Drug Therapy of Pituitary Adenomas

N.V. Vorokhobina, V.R. Slobodskoy

(Faculty of Endocrinology named after V.G. Baranov;
Saint Petersburg Medical Academy of Postgraduate Education of Nurses and Parmaceutists, Saint Petersburg)

Pituitary adenomas are widespread pathology. The rate of diagnosed pituitary adenomas is 7.0 per 100 000 men. Each clinical case is opposed by 500-1000 subclinical cases, revealed by MRI (the so-called incidentalomas). For many years treatment of patients with pituitary adenomas consisted in surgery or radiation therapy. However, the 70s of the last century brought wider use of drug therapy. The greatest experience has been gained in the field of drug therapy of STH-producing adenomas (somatotropinomas) and prolactin-secreting adenomas (prolactinomas).

Drug Therapy of Somatotropinomas

Dopamine Agonists

They have been used for treatment of acromegaly since 1972. These drugs effect dopamine receptors of the second type and suppress STH secretion. Bromocriptine is the most widespread drug. Its dose is individual (up to 20 mg/day). The greatest effect is watched in cases with pituitary adenoma, secreting both STH and prolactin. Bromocriptine normalizes a level of STH in 20% of cases, but reduction of an adenoma size is a rare phenomenon. Though the STH level is still high in the majority of cases, they report improvement of their state. It should be noted, that bromocriptine has side effects (nausea, dizzeness, etc.). Dopamine agonist of a new generation, used for treatment of acromegaly, include quinagolide (norprolac) and cabergoline (dostinex). They are prescribed in doses of 0.3-0.6 mg/day and 1-2 mg/day respectively.

Somatostatin Analogues

Octreotide has been used since 1980. It is administered intramuscularly in a dose of 100 mg three times a day. Such drugs with a prolonged effect as sandostatin-Lar and lanreotide (somatuline) are prescribed more often. Treatment with sandostatin-LAR lasts three months. It is administered intramuscularly in a dose of 20 mg once in 28 days. Then, if necessary, a dose can be corrected. Intramuscular administration of lanreotide in a dose of 30 mg takes place once in 14 days. As for somatuline-autogel, it is administered intramuscularly in a dose of 120 mg once in 56 days. Somatostatin analogues normalize a level of STH in 70% of cases and reduce an adenoma size in 20-50% of them.

Antagonists of STH Receptors

Pegvisomant binds with STH receptors. It prevents development of peripheral effects of STH on tissues irrespective of its level. Pegvisomant is administered subcutaneously in a dose of 10-40 mg. Regression of clinical symptoms and a normal level of IGF-I are watched soon after the beginning of treatment. There is no change in an adenoma size and a level of STH. Combined therapy with dopamine agonists and somatostatin analogues gives promising results. It should be noted, that drug therapy is often carried out in cases with acromegaly, who demand surgical treatment. It is done before operation. It promotes reduction of an adenoma size and improvement of operation results. As for cases, subjected to radiation therapy, the above drugs are administered until the appearance of its effect.

Drug Therapy of Prolactin-Secreting Pituitary Adenomas

Drug therapy is the main method of prolactinoma treatment. Used as a primary method in cases with large prolactinomas, who need surgical treatment, it helps to reduce their size and to make subsequent operation much easier. Drug therapy is based on dopamine agonists and somatostatin analogues. A dose of bromocriptine, used for treatment of prolactinomas for more than 30 years, is 7.5 mg/day. Normal levels of prolactin, a restored menstrual cycle and galactorrhea arrest are observed in the majority of cases. Treatment with bromocriptine results in reduction of an adenoma size; complete resorption of microprolactinomas is revealed in 20% of cases. One should keep in mind possible side effects of the drug and resistance to bromocriptine, typical of some cases and necessitating increase of a dose up to 15-20 mg/day. Quinagolide and cabergoline are the most effective drugs. They are tolerated much better and resistance to them is less frequent. Their doses are as follows: quinagolide 75-150 mg/day and cabergoline 0.5-1.0 mg twice a week.

Drug therapy of other types of pituitary adenomas need further study. There are data on effectiveness of somatostatin analogues in treatment of TTH-secreting pituitary adenomas. Some authors report attempts to use dopamine agonists for treatment of the so-called hormonally inactive adenomas.

Development of new prospective drugs can limit indications for surgery and radiation therapy in cases with pituitary adenomas.