How is Cushing's syndrome treated medically?

Medical treatment of Cushing's syndrome is not curative, and is rarely used as long-term therapy. It is occasionally used as palliative treatment for those with inoperable tumours or metastases. It is useful for controlling cortisol levels while the cause of the raised cortisol is established. It is used preoperatively to render patients safe for surgery.

The drugs used to treat Cushing's syndrome can be classified as:

  • those that act on the adrenal gland
  • those that act by inhibiting ACTH release from the pituitary
  • those that act on the neurotransmitters in the brain that control CRH secretion.

Metyrapone

This acts on the adrenal gland, inhibiting the final step of cortisol synthesis. However, as a consequence, the precursor of cortisol will form androgens and may cause virilisation.

Mitotane

This is an adrenolytic, used for patients with metastasising adrenal tumours. It has become popular due to its cytotoxicity to the adrenal tissue. However it has limited long term use, as it is a cause of raised blood cholesterol levels.

Ketoconazole

This is used to suppress ACTH production, as well as interfering with hormone production in the adrenal gland. An unwanted side effect is liver damage, limiting its effectiveness.

Octreotide

This is a somatostatin analogue, useful in controlling Cushing's syndrome caused by ectopic ACTH-secreting tumours.

How is Cushing's syndrome treated surgically?

Surgery is normally the first choice of treatment for Cushing's syndrome. While medical treatments delay further symptoms or complications, they are limited as they provide only a short-term solution, and are associated with many side effects. Details of the operations are included in the surgery section.

What type of operations can be performed?

1. Cushing's disease:

The management of a patient with Cushing's disease depends in part on the local expertise of the surgeon involved. A good microsurgeon can remove microadenomas trans-sphenoidally (see 'Surgery' section) with more than a 75% rate of remission. By using appropriate imaging techniques both before and during the operation to identify the tumour, the rate of remission can be increased considerably. In some cases, interstitial or external irradiation (radiation applied to the tumour from inside the body or inside the body, respectively) and also bilateral adrenalectomy (removal of both adrenal glands) are used. The choice depends on the type of patient, local expertise and also the available resources. Irradiation of the pituitary has a high success rate for children, although it is of limited value in adults, as its progress is slow and may only be effective in 50-60% of cases.

2. Adrenal adenomas:

These should be removed after pre-operative normalisation of cortisol levels using metyrapone or ketoconazole. The usual operation is a laparoscopic adrenalectomy, although the cortisol-weakened tissues make the surgery difficult. In the case of carcinomas open operation is indicated, but even with apparently complete removal the prognosis is poor. The tumour may be removed surgically, although this will not account for metastases, and so medical treatment and radiotherapy are also indicated.

3. Ectopic ACTH-secreting tumours:

Where possible, the treatment of choice for ectopic ACTH-secreting tumours is resection of the primary tumour. The best results have been achieved when the tumour is found to be carcinoid in origin. In many cases, the primary is found to be an inoperable carcinoma of the bronchus. In these cases the prognosis is so poor that surgery is often not indicated. In cases where the primary tumour cannot be localised, the treatment of choice is bilateral adrenalectomy.