Cushing Disease Quiz

Comprehensive Guide to Cushing Disease

Cushing disease is a specific type of Cushing syndrome caused by a pituitary adenoma (a benign tumor on the pituitary gland) that secretes excess adrenocorticotropic hormone (ACTH). This guide provides essential information for medical students, healthcare professionals, and patients seeking to understand this complex endocrine disorder.

What are the Causes and Types of Cushing Syndrome?

Understanding the etiology is crucial for diagnosis and treatment. Cushing syndrome can be broadly categorized into two types:

• Exogenous Cushing Syndrome: The most common cause overall, resulting from the long-term use of high-dose corticosteroid medications (e.g., prednisone) for treating inflammatory conditions.
• Endogenous Cushing Syndrome: Caused by the body’s own overproduction of cortisol. This is further divided into:
  • Cushing Disease (Pituitary-dependent): Accounts for ~70% of endogenous cases. A pituitary adenoma produces excess ACTH, which stimulates the adrenal glands to produce excess cortisol.
  • Ectopic ACTH Syndrome: A non-pituitary tumor (often in the lungs, pancreas, or thyroid) produces ACTH.
  • Adrenal Tumors: A tumor on one of the adrenal glands (adenoma or carcinoma) directly produces excess cortisol, independent of ACTH.

Key Symptoms and Clinical Manifestations

The clinical presentation of Cushing disease is diverse, reflecting the systemic effects of hypercortisolism. Recognizing these signs is the first step towards diagnosis.

1. Central Obesity: Weight gain concentrated in the face (“moon facies”), upper back (“buffalo hump”), and abdomen, with slender limbs.
2. Skin Changes: Thin, fragile skin that bruises easily, poor wound healing, and characteristic wide, purplish striae (stretch marks) on the abdomen, thighs, and breasts.
3. Metabolic Disturbances: Hyperglycemia or new-onset type 2 diabetes, hypertension, and dyslipidemia.
4. Musculoskeletal Effects: Proximal muscle weakness and osteoporosis, leading to an increased risk of fractures.
5. Neuropsychiatric Symptoms: Mood swings, depression, anxiety, irritability, and cognitive difficulties.
6. Reproductive Issues: Menstrual irregularities in females and decreased libido or erectile dysfunction in males.

The Diagnostic Process

Diagnosing Cushing disease involves a multi-step process to first confirm hypercortisolism and then to identify its source.

• Step 1: Confirm Hypercortisolism. Initial screening tests include:
  • 24-hour urinary free cortisol (UFC) measurement
  • Late-night salivary cortisol measurement
  • Low-dose dexamethasone suppression test (LDDST)
• Step 2: Determine ACTH-Dependency. Once hypercortisolism is confirmed, a plasma ACTH level is measured. Low ACTH suggests an adrenal tumor, while normal or high ACTH points towards Cushing disease or an ectopic source.
• Step 3: Differentiate Pituitary vs. Ectopic Source. This is often the most challenging step and may involve:
  • High-dose dexamethasone suppression test (HDDST)
  • CRH stimulation test
  • Pituitary MRI to visualize the adenoma
  • Bilateral inferior petrosal sinus sampling (BIPSS) – the gold standard for confirmation.

Treatment Strategies for Cushing Disease

The primary goal of treatment is to normalize cortisol levels while preserving pituitary and adrenal function. The first-line treatment for Cushing disease is transsphenoidal surgery to selectively remove the pituitary adenoma. When surgery is not successful or possible, other options include radiation therapy, bilateral adrenalectomy, or medical therapy with drugs that inhibit steroidogenesis (e.g., ketoconazole, metyrapone) or target the tumor (e.g., pasireotide).

This information is for educational purposes only and does not constitute medical advice. Always consult with a qualified healthcare professional for diagnosis and treatment of any medical condition.