Cushing disease

Cushing Disease

Cushing disease is a condition characterized by the overproduction of adrenocorticotropic hormone (ACTH) by the pituitary gland, leading to excessive cortisol production by the adrenal glands. This condition is a specific form of Cushing syndrome, which encompasses all causes of excess cortisol.

Pathophysiology

Cushing disease is caused by a pituitary adenoma, a benign tumor of the pituitary gland, which secretes excess ACTH. The increased ACTH stimulates the adrenal cortex to produce more cortisol, a glucocorticoid hormone that plays a crucial role in metabolism, immune response, and stress regulation. The excess cortisol leads to the clinical manifestations of Cushing disease.

Clinical Features

Patients with Cushing disease often present with a variety of symptoms due to prolonged exposure to high levels of cortisol. Common features include:

• Weight gain: Particularly in the face ("moon face"), abdomen, and upper back ("buffalo hump").
• Skin changes: Thinning of the skin, easy bruising, and purple striae (stretch marks) on the abdomen.
• Muscle weakness: Proximal muscle weakness is common.
• Hypertension: High blood pressure is frequently observed.
• Glucose intolerance: Patients may develop diabetes mellitus.
• Osteoporosis: Increased risk of fractures due to bone loss.
• Psychiatric symptoms: Depression, anxiety, and cognitive dysfunction.

Diagnosis

The diagnosis of Cushing disease involves several steps:

1. Clinical suspicion: Based on the characteristic signs and symptoms. 2. Biochemical testing: Initial tests include 24-hour urinary free cortisol, late-night salivary cortisol, and low-dose dexamethasone suppression test. 3. ACTH levels: Elevated ACTH levels suggest a pituitary source. 4. Imaging: MRI of the pituitary gland is used to identify the adenoma. 5. Inferior petrosal sinus sampling: This test may be used to confirm the pituitary source of ACTH.

Treatment

The primary treatment for Cushing disease is surgical removal of the pituitary adenoma, typically through a transsphenoidal approach. Other treatment options include:

• Radiation therapy: Used if surgery is not possible or if residual tumor remains.
• Medications: Drugs such as ketoconazole, metyrapone, or pasireotide may be used to control cortisol levels.
• Bilateral adrenalectomy: In rare cases, removal of the adrenal glands may be necessary.

Prognosis

The prognosis for patients with Cushing disease depends on the success of treatment. Surgical removal of the adenoma can lead to remission in many cases, but some patients may experience recurrence. Long-term follow-up is essential to monitor for recurrence and manage any persistent symptoms or complications.

Also see

• Cushing syndrome
• Pituitary adenoma
• Adrenal gland
• Hypercortisolism