What is Carney Complex?
Carney complex is a rare genetic condition that causes tumor growth and is usually linked with a group of conditions called multiple endocrine neoplasia syndromes (MEN) or with another condition known as primary pigmented nodular adrenal dysplasia (PPNAD). Carney complex affects various glands like the thyroid, pituitary, and adrenal glands in the body. It mostly influences the region responsible for adrenal cortisol production and can cause a condition known as Cushing syndrome. However, it can also affect other hormone-related systems.
Conditions associated with Carney complex include cardiac myxomas (tumors in the heart), skin pigmentation abnormalities and tumors, breast tumors, skin-related nerve tumors (melanotic schwannoma), and testicular and ovarian tumors. The majority of health complications and deaths due to Carney complex arise from heart tumors and nerve tumors. Treatment generally involves the surgical removal of both adrenal glands, but in some cases, non-surgical treatment options can also be effective.
What Causes Carney Complex?
Approximately one-fourth of cases appear randomly due to a new mutation that was not inherited from the parents. In the past, Carney complex was believed to be an inherited trait passed from one generation to the next, but recent discoveries linked it to two specific genes.
The first gene, called CNC gene 1, carries a mutation located at a specific part of our genetic code (17q22-24). This mutation affects a part of a protein called protein kinase A (PRKAR1A) and is seen in about two thirds of people with Carney complex.
The second gene is found on a different part of our genetic code (2p16). However, scientists have not been able to identify the specific gene yet. Some changes in this gene have been found in people carrying the mutation in PRKAR1A.
Two other genes, known as PDE11A and PDE8B, have been found to carry mutations in people with isolated tiny pigmented or non-pigmented overgrowth of cells. These mutations either create a premature “stop” signal for protein production or alter the protein’s building block in the part of the protein involved in Carney complex.
Risk Factors and Frequency for Carney Complex
Carney complex is a rare disorder and its exact prevalence is not known. Since 1985, approximately 750 cases have been documented globally, spanning various ethnicities. It’s worth noting that these numbers may not fully reflect the true prevalence of the condition. This is due to the difficulty in diagnosing Carney complex and a lack of awareness about this complex disorder within the medical community.
Signs and Symptoms of Carney Complex
Carney complex is a condition that has numerous effects on the body. One of the major effects is the formation of various types of tumors, both benign and malignant, in different parts of the body.
The most common places for tumors to form are in the endocrine glands, the pituitary gland, the thyroid, and the gonads (testicles and ovaries). These tumors can cause a variety of symptoms and health problems.
On the endocrine side, many people with Carney complex develop Cushing syndrome. This is due to an adrenal disorder known as nodular primary pigmented adrenocortical disease (PPNAD), which causes increased cortisol levels. This condition tends to be more common in women and younger adults and usually appears in the second or third decade of life.
In the pituitary gland, tumors often cause a condition called acromegaly. This condition, which causes enlargement of the hands and feet, has a slow onset and usually doesn’t appear until the third decade of life. Around 10% to 15% of people with Carney complex will develop clinical acromegaly, while about 75% may have high levels of growth hormone without displaying symptoms.
The thyroid is another area commonly affected by Carney complex. About 75% of people with this condition will develop cystic or multinodular disease. While the majority of these thyroid nodules are benign adenomas, around 3% can develop into thyroid cancer, usually of the papillary type, necessitating regular thyroid check-ups.
- In men, testicular tumors are common and occur in 20-50% of Carney complex patients. These tumors can cause fertility issues.
- In women, ovarian cysts and tumors are common, with some eventually progressing to ovarian cancer.
Beyond the endocrine system, Carney complex can also lead to heart tumors, skin manifestations (such as lentigines, blue nevi, and cutaneous myxoma), breast lesions, melanotic schwannoma, osteochondromyxoma, and other uncommon lesions. These manifestations can cause a wide array of symptoms and complications and often require regular monitoring and treatment.
Testing for Carney Complex
Once a patient is diagnosed with Carney complex, they have to be monitored for the rest of their lives. This means that they should have regular health check-ups at least once a year. These check-ups should begin in infancy for some patients.
These health check-ups will look at various parts of the body:
– Adrenal Glands: Here, doctors will examine hormone production and may order a dexamethasone suppression test. This test is given to see how the body reacts to dexamethasone, a medicine which usually lowers cortisol production. If someone has Carney complex, their body might respond differently and actually make more cortisol. Even if the cortisol level is usual and the patient isn’t showing signs of Cushing syndrome, the test might still reveal Carney complex. Doctors also examine the adrenal glands using CT scans, looking for any lumps or nodules that can be a sign of the condition.
– Pituitary: Most patients with the Carney complex show abnormalities linked to growth hormone (GH) production. These irregularities often show up even before there are visible signs of a pituitary tumor. To monitor these changes, doctors might recommend regular MRI scans and an oral glucose tolerance test. If a tumor begins to form, surgery may be needed. If the growth hormone level increases but no tumor is present, medication to reduce the growth hormone might be prescribed.
– Thyroid: Many people with Carney complex experience issues with their thyroid. This typically includes having cystic disease or multiple nodules. An annual examination of the thyroid using ultrasound is recommended. If a nodule is detected, doctors might use a fine needle to extract some tissue and examine it further.
