endogenous Cushing syndrome requires confirmation on at least 2 different first-line screening tests. Options include: Low-dose overnight dexamethasone suppression test (ODST)Late-night salivary cortisol24-hour urine free cortisol Low-dose overnight dexamethasone suppression test (ODST) Low-dose overnight dexamethasone suppression test (ODST) Late-night salivary cortisol Late-night salivary cortisol 24-hour urine free cortisol 24-hour urine free cortisol ODST measures early-morning serum cortisol levels following dexamethasone administration. In normal individuals, dexamethasone suppresses production of cortisol, but patients with Cushing syndrome have continued secretion (morning cortisol >1.8 µg/dL). Cortisol is bound to circulating albumin and cortisol-binding globulin (CBG). Estrogen (eg, oral contraceptives) increases CBG and total cortisol, causing a false-positive result. Therefore, this patient's evaluation should begin with a 24-hour free cortisol measurement or late-night salivary cortisol assay rather than ODST (Choice E). A small amount of cortisol is secreted in the saliva and follows normal circadian rhythm, with very low levels late at night; elevated late-night salivary cortisol is the most sensitive single test (>90%) for Cushing syndrome. (Choice A) ACTH levels help differentiate between ACTH-dependent (normal/high ACTH) and ACTH-independent (suppressed ACTH) causes of Cushing syndrome. However, ACTH is not used as an initial screening test and is performed after the diagnosis of Cushing syndrome has been confirmed. (Choice B) Morning cortisol levels without dexamethasone suppression have a low sensitivity and specificity for Cushing syndrome and are not recommended as a screening test. (Choice D) This patient most likely has Cushing disease (pituitary ACTH-dependent Cushing syndrome), but imaging is deferred until the biochemical diagnosis is confirmed. Educational objective: Diagnosis of endogenous Cushing syndrome requires confirmation on at least 2 different screening tests. Options include low-dose overnight dexamethasone suppression test, late-night salivary cortisol, and 24-hour urine free cortisol. Estrogen (eg, oral contraceptive pills) increases cortisol-binding globulin and total cortisol, resulting in a false positive on a dexamethasone suppression test. __________ References: The diagnosis of Cushing's syndrome: an Endocrine Society Clinical Practice Guideline. (http://www.ncbi.nlm.nih.gov/pubmed/18334580) Measurement of salivary cortisol in 2012 - laboratory techniques and clinical indications. (http://www.ncbi.nlm.nih.gov/pubmed/22812714)

A 35-Year-Old Woman Comes to the Office Due to Fatigue