Primary medical therapy for acromegaly: An open, prospective, multicenter study of the effects of subcutaneous and intramuscular slow-release octreotide on growth hormone, insulin-like growth factor-I, and tumor size

J. S. Bevan, Stephen Atkin, A. B. Atkinson, P. M. Bouloux, F. Hanna, P. E. Harris, R. A. James, M. McConnell, G. A. Roberts, M. F. Scanlon, P. M. Stewart, E. Teasdale, H. E. Turner, J. A H Wass, J. M. Wardlaw

Research output: Contribution to journalArticle

234 Citations (Scopus)

Abstract

Conventional surgery and radiotherapy for acromegaly have limitations. There are few data on the use of the somatostatin analog octreotide (Oct) as primary medical therapy. An open prospective study of 27 patients with newly diagnosed acromegaly was conducted in nine endocrine centers in the United Kingdom. Twenty patients had macroadenomas, and 7 had microadenomas. For the first 24 wk (phase 1), patients received sc Oct in an initial dose of 100 μg, 3 times daily, increased to 200 μg three times daily after 4 wk in the 13 patients whose mean serum GH remained greater than 5 mU/liter (2 μg/liter). Five-point GH profiles were performed at 0, 4,12, and 24 wk, and high resolution pituitary imaging using a standard protocol was performed at 0, 12, and 24 wk (magnetic resonance imaging in 25 patients and computed tomography in 2). Tumor dimensions and volumes were calculated by a central, reporting neuroradiologist, and the results were audited by a second, independent neuroradiologist. After 24 wk, 15 patients proceeded to phase 2 of the study with a direct switch to monthly injections of the depot formulation of Oct, Sandostatin long-acting release (Oct-LAR). Further GH profiles were performed at 36 and 48 wk, and pituitary imaging was performed at 48 wk. The median pretreatment serum GH concentration was 30.7 mU/liter (range, 6.7-141.4). During sc Oct, serum GH fell to less than 5 mU/liter in 9 patients (38%), and IGF-I fell to normal in 8 patients (33%). All 27 tumors shrank during sc Oct; for microadenomas the median tumor volume reduction was 49% (range, 12-73), and for macroadenomas it was 43% (range, 6-92). After 24 wk of Oct-LAR (end of phase 2), the GH level was less than 5 mU/liter in 11 of 14 patients (79%), and IGF-I was normal in 8 of 15 patients (53%). In the 15 patients given Oct-LAR (10 macroadenomas), wk 48 scans showed a further overall median tumor volume reduction of 24%. At the end of the study 79% of patients had mean serum GH levels below 5 mU/liter, 53% had normal IGF-I levels, and 73% showed greater than 30% tumor shrinkage. Twenty-nine percent of patients achieved all 3 targets, but no patient with pretreatment GH levels above 50 mU/liter did so at any stage of the study. Primary medical therapy with Oct offers the prospect of normalization of GH/IGF-I levels together with substantial tumor shrinkage in a significant subset of acromegalic patients. This is most likely to occur in patients with pretreatment GH levels less than 50 mU/liter (20 μg/liter).

Original languageEnglish
Pages (from-to)4554-4563
Number of pages10
JournalJournal of Clinical Endocrinology and Metabolism
Volume87
Issue number10
DOIs
Publication statusPublished - 1 Oct 2002
Externally publishedYes

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Acromegaly
Octreotide
Insulin-Like Growth Factor I
Growth Hormone
Multicenter Studies
Tumors
Prospective Studies
Neoplasms
Therapeutics
Imaging techniques
Tumor Burden
Serum
Radiotherapy
Magnetic resonance
Somatostatin
Surgery
Tomography
Switches

ASJC Scopus subject areas

  • Biochemistry

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Primary medical therapy for acromegaly : An open, prospective, multicenter study of the effects of subcutaneous and intramuscular slow-release octreotide on growth hormone, insulin-like growth factor-I, and tumor size. / Bevan, J. S.; Atkin, Stephen; Atkinson, A. B.; Bouloux, P. M.; Hanna, F.; Harris, P. E.; James, R. A.; McConnell, M.; Roberts, G. A.; Scanlon, M. F.; Stewart, P. M.; Teasdale, E.; Turner, H. E.; Wass, J. A H; Wardlaw, J. M.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 87, No. 10, 01.10.2002, p. 4554-4563.

