What is Nelson Syndrome (Post Adrenalectomy Syndrome)?

Nelson syndrome is a condition named after Dr. Don H. Nelson, who first documented it in 1958. It was originally named “post adrenalectomy syndrome” asit was associated with the removal of both adrenal glands – a procedure known as bilateral adrenalectomy – which is typically done to treat Cushing’s disease. Dr. Nelson’s work was later expanded upon by another doctor, Salassa, leading some people to refer to it as the Nelson-Salassa syndrome.

The condition represents a range of symptoms that tend to occur after the removal of both adrenal glands. It is thought that once the adrenal glands are removed, it disrupts a regulating mechanism in the body – the hypothalamic-pituitary-adrenal axis, resulting in an overproduction of the adrenocorticotropic hormone (ACTH) which then leads to the growth of a tumor in the pituitary gland. This condition typically develops between one to five years after the adrenal gland removal surgery.

What Causes Nelson Syndrome (Post Adrenalectomy Syndrome)?

Nelson syndrome is a condition that can happen after both adrenal glands are removed to treat Cushing disease. About 7% of people diagnosed with Cushing disease end up having both adrenal glands removed.

Removing the adrenal glands can help to quickly improve the symptoms of Cushing disease, such as high blood pressure, diabetes, and muscle weakness. This is because the adrenal glands produce cortisol, a hormone that when made in excess, can cause these symptoms. After the adrenal glands are removed, cortisol levels drop significantly. This causes the hypothalamus (part of the brain) to signal the pituitary gland (another part of the brain), to make a hormone called ACTH. Too much ACTH can cause the pituitary gland to grow and form a new tumor – this is the start of Nelson syndrome.

Some researchers suggest that the cells that originally caused the Cushing disease might also contribute to the growth of the tumor in Nelson syndrome. These days, doctors rarely remove both adrenal glands, and usually reserve it for patients with severe health conditions or for those who didn’t respond well to other treatments.

Knowing the risk factors for Nelson syndrome could help doctors to spot and treat the condition earlier. High levels of ACTH one year after both adrenal glands are removed could suggest a higher chance of developing Nelson syndrome. Doctors will often use a brain MRI (a detailed picture of the brain) to check for a pituitary tumor.

If no tumor is found, doctors usually recommend regular brain MRIs to keep checking. High levels of cortisol in the body before the adrenal glands are removed could also be a sign of a higher chance of developing Nelson syndrome. Age, gender, and how long someone had Cushing disease are not linked to the chance of getting Nelson syndrome. However, younger patients who have both adrenal glands removed may have a higher chance of developing a tumor over their lifetime.

There’s also some evidence that having had radiotherapy to treat the original Cushing disease might be linked to a higher chance of developing Nelson syndrome. However, this depends on the types of radiotherapy used over different periods of time, which may have influenced the findings.

Risk Factors and Frequency for Nelson Syndrome (Post Adrenalectomy Syndrome)

Nelson syndrome is a rare condition that can develop after a surgical procedure known as bilateral adrenalectomy. The likelihood of Nelson syndrome occurring after this surgery varies, with rates ranging from 8% to 47% in adults and 25% to 66% in children. However, in recent times, the number of people developing Nelson syndrome has greatly dropped since the surgery is not performed as often as before. The symptoms of Nelson syndrome can start to appear up to 24 years after the surgery. The condition’s prevalence is 38% three years after surgery, increasing to 47% seven years later, after which it becomes steady.

The incidence of Nelson syndrome is 15% to 25%, usually showing up one to four years after surgery, according to a group at the University of California Los Angeles.
A large study in Argentina found an incidence of 46% for people seen from 1974 to 2011, with the average time for symptoms to appear being 24 months post-surgery.
An equally large study in Mexico reported an incidence of 41.6%.
The most extensive series of patient records from 1956 to 2015 revealed an incidence of 53%.
A systematic review in 2013, covering articles published from 1980 to 2012, found an incidence of 21% (with a range of 0 to 47%), with symptoms generally appearing five years after surgery.

