What is commonly seen in a patient with Cushing syndrome?

Clinical Features of Cushing Syndrome

Hypokalemia is a common finding in patients with Cushing syndrome, particularly in cases of ectopic ACTH production.

Key Clinical Manifestations of Cushing Syndrome

Cushing syndrome represents a constellation of signs and symptoms resulting from chronic exposure to excess cortisol. The clinical presentation varies depending on the etiology, but several characteristic features are commonly observed:

Metabolic and Electrolyte Abnormalities

• Hypokalemia: Present in up to 57% of patients with ectopic ACTH syndrome 1, and is significantly more common in patients with severe hypercortisolism 2, 1
• Hyperglycemia: Due to cortisol-induced insulin resistance 3
• Metabolic alkalosis: Often accompanies hypokalemia 1

Cardiovascular Features

• Hypertension: Present in approximately 70-90% of patients 4, making it one of the most common manifestations
• Increased cardiovascular risk: Due to multiple metabolic derangements 1

Physical Appearance

• Central obesity: With fat deposition in face (moon facies), back of neck (buffalo hump), and visceral organs 3
• Purple striae: Particularly on the abdomen 2, 3
• Facial plethora: Due to capillary fragility 3
• Easy bruising: From skin atrophy and capillary fragility 2
• Muscle atrophy: Leading to proximal muscle weakness 2

Diagnostic Approach

The diagnosis of Cushing syndrome is not based on a single fasting cortisol level (option C is incorrect). Instead, the diagnostic approach involves:

1. Initial screening tests 2, 4:

   • 24-hour urinary free cortisol (UFC)
   • Late-night salivary cortisol
   • Overnight 1-mg dexamethasone suppression test

2. Confirmation of ACTH dependence/independence 2:

   • Plasma ACTH levels help distinguish adrenal causes (suppressed ACTH) from ACTH-dependent forms (normal to elevated ACTH)

3. Localization studies 5:

   • Pituitary MRI for suspected Cushing disease
   • CT/MRI of chest/abdomen for suspected ectopic ACTH production
   • Adrenal imaging for ACTH-independent causes

Etiology of Cushing Syndrome

Regarding the cause of Cushing syndrome (option D is incorrect):

• Cushing disease (pituitary ACTH-secreting adenoma) accounts for 60-70% of endogenous Cushing syndrome cases 3
• Ectopic ACTH production accounts for 5-20% of cases 6
• Adrenal causes (adenomas, carcinomas, bilateral hyperplasia) account for approximately 15-20% of cases 7

Pathophysiology of Hypokalemia in Cushing Syndrome

Hypokalemia is particularly common in ectopic ACTH syndrome but can occur in any form of severe Cushing syndrome. The mechanisms include:

1. Mineralocorticoid effects of excess cortisol: When cortisol levels are extremely high, they overwhelm the 11β-hydroxysteroid dehydrogenase type 2 enzyme that normally prevents cortisol from binding to mineralocorticoid receptors 1

2. Severity correlation: There is a significant relationship between 24-hour urinary cortisol excretion and the presence of hypokalemia 1

3. Clinical impact: Hypokalemia contributes to muscle weakness, cardiac arrhythmias, and metabolic alkalosis 1, 6

Treatment Considerations

Treatment depends on the underlying cause but generally involves:

1. Surgical approach: Removal of the ACTH or cortisol-producing tumor 4, 7

2. Medical therapy: When surgery is not possible or effective

   • Steroidogenesis inhibitors (ketoconazole, metyrapone, osilodrostat) 4
   • Glucocorticoid receptor antagonists (mifepristone) 4
   • Pituitary-directed therapies for Cushing disease 4

3. Management of complications: Including hypertension (mineralocorticoid receptor antagonists as first-line) and hypokalemia (potassium supplementation) 4

In conclusion, while hypotension is not a feature of Cushing syndrome (option A is incorrect), and the diagnosis is not based on fasting cortisol levels (option C is incorrect), and adrenal masses are not the most frequent cause (option D is incorrect), hypokalemia is indeed a common finding (option B is correct), especially in cases of ectopic ACTH production or severe hypercortisolism.