What is the differential diagnosis for purple striae?

Differential Diagnosis for Purple Striae

Purple striae are most commonly caused by Cushing syndrome (either endogenous or iatrogenic from exogenous corticosteroid use), and this should be the primary diagnostic consideration when evaluating this finding. 1

Primary Diagnostic Consideration: Cushing Syndrome

Purple striae represent a highly specific clinical feature of hypercortisolism and should immediately prompt evaluation for Cushing syndrome. 1 The presence of purple striae, particularly when wide (>1 cm) and located in characteristic distributions (abdomen, thighs, breasts, axillae), strongly suggests pathologic cortisol excess rather than simple obesity or rapid weight changes. 2, 3, 4

Key Clinical Context to Assess

When purple striae are identified, look specifically for these accompanying features that increase diagnostic specificity for Cushing syndrome:

• Centripetal/truncal obesity with supraclavicular fat pad enlargement and buffalo hump 1
• Proximal muscle weakness (difficulty rising from a chair or climbing stairs without using arms) 1, 3
• Facial plethora and moon facies 1, 5
• Easy bruising and skin atrophy 2, 5
• Hypertension and hyperglycemia/diabetes 1, 2
• Hypokalemia with metabolic alkalosis (particularly suggests ectopic ACTH production) 1
• Psychiatric disturbances and mood disorders 1, 2
• In children: decreased linear growth with continued weight gain 3

Etiologic Categories of Cushing Syndrome

1. Iatrogenic (Exogenous) Cushing Syndrome

This is the most common cause overall and must be excluded first. 1, 2

• Chronic use of systemic corticosteroids (oral, intravenous, intramuscular) 6
• Prolonged use of potent topical corticosteroids, especially under occlusive dressings or over large surface areas 6
• Inhaled or intranasal corticosteroids in high doses 1

Critical pitfall: The Endocrine Society emphasizes that failure to exclude exogenous glucocorticoid use before biochemical testing leads to unnecessary evaluation and potential harm. 1

2. Endogenous Cushing Syndrome (Incidence: 2-8 per million annually) 2

A. ACTH-Dependent (85% of endogenous cases)

Cushing Disease (Pituitary Adenoma): 60-70% of endogenous cases 2, 3

• Benign pituitary corticotroph adenoma secreting ACTH 2
• Typically presents with full constellation of features including purple striae 1

Ectopic ACTH Syndrome: 15% of endogenous cases 3

• Small cell lung cancer (SCLC): Most common malignant cause; clinically apparent in 1.6-4.5% of SCLC cases, but biochemical abnormalities in 30-50% 1
• Bronchial carcinoid tumors: More indolent presentation 1
• Other neuroendocrine tumors (thymic, pancreatic) 1

Key distinguishing features of ectopic ACTH:

• More prominent skin hyperpigmentation 1
• Severe hypokalemia and metabolic alkalosis 1
• Weight loss may occur (in ~10% of SCLC-associated cases) despite Cushing features 1
• Associated with poor prognosis 1

B. ACTH-Independent (15% of endogenous cases) 3

Adrenocortical Carcinoma (ACC): 1

• Incidence: 1-2 per million 1
• Bimodal age distribution (early childhood and 40-50 years) 1
• Female predominance (1.5:1) 1
• ~60% present with hormone excess including Cushing features 1
• May present with virilization (androgen excess) or other hormone combinations 1
• Associated with hereditary syndromes: Li-Fraumeni, Beckwith-Wiedemann, MEN 1 1

Adrenal Adenoma: 3

• Benign cortisol-secreting tumor 3, 7
• Unilateral adrenal mass on imaging 7

Primary Aldosteronism (Rare cause of striae): 1

• Primarily presents with hypertension, weakness, and hypokalemia 1
• Purple striae are not typical unless concurrent cortisol excess 1
• Suspect malignancy if: irregular morphology, lipid-poor, >3 cm, or multi-hormone secretion 1

Diagnostic Algorithm

Step 1: Exclude Iatrogenic Causes

• Obtain detailed medication history including all forms of corticosteroids (topical, inhaled, oral, injectable) 1
• Review use of occlusive dressings with topical steroids 6

Step 2: Screen for Endogenous Hypercortisolism (if exogenous use excluded)

The Endocrine Society recommends one or more of the following initial tests: 1

• 24-hour urinary free cortisol (>1 measurement; >4× normal strongly suggests Cushing syndrome) 1, 4
• Late-night salivary cortisol (>1 measurement) 1, 2
• Dexamethasone suppression test (1 mg overnight OR 2 mg/day for 2 days) 1, 2, 4

Step 3: Determine Etiology if Screening Positive

Measure plasma ACTH: 2, 3

• Suppressed ACTH (<5 pg/mL): Suggests adrenal source (adenoma or carcinoma) 2, 3
• Mid-normal to elevated ACTH: Suggests ACTH-dependent disease (pituitary vs. ectopic) 2, 3

For ACTH-dependent disease:

• Pituitary MRI to identify adenoma 2
• Bilateral inferior petrosal sinus sampling with ACTH measurement before and after CRH administration (most accurate test to distinguish pituitary from ectopic ACTH) 3

For ACTH-independent disease:

• Adrenal CT or MRI to characterize adrenal mass 2, 3
• Assess for features suggesting malignancy (size >4 cm, irregular borders, heterogeneity, delayed washout) 1

Step 4: Additional Evaluation for Ectopic ACTH

If ectopic ACTH suspected: 1

• Chest CT for bronchial carcinoid or SCLC 1
• Whole-body imaging (CT chest/abdomen/pelvis, octreotide scan) for other neuroendocrine tumors 1

Other Differential Considerations (Less Common)

Pseudo-Cushing States

These conditions may cause mild hypercortisolism but typically do not produce purple striae: 4

• Severe depression or psychiatric disorders 4
• Chronic alcoholism 4
• Morbid obesity 4
• Uncontrolled diabetes mellitus 4
• Sleep apnea 1, 4

Distinguishing features: Use midnight cortisol measurements, 2-day 2-mg dexamethasone suppression test, or dexamethasone-CRH stimulation test. 4

Hypertension-Related Evaluation

When purple striae occur with hypertension, consider screening for: 1

• Pheochromocytoma: 24-hour urinary metanephrine/normetanephrine (presents with paroxysmal hypertension, headache, palpitations, perspiration) 1
• Renovascular hypertension: Doppler flow study or MRA (abdominal bruit, age <30 or >55 at onset) 1

Critical Clinical Pearls

• Purple striae >1 cm wide are highly specific for Cushing syndrome and should not be attributed to simple obesity or pregnancy. 3, 4
• Always exclude exogenous corticosteroid use before pursuing expensive biochemical testing. 1
• In patients with lung cancer presenting with purple striae, suspect paraneoplastic Cushing syndrome from ectopic ACTH. 1
• Topical corticosteroids can cause systemic absorption and Cushing syndrome, especially in children, with large surface area application, or under occlusive dressings. 6
• If screening tests are abnormal or clinical suspicion remains high despite normal tests, refer to endocrinology for specialized evaluation. 1, 5