Research output: Contribution to journalArticle

Bevan, JS, Atkin, S, Atkinson, AB, Bouloux, PM, Hanna, F, Harris, PE, James, RA, McConnell, M, Roberts, GA, Scanlon, MF, Stewart, PM, Teasdale, E, Turner, HE, Wass, JAH & Wardlaw, JM 2002, 'Primary medical therapy for acromegaly: An open, prospective, multicenter study of the effects of subcutaneous and intramuscular slow-release octreotide on growth hormone, insulin-like growth factor-I, and tumor size', Journal of Clinical Endocrinology and Metabolism, vol. 87, no. 10, pp. 4554-4563. https://doi.org/10.1210/jc.2001-012012
Bevan, J. S. ; Atkin, Stephen ; Atkinson, A. B. ; Bouloux, P. M. ; Hanna, F. ; Harris, P. E. ; James, R. A. ; McConnell, M. ; Roberts, G. A. ; Scanlon, M. F. ; Stewart, P. M. ; Teasdale, E. ; Turner, H. E. ; Wass, J. A H ; Wardlaw, J. M. / Primary medical therapy for acromegaly : An open, prospective, multicenter study of the effects of subcutaneous and intramuscular slow-release octreotide on growth hormone, insulin-like growth factor-I, and tumor size. In: Journal of Clinical Endocrinology and Metabolism. 2002 ; Vol. 87, No. 10. pp. 4554-4563.
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abstract = "Conventional surgery and radiotherapy for acromegaly have limitations. There are few data on the use of the somatostatin analog octreotide (Oct) as primary medical therapy. An open prospective study of 27 patients with newly diagnosed acromegaly was conducted in nine endocrine centers in the United Kingdom. Twenty patients had macroadenomas, and 7 had microadenomas. For the first 24 wk (phase 1), patients received sc Oct in an initial dose of 100 μg, 3 times daily, increased to 200 μg three times daily after 4 wk in the 13 patients whose mean serum GH remained greater than 5 mU/liter (2 μg/liter). Five-point GH profiles were performed at 0, 4,12, and 24 wk, and high resolution pituitary imaging using a standard protocol was performed at 0, 12, and 24 wk (magnetic resonance imaging in 25 patients and computed tomography in 2). Tumor dimensions and volumes were calculated by a central, reporting neuroradiologist, and the results were audited by a second, independent neuroradiologist. After 24 wk, 15 patients proceeded to phase 2 of the study with a direct switch to monthly injections of the depot formulation of Oct, Sandostatin long-acting release (Oct-LAR). Further GH profiles were performed at 36 and 48 wk, and pituitary imaging was performed at 48 wk. The median pretreatment serum GH concentration was 30.7 mU/liter (range, 6.7-141.4). During sc Oct, serum GH fell to less than 5 mU/liter in 9 patients (38{\%}), and IGF-I fell to normal in 8 patients (33{\%}). All 27 tumors shrank during sc Oct; for microadenomas the median tumor volume reduction was 49{\%} (range, 12-73), and for macroadenomas it was 43{\%} (range, 6-92). After 24 wk of Oct-LAR (end of phase 2), the GH level was less than 5 mU/liter in 11 of 14 patients (79{\%}), and IGF-I was normal in 8 of 15 patients (53{\%}). In the 15 patients given Oct-LAR (10 macroadenomas), wk 48 scans showed a further overall median tumor volume reduction of 24{\%}. At the end of the study 79{\%} of patients had mean serum GH levels below 5 mU/liter, 53{\%} had normal IGF-I levels, and 73{\%} showed greater than 30{\%} tumor shrinkage. Twenty-nine percent of patients achieved all 3 targets, but no patient with pretreatment GH levels above 50 mU/liter did so at any stage of the study. Primary medical therapy with Oct offers the prospect of normalization of GH/IGF-I levels together with substantial tumor shrinkage in a significant subset of acromegalic patients. This is most likely to occur in patients with pretreatment GH levels less than 50 mU/liter (20 μg/liter).",
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AU - Bevan, J. S.

AU - Atkin, Stephen

AU - Atkinson, A. B.

AU - Bouloux, P. M.

AU - Hanna, F.

AU - Harris, P. E.

AU - James, R. A.

AU - McConnell, M.

AU - Roberts, G. A.

AU - Scanlon, M. F.

AU - Stewart, P. M.

AU - Teasdale, E.

AU - Turner, H. E.

