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Future treatment strategies of aggressive pituitary tumors.

Lamberts SW, Hofland LJ - Pituitary (2009)

Bottom Line: In acromegaly, the existing somatostatin analogs, octreotide and lanreotide, will remain the medical treatment of choice for the foreseeable future.There is an urgent need for medical therapies in Cushing's disease, and the SSTR(5) analogs could offer an effective treatment in a proportion of patients within the next few years.Finally, the medical management options for non-functioning pituitary adenomas are also very limited, and a new chimeric agent with activity towards dopamine receptors, SSTR(5) and SSTR(2) may help reduce adenoma recurrence in the future.

View Article: PubMed Central - PubMed

Affiliation: Department of Internal Medicine, Division of Endocrinology, Erasmus Medical Center, 3015 CE Rotterdam, The Netherlands. s.w.j.lamberts@erasmusmc.nl

ABSTRACT
While surgery remains the first-line treatment of most aggressive pituitary adenomas, medical therapy is important as second-line or adjunctive therapy in a large proportion of patients. Dopamine agonists (DAs) are the best treatment for prolactinomas, but when DAs are not tolerated, new somatostatin receptor subtype 5 (SSTR(5)) inhibitors may offer an alternative in the future. Unfortunately, these are unlikely to be effective in DA-resistant prolactinomas. In acromegaly, the existing somatostatin analogs, octreotide and lanreotide, will remain the medical treatment of choice for the foreseeable future. There is an urgent need for medical therapies in Cushing's disease, and the SSTR(5) analogs could offer an effective treatment in a proportion of patients within the next few years. Finally, the medical management options for non-functioning pituitary adenomas are also very limited, and a new chimeric agent with activity towards dopamine receptors, SSTR(5) and SSTR(2) may help reduce adenoma recurrence in the future.

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Related in: MedlinePlus

Effect of SSTR5-specific analog on prolactin secretion from DA-susceptible and DA-resistant human prolactinomas. From Jaquet et al. [1]
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Fig1: Effect of SSTR5-specific analog on prolactin secretion from DA-susceptible and DA-resistant human prolactinomas. From Jaquet et al. [1]

Mentions: SSTR are expressed in prolactinomas, but the majority express SSTR5 and not SSTR2 [1]. When quantified, SSTR5 mRNA was detected at 40-fold higher concentrations than SSTR2 mRNA (SSTR1 was also expressed in prolactinomas but the significance of this is not known) [1]. This expression pattern means that established somatostatin analogs (SSAs) such as octreotide and lanreotide that bind primarily to SSTR2 are ineffective in suppressing prolactin secretion from these adenomas [2]. This has been demonstrated by comparing the inhibition of prolactinomas by octreotide and the experimental compound pasireotide (SOM-230), which has 40-fold greater binding affinity to SSTR5 than octreotide. This study showed slight inhibition of prolactin secretion in one out of three adenomas by octreotide, while pasireotide significantly inhibited prolactin secretion in all three adenomas [2]. Unfortunately, potent SSTR5 inhibitors may not be of value in treating prolactinomas, because their potential efficacy is most needed for treating DA-resistant prolactinomas, and most of these prolactinomas appear to express no (or low levels) of SSTR5 and are also resistant to SSAs that bind to this receptor (Fig. 1) [1]. Furthermore, there was no additive effect on prolactin secretion when a SSTR5 inhibitor was added to a DA [1].Fig. 1


Future treatment strategies of aggressive pituitary tumors.

Lamberts SW, Hofland LJ - Pituitary (2009)

Effect of SSTR5-specific analog on prolactin secretion from DA-susceptible and DA-resistant human prolactinomas. From Jaquet et al. [1]
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2712619&req=5

Fig1: Effect of SSTR5-specific analog on prolactin secretion from DA-susceptible and DA-resistant human prolactinomas. From Jaquet et al. [1]
Mentions: SSTR are expressed in prolactinomas, but the majority express SSTR5 and not SSTR2 [1]. When quantified, SSTR5 mRNA was detected at 40-fold higher concentrations than SSTR2 mRNA (SSTR1 was also expressed in prolactinomas but the significance of this is not known) [1]. This expression pattern means that established somatostatin analogs (SSAs) such as octreotide and lanreotide that bind primarily to SSTR2 are ineffective in suppressing prolactin secretion from these adenomas [2]. This has been demonstrated by comparing the inhibition of prolactinomas by octreotide and the experimental compound pasireotide (SOM-230), which has 40-fold greater binding affinity to SSTR5 than octreotide. This study showed slight inhibition of prolactin secretion in one out of three adenomas by octreotide, while pasireotide significantly inhibited prolactin secretion in all three adenomas [2]. Unfortunately, potent SSTR5 inhibitors may not be of value in treating prolactinomas, because their potential efficacy is most needed for treating DA-resistant prolactinomas, and most of these prolactinomas appear to express no (or low levels) of SSTR5 and are also resistant to SSAs that bind to this receptor (Fig. 1) [1]. Furthermore, there was no additive effect on prolactin secretion when a SSTR5 inhibitor was added to a DA [1].Fig. 1

Bottom Line: In acromegaly, the existing somatostatin analogs, octreotide and lanreotide, will remain the medical treatment of choice for the foreseeable future.There is an urgent need for medical therapies in Cushing's disease, and the SSTR(5) analogs could offer an effective treatment in a proportion of patients within the next few years.Finally, the medical management options for non-functioning pituitary adenomas are also very limited, and a new chimeric agent with activity towards dopamine receptors, SSTR(5) and SSTR(2) may help reduce adenoma recurrence in the future.

View Article: PubMed Central - PubMed

Affiliation: Department of Internal Medicine, Division of Endocrinology, Erasmus Medical Center, 3015 CE Rotterdam, The Netherlands. s.w.j.lamberts@erasmusmc.nl

ABSTRACT
While surgery remains the first-line treatment of most aggressive pituitary adenomas, medical therapy is important as second-line or adjunctive therapy in a large proportion of patients. Dopamine agonists (DAs) are the best treatment for prolactinomas, but when DAs are not tolerated, new somatostatin receptor subtype 5 (SSTR(5)) inhibitors may offer an alternative in the future. Unfortunately, these are unlikely to be effective in DA-resistant prolactinomas. In acromegaly, the existing somatostatin analogs, octreotide and lanreotide, will remain the medical treatment of choice for the foreseeable future. There is an urgent need for medical therapies in Cushing's disease, and the SSTR(5) analogs could offer an effective treatment in a proportion of patients within the next few years. Finally, the medical management options for non-functioning pituitary adenomas are also very limited, and a new chimeric agent with activity towards dopamine receptors, SSTR(5) and SSTR(2) may help reduce adenoma recurrence in the future.

Show MeSH
Related in: MedlinePlus