Endocrine · Year 2 · from Endocrine
Case 3: Cushing Disease
Patient Demographics
- Age: 38 years
- Sex: Female
- Occupation: Elementary school teacher
Chief Complaint
"I've gained 30 pounds in my trunk despite dieting, and I bruise at the slightest touch."
History of Present Illness
A 38-year-old woman presents with a 2-year history of progressive weight gain (30 lbs), predominantly in her abdomen and face, despite attempts at diet and exercise. She has noticed easy bruising, facial plethora, and development of purple streaks on her abdomen. She reports proximal muscle weakness, difficulty climbing stairs and getting up from chairs. She has developed new-onset hypertension and was recently diagnosed with type 2 diabetes. She also reports mood changes with irritability and depression, as well as irregular menstrual periods.
Physical Examination
- Vital Signs: BP 158/96 mmHg, HR 82 bpm
- General: Central obesity with relatively thin extremities
- Face: Moon facies, facial plethora, mild hirsutism
- Skin: Thin skin, multiple ecchymoses, wide (>1 cm) violaceous striae on abdomen
- Back: Dorsocervical fat pad ("buffalo hump"), supraclavicular fat pads
- Extremities: Proximal muscle weakness (difficulty rising from squat), thin arms and legs with muscle wasting
- Neurologic: Mild proximal weakness 4/5
Workup
- Initial Screening Tests:
- 24-hour urine free cortisol: 486 μg/24h (elevated, normal <50)
- Late-night salivary cortisol: 0.52 μg/dL (elevated, normal <0.09)
- 1 mg overnight dexamethasone suppression test: AM cortisol 14.2 μg/dL (fails to suppress <1.8)
- ACTH Level: 58 pg/mL (normal/elevated - indicating ACTH-dependent)
- High-dose dexamethasone suppression test: >50% suppression of cortisol
- MRI Pituitary with Contrast: 6 mm microadenoma in left side of pituitary
- Inferior petrosal sinus sampling (if MRI inconclusive): ACTH central-to-peripheral gradient >3:1 after CRH stimulation
Diagnosis
Cushing disease (ACTH-secreting pituitary adenoma causing hypercortisolism)
Treatment
- First-line: Transsphenoidal surgical resection of pituitary adenoma
- Post-operative management:
- Monitor for adrenal insufficiency (hypothalamic-pituitary-adrenal axis suppression)
- Glucocorticoid replacement until axis recovers
- If surgery fails or recurrence:
- Repeat surgery
- Radiation therapy (conventional or stereotactic)
- Medical therapy: Pasireotide, cabergoline, ketoconazole, metyrapone, osilodrostat
- Bilateral adrenalectomy (last resort - risk of Nelson syndrome)
- Management of comorbidities: Diabetes, hypertension, osteoporosis, psychiatric symptoms
Clinical Pearl
Cushing disease specifically refers to ACTH-dependent hypercortisolism caused by a pituitary adenoma, while Cushing syndrome is the broader term for hypercortisolism of any cause. The diagnostic workup follows a stepwise approach: (1) confirm hypercortisolism with 24-hour urine free cortisol, late-night salivary cortisol, or low-dose dexamethasone suppression test; (2) determine if ACTH-dependent or independent by measuring ACTH; (3) if ACTH-dependent, localize the source (pituitary vs. ectopic). Wide violaceous striae (>1 cm) are highly specific for Cushing syndrome and help distinguish pathologic hypercortisolism from simple obesity.
Clinical Image
Clinical photograph demonstrating characteristic features of Cushing syndrome including moon facies, central obesity, and abdominal striae.
Image Source: Wikimedia Commons - "Cushing syndrome" License: CC BY-SA 4.0 URL: https://commons.wikimedia.org/wiki/File:Cushing_syndrome.jpg