Carney Complex

Carney complex consists of spotty skin pigmentation in association with multiple neoplasias (mainly cardiac and endocrine tumors). The two types of Carney complex are type I and type II. Both types show the same clinical features.

Myxoma-Spotty Pigmentation-Endocrine Overactivity; Carney Syndrome.

Initially, the term NAME syndrome (acronym for nevi, atrial myxomas, myxoid neurofibroma, ephelides) was proposed for this condition. Later, the term LAMB syndrome (acronym for lentigines, atrial myxomas, mucocutaneous myxomas, blue nevi) was suggested. Both syndromes now are part of the Carney complex. The American physician J.A. Carney reviewed several of these cases in 1985 and suggested a common pathogenetic link between the clinical findings.

In the United States, cardiac myxomas occur with a frequency of 5-10:10,000, of which approximately 7% are associated with Carney syndrome. The syndrome can present at any age and in either sex. No sexual predilection has been found.

Autosomal dominant with variable penetrance. Because type I has been researched more thoroughly, we discuss this type here. It is caused by mutations of the PRKAR1A gene (protein kinase, c-AMP-dependent, regulatory, type I, alpha, also called tissue specific extinguisher 1), which is an important regulator of the serine-threonine kinase activity catalyzed by the protein kinase A holoenzyme, and has been mapped to 17q22-q24. The exact function of PRKAR1A in cell cycle regulation, growth, and/or proliferation in general and Carney complex syndrome in particular remains to be elucidated, but a function as a tumor suppressor gene has been discussed.

Cardiac myxomas, while histologically benign, may cause embolic phenomena, valvular obstruction, and heart failure. Myxomas are also found in the thyroid and adrenal glands, brain, breasts, and testes. Nonmyxomatous tumors, such as Sertoli cell tumors of the testis, pituitary adenomas, and psammomatous melanotic schwannomas, may occur. Primary pigmented nodular adrenocortical disease, a characteristic micronodular form of bilateral adrenal hyperplasia, causes a unique, inherited form of Cushing syndrome. Thyroid and pituitary dysfunction have been observed. Systemic symptoms may be caused by overproduction of the proinflammatory cytokine interleukin-6 by myxoma cells.

Based on the clinical findings of pigmented skin lesions associated with neoplasias (particularly myxomas). The mean age at the time of diagnosis is 10 to 20 years.

Skin manifestations include dark pigmented skin lesions (lentigines). Although they can be found anywhere on the body, they typically are located in the center of the face (i.e., periorally, perinasally, periorbitally, and in the sclerae). The finding of lentigines on the lips in association with a myxoma or an endocrine disorder/tumor should prompt further examinations to rule out Carney complex. Urogenital (vulvar) lentigines also are considered characteristic for this disorder. Cardiac myxomas may be solitary or multiple and can occur in any cardiac chamber, although almost 90% occur in one of the atria. The left atrium accounts for 80% of all atrial myxomas. After resection they may recur (approximately in 10-20% of cases) at the same or different intracardiac and/or extracardiac sites. Cardiac myxomas account for 25% of deaths in patients with Carney complex. A history of neurologic deficits or transient ischemic attacks may be present if tumor embolization has occurred. Systemic manifestations such as fever, arthralgia, elevated erythrocyte sedimentation rate, and lupus-like rashes may accompany some myxomas. Extracardiac myxomas (of breast, testis, thyroid, brain, adrenal gland) and nonmyxomatous tumors (e.g., Sertoli cell and Leydig cell tumor of the testis, pituitary adenomas, and psammomatous melanotic schwannomas [mainly esophagus and stomach, but also along the paraspinal sympathetic ganglia]) have been described. Pituitary adenomas may result in hyperprolactinemia and acromegaly.

Anesthesia management will be influenced by the presence of cardiac involvement and the type of endocrinopathy. Initial biochemical endocrine assessment should consist of venous thyroxine/thyroid-stimulating hormone, cortisol, and growth hormone levels. Abnormalities should be further assessed by an endocrinologist. Renal function and glucose and electrolyte levels should be checked. Echocardiography should be performed to determine the presence, size, number, localization, and hemodynamic significance of cardiac myxomas. Results of electrocardiography usually are normal unless valvular dysfunction is present. The presence of back pain and/or radiculopathy may indicate a spinal tumor and warrants further (predominately radiologic) investigation.

Cardiac myxomas may cause low cardiac output by valvular obstruction. Hypoxemia may occur secondary to tumor embolization and intracardiac right-to-left shunts via a patent foramen ovale. Intraoperative transesophageal echocardiography may be useful in guiding volume management and inotropic support. Pulmonary artery catheterization is relatively contraindicated (especially with right-sided intracardiac myxomas). The hemodynamic effects of the myxoma may be position dependent. Cardiovascular collapse on induction of anesthesia and sudden death have been reported. Preoperative pharmacological control of endocrinopathy is indicated. Close perioperative control of blood glucose levels in the presence of diabetes (Cushing syndrome, acromegaly) is mandatory. Airway management could be difficult if the features of acromegaly are pronounced (macroglossia, prominent jaw). Hypertension and hypokalemia may occur in association with Cushing syndrome and warrant correction.

Antibiotic prophylaxis may be indicated in the presence of valvular involvement. Anticoagulation does not appear to reduce the incidence of embolic events from myxomas. Patients who are receiving or have undergone previous medical or surgical treatment for Cushing syndrome may require perioperative steroidal supplementation.

Multiple Endocrine Neoplasia (MEN): Consists of benign, and sometimes malignant tumors (often multiple in a tissue) of the parathyroids, enteropancreatic neuroendocrine system, anterior pituitary gland, and other tissues. Skin angiofibromas and skin collagenomas are common.