Predicting Therapeutic Response and Degree of Pituitary Tumour Shrinkage during Treatment of Acromegaly with Octreotide LAR

Abstract

Background/Aims: The efficacy of transsphenoidal surgery in the treatment of patients with acromegaly is largely dependent on tumour size. A reduction in pituitary tumour volume by medical therapy might therefore improve subsequent surgical cure rates. This study prospectively determined the effects of the depot somatostatin analogue octreotide LAR on pituitary tumour size, GH and IGF-I levels and clinical symptoms in a cohort of previously untreated patients with acromegaly. Methods: Six patients newly diagnosed with acromegaly (mean age 53 years; range 42–76 years) received intramuscular octreotide LAR every 28 days for 6 months. The initial dose of LAR was 20 mg, but increased to 30 mg after the initial 3 injections if mean GH levels were >5 mU/l. Prior to commencing LAR therapy, each patient received 3 injections of subcutaneous octreotide (50, 100 and 200 µg) in a randomized order on separate days, and the serum GH response was measured. Pituitary tumour volume was calculated from MRI or computed tomography scans at baseline, then 3 and 6 months after initiation of treatment, and assessed by a ‘blinded’ radiologist in random order. At baseline, 4 patients had a macroadenoma and 2 patients had a microadenoma. For the latter, the whole gland volume was measured. Results: Serum GH levels decreased from 29.6 ± 19.2 mU/l (mean ± SD) at baseline to 12.1 ± 10.5 mU/l at 3 months and 10.4 ± 9.3 mU/l at 6 months. Three patients achieved a mean serum GH level of <5 mU/l. In these patients, the serum GH had declined to <5 mU/l in response to a single 100 µg subcutaneous octreotide injection. Serum IGF-I levels decreased by a mean of 45 ± 7.4%. Tumour volume decreased in all patients: mean baseline volume 2,175 mm³ (range 660–6,998) decreasing to 1,567 mm³ (range 360–4,522) at 3 months (p < 0.05) and 1,293 mm³ (range 280–4,104) at 6 months (p < 0.002). The mean percentage decrease in size was 29% (range –54 to +4%) at 3 months (p < 0.02) and 47% (range 21–97%) at 6 months (p < 0.002). There was no statistically significant correlation between GH response and tumour shrinkage. Conclusions: A single test dose of subcutaneous octreotide may be useful in predicting the subsequent efficacy of octreotide LAR. Octreotide LAR results in significant shrinkage of pituitary tumours of newly diagnosed patients with acromegaly. Whether its administration to such patients for 6–12 months can improve the efficacy of subsequent transsphenoidal surgery will require further study.

Immunohistochemical Detection of Somatostatin Receptor (SSTR) Subtypes 2A and 5 in Pituitary Adenoma from Acromegalic Patients: Good Correlation with Preoperative Response to Octreotide

“…Reduction of serum GH and IGF-1 levels reduces the morbidity and complications associated with this disease [1][2][3][4][5][6][7]. According to current guidelines transsphenoidal surgery by an experienced pituitary surgeon is the procedure of choice in the initial management of acromegaly [6,26].…”

“…Surgery, radiotherapy, and therapy with dopamine agonists, somatostatin analogs, or GH receptor antagonists are variably used to treat acromegaly [6]. Reduction of serum GH and IGF-1 levels in these patients decreases the morbidity and complications associated with this disease [7]. The therapeutic goals in acromegaly are to eliminate morbidity and to reduce mortality.…”

“…More recently, the development of long-acting depot SSA has led to improved control of serum GH levels in 49-56% of patients and IGF-1 levels in 48-66% of them [24]. According to previous reports, octreotide LAR also mediated tumor shrinkage in 80% of acromegalic patients [7]. With increased use of this drug, some reports on predictive factors for the clinical effect are beginning to appear.…”

The value of an acute octreotide suppression test in predicting short-term efficacy of somatostatin analogues in acromegaly

“…After the long-acting formulations became available, several studies evaluated the efficacy of OST as a predictor of long-term response (shown in Supplementary Table 1). However, the results of different studies were conflicting, but with more publications in favor of using the OST [13][14][15][27][28][29][30][31], than discarding it [7,12,25,32]. The conflicting results might be caused by different OST protocols, octreotide dosages, outcome criteria and various parameters selected for evaluation.…”

Is There Still a Role for Radiotherapy in Acromegaly?

“…However, the majority of patients who have had suboptimal response to surgery will require therapy with a somatostatin analogue, usually administered in a depot formulation (octreotide LAR or lanreotide autogel). Somatostatin analogues provide adequate control of GH excess in approximately 65% of patients with the additional benefit of control of tumour volume or shrinkage [7, 8]. Indeed, a case has been made for primary medical therapy in selected patients.…”