Nelson's Syndrome

Nelson’s syndrome is the term used to describe an enlargement of an adrenocorticotropic hormone-producing tumour in the pituitary gland, following surgical removal of both adrenal glands in a patient with Cushing’s disease. The syndrome is the name given to the effects of the enlarging tumour in the pituitary gland. The tumour produces an excess of a hormone called adrenocorticotropic hormone, which is involved in the production of other steroid hormones (such as cortisol). Large tumours can sometimes also invade areas around the pituitary gland, which may cause a reduction in levels of other hormones, visual problems or it may affect nerves and blood vessels. It can also cause an increase in skin pigmentation, so patients may look as if they have a suntan.

What causes Nelson’s syndrome?

Nelson’s syndrome results from a reduction in feedback of steroid hormones and is a consequence of removal of the adrenal glands (an adrenalectomy). In healthy individuals, the pituitary gland stimulates the adrenal glands to produce steroid hormones (such as cortisol) through production of a hormone called adrenocorticotropic hormone. These steroid hormones then act on the pituitary gland to stop it producing more adrenocorticotropic hormone. This feedback system means that levels of the hormones are kept within the normal range. In patients who have had an adrenalectomy, this negative feedback system does not work and the pituitary tumour may expand and produce more 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 amount 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 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 on the face. Occasionally, patients will also experience a headache as a result of the enlarging tumour.

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. The tanned complexion is not confined to areas exposed to the sun and frequently affects the inside of the mouth and old scars.

How common is Nelson’s syndrome?

Surgical removal of both adrenal glands to treat Cushing’s disease is rarely performed nowadays due to improvements in other treatment options for this condition. However, in patients who do require this operation, Nelson’s syndrome develops in 20% to 40% of cases.

Is Nelson’s syndrome inherited?

Nelson's syndrome only occurs in patients with Cushing’s disease if they have had both adrenal glands removed. Most cases of Cushing’s disease are not inherited, but rarely, 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 in patients who have previously undergone surgical removal of the adrenal glands when they develop symptoms suggestive of pituitary enlargement such as headache, visual disturbance, skin pigmentation or other symptoms resulting from pituitary hormone deficiencies. The doctor will request blood tests to look for a high adrenocorticotropic hormone level along with possible low levels of other pituitary hormones. A scan of the pituitary gland will be organised to assess 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 frequently treated by surgical removal of the pituitary tumour, and this is usually the case if there is visual impairment or other evidence of significant growth of the tumour outside the pituitary gland. Occasionally, medical treatment aimed at shrinking the tumour may be suggested and radiotherapy may also be used, especially if surgery is not felt to be safe.

Hormone deficiencies may resolve after removal of the tumour, but these will be treated if symptoms persist. This may involve thyroid hormone replacement, growth hormone replacement and testosterone or oestrogen replacement. Most patients with Nelson’s syndrome will already be taking steroid replacement therapy.

Are there any side-effects to the treatment?

Surgery is generally safe and well tolerated, although a surgeon will go through the particular risks of the operation with a patient. Medications that are currently used to induce tumour shrinkage include dopamine agonists and these can be associated with headaches, dizziness and gastrointestinal symptoms such as constipation.

Radiotherapy can be associated with damage to areas around the pituitary gland. The risks and benefits of this treatment will need to be discussed with a specialist in radiation treatment.

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

The successful treatment of Nelson’s syndrome depends on the involvement 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 of patients who have had surgical removal of their adrenal glands.

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