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A 67-year-old woman is evaluated for a 2-day history of severe muscle weakness. The patient experienced significant weight gain and developed hypertension and type 2 diabetes mellitus 2 years ago. She also reports developing muscle weakness of the lower extremities 6 months ago. Her diabetes is only partially controlled by metformin; her blood glucose measurements at home are usually greater than 250 mg/dL (13.9 mmol/L).

Other medications are hydrochlorothiazide, lisinopril, amlodipine, and metoprolol.

Physical examination shows a woman who appears chronically ill. Blood pressure is 154/92 mm Hg, and other vital signs are normal; BMI is 40. Skin examination is notable for facial hirsutism. Central obesity, mild proximal muscle weakness, and 2+ peripheral edema are noted.

Results of laboratory studies show a serum creatinine level of 1.3 mg/dL (115 µmol/L), a plasma glucose level of 144 mg/dL (8.0 mmol/L), and a serum potassium level of 2.9 mEq/L (2.9 mmol/L).

Which of the following tests should be performed to reveal the cause of her diabetes?

A) Adrenal CT
B) C-peptide measurement
C) Glutamic acid decarboxylase antibody titer
D) Pancreatic MRI
E) 24-hour urine free cortisol excretion

MKSAP Answer and Critique

The correct answer is E) 24-Hour urine free cortisol excretion. This item is available to MKSAP 16 subscribers as item 6 in the Endocrinology and Metabolism section.

Measurement of the 24-hour excretion of urine free cortisol is the most appropriate next test in this patient to determine the cause of her diabetes mellitus. Various secondary causes of diabetes exist, most involving other endocrinopathies, effects of medications, pancreatic diseases, or genetic conditions. Cushing syndrome is one of these secondary causes of diabetes. The most common cause of Cushing syndrome is corticosteroid therapy, followed by the secretion of adrenocorticotropic hormone (ACTH) by a pituitary adenoma (Cushing disease) and the hyperfunctioning of an adrenocortical adenoma. In this patient, the combination of diabetes, hypertension, central obesity, hypokalemia, proximal muscle weakness, and edema strongly suggests the presence of Cushing syndrome. The diagnosis can be confirmed by several tests, including measurement of 24-hour excretion of urine free cortisol, an overnight dexamethasone suppression test, or a midnight salivary cortisol measurement.

Adrenal CT is appropriate after Cushing syndrome is diagnosed, especially when it is non–ACTH dependent, to identify the type of adrenal condition responsible. This test would be premature in this patient in whom the diagnosis has not been confirmed.

Residual beta-cell function can be assessed by measuring the C-peptide level, which is often high-normal in early type 2 diabetes because of insulin resistance. Similarly, measuring the glutamic acid decarboxylase antibody titer is useful to confirm the presence of autoimmune (type 1) diabetes when no other evidence exists. However, the C-peptide level will not indicate the cause of diabetes in this patient, and measuring the glutamic acid decarboxylase level also is unlikely to be helpful because she does not have type 1 diabetes.

Pancreatic imaging could be considered when signs and symptoms (such as abdominal or back pain, jaundice, or chronic diarrhea) suggest that an underlying pancreatic disorder is the cause of diabetes. This patient has none of these signs or symptoms, and thus a pancreatic MRI is unlikely to be revealing.

Key Point

• Cushing syndrome is a likely cause of diabetes mellitus in a patient with hypertension, central obesity, and hypokalemia.

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