Overview

Carney complex (CNC) is a rare genetic inherited disorder, which predominantly impacts the endocrine system, nervous system and the heart. The disorder is characterised by benign tumours and spotty skin pigmentation, with the tumours often impacting the endocrine system leading to hormonal imbalances. More specifically, the adrenal gland is affected.  An organ that comprises the endocrine system, its sole purpose is to regulate bodily functions like metabolism and stress through the secretion of hormones. For people with CNC, any disruption to its function significantly impacts the day to day bodily functions in the human body. 

Causes of Carney complex

CNC is caused primarily by a mutation to the PRKAR1A gene, found on chromosome 17, but another gene (CNC2), has also been implicated in this disorder, however its role is still severely misunderstood.¹ The PRKAR1A gene is responsible for encoding a subunit of the protein kinase A, an enzyme which functions by stimulating the proliferation of cell growth.² Subsequent mutation to the gene results in an increased production of protein kinase A, and consequently uncontrolled cell growth, leading to the generation of tumours.  Approximately 60% of CNC cases are due to mutation of the PRKAR1A gene. 

Although the main cause of CNC can be pinned on mutations to the PRKAR1A gene, how they arise is dependent on the person.  There are some indications as to how a person may develop this disorder. The following two known causes are often heralded as the reason for its development:

• Inherited mutations 
• Sporadic mutations 

Individuals impacted by CNC will often have their disorder as a result of inheriting the faulty gene, since the gene is autosomal dominant. This results in an increased likelihood of an offspring having this disorder if their parent carries just one copy of the mutated gene.

Signs and symptoms of Carney Complex

Signs of CNC can present early on in a person’s life, including infancy, but tends to become more evident in teenagers and young adults. Symptoms can vary person to person and the intensity can differ depending on the age of the affected. The majority of signs involve tumours (that are often benign) that appear on certain organs, or the presence of an overactive endocrine gland.

Below details the main body areas that are affected, and the signs and symptoms associated with the disorder. 

• Skin: Lentigines, blue nevi and myxomas 
• Heart: shortness of breath, faintness and chest pain

The endocrine system’s signs and symptoms are even more extensive; issues pertaining to the system are evident due to hormone imbalances.³ People that have CNC affecting these organs will often develop other conditions as a result of it. Below details the organs impacted and the symptoms exhibited due to the disorder.

• Adrenal glands: Can cause Primary Pigmented Nodular Adrenocortical Disease (PPNAD) which can lead to Cushing’s syndrome
• Pituitary gland: Can lead to the development of acromegaly
• Thyroid gland: Causes hyperthyroidism 

These symptoms in the endocrine system tend to be internal and would require blood tests or even urine tests to diagnose. Physical symptoms can sometimes be the primary sign of hormonal imbalance as a result of CNC; these symptoms include:

• Mood changes 
• Changes in weight/appearance
• Unusual fatigue 
• High blood sugar or Diabetes 

It must be emphasised that these physical symptoms can also be caused by other conditions that are not CNC. A blood test plus further diagnostic tools used by your GP can be used to rule it out. 

What are the adrenal glands and what issues present with CNC?

Located above the kidneys, the adrenal glands are essential for producing hormones such as adrenaline, noradrenaline and cortisol.⁴ These hormones play an important role in regulating metabolism, secretion of other chemicals and guiding the body through stress responses to maintain normal bodily functions. In particular, cortisol has the greatest responsibility, since it's in charge of a wide range of body functions, including:

• The immune system
• Blood sugar regulation 
• Metabolism 
• Sleep-Wake-Cycle 

Disruption of the cortisol function will have a knock on impact to these bodily functions.

When to see a GP

A GP examination may be necessary if:

• You begin to persistently present CNC symptoms 
• Family history of CNC or Cushing’s syndrome 
• Rapid changes in weight, skin, mood, or blood pressure

Early diagnosis of CNC allows for an easier and smoother preparation on how to manage the condition throughout your life and in preventing any complications due to the disorder.

Diagnosis

Initial diagnosis will begin with physical examinations and looking at family history to determine if CNC is pre-existing within your family. Genetic testing may also be employed if found that a family member has the condition to determine whether the PRKAR1A gene is mutated. If CNC is suspected further tests are required; your GP may require a blood and urine sample test to detect abnormalities in the levels of cortisol, ACTH and growth hormone in the body.

Moreover, MRI or CT imaging may also be requested to assess any abnormalities (i.e tumours) to organs like the adrenal glands and the thyroids. 

Treatment and management options

There are a range of treatments that can be used to manage hormonal imbalances and adrenal gland issues for people with CNC. Treatment will depend on the severity of CNC, but will predominantly involve taking specific medications to manage hormonal imbalances.These include:

• GH receptor antagonists (for excessive growth hormone secretion)
• Somatostatin analogs (for excessive growth hormone secretion)

Generally, monitoring hormone levels and being prescribed the accurate medication for excess hormone production would be the main action plan for managing hormonal imbalance.

For people that have CNC which impacts the adrenal glands, to combat excess cortisol production by this gland, steroidogenesis inhibitors can be used to manage this.⁵ However, for more severe cases where general management by medication fails, bilateral adrenalectomy may be used alternatively resulting in the person needing long term hormone replacement therapy to compensate for the loss of their adrenal glands.

The presence of any benign tumors would need surgical removal. If cancerous, they would require a cancer-specific treatment plan.

Living with carney complex

CNC is a long-term disorder requiring regular checkups with a specialist, ensuring frequent screenings for new tumours or hormonal changes. Lifestyle changes will also play a factor into living with CNC; ensuring you maintain a healthy diet, exercise regularly, and avoid excessive stress will also be essential.

Additionally, there are many mental health and emotional wellbeing support groups which you could join to help with coping with this chronic condition.

Support and resources

• NHS - Genetic and Genomic Testing
• Pituitary Foundation (UK)
• Endocrine Society

Frequently Asked Questions (FAQs)

Is Carney Complex curable?

No, but it can be managed effectively with proper treatment.

Can I live a normal life with CNC?

Yes, with regular follow-ups, many people lead active, fulfilling lives.

Can children inherit it?

Yes, each child of an affected parent has a 50% chance of inheriting it.

Do all people with CNC get Cushing’s syndrome?

Not all, but many do, especially due to PPNAD.

Summary

Carney Complex (CNC) is a rare genetic condition that can affect the skin, heart, and hormone-producing glands. One of the most common problems is hormonal imbalance, often due to changes in the adrenal glands. Many people with CNC develop primary pigmented nodular adrenocortical disease (PPNAD), which causes the adrenal glands to make too much cortisol, leading to Cushing’s syndrome.

Symptoms can include rapid weight gain, muscle weakness, changes in skin appearance, high blood pressure, and mood changes. Other hormone glands, such as the pituitary, thyroid, and reproductive organs, may also be affected, causing further imbalances.

Diagnosis of CNC usually involves blood and urine hormone tests, imaging scans, and genetic testing for mutations to the PRKAR1A gene. Treatment depends on the hormones involved and may include medicines, surgery to remove affected glands, and long-term hormone replacement therapy.

With regular monitoring, early treatment of hormone problems, and support from specialists, most people with CNC can manage their symptoms and maintain a good quality of life.