What are the symptoms and treatment options for hypercortisolism?

Symptoms of Hypercortisolism

Hypercortisolism presents with a constellation of clinical features that vary by age, with weight gain combined with growth deceleration being the most sensitive indicator in children, while adults typically manifest with central obesity, facial plethora, proximal muscle weakness, and wide purple striae. 1

Key Clinical Features by Age Group

Children and Adolescents

• Weight gain with simultaneous height deceleration is the hallmark presentation—this combination has high sensitivity and specificity for Cushing syndrome in prepubertal children 1
• Growth failure (subnormal growth velocity) with short stature and elevated BMI for age and sex 1
• Important caveat: Not all children with Cushing syndrome have obesity, and growth failure is unreliable in post-pubertal adolescents who require assessment according to adult guidelines 1
• Boys tend to have more aggressive disease with higher BMI, shorter height, and elevated plasma ACTH levels compared to girls 1

Adults

• Central/truncal obesity with fat redistribution causing moon facies, buffalo hump, and supraclavicular fat pads 1, 2
• Facial plethora (reddish appearance) 1
• Wide purple striae (>1 cm), particularly on the abdomen 1
• Proximal muscle weakness affecting hip and shoulder girdle muscles 1
• Temporal fat pad deposits (bitemporal masses) may develop, representing an underappreciated feature 2

Metabolic and Cardiovascular Manifestations

• Hypertension requiring treatment according to high cardiovascular risk guidelines 1
• Diabetes mellitus or impaired glucose tolerance 3, 4
• Spontaneous hypokalemia (particularly severe in ectopic ACTH syndrome) 3
• Increased risk of cardiovascular events and mortality even with mild cortisol elevations 4

Dermatologic and Musculoskeletal Features

• Thin, fragile skin with easy bruising 1
• Facial acne and hirsutism 1
• Osteoporosis and fractures from prolonged cortisol exposure 4
• Poor wound healing 1

Psychiatric and Neurologic Symptoms

• Depression, anxiety, and mood disturbances 1
• Cognitive impairment 1
• Insomnia 1

Severe Hypercortisolism (Medical Emergency)

Severe hypercortisolism is a life-threatening condition requiring urgent intervention, typically presenting with: 5, 3

• Multiorgan failure 3
• Severe hypertension with hypokalemia 3
• Acute onset diabetes 3
• Sepsis or opportunistic infections 5
• Psychiatric decompensation 5
• Markedly elevated cortisol levels (>5000 nmol/L) 3

Important Diagnostic Considerations

Screening Indications

• Screen children with obesity only if weight gain is unexplained AND combined with either decreased height SD score or height velocity 1
• Screen adults with multiple features suggestive of Cushing syndrome, particularly if progressive 4
• Common pitfall: Many patients with mild autonomous cortisol secretion lack overt Cushingoid features (plethora, striae, muscle weakness) but still experience significant morbidity 4

Subclinical Presentation

• Mild autonomous cortisol secretion is more prevalent and difficult to detect than overt disease 6
• Even slight cortisol elevations cause increased risk of diabetes, hypertension, fractures, cardiovascular events, and mortality 4
• Early diagnosis and treatment are critical as some adverse effects may not fully resolve even after treatment 6

Associated Complications

• Hypercoagulability with increased risk of venous thromboembolism requiring consideration of prophylactic anticoagulation perioperatively 1
• Increased infection risk from immunosuppression 5
• Cardiovascular disease requiring aggressive risk factor management 1

Clinical pearl: The absence of classic Cushingoid features does not exclude hypercortisolism, particularly in cases of adrenal adenomas or mild autonomous cortisol secretion. 4 Maintain high clinical suspicion in patients with multiple metabolic comorbidities (diabetes, hypertension, osteoporosis) that are difficult to control. 6