Carney complex is a multisystem disease initially described by Dr. J.A. Carney at the Mayo Clinic in 1985, as a combination of manifestations:
Since the time of its initial description, the complex has been expanded slightly to include a number of other specific conditions, including pigmented Schwannomas (a tumor of the nerve root), and thyroid nodules and cancer. A description of the clinical syndrome follows, but for another opinion you might want to look at the Online Mendelian Inheritance in Man's listing for Carney complex.
Cushing syndrome is caused by the presence of too much glucocorticoids in the body. In general, this can be caused by exogenous means (steroid abuse) or endogenous oversecretion. Glucocorticoids, which in humans means the hormone cortisol, are normally produced in the adrenal glands under the regulation of the pituitary hormone ACTH. When Cushing syndrome is caused by overstimulation of the adrenals by pituitary-derived ACTH, this is known as Cushing disease, after Harvey Cushing who described it in the early 1900's.
In Carney complex, Cushing syndrome is caused by a primary defect at the level of the adrenal gland, so that this tissue secretes cortisol without its normal regulatory control. The adrenal glands have a particular appearance, with many small darkly-pigmented nodules present in an otherwise shrunken gland. This is known pathologically as primary pigmented nodular adrenocortical disease (PPNAD), and is in sharp contrast to the type of adrenal pathology seen in another primary adrenal disease known as massive macronodular adrenocortical disease (MMAD). In MMAD, the adrenal glands are markedly enlarged to 10 to 50 times their normal size, and are composed of large nodules which are yellowish in color, similar to the color of normal adrenal glands. Both of the conditions, which have low serum ACTH levels, are quite distinct from adrenal adenomas and carcinomas, which are focal neoplastic processes, most likely arising from a single cell containing a mutation.
Acromegaly is the name given to the syndrome caused by the presence of excess growth hormone (GH) in the body. GH is produced directly by the pituitary gland, and most acromegalics have a pituitary tumor to account for their disease. In Carney complex, patients may either have a specific pituitary tumor, or may have evidence of diffuse enlargement (hyperplasia) of the GH-poroducing cells. Because of the common origin of the pituitary cells that produce GH and another pituitary hormone Prolactin (PRL), Carney patients (as well as other acromegalics) may have evidence of oversecretion of both hormones concurrently.
The most notable symptom of acromegaly is unregulated growth. When this occurs in adults whose long bones are no longer capable of growing, the growth is localized to specific features that can still grow in size. Specifically, changes are often seen in the hands, feet, jaw, forehead, and nose. Typically, the effects of excess growth hormone secretion become evident over the course of many years, so people often don't recognize the subtle changes that are occurring. When they present to medical attention, there is often a history in retrospect of a change in shoe or ring size, and pictures dating back many years will frequently document the facial changes.
Carney complex is one of a number of disorders that involve specific changes in skin pigmentation. In particular, patients with Carney complex get a specific type of skin freckles known as lentigines. These tend to be dark brown and do not change much with sun exposure, in contrast to common freckles (ephiledes). In African-American patients, the lentigines are often seen as especially dark "freckles" that are slightly raised.
The lentigines seen in Carney complex, like those in another genetic syndrome known as Peutz-Jeghers Syndrome, are typically located in the central part of the face, most notably around the lips, nose and eyes. The finding of lentigines on the lips themselves in the context of an endocrine disorder or myxoma (see below) should raise the suspicion for this disorder. Although the lentigines can also be scattered throughout the body, the finding of lentigines on the vulva of women is also fairly characteristic of this disorder.
Although lentigines are the most common skin finding, a variety of lesions can also be seen, including junctional nevi or blue nevi. The diagnosis of any of these skin findings must be documented by biopsy, in order to verify the distinction from other look-alike skin conditions.
Myxomas are abnormal growths of relatively undifferentiated tissue in the body that occur sporadically, or in association with Carney complex. They are generally not malignant, and exhibit slow but continuous growth. The myxomas in Carney complex are found throughout the body, but there are a number of typical locations.
The most potentially dangerous location from myxomas are within the chambers of the heart. These can grow to a few centimeters in size without causing symptoms. The danger from these growths comes when they reach a size at which pieces of the tumor begin to break off and embolize to different parts of the body. The serious complications that can arise in this matter include pulmonary emboli and stroke. A stroke-like episode that occurs suddenly in a young person with no other risk factors should raise suspicion for the possibility of a cardiac myxoma, and this can be sought using echocardiography (although generally not with 100% sensitivity). The finding of a cardiac myxoma, either because of a stroke-like episode, or for unrelated reasons, is a medical urgency, and the tumor needs to be removed as soon as appropriate cardiac surgery facilities can be arranged.
When myxomas occur outside of the heart, they generally are of little clinical significance, except occasionally for cosmetic reasons. They are ususally noted as small bumps under the skin which grow very slowly. We recommend their removal for diagnostic purposes when the suspicion of Carney complex is entertained, but otherwise this is generally unnecessary. In addition to the skin of the body, myxomas in Carney complex may be located in the eyelid or the ear.
The other place that myxomas may be found in Carney complex is the breast. Typically, women that are affected will have breasts that exhibit a lumpy character. However, as many younger women have breasts of this texture, it is often difficult to say with any certainty if myxomas are present. Myxomas can also present as a noticable lump in women of young to middle years, thus raising the diagnostic concern for breast cancer.
At the NIH, we have developed a specialized magnetic resonance imaging (MRI) sequence that causes myxomas to have a bright appearance, and thus differentiate them from other breast lumps. This may help women affected by this syndrome from undergoing unnecessary breast biopsies to rule out cancer.
- Psammomatous Melanotic Schwanomma
- Testicular tumors
- Ovarian tumors
- Clinical and molecular features of the Carney complex: diagnostic criteria and recommendations for patient evaluation.
- Mutations of the gene encoding the protein kinase A type I-alpha regulatory subunit in patients with the Carney complex.
- The lentiginoses: cutaneous markers of systemic disease and a window to new aspects of tumourigenesis.