Signs and Symptoms of Nelson Syndrome (Post Adrenalectomy Syndrome)

Nelson Syndrome causes dark skin patches, which is its most easily seen symptom. This symptom is special to this type of pituitary tumor. The dark skin color in Nelson Syndrome is very distinct compared to other skin discoloration disorders. Notably, a dark line running from the pubic area up to the bellybutton is often seen. Other spots like scars, around the nipples, gums, and the male genitals may also have the increased pigmentation. Some other problems are partial blindness, gradually worsening vision in cases of bigger tumors, and pituitary dysfunction. This happens because the tumor can block the release of other hormones from the pituitary gland. Patients may feel headaches, weakness, and tiredness.

Medical history often shows that the person with Nelson syndrome had Cushing disease and underwent surgery to get both adrenal glands removed.

Testing for Nelson Syndrome (Post Adrenalectomy Syndrome)

If your doctor suspects you have a condition called Nelson syndrome, they may begin by checking your ACTH hormone levels through a fasting blood test. ACTH stands for Adrenocorticotropic Hormone, which helps regulate your body’s response to stress. Extremely high ACTH levels can help point towards this diagnosis. If the levels of ACTH rise by more than 30% after the removal of both your adrenal glands (an operation called bilateral adrenalectomy), then it is more likely that the diagnosis could be Nelson syndrome.

To understand your pituitary gland’s function, your doctor may run some tests. The pituitary gland is a small, bean-shaped gland situated at the base of your brain. If these tests show a lower-than-normal level of some hormones made in the front part of your pituitary gland, it may confirm the diagnosis.

You may also have a visual field test. This checks if your field of vision is normal. If you have a pituitary tumor pressing on certain parts of the brain, it could cause you to lose the outer part of your field of vision in both eyes, a condition known as bitemporal hemianopia.

Next, you may have a brain MRI which can provide detailed pictures of your pituitary gland and surrounding areas. This can confirm the diagnosis of Nelson syndrome if a new pituitary tumor is spotted or an already known one is found to be larger.

Finally, if you’ve had both adrenal glands removed (bilateral adrenalectomy), your doctor will keep a close check-up on you by routinely testing your fasting plasma ACTH levels and conducting regular brain MRI scans. This is to ensure early detection of any changes that could suggest the onset of Nelson syndrome.

Treatment Options for Nelson Syndrome (Post Adrenalectomy Syndrome)

The first suggested treatment for Nelson syndrome, a disease that involves the growth of a tumor in the pituitary gland after removal of the adrenals, is to have surgery to take out the tumor. The surgery can be done with a microscope or using an endoscope (a flexible instrument that allows doctors to see inside your body) through the nasal cavity. If the tumors have extended widely, a more complex operation called a craniotomy (where they open a part of the skull) might be necessary. Unfortunately, complete recovery from the syndrome after surgery only happens in about half of the cases. This is partly due to issues such as the tumor having spread into surrounding areas.

Sometimes, the recommended approach may be to keep a close watch on the condition, as a number of tumors may not cause visible symptoms or grow slower than 5 millimeters each year. Surgery does come with risks, such as causing a decrease in the production of important hormones in about 30% of cases or permanent diabetes insipidus (a rare type of diabetes that involves extreme thirst and the production of large amounts of urine) in about 20% of the cases.

Radiotherapy, which uses radiation to destroy the tumor, can also be used as treatment. This can be done as a series of small treatments or a single large dose technique known as stereotactic radiosurgery. Stereotactic radiosurgery using a gamma knife (a tool used in brain surgery that uses focused radiation) has proven to be effective in controlling tumor growth and reducing the level of ACTH, a hormone that regulates cortisol levels in the body. However, this method might not be a good fit for certain patients who have already received radiation for a related condition called Cushing’s disease, as they may be at risk of excess radiation. Additionally, radiotherapy can lead to a decrease in hormone production in 5 to 10 years, requiring replacement of these hormones. This therapy also carries the risk of causing new vision problems. Despite these drawbacks, radiotherapy can be an option if surgery doesn’t work.

