Table 3.

Clinical manifestations of adrenal hormone excess

Hormone excess		General considerations	Clinical manifestations
Cortisol excess	MACS	• Diagnosed in up to 50% of patients with incidentalomas. • Absence of stigmata of overt cortisol excess (Cushing syndrome). • Associated with frailty and an increased cardiometabolic morbidities.	• Metabolic syndrome: hyperglycemia; hypertension; dyslipidemia; obesity. • Cardiovascular events. • Atrial fibrillation and other arrhythmias. • Osteoporosis and fragility fractures (high prevalence of asymptomatic vertebral fractures). • Anxiety/depression. • Chronic kidney disease. • Frailty
	Cushing syndrome	• Rare (3%-5% of patients with adrenal adenomas). • Up to 50% are diagnosed during adrenal incidentaloma work up. • Requires prompt recognition and work up to confirm the diagnosis and offer treatment. • If untreated, it is associated with high morbidity and mortality. • Concomitant adrenal androgen excess indicates adrenocortical carcinoma.	• Stigmata of cortisol excess: facial plethora; dorsocervical fat pad; supraclavicular fat pads; muscle loss, proximal myopathy, and muscle weakness; easy bruising; red stretchmarks. • Increased mortality risk, mainly driven by cardiovascular and thromboembolic events. • Metabolic syndrome: hyperglycemia; hypertension; dyslipidemia; obesity. • Osteoporosis and fragility fractures. • Immunosuppression and susceptibility to infections. • Depression and other psychiatric disorders, insomnia, memory loss, irritability, panic attacks. • Amenorrhea and reduced fertility. • Heart failure.
Aldosterone excess		• Incidentalomas causing primary aldosteronism are almost invariably benign. • Hypokalemia is not required to make the diagnosis. • Associated with increased cardiometabolic risk. • Concomitant cortisol excess (usually MACS) is common.	• Hypertension. • Hypokalemia (10%-40% of cases). • Symptoms and complications related to hypokalemia: polyuria and nocturia; fatigue and weakness; muscle cramps; constipation. • Cardiovascular and cerebrovascular events. • Chronic kidney disease. • Heart failure and atrial fibrillation. • Left ventricular hypertrophy. • Metabolic syndrome: hyperglycemia; obesity. • Osteoporosis. • Depression. • The spectrum of biochemically proven primary aldosteronism includes also subjects with normal blood pressure. Primary aldosteronism should be suspected in young normotensive subjects with unexplained hypokalemia.
Androgen excess		• Adrenal androgen excess typically indicates adrenocortical carcinoma. Androgen-producing adenomas are extremely rare. • Androgen and cortisol co-secretion (both MACS and Cushing syndrome) are common in adrenocortical carcinoma.	Women can present with: • Hirsutism. • Oily skin and acne. • Hair loss. • Changes in libido. • Menstrual irregularities. • Metabolic syndrome (chronic androgen excess).
Catecholamine excess		• Pheochromocytomas are increasingly diagnosed incidentally (60%). • Most patients do not have the classic “spell” symptoms. • Germline pathogenic variants are common (up to 40%-50%). Syndromic associations can be a clue to the diagnosis (Table 4).	• Hypertension in up to 90% cases (paroxysmal in 50%). • Classic triad (“spell”): headaches, sweating, palpitations. • Pallor, nausea, tremor, anxiety. • Postural hypotension • Supraventricular tachycardia. • Myocardial ischemia/ infarction. • Cardiomyopathy and heart failure (takotsubo syndrome). • Hypertensive crisis triggered by stressors (e.g., surgery, colonoscopy, some medications).

Abbreviation: MACS, mild autonomous cortisol secretion.