What is Nelson’s syndrome?

Nelson’s syndrome is when a tumour in the pituitary gland continues to grow larger and produces too much adrenocorticotropic hormone. This occurs in some patients with Cushing’s disease after they have had surgical removal of both of their adrenal glands.

These growing tumours can sometimes invade areas around the pituitary gland. Depending on where it grows, this can lead to lower levels of other hormones, visual problems or issues with the surrounding nerves and blood vessels. Some patients may also look as if they have a suntan, as Nelson’s Syndrome can cause an increase in skin pigmentation.

What causes Nelson’s syndrome?

In healthy people, the pituitary gland produces adrenocorticotrophic hormone. This hormone makes the adrenal glands produce steroid hormones (such as cortisol). These then loop back around and act on the pituitary gland to stop it producing more adrenocorticotropic hormone. This process is referred to as a negative feedback loop and it stops the over-production of adrenocorticotropic hormone.

In patients who have had their adrenal glands removed (adrenalectomy), this negative feedback system does not work. As a result, Nelson’s syndrome can develop, where a pituitary tumour expands and produces too much adrenocorticotropic hormone.

What are the signs and symptoms of Nelson’s syndrome?

The signs and symptoms of Nelson’s syndrome result from the enlarged tumour and the increased adrenocorticotropic hormone production. The enlarged tumour compresses the rest of the pituitary gland and therefore reduces the levels of other hormones produced. This can result in poor functioning of the thyroid gland (hypothyroidism), a lack of growth hormone (growth hormone deficiency) and deficiencies of the gonadotrophic hormones, luteinising hormone and follicle stimulating hormone. The tumour can also grow upwards from the pituitary gland and compress vital nerves involved in vision. This may result in blind spots in the patient’s vision or, occasionally, complete blindness. The tumour may grow to each side of the pituitary gland and affect important nerves that are found in this area. This can result in difficulty moving the eyes, double vision or numbness in the face. Occasionally, patients may also experience a headache as a result of the enlarging tumour.

Additionally, the raised levels of adrenocorticotropic hormone act on cells in the skin to increase pigmentation. This results in darkened or tanned skin, especially in skin creases. This tanned skin does not only appear in areas exposed to the sun, it may also affect the inside of the mouth and old scars.

How common is Nelson’s syndrome?

The surgical removal of both adrenal glands to treat Cushing’s disease is rarely performed nowadays, as other treatment options for this condition are now available. However, Nelson’s syndrome develops in 20% to 40% of patients who have had this operation.

Is Nelson’s syndrome inherited?

No. Nelson's syndrome only occurs in patients with Cushing’s disease if they have had both adrenal glands removed. Cushing’s disease is also usually not inherited but there are rare cases when these tumours can be part of a genetic condition, such as multiple endocrine neoplasia.

How is Nelson’s syndrome diagnosed?

Nelson’s syndrome is suspected if patients have had surgical removal of their adrenal glands and they then begin to develop certain symptoms linked to pituitary enlargement. These symptoms include headache, visual disturbance, skin pigmentation or other symptoms resulting from pituitary hormone deficiencies. Nelson’s syndrome usually occurs within three years after removal of both adrenal glands. Blood tests will be carried out to look for a high adrenocorticotropic hormone level, as well as possible low levels of other pituitary hormones. A scan of the pituitary gland will be organised to measure the growth of the tumour and to look for effects on other areas in the brain around the pituitary gland. Often a visual field test will be organised to check for loss of vision. Frequently, these tests will be performed as an outpatient, but occasionally the doctor may advise an admission to hospital if treatment is required urgently.

How is Nelson’s syndrome treated?

Nelson’s syndrome is most commonly treated by removing the pituitary tumour through surgery. This is especially needed if there is any vision loss or other evidence of significant growth of the tumour outside the pituitary gland. Smaller tumours have a high success rates of surgery. Occasionally, medical treatment aimed at shrinking the tumour may be suggested and radiotherapy (gamma knife) may also be used, especially if surgery is not felt to be safe.

After pituitary surgery/radiotherapy, hormone levels will be monitored by the care team. If there are still symptoms of hormone deficiencies, additional treatment will be given. This may involve thyroid hormone replacement, growth hormone replacement, and testosterone or oestrogen replacement.

All patients with Nelson’s syndrome will already be taking steroid replacement therapy.

Are there any side-effects to the treatment?

For all treatment options, risks and side effects will be discussed with the patient. Surgery has a high success rate and is generally well tolerated. There are medications that that can be used to shrink the tumour, such as dopamine agonists. These can be associated with headaches, dizziness and gastrointestinal symptoms (e.g., constipation). Radiotherapy can also be used and can cause damage to areas surrounding the target area. 

What are the longer-term implications of Nelson’s syndrome?

The successful treatment of Nelson’s syndrome depends on a team of specialists, including an endocrinologist, a specialist pituitary surgeon and occasionally, a radiotherapist. The outcome is good if the condition is detected early, and this is one of the reasons for long-term follow-up with patients who have had surgical removal of their adrenal glands.

It is very important that any hormone deficiencies are diagnosed and treated properly. This helps to avoid long-term complications such as osteoporosis, heart disease and depression.

Are there patient support groups for people with Nelson's syndrome?

Pituitary Foundation may be able to provide advice and support to patients and their families dealing with Nelson's syndrome.