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N2 - Conventional surgery and radiotherapy for acromegaly have limitations. There are few data on the use of the somatostatin analog octreotide (Oct) as primary medical therapy. An open prospective study of 27 patients with newly diagnosed acromegaly was conducted in nine endocrine centers in the United Kingdom. Twenty patients had macroadenomas, and 7 had microadenomas. For the first 24 wk (phase 1), patients received sc Oct in an initial dose of 100 μg, 3 times daily, increased to 200 μg three times daily after 4 wk in the 13 patients whose mean serum GH remained greater than 5 mU/liter (2 μg/liter). Five-point GH profiles were performed at 0, 4,12, and 24 wk, and high resolution pituitary imaging using a standard protocol was performed at 0, 12, and 24 wk (magnetic resonance imaging in 25 patients and computed tomography in 2). Tumor dimensions and volumes were calculated by a central, reporting neuroradiologist, and the results were audited by a second, independent neuroradiologist. After 24 wk, 15 patients proceeded to phase 2 of the study with a direct switch to monthly injections of the depot formulation of Oct, Sandostatin long-acting release (Oct-LAR). Further GH profiles were performed at 36 and 48 wk, and pituitary imaging was performed at 48 wk. The median pretreatment serum GH concentration was 30.7 mU/liter (range, 6.7-141.4). During sc Oct, serum GH fell to less than 5 mU/liter in 9 patients (38%), and IGF-I fell to normal in 8 patients (33%). All 27 tumors shrank during sc Oct; for microadenomas the median tumor volume reduction was 49% (range, 12-73), and for macroadenomas it was 43% (range, 6-92). After 24 wk of Oct-LAR (end of phase 2), the GH level was less than 5 mU/liter in 11 of 14 patients (79%), and IGF-I was normal in 8 of 15 patients (53%). In the 15 patients given Oct-LAR (10 macroadenomas), wk 48 scans showed a further overall median tumor volume reduction of 24%. At the end of the study 79% of patients had mean serum GH levels below 5 mU/liter, 53% had normal IGF-I levels, and 73% showed greater than 30% tumor shrinkage. Twenty-nine percent of patients achieved all 3 targets, but no patient with pretreatment GH levels above 50 mU/liter did so at any stage of the study. Primary medical therapy with Oct offers the prospect of normalization of GH/IGF-I levels together with substantial tumor shrinkage in a significant subset of acromegalic patients. This is most likely to occur in patients with pretreatment GH levels less than 50 mU/liter (20 μg/liter).

AB - Conventional surgery and radiotherapy for acromegaly have limitations. There are few data on the use of the somatostatin analog octreotide (Oct) as primary medical therapy. An open prospective study of 27 patients with newly diagnosed acromegaly was conducted in nine endocrine centers in the United Kingdom. Twenty patients had macroadenomas, and 7 had microadenomas. For the first 24 wk (phase 1), patients received sc Oct in an initial dose of 100 μg, 3 times daily, increased to 200 μg three times daily after 4 wk in the 13 patients whose mean serum GH remained greater than 5 mU/liter (2 μg/liter). Five-point GH profiles were performed at 0, 4,12, and 24 wk, and high resolution pituitary imaging using a standard protocol was performed at 0, 12, and 24 wk (magnetic resonance imaging in 25 patients and computed tomography in 2). Tumor dimensions and volumes were calculated by a central, reporting neuroradiologist, and the results were audited by a second, independent neuroradiologist. After 24 wk, 15 patients proceeded to phase 2 of the study with a direct switch to monthly injections of the depot formulation of Oct, Sandostatin long-acting release (Oct-LAR). Further GH profiles were performed at 36 and 48 wk, and pituitary imaging was performed at 48 wk. The median pretreatment serum GH concentration was 30.7 mU/liter (range, 6.7-141.4). During sc Oct, serum GH fell to less than 5 mU/liter in 9 patients (38%), and IGF-I fell to normal in 8 patients (33%). All 27 tumors shrank during sc Oct; for microadenomas the median tumor volume reduction was 49% (range, 12-73), and for macroadenomas it was 43% (range, 6-92). After 24 wk of Oct-LAR (end of phase 2), the GH level was less than 5 mU/liter in 11 of 14 patients (79%), and IGF-I was normal in 8 of 15 patients (53%). In the 15 patients given Oct-LAR (10 macroadenomas), wk 48 scans showed a further overall median tumor volume reduction of 24%. At the end of the study 79% of patients had mean serum GH levels below 5 mU/liter, 53% had normal IGF-I levels, and 73% showed greater than 30% tumor shrinkage. Twenty-nine percent of patients achieved all 3 targets, but no patient with pretreatment GH levels above 50 mU/liter did so at any stage of the study. Primary medical therapy with Oct offers the prospect of normalization of GH/IGF-I levels together with substantial tumor shrinkage in a significant subset of acromegalic patients. This is most likely to occur in patients with pretreatment GH levels less than 50 mU/liter (20 μg/liter).

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