Updates in the Medical Treatment of Pituitary Adenomas

Abstract

Pituitary adenomas represent approximately 15% of brain tumors; incidence is significantly on the increase due to widespread use of magnetic resonance imaging. Surgery remains the first-line treatment for most tumors overall. The role of dopaminergic agonists (DAs) and somatostatin receptor ligands (SRLs) in the treatment of pituitary adenomas is quite well established for prolactinomas and growth hormone (GH) excess. However, over the last decade new multi-receptor binding SRLs are increasingly used for treatment of acromegaly and Cushing’s disease. SRLs/DA chimeric compounds seem to have enhanced potency and efficacy when compared to that of individual SRLs or DA receptor agonists according to preclinical data. However, following negative results, more research is needed to determine if this interesting mechanism will translate into positive clinical effects for acromegaly patients. Furthermore, new agents that block adrenal steroidogenesis have been developed in phase III clinical trials for Cushing’s disease and several new compounds working at the pituitary level and/or blocking the glucocorticoid receptor are also in development. Combination therapy of drugs with similar or different mechanisms (possibly synergistic) are also on the increase. A growing awareness regarding all mechanisms involved in both control of pituitary secretion and cellular proliferation might allow for sole medical treatment of pituitary adenomas, especially macroadenomas, rather than surgery and/or radiation therapy, in the future. Moreover, the underlying decision on how to treat patients with pituitary adenomas should be individualized on a case-by-case basis with not only a goal of tumor shrinkage and biochemical control, but also of improving patients’ quality of life.

Gonadotroph Tumors Show Subtype Differences that Might Have Implications for Therapy

“…The second medical treatment option, D2R agonists, demonstrated so far to be more effective than SSTs ligands in controlling tumor growth (including tumor shrinkage) in a couple of studies that were mostly retrospective and included various combinations of NF-PitNETs [4,6,18,[22][23][24][25][26]. As predictive factors of response to D2R agonists, so far the most investigated was the expression of D2R, that yielded inconsistent results [22,25,26].…”

“…Other than surgery, which remains the main treatment option, radiotherapy may sometimes be proposed, but in comparison to the other types of PitNETs, no established medical treatment is available or recommended for NF-PitNETs, including gonadotroph tumors [6]. As some of these tumors express dopamine receptor type 2 (D2R) [4,6] and somatostatin receptors (SSTs) [4], a role for D2R agonists and SSTs ligands has been envisioned.…”

“…Other than surgery, which remains the main treatment option, radiotherapy may sometimes be proposed, but in comparison to the other types of PitNETs, no established medical treatment is available or recommended for NF-PitNETs, including gonadotroph tumors [6]. As some of these tumors express dopamine receptor type 2 (D2R) [4,6] and somatostatin receptors (SSTs) [4], a role for D2R agonists and SSTs ligands has been envisioned. In the few studies published, these treatments showed some effect, but additional results from larger and long-term prospective randomized trials are necessary before recommending these medical options and, also, in order to establish whether there are subgroups of patients that would be better responders [4,6].…”

Medical Treatment of Pituitary Adenomas: A Celebration of Endocrinology (and Oncology)!

“…There is therefore no better way to celebrate our anniversary than featuring in this issue a review by Maria Fleseriu and her colleagues on the medical treatment of pituitary adenomas [3]. This extensive article covers all recent updates on the use of a variety of pharmacological approaches to the treatment of pituitary adenomas and/or their hormonal consequences from the use of dopaminergic agonists and somatostatin receptor ligands to steroidogenesis inhibitors and glucocorticoid receptor antagonists in Cushing syndrome due to corticotropin-producing adenomas.…”

A Century After the Description of “Hormones”, Our Golden Jubilee Celebration Goes on with What is New in Endocrine Oncology: And a Lot is New!

“…Today, we are well beyond recognition of a disease that is as ancient as Greek mythology [9]: not only MRI scans recognize ever smaller growth-hormone (GH)-producing tumors, but we also understand their formation (as the histological diagram of the figure demonstrates) and their genetic causes [6,7]. Importantly, as Fleseriu et al recently wrote at HMR, these advances allow us to design new medical therapies for pituitary tumors [10].…”