One way to prevent Nelson syndrome is to use radiotherapy as a preventive measure when you’re planning to have both adrenal glands removed. But this isn’t always the go-to method, as some researchers have not found this preventive radiation to be helpful. Now, radiosurgery can be used to direct the radiation specifically to the pituitary gland tissue.

Medical treatment options are limited, but promising results have been seen with the use of certain medications such as somatostatin-analogs, dopamine agonists, sodium valproate, and temozolomide.

As for patients with this syndrome, they’ll need to take medication that replaces cortisol, a hormone that the body can no longer produce. They may also require a drug called fludrocortisone acetate, which replaces another group of hormones called mineralocorticoids that are essential for regulating water and electrolyte balance in the body.

Nelson syndrome is a type of pituitary gland tumor. This means that other types of pituitary gland tumors might appear similar when viewed on medical imaging. However, a defining characteristic of Nelson syndrome is skin hyperpigmentation, or darkening. There are several other conditions that may be confused with Nelson syndrome, including:

Sellar tumors (tumors located in a part of the skull called the sella turcica)
Primary adrenal insufficiency (a disorder where the adrenal glands don’t produce enough certain hormones)
Congenital adrenal hyperplasia/hypoplasia (genetic disorders that impact the adrenal glands)
Hypothalamic tumors that secrete CRH (tumors in the hypothalamus producing a hormone called corticotropin-releasing hormone)
Addison’s disease (an autoimmune disease that damages the adrenal glands)
Ectopic secretion of ACTH (a condition where ACTH, a hormone usually produced by the pituitary gland, is produced somewhere else in the body)
Glucocorticoid therapy (treatment with drugs that affect your immune response)

What to expect with Nelson Syndrome (Post Adrenalectomy Syndrome)

Nelson syndrome can be a life-threatening condition, but it usually responds well to surgical treatments. Sometimes, even after surgery, a hormone called ACTH can remain abnormally high because of remaining tumor tissue, especially in a part of the brain called the cavernous sinus. Radiation therapy can also be effective, although the results may take some time to show and can permanently reduce the pituitary gland’s function (known as hypopituitarism).

Patients undergoing a particular type of radiation treatment called gamma knife radiosurgery or any other form of radiotherapy for Nelson syndrome may need to stay on their medication till their hormones are well-regulated.

Possible Complications When Diagnosed with Nelson Syndrome (Post Adrenalectomy Syndrome)

Potential complications include:

Skin becoming darker in color
Underactive pituitary gland condition
Loss of vision
Sudden and severe worsening of Addison’s disease symptoms

Preventing Nelson Syndrome (Post Adrenalectomy Syndrome)

It’s crucial for patients and their family members to understand the importance of certain medications called glucocorticoids and mineralocorticoids. Patients should wear a bracelet that identifies their need for these medications to help ensure they receive proper care at all times.

If a patient is diagnosed with a condition called Nelson syndrome, prompt medical evaluation is necessary because the chances of successful treatment are higher the sooner it is managed. The first step to treat Nelson syndrome is usually surgery. Surgery often produces the best results when the tumors are small in size. However, if the tumors have spread to a nearby structure called the cavernous sinus, additional treatments such as medications or radiotherapy may be needed.

The goal of treating Nelson syndrome is to bring the levels of a hormone called ACTH back to normal in order to alleviate the symptoms of the condition.

Frequently asked questions

The prognosis for Nelson Syndrome (Post Adrenalectomy Syndrome) is generally good, as it usually responds well to surgical treatments. However, there may be cases where the hormone ACTH remains abnormally high due to remaining tumor tissue, and radiation therapy may be necessary. In some cases, radiation therapy can permanently reduce the function of the pituitary gland. Patients undergoing radiation treatment may need to continue taking medication until their hormones are well-regulated.

Nelson Syndrome can occur after the surgical procedure known as bilateral adrenalectomy, which involves removing both adrenal glands.

