Medical Therapy

Medical therapy has become important for the treatment of some functioning pituitary tumors, primarily PRL and GH-secreting tumors. Unfortunately, despite several clinical studies, no clearly effective medical therapy for nonfunctioning pituitary tumors has emerged. The following therapies have been evaluated (2,15).

Dopamine Agonist Therapy

The presence of dopamine receptors has been established in clinically nonfunctioning and gonadotropin tumors, and administration of dopamine agonists can lead to decreases in serum levels of gonadotropins. Based on these findings, several patients with such tumors have been given bromocriptine or other dopamine agonists (21-23). Results of long-term therapy of these tumors with dopamine agonists have been variable. There are case reports of improvements in visual fields and/or tumor shrinkage with dopaminergic agents administered for 6 wk to 7 yr, although reduction of tumor size was quite variable (0% to 50%). In addition, these patients often required high doses of dopamine agonists, which are difficult to tolerate. Based on these data, dopamine agonists can be tried in unusual cases when other treatment options have failed or are refused.

Somatostatin Analog Therapy

Somatostatin regulates gonadotropin and subunit secretion in healthy subjects and in many disease states. Many endocrine tumors, including nonfunctioning and gonadotropin adenomas, contain somatostatin receptors. In-vitro incubation of gonadotropin adenomas with somatostatin or its analogs suppresses gonadotropin or subunit secretion in up to two thirds of tumors, although this is variable. Somatostatin analogs also appear to inhibit cell growth of nonfunctioning tumors in vitro.

To date, several reports have been published regarding octreotide therapy of patients with clinically nonfunctioning, gonadotropin, or a-subunit tumors (24,25). These studies have shown heterogeneous clinical and biochemical responses, with individual reports of decreased serum gonadotropin levels, improved visual fields, and/or decreased tumor size. Visual improvements have been reported to be more common than reduction in tumor size, suggesting an independent effect on the visual pathway. Based on these findings, octreotide, like dopamine agonists, may be tried in select patients with refractory tumors. Whether to use octreotide or dopamine agonists as adjuvant therapy is unclear; acute responses to dopamine or somatostatin infusions do not necessarily predict chronic effects of these agents. One study suggests that combination therapy with octreotide and a dopamine agonist may be effective, but this study included only 10 patients who were followed for 6 mo (26).

GnRH Analog Therapy

Recently, long-acting gonadotropin-releasing hormone (GnRH) analogs have been developed to treat many sex-steroid-dependent conditions. In normal subjects, these drugs initially act as GnRH agonists by binding to GnRH receptors, but eventually cause GnRH-receptor downregulation, with decreases in gonadotropin secretion and bioactivity. Subsets of nonfunctioning pituitary tumors contain GnRH receptors at levels comparable to those in normal human pituitar-ies. These findings form the basis of attempts to treat gonadotroph adenomas with GnRH agonists.

A small number of patients with gonadotropin tumors have been given GnRH agonists to reduce tumorous hormone secretion and tumor size after surgical resection (27-31). GnRH agonists were given at various doses for periods of time ranging between 3 wk and 3 mo. A few patients had decreases in serum FSH and LH levels during treatment, but most had increased gonadotropin subunit levels. Cell culture studies confirm these clinical findings, showing persistent stimulation of gonadotropin secretion in adenomatous cells during continuous GnRH exposure. The mechanism for this chronic agonist effect is unknown, but may indicate that GnRH agonists are not effective in downregulating GnRH receptors on adenomatous tissue. In any case, these drugs are usually not effective in treating gonadotropin tumors and may be deleterious.

More promising are the GnRH antagonists, which do not have an initial agonist effect in normal subjects. To date, one study has reported results of 3-12 mo of GnRH antagonist treatment of five men with FSH secreting tumors (32). All five had normalization of serum FSH levels, but a-subunit levels were not reported. None of the patients had any change in pituitary volume, and one had worsening visual fields. These preliminary data suggest that GnRH antagonists may be useful as adjuvant therapy for persistent or recurrent gonadotropin tumors but do not support their use to control tumor size. However, more extensive long-term studies are clearly necessary to adequately assess the role of these new agents in gonadotropin adenomas.

Was this article helpful?

0 0

Post a comment