What is the recommended management for a patient with Carney complex who has cardiac myxomas and multiple endocrine tumors?

Management of Carney Complex with Cardiac Myxomas and Endocrine Tumors

Patients with Carney complex require immediate surgical resection of cardiac myxomas when detected, combined with lifelong echocardiographic surveillance every 6-12 months, as cardiac myxomas are the leading cause of mortality in this syndrome. 1, 2

Immediate Cardiac Management

Surgical Intervention for Myxomas

• Perform surgical excision of all detected cardiac myxomas promptly, as they cause mortality through embolic events (including stroke), arrhythmias, heart failure, and sudden cardiac death 2, 3
• Utilize multi-imaging modalities including transthoracic echocardiography, transesophageal echocardiography, and cardiac MRI to delineate the mass location and attachment before planned resection 4, 5
• Recognize that myxomas in Carney complex can occur in atypical locations including the right ventricle and right atrium, not just the left atrium 4, 3

Lifelong Cardiac Surveillance Protocol

• Perform echocardiography every 6-12 months indefinitely, as recurrence rates reach 22% in Carney complex patients compared to only 2-3% in sporadic myxoma cases 1, 2
• Continue surveillance even decades after initial resection, as recurrence has been documented 10-16 years after primary tumor removal 2, 3

Comprehensive Endocrine Tumor Management

Annual Screening Requirements

• Measure serum IGF-1 levels and assess for acromegalic features annually to detect growth hormone-producing pituitary adenomas 1, 6
• Screen annually for primary pigmented nodular adrenocortical disease (PPNAD) starting at diagnosis, as at least 50% of patients with isolated PPNAD harbor PRKAR1A mutations and will develop life-threatening cardiac myxomas later 1, 6
• Perform annual thyroid ultrasound and TSH screening given the association with thyroid papillary carcinoma and multiple nodules 1, 6, 7
• Conduct testicular ultrasound in males to detect large-cell calcifying Sertoli cell tumors 5

Treatment of Growth Hormone Excess

• Offer transsphenoidal surgery as first-line treatment for GH-producing adenomas, even when surgical cure is unlikely, to reduce GH burden and prevent complications 1
• Consider pre-operative medical therapy with somatostatin analogues and/or GH receptor antagonists to rapidly control symptoms and facilitate perioperative airway management 1
• Assess treatment efficacy using both height velocity measurements and serum GH/IGF-1 levels 1

Management of PPNAD-Related Cushing Syndrome

• Perform bilateral adrenalectomy when laboratory findings confirm ACTH-independent hypercortisolism from PPNAD 7, 5
• Recognize that PPNAD may present with cyclic hypercortisolism and normal ACTH levels 7

Diagnostic Confirmation and Genetic Testing

Establishing the Diagnosis

• Confirm Carney complex when at least two major criteria are present OR one major criterion plus a PRKAR1A mutation 8, 1
• Major criteria include: spotty brown-to-black lentigines on lips/conjunctiva/canthi/genital mucosa, cardiac myxomas, cutaneous/mucosal myxomas, PPNAD, GH-producing adenomas, large-cell calcifying Sertoli cell tumors, thyroid carcinoma, psammomatous melanotic schwannoma, multiple blue nevi, multiple breast ductal adenomas, and osteochondromyxomas 8, 1, 9

Mandatory Genetic Testing

• Perform PRKAR1A mutation analysis in all suspected cases, as 71% of patients meeting at least two major criteria have identifiable mutations 8, 1
• Conduct family screening when a PRKAR1A mutation is identified, given autosomal dominant inheritance with variable penetrance 4, 5

Additional Surveillance Components

• Assess clinically and with imaging for osteochondromyxomas if bone symptoms develop 1, 6
• Screen for psammomatous melanotic schwannoma, a rare but potentially malignant nerve sheath tumor 8, 1
• Evaluate breast tissue in females for myxomatosis and multiple ductal adenomas using fat-suppressed MRI 8, 6
• Monitor for superficial angiomyxomas and other cutaneous manifestations 5

Critical Clinical Pitfalls

Do Not Dismiss Mucosal Pigmentation

• Never dismiss lentigines as benign freckles—Carney complex lentigines characteristically involve mucosal surfaces (lips, conjunctiva, canthi, genital mucosa), not just skin, which distinguishes them from common freckles 1, 6

Do Not Overlook Isolated Endocrine Findings

• Never overlook isolated endocrine presentations—at least 50% of patients presenting with only PPNAD have PRKAR1A mutations and may develop life-threatening cardiac myxomas years later 1, 6

Recognize Young Age and Recurrence Patterns

• Consider Carney complex when cardiac myxomas are multiple, recurrent, or occur at relatively young age (under 40 years), even without other syndromic features initially 3, 6
• Cardiac myxomas in Carney complex affect both sexes equally, unlike sporadic myxomas which predominate in females 4

Multidisciplinary Coordination

• Coordinate care through a multidisciplinary team including cardiothoracic surgery, endocrinology, medical genetics, cardiology, and dermatology to address the multiple organ systems involved 1