Cushing Syndrome Quiz

Cushing Syndrome: Practice Guide for Exam-Style Questions

Core Definition: Endogenous vs. Exogenous

Cushing syndrome is a clinical state resulting from chronic exposure to excess corticosteroids. It’s crucial to distinguish between its two main origins for diagnosis and treatment. Exogenous (iatrogenic) Cushing syndrome is the most common cause overall, resulting from long-term use of glucocorticoid medications. Endogenous Cushing syndrome is rarer and caused by the body’s own overproduction of cortisol.

Causes of Endogenous Cushing Syndrome

Endogenous causes are further divided into ACTH-dependent and ACTH-independent types. Understanding this division is key to answering questions about diagnostic workup.

• ACTH-Dependent (80-85%): Excess ACTH from a tumor stimulates the adrenal glands. This is most commonly Cushing’s disease, caused by a pituitary adenoma. Less commonly, it’s from an ectopic ACTH-producing tumor (e.g., small cell lung cancer).
• ACTH-Independent (15-20%): The adrenal glands themselves are the source of excess cortisol, typically from an adrenal adenoma, carcinoma, or hyperplasia. In these cases, pituitary ACTH production is suppressed.

Pathophysiology of Cortisol Excess

Cortisol, a glucocorticoid, affects nearly every system in the body. Its catabolic effects on protein lead to muscle wasting and thin skin. Its effects on fat metabolism cause the characteristic central fat redistribution. It also increases gluconeogenesis and insulin resistance, leading to hyperglycemia, and has mineralocorticoid effects that can cause hypertension and hypokalemia.

Classic Clinical Manifestations

Exam questions often present a patient with a classic constellation of symptoms. Recognizing these is the first step.

• Central (truncal) obesity with slender extremities
• A rounded, plethoric face (“moon facies”)
• Fat accumulation on the upper back (“buffalo hump”)
• Wide (>1 cm), purplish striae, typically on the abdomen
• Proximal muscle weakness (difficulty standing from a chair)
• Easy bruising and thin, fragile skin
• Hypertension and hyperglycemia

Diagnostic Screening Tests: The First Step

Initial testing aims to confirm the presence of hypercortisolism. Exam questions will test your knowledge of first-line screening options. At least one of the following is required:

• 24-hour urinary free cortisol (UFC): Measures total cortisol excretion over a full day.
• Late-night salivary cortisol: Cortisol levels should be lowest at night; elevated levels are suggestive.
• Low-dose dexamethasone suppression test (LDDST): A healthy person’s cortisol will be suppressed by a small dose of dexamethasone; failure to suppress is abnormal.

Differentiating Cushing’s Disease from Ectopic ACTH

If a patient has ACTH-dependent Cushing syndrome, the next step is to find the source. The high-dose dexamethasone suppression test is a classic tool for this. Most pituitary adenomas (Cushing’s disease) will show some suppression of cortisol with a high dose of dexamethasone, whereas ectopic tumors typically do not.

Treatment Principles and Key Interventions

Treatment is directed at the underlying cause. For Cushing’s disease, the primary treatment is transsphenoidal surgery to remove the pituitary adenoma. For adrenal tumors, surgical resection is the standard. Medical therapy (e.g., ketoconazole, metyrapone) may be used to control cortisol levels before surgery or if surgery is not an option.

Key Takeaways

• The most common cause of Cushing syndrome is iatrogenic (exogenous glucocorticoid use).
• The most common endogenous cause is Cushing’s disease (an ACTH-secreting pituitary adenoma).
• Diagnosis is a two-step process: first, confirm hypercortisolism, then determine the cause.
• Plasma ACTH level is the critical test to differentiate between adrenal (low ACTH) and pituitary/ectopic (normal/high ACTH) causes.
• Classic signs include central obesity, wide purple striae, moon facies, and proximal muscle weakness.

This guide is for informational purposes and exam preparation only. It is not a substitute for professional medical advice, diagnosis, or treatment from a qualified healthcare provider.