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MKSAP Quiz: 1-year history of weight gain, easy bruising

A 52-year-old woman is evaluated for a 1-year history of a 6.8-kg (15-lb) weight gain, easy bruising, hypertension, and worsening diabetes control. Lab studies reveal hypercortisolism. What is the most likely cause?


A 52-year-old woman is evaluated for a 1-year history of a 6.8-kg (15-lb) weight gain, easy bruising, hypertension, and worsening diabetes control. Medical history is also significant for a history of depression and anxiety. Medications are metformin and lisinopril.

On physical examination, blood pressure is 155/97 mm Hg and pulse rate is 82/min. Other vital signs are normal. BMI is 33. The patient has central obesity, supraclavicular and dorsocervical fat pads, and facial hirsutism. There are a few bruises on her arms and no abdominal striae.

Laboratory studies show a 24-hour urine free cortisol level of 205 µg/24 h, (564.9 nmol/24 h), midnight salivary cortisol of 298 ng/mL (821.2 nmol/L) (normal <100 ng/mL [275.6 nmol/L]), and adrenocorticotropic hormone (ACTH) less than 5 pg/mL (1.1 pmol/L).

Which of the following is the most likely cause of this patient's hypercortisolism?

A. Adrenal tumor
B. Bronchial carcinoid
C. Pituitary tumor
D. Psychiatric illness

Reveal the Answer

MKSAP Answer and Critique

The correct answer is A. Adrenal tumor. This content is available to MKSAP 18 subscribers as Question 15 in the Endocrinology and Metabolism section. More information about MKSAP is available online.

The most likely cause of this patient's hypercortisolism is adrenocorticotropic hormone (ACTH)-independent Cushing syndrome caused by an adrenal tumor. The diagnosis of Cushing syndrome is confirmed by the combination of clinical features (central obesity, dorsocervical and supraclavicular fat pads, new onset hypertension, and worsening diabetes control), in the setting of two positive diagnostic tests for Cushing syndrome: elevated 24-hour urine free cortisol level and elevated midnight salivary cortisol level. A 24-hour urine free cortisol that is three times the upper limit of the normal range (as in this patient) is considered to be confirmatory for Cushing syndrome if compatible clinical features are also present. Once Cushing syndrome is confirmed, the next step in the diagnosis is to categorize Cushing syndrome into ACTH-dependent and ACTH-independent types, which in turn governs subsequent localization tests. A low serum ACTH level, as in this patient, indicates ACTH-independent Cushing syndrome. Excluding glucocorticoid administration, the most common cause of ACTH-independent Cushing syndrome is a cortisol-secreting adrenal tumor. ACTH is suppressed in this situation due to elevated cortisol levels causing negative feedback at the level of the hypothalamus and pituitary gland, which inhibits ACTH production.

Cushing syndrome in the presence of a detectable or elevated serum ACTH indicates ACTH-dependent disease. Causes of ACTH-dependent Cushing syndrome include ACTH secretion from a pituitary tumor (most commonly) or from an ectopic source such as a bronchial carcinoid tumor.

Hypercortisolism in the absence of Cushing syndrome can occur with psychiatric illness. The mechanism of hypercortisolism associated with psychiatric illness is activation of the hypothalamic-pituitary axis; in this situation ACTH production is not suppressed. In addition, patients do not manifest clinical features of Cushing syndrome. This patient's suppressed serum ACTH rules out psychiatric illness as the primary cause of her hypercortisolism.

Key Point

  • Excluding glucocorticoid administration, the most common cause of adrenocorticotropic hormone (ACTH)-independent Cushing syndrome is an adrenal tumor.