The signs and symptoms of Nelson Syndrome (Post Adrenalectomy Syndrome) include: 1. Dark skin patches: This is the most easily seen symptom of Nelson Syndrome. The dark skin color is distinct and different from other skin discoloration disorders. A dark line running from the pubic area up to the bellybutton is often seen, along with increased pigmentation in spots like scars, around the nipples, gums, and the male genitals. 2. Partial blindness and gradually worsening vision: In cases of bigger tumors, Nelson Syndrome can cause partial blindness and gradually worsening vision. This is due to the tumor blocking the release of other hormones from the pituitary gland. 3. Pituitary dysfunction: The tumor in Nelson Syndrome can also lead to pituitary dysfunction. This can result in various problems such as headaches, weakness, and tiredness. 4. Medical history of Cushing disease and adrenal gland removal: It is often observed in the medical history of individuals with Nelson Syndrome that they had previously suffered from Cushing disease and underwent surgery to have both adrenal glands removed.

The types of tests that are needed for Nelson Syndrome (Post Adrenalectomy Syndrome) include: 1. Fasting blood test to check ACTH hormone levels. 2. Pituitary gland function tests to measure hormone levels. 3. Visual field test to check for bitemporal hemianopia. 4. Brain MRI to obtain detailed images of the pituitary gland and surrounding areas. 5. Routine testing of fasting plasma ACTH levels and regular brain MRI scans for patients who have had both adrenal glands removed. 6. Additional tests may be done depending on the individual case and symptoms. These tests are important for diagnosing and monitoring Nelson Syndrome and determining the appropriate treatment approach.

The other conditions that a doctor needs to rule out when diagnosing Nelson Syndrome (Post Adrenalectomy Syndrome) are: - Sellar tumors (tumors located in a part of the skull called the sella turcica) - Primary adrenal insufficiency (a disorder where the adrenal glands don't produce enough certain hormones) - Congenital adrenal hyperplasia/hypoplasia (genetic disorders that impact the adrenal glands) - Hypothalamic tumors that secrete CRH (tumors in the hypothalamus producing a hormone called corticotropin-releasing hormone) - Addison's disease (an autoimmune disease that damages the adrenal glands) - Ectopic secretion of ACTH (a condition where ACTH, a hormone usually produced by the pituitary gland, is produced somewhere else in the body) - Glucocorticoid therapy (treatment with drugs that affect your immune response)

The side effects when treating Nelson Syndrome (Post Adrenalectomy Syndrome) can include: - Decrease in the production of important hormones in about 30% of cases after surgery - Permanent diabetes insipidus (a rare type of diabetes that involves extreme thirst and the production of large amounts of urine) in about 20% of cases after surgery - Decrease in hormone production in 5 to 10 years after radiotherapy, requiring replacement of these hormones - New vision problems as a result of radiotherapy - Potential complications such as skin becoming darker in color, underactive pituitary gland condition, loss of vision, and sudden and severe worsening of Addison's disease symptoms for patients with this syndrome.

An endocrinologist.

The incidence of Nelson syndrome varies, with rates ranging from 8% to 47% in adults and 25% to 66% in children.

Nelson Syndrome (Post Adrenalectomy Syndrome) can be treated through various methods. The first suggested treatment is surgery to remove the tumor in the pituitary gland. This can be done using a microscope or an endoscope through the nasal cavity. In more complex cases, a craniotomy may be necessary. However, complete recovery after surgery only occurs in about half of the cases. Another treatment option is radiotherapy, which uses radiation to destroy the tumor. This can be done through a series of small treatments or a single large dose technique known as stereotactic radiosurgery. Medical treatment options such as somatostatin-analogs, dopamine agonists, sodium valproate, and temozolomide have also shown promising results. Additionally, patients with Nelson Syndrome will need to take medication to replace cortisol and may require fludrocortisone acetate to replace mineralocorticoids.

Nelson Syndrome, also known as Post Adrenalectomy Syndrome, is a condition that occurs after the removal of both adrenal glands. It is characterized by the overproduction of the adrenocorticotropic hormone (ACTH), leading to the growth of a tumor in the pituitary gland. This condition typically develops one to five years after the surgery.