Introduction

Carney Complex (CNC) is a rare inherited condition that can cause different types of non- cancerous tumours and affects different endocrine glands in the body. People with CNC may have unusual skin pigmentation, hormone problems and tumours in organs like the heart, adrenal glands and sometimes even the reproductive organs, such as the testicles in males or ovaries in females.
While many of these tumours are not life-threatening except for the cardiac tumours, some can affect hormones and fertility. That’s why it's important for people with this genetic condition to get regular check-ups and monitoring, especially for their reproductive health. In this article we are going to discuss the importance of monitoring testicular and ovarian tumours in Carney Complex.¹

Understanding Carney Complex and Its Genetic Basis

Role of PRKAR1A gene mutations

The Carney Complex is usually caused by a change (mutation) in a gene called PRKAR1A (protein kinase A regulatory subunit 1A). This gene is thought to function as a tumour suppressor, helping to regulate cell growth, repair DNA damage, and trigger cell death when necessary, a normal process called apoptosis. It also regulates cell growth and hormone signals. When it doesn’t work properly, the body can start forming tumours in multiple parts of the body. The precise role of this protein and the way gene mutations contribute to the development of Carney complex symptoms remain unclear.²

Inheritance patterns and de novo mutations

CNC is often passed from parent to child in an autosomal dominant pattern—meaning if either of the parents has a single copy of the faulty gene, there's a 50% chance each child will have it too. However, in some people with CNC, the mutation happens randomly without any family history,  approximately 25% known as de novo mutations.^1,2

Relevance of genetic counselling in affected families

Genetic testing can help confirm this genetic condition. Knowing this early allows doctors to monitor people closely before symptoms start.

Gonadal Manifestations in Carney Complex

CNC can affect the reproductive organs—testicles in males and ovaries in females. These tumours are not cancerous but often benign (slow-growing and non-spreading), but they can disturb the hormone levels and reproductive function, i.e., ovulation and period cycles. In some cases, they may lead to early puberty, infertility, or other hormone-related symptoms.

Testicular Tumours in Carney Complex

About 20% to 50% of males with CNC may develop testicular tumours, among the below tumour types. ¹

• Large-cell calcifying Sertoli cell tumours (LCCST)
• Nodular adrenocortical 
• Leydig cell tumours

The most common reproductive tumour in CNC is LCCSCT, although it is rare in the general population. It usually develops with age and can slowly replace healthy testicular tissue, possibly leading to fertility problems because it may block the seminiferous tubules (sperm-producing tubes) in both testicles.³

Signs and Symptoms

Most of these tumours don’t cause symptoms and can’t be felt by touch. However, in rare cases, they may show the following signs and symptoms, such as:³

• Small, hard lumps in the testicles
• Early signs of puberty in young boys
• Feminine signs in males assigned at birth, like breast enlargement
• Hormonal imbalances, which may lead to abnormal sperm production

Diagnosis and Treatment

These tumours are often slow-growing and don’t spread, as they are benign. Doctors usually detect them with a testicular ultrasound, and they may test hormone levels in the blood. Sometimes, surgery is needed, but often these tumours are just monitored regularly unless they cause problems.^1,3

Ovarian Tumours in Carney Complex

Women with CNC can develop fluid-filled sacs called cysts or growths on the surface of the ovary, such as cystic teratomas or ovarian stromal tumors, especially Sertoli-Leydig cell tumours, although it is less common than in testicular tumours.
These are usually non-cancerous, but in some cases, especially later in life  (around age 50 years), they can turn into ovarian cancer-like endometrial cancer. In fact, studies found that around 60% of people with Carney Complex had ovarian changes like these when examined after death (autopsy).^1,4

Signs and Symptoms

These tumours can produce male hormones (like testosterone and increase the level of androgen), which may cause:⁴

• Irregular or absent periods
• Excess facial or body hair (hirsutism)
• Acne or oily skin
• Deepening of the voice
• Bald patches on the head

Diagnosis and Treatment

It is usually diagnosed by ultrasound or hormonal tests. The majority of these ovarian tumours are benign and surgically removable. Women who are diagnosed at an early stage often have excellent outcomes, as regular follow-up is done to make sure they don’t turn into something more serious.⁴

Impact on Fertility and Reproductive Function

Fertility may be impacted by these tumours, as they can affect hormone production because of endocrine dysfunction; they can also affect fertility.