– Gonads: An ultrasound may be used to check the ovaries and testes for any abnormal changes or growths. Larger growths or suspicious lesions need to be regularly monitored to ensure they don’t develop into cancer, particularly if they are larger than 6 cm.
– Heart: Patients should undergo screening for heart tumors, called cardiac myxoma, starting from when they are just a few months old. Regular screenings using an echocardiogram are needed, and in some difficult cases, other tests like a transesophageal ultrasound or MRI might be required.
– Breast: Regular mammograms don’t seem to significantly improve survival rates, but if previous tumors were found, a breast MRI might be used. The treatment and follow-up care for breast conditions in patients with Carney complex isn’t standardized and will depend on each individual’s unique circumstance.
Treatment Options for Carney Complex
Cushing syndrome caused by PPNAD needs treatment to manage the effects of too much cortisol in the body. The usual treatment is a bilateral adrenalectomy, which is surgery to remove both adrenal glands. However, in some situations, medications like ketoconazole or mitotane can be used to reduce cortisol levels.
If you have thyroid nodules, your doctor might use a method called a fine-needle aspiration to take a small sample. If the results suggest possible cancer, you’ll be referred for surgery.
In rare cases, a person with Carney complex and acromegaly, an abnormal growth condition, may need surgery or even radiation treatment to manage an aggressively growing tumor. Medications known as somatostatin analogs can also be used for treatment, either on their own or as a supplement to surgery.
LCCSCTs, a specific kind of tumor, are usually benign or non-cancerous, especially when they occur on both testicles. They are typically monitored using imaging technology. If any abnormality is found on the images or tumor markers, minor surgery may be considered to examine small tumors closely. There have been a few cases where prepubescent boys with LCCSCT were treated with medications called aromatase inhibitors. On the other hand, malignant or cancerous LCCSCTs are more common in older patients and usually require the removal of one testicle, known as orchiectomy.
Treatment for cardiac myxomas, a type of heart tumor, is typically surgical removal. Since these tumors might recur, regular monitoring is important. Psammomatous melanotic schwannomas, a type of nerve sheath tumor, are treated with surgical removal of the entire tumor, maintaining a safe area around it. There might be a need for chemotherapy or radiation therapy if the tumor is malignant or cancerous.
What else can Carney Complex be?
To come up with the correct diagnosis, doctors might consider a wide variety of conditions that display similar characteristics. These can include:
- Cushing disease: a condition caused by high levels of the hormone cortisol
- Adrenal carcinoma: a type of cancer that affects the adrenal glands
- Adrenal incidentaloma: an unexpected growth in the adrenal gland
- Breast cancer: a type of cancer that forms in the cells of the breasts
- Intracardiac thrombus: a blood clot forming within the heart
- Lentigo: a condition characterized by small brown spots on the skin
- Melanotic nevi: dark-colored, potentially malignant patches or bumps on the skin
- Primary cardiac neoplasms: tumors that originate in the heart
- Rhabdomyoma: a type of benign (non-cancerous) tumor that develops in muscle tissue
Making the appropriate diagnosis requires a careful consideration of these possibilities and appropriate testing.
What to expect with Carney Complex
The greatest risk of death related to Carney complex is associated with heart disease, accounting for 57% of cases. This includes heart myxomas, a type of benign heart tumor, and complications arising from heart surgery.
Other significant causes of death include a type of tumor called intracranial psammomatous melanotic schwannoma, which can spread to other parts of the body or grow within the brain, and carcinoma or cancer that has spread to other areas of the body. Both contribute to 14% of the mortality rate. Finally, complications following surgery, excluding those related to the heart, contribute to 12% of deaths.
Possible Complications When Diagnosed with Carney Complex
The main risk of Carney complex is death that’s linked with heart tumors, a specific type of nerve tumor, and cancers or the spreading of cancer. These complications are quite common in people with a disorder known as multiple endocrine neoplasia (MEN) syndrome. A common treatment strategy includes the surgical removal of the adrenal glands. This results in patients needing to rely on external steroid supplements for the rest of their lives and exposes them to the risk of having too little cortisol in their bodies.
Here’s a brief rundown of Carney complex risks:
- Death linked to heart tumors
- Specific type of nerve tumor
- Cancers or the spreading of disease
- Common in people with MEN syndrome
- Lifelong reliance on external steroid supplements after adrenal gland removal surgery
- Risk of lowered cortisol levels
Preventing Carney Complex
Adults and children who have or may be at risk for Carney complex should be informed about the probable hazards their children may encounter due to it. They need to be made aware, before their childbearing years, of the possibility of conducting genetic diagnosis tests both before remaining embryos are implanted and after conception. Looking specifically for changes in the PRKAR1A gene, responsible for Carney complex, can be useful for other family members who may be at risk.
However, it is still advisable for family members who may carry this risk to be regularly monitored by healthcare professionals, even if they don’t test positive for the PRKAR1A gene mutation. Patients should be given a good understanding of their condition, what symptoms to look out for, such as hints of heart-related blood clots or the development of tumors. Regular follow-ups are essential to minimize complications linked with Carney complex.
