Nelson’s syndrome is the name given to the effects of a tumour in the pituitary gland getting bigger and producing too much adrenocorticotropic hormone. This occurs in patients with Cushing’s disease after they have undergone surgical removal of both adrenal glands.
The large tumours can sometimes also invade areas around the pituitary gland. This can lead to lower levels of other hormones, visual problems or affect 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.
In healthy individuals, the pituitary gland produces adrenocorticotrophic hormone, which makes the adrenal glands produce steroid hormones (such as cortisol). These steroid hormones then act on the pituitary gland to stop it producing more adrenocorticotropic hormone. This process is referred to as a negative feedback loop.
In patients who have had their adrenal glands removed (adrenalectomy), this negative feedback system does not work. As a result, Nelson’s syndrome occurs, where the pituitary tumour may expand and produce more adrenocorticotropic hormone.
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.
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, Nelson’s syndrome develops in 20% to 40% of patients who do require this operation.
No. 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.
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. Nelson’s syndrome usually occurs within 3 years after removal of both adrenal glands. 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.
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. Success rates of surgery are higher with smaller tumors. 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.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.
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.
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.
Pituitary Foundation may be able to provide advice and support to patients and their families dealing with Nelson's syndrome.
Last reviewed: Mar 2019