• In males, tumours or surgery may reduce sperm production
• In females, hormone imbalances or surgery involving the ovaries can make it more difficult to get pregnant

That’s why, before starting treatment, doctors may suggest fertility preservation options like sperm banking for men or egg freezing for women, known as cryopreservation, especially if surgery is needed.^1,5

Monitoring Strategies for Reproductive Health

People with CNC should have regular monitoring to catch early problems so they can receive the treatment as soon as possible.

For males assigned at birth

• Annual testicular ultrasounds starting in adolescence
• Hormone blood tests (e.g., testosterone, Estradiol)
• Physical examination to check for lumps in testicles or early puberty ^1,3

For females assigned at birth

• Pelvic ultrasounds can be performed if period issues, either irregular or absent, are present
• Hormonal blood tests (e.g., Estrogen, Progesterone, Luteinizing Hormone (LH), Follicle-Stimulating Hormone (FSH) and testosterone)
• Tracking of Period cycle

This ongoing care is best managed by a multidisciplinary team, including endocrinologists, reproductive specialists like urologist, gynaecologist and genetic counsellors.^1,4

Therapeutic Approaches and Management

Most reproductive tumours in CNC don't spread, as they are non-cancerous and don’t always require treatment. However, if they grow or cause hormonal problems, physicians may recommend:

• Surgery to remove tumours while preserving as much reproductive tissue as possible
• Hormonal therapies to manage endocrine effects

To manage puberty-related issues or hormonal imbalances, synthetic hormones can be given to manage the symptoms, like in males with breast growth, medical treatment is given to correct the oestrogen and androgen imbalance by three possible pathways:⁶

• Blocking the oestrogen’s effects on the breast (e.g., tamoxifen, clomiphene, raloxifene)
• Administering androgens (e.g., danazol)
• Inhibiting oestrogen production by giving aromatase inhibitors that reduce excess oestrogen (e.g., anastrozole, testolactone)

Fertility preservation options

Fertility counselling should always be part of the care plan; also, egg and sperm freezing can be considered, especially if surgical removal of reproductive organs is necessary.⁵

Psychosocial and Quality of Life Considerations

Counselling for patients and families

Living with a rare condition like CNC can be emotionally challenging. Concerns about fertility, body image, and future relationships are common, particularly in teenagers and young adults.

Supportive care is important to provide comprehensive care, including psychological counselling for the above issues, along with the physical treatment, which can help people with these conditions and their families cope with emotional stress, fears about passing on the condition to children, and the uncertainty surrounding their reproductive future.

As a part of this counselling, genetic counselling is highly recommended. It helps families understand the potential risks for the offspring and how it is inherited.

For those planning and trying to conceive, prenatal testing and pre-implantation genetic diagnosis (PGD) can be discussed. These options help in the early detection of CNC in embryos or during pregnancy, helping families make informed and better choices.^1,7

Support groups and long-term survivorship planning

Together with the above, counselling and connecting with support groups can also reduce isolation and provide a sense of community.

Summary

Carney Complex (CNC) is a rare genetic condition caused by mutations in the PRKAR1A gene. It leads to non-cancerous tumours in various organs, including the testes and ovaries, which can affect hormone levels and fertility. Males may develop testicular tumours like LCCST, causing early puberty, breast growth, or fertility issues. Females may develop ovarian tumours like Sertoli-Leydig cell tumours, leading to irregular periods, excess hair, acne or voice deepening. Regular monitoring with ultrasounds and hormone tests is essential. Treatment may include surgery, hormonal therapy, and fertility preservation (e.g., sperm or egg freezing). Genetic counselling and psychological support are important for managing emotional stress and planning for the future.

FAQs

Can the Carney Complex affect reproductive organs?

Yes, it can cause tumours in the testicles of males and ovaries of females, which may impact hormone levels and fertility.

Are the tumours cancerous?

Most tumours in CNC are benign and don’t spread, but they can still cause hormonal imbalances and reproductive issues. Rarely, ovarian tumours may become cancerous later in life.

How are these tumours diagnosed?

Through ultrasounds and blood hormone tests. Genetic testing can confirm CNC.

Can fertility be preserved?

Yes, options like sperm banking for males and egg freezing for females are available, especially before surgery.

How often should patients be monitored? 

• Males assigned at birth: Yearly testicular ultrasounds and hormone checks
• Females assigned at birth: Pelvic ultrasounds and regular hormone testing if symptoms occur like irregular or absent periods, etc.

What kind of doctors manage CNC?

A multidisciplinary team of doctors manage CNC, like endocrinologist, gynaecologist/urologist, genetic counselor and fertility specialist.

Is genetic counselling necessary?

Yes. It helps families understand the risk of passing CNC to children and explore options like prenatal or preimplantation genetic diagnosis (PGD).