Treatment of the Pituitary Tumour

Pituitary surgery consists in extirpating the tumour, leaving the healthy tissue of the gland intact. Pituitary surgery has markedly improved in the last few years, mainly due to the approach by the trans-sphenoidal route, which consists of extirpating the tumour by making an incision at the level of the nose, entering through the sphenoidal sinus (a cavity located behind the nose).

Classically, it was performed through a craniotomy (transcranial route), in which the skull was opened to enter and remove the tumour. Currently, this technique is only used in exceptional cases where the trans-sphenoidal approach is not possible. 

To visualise the surgical area for the trans-sphenoidal route, microscopic surgery or a fibre optics endoscope is used, which permits a minimally invasive approach to the pituitary.

The benefits of this technique compared with the classic technique have a direct impact on the patient, with a significant reduction in local complications, a decrease in surgical time, an increase in patient comfort (absence of post-surgical nasal plugging, and a decrease in post-surgical pain), as well as a reduction in the mean hospital stay, which may be only 24-48 hours.

On many occasions, the whole tumour can be removed, leaving just the healthy tissue, but, in others, the tumour is very large and can invade neighbouring structures, leaving remains of the tumour or removing some of the healthy tissue. For this reason, there may be some pituitary hormone deficiencies. In that case, medical treatment is required to correct these deficiencies.

The outcomes in pituitary surgery are directly related to the experience and training of the neurosurgeon dedicated to this field.

Radiotherapy is a type of treatment that uses high-energy particles or waves to eliminate tumour cells in order to prevent them growing and dividing. It can be administered in both benign and malignant tumours.

In the case of pituitary tumours, it is used when the tumour persists, grows, or re-appears after surgery, when surgery cannot be performed due to a contraindication, or a low probability of success.

There are different ways to administer radiotherapy in pituitary tumours:

• Fractionated stereotactic radiotherapy. This consists in administrating radiation in small doses in multiple sessions. Each session lasts about 10-15 minutes, but the treatment per session lasts between 1-2 minutes, the rest of the time is used in the preparation.
• Stereotactic radiosurgery. It consists in administrating a high dose of radiation in a single session. This option is not possible in large tumours or those very near the visual pathway. It takes longer (between 30 minutes and 2 hours). In general, it is very well-tolerated and does not hurt. There are no significant side-effects. Over the weeks, patients may feel more tired, and lose small areas of hair in the region where the radiation penetrates. There may also be headaches and a feeling of nausea.

The radiotherapy can affect healthy cells, therefore, with time, it is possible that it could affect some of the pituitary hormones and trigger hypopituitarism. This risk increases with the months and can even occur years after the end of the treatment.

Over time, more than half of the patients subjected to radiotherapy have at least one hormone deficiency. For this reason, it is important to have a long-term follow-up in order to evaluate these deficiencies, which will last indefinitely, although the controls can be spaced out. Very exceptionally, and many years after treatment, second tumours may also appear in the region affected by the radiation.

The medical treatment consists of, on the one hand, the treatment of the hormone deficiencies that may appear due to the presence of the tumour, or once it has been extirpated and, on the other hand, of the medical treatment that some tumours need in order to control excessive hormone secretion and their growth.

Medical treatment of hormone deficiencies

The treatment of hormone deficiencies is specific, depending on the hormone deficiency:

• Thyroxin, to stimulate thyroid hormones.
• Hydrocortisone, to treat the lack of cortisol.
• Desmopressin, for the antidiuretic hormone.
• Testosterone, in order to stimulate this hormone.
• Depending on the age of the woman, an oestrogen deficiency will be treated.
• In the case of growth hormone, the need for treatment will be assessed individually.
• The rest of the deficiencies, such as that of prolactin, are not treated.

After the operation, it is important that there is no cortisol or antidiuretic hormone deficiency. For this reason, on the day of the operation and the days following, corticosteroids will be given to prevent the clinical symptoms associated with the deficiency. The dose is gradually reduced in the following days. In the subsequent monitoring with endocrinology, it will be checked if there really is a deficiency, and if the corticosteroids can be withdrawn. Sometimes, after the operation, there may be an increase in urine production and have sensation of thirst, due to the lack of antidiuretic hormone. In general, this deficit is temporary, and disappears in a few days.

At a few weeks from the surgery, blood tests are performed, as well as visit to endocrinology where it is assessed whether pituitary function is normal or if replacement therapy of the hormone deficiency should be administered.

Medical treatment to control tumour secretion

On the other hand, there is medical treatment for the tumour secretion itself. The prolactinoma is the most common tumour secretor, and unlike what occurs with pituitary tumours, other hormones are secreted. In this case, the treatment of choice is pharmacological. Surgical treatment is indicated when there is compression of the vision pathways or when there is no response to pharmacological treatment.

The medical treatment consists of:

• Dopaminergic agonists, which exercise a similar effect to dopamine, and include cabergoline, bromocriptine and quinagolide. These drugs act by decreasing the levels of prolactin and reducing the tumour size. In general, treatment is started with cabergoline, orally, 1 or 2 times per week. The dose is decided depending on the tumour secretion and the response to the treatment, and usually produces few side effects, although there may be mild gastrointestinal discomfort or drops in blood pressure. In the rest of the pituitary tumours, the treatment of choice is generally surgery, and drugs are used in cases in which the hormonal excess persists after the intervention, or, on occasions, prior to the surgery in order to improve the symptoms and conditions beforehand.
• Somatostatin analogues. It is a group of drugs that are used in GH secreting tumours (acromegaly), TSH (TSHoma), ACTH (Cushing’s disease). Somatostatin slows down the GH secretion. As such the analogues of somatostatin exercise the same effect, but are more powerful and longer lasting. There are three active ingredients: octreotide, lanreotide, and, pasireotide. They are generally administered by weekly intramuscular or subcutaneous injections. They usually cause mild gastrointestinal discomfort the first days after the injection, and can be associated with a higher risk of gallstones. It is used especially in GH secreting tumours, and in cases with a good response to treatment it is usually of long-term use. In cases with a lack of response or resistance to the drug, pegvisomant may be used.
• Pegvisomant blocks the pathway by which GH exercises its effect on the tissues and organs. It is administered subcutaneously daily, or several times per week. It is a very effective treatment, which improves the diabetes of the patients with acromegaly, but it has no effect on the tumour mass. The efficacy of somatostatin analogues or pegvisomant in acromegaly is measured using a marker produced in the liver called IGF-1. This marker is elevated in acromegaly and, after treatment, it decreases.
• In the case of Cushing’s disease, drugs can be used that decrease the cortisol secretion by the adrenal glands (such as ketoconazole, metopirone or mitotane) or by means of blocking the effect of the corticosteroids (mifepristone). These drugs require close monitoring by the endocrinologist, since on inhibiting the manufacture of cortisol they can trigger adrenal insufficiency.