A 38-year-old man comes to the office due to disturbed sleep and depressed mood for the past several months. The patient has difficulty falling and staying asleep and says, "I lie awake at night thinking about all the weight I've gained and how I am too tired to even do anything about it." He constantly feels exhausted at work, which involves "sitting all day in a cubicle." The patient has also felt depressed and irritable, which he attributes to his appearance. He has no previous medical conditions and takes no medications. Family history is significant for bipolar disorder in his brother. Temperature is 36.8 C (98.2 F), blood pressure is 148/90 mm Hg, and pulse is 86/min. BMI is 34 kg/m2. On physical examination, the patient has a flat affect and a ruddy appearance with central obesity. The thyroid is normal to palpation. The lungs are clear to auscultation and heart sounds are normal. The abdomen is soft and nontender. There is no extremity edema. Proximal limb muscles are mildly weak with no associated pain or tenderness. The patient is tearful throughout the evaluation but has no suicidal ideation. Laboratory results are as follows:
| Complete blood count | |
| Hemoglobin | 14.4 g/dL |
| Platelets | 320,000/mm3 |
| Leukocytes | 9,000/mm3 |
| Serum chemistry | |
| Sodium | 140 mEq/L |
| Potassium | 3.4 mEq/L |
| Creatinine | 1.0 mg/dL |
| Glucose | 140 mg/dL |
| TSH | 2.9 µU/mL |
Which of the following is the most appropriate next step in management of this patient?
Features of Cushing syndrome | |
Clinical manifestations |
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Diagnosis |
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This patient's depression and sleep disturbances, in the context of centralized obesity, proximal muscle weakness, a ruddy appearance, hypertension, hypokalemia, and hyperglycemia, are suggestive of Cushing syndrome. Cushing syndrome is characterized by excess cortisol production, most commonly due to adrenal disorders, ACTH-producing pituitary adenomas, or ectopic ACTH production. Other manifestations of hypercortisolism include hirsutism, bone loss, easy bruising, and hypokalemia (due to cortisol's mineralocorticoid effects).
Neuropsychiatric symptoms in Cushing syndrome are common and include depressed or labile mood, anxiety or panic attacks, irritability, insomnia, memory deficits, and fatigue. Mania and paranoia occasionally occur. Patients who initially have psychiatric symptoms may be mistakenly diagnosed with a primary psychiatric disorder.
Patients with new-onset depression associated with physical or laboratory abnormalities warrant medical evaluation for underlying metabolic causes of depressed mood. Initial diagnostic tests for Cushing syndrome include 24-hour urinary cortisol excretion, late-night salivary cortisol assay, and overnight low-dose dexamethasone suppression test.
(Choice A) Anti–Jo-1 antibodies are specific for polymyositis and dermatomyositis. These inflammatory myopathies are characterized by proximal muscle weakness, with (dermatomyositis) or without (polymyositis) characteristic skin manifestations. However, affective symptoms, as well as central obesity, ruddy appearance, hyperglycemia, and hypokalemia, are more consistent with Cushing syndrome.
(Choice C) Insulin-like growth factor-1 is elevated in acromegaly, which can cause hyperglycemia and weight gain. It is accompanied by overgrowth of soft tissue, which manifests with enlarged jaws and facial features, hands, and feet. However, it is not typically associated with centralized obesity, a ruddy appearance, or hypokalemia.
(Choices D and E) Selective serotonin reuptake inhibitors (eg, paroxetine) and cognitive-behavioral therapy are first-line treatments for major depressive disorder. Before a primary depressive disorder is diagnosed, however, medical causes of depressed mood, such as Cushing syndrome, must be ruled out.
(Choice F) Bariatric surgery is generally indicated for patients with a BMI ≥40 kg/m2 or for those with a BMI ≥35 kg/m2 in association with obesity-related comorbidities (eg, type 2 diabetes mellitus). This patient's weight gain is likely a manifestation of hypercortisolism, which should be treated prior to consideration of bariatric surgery.
Educational objective:
Neuropsychiatric manifestations of Cushing syndrome include depressed or labile mood, anxiety, irritability, insomnia, memory deficits, and fatigue. Patients with these symptoms may be mistakenly diagnosed with primary psychiatric disorders. Initial diagnostic tests include 24-hour urinary cortisol excretion, late-night salivary cortisol assay, and overnight low-dose dexamethasone suppression test.