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Published in: Pituitary 6/2014

01-12-2014

Tamoxifen as a therapeutic agent in acromegaly

Authors: Irida Balili, Ariel Barkan

Published in: Pituitary | Issue 6/2014

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Abstract

Objective

Administration of high doses of estrogens to patients with acromegaly has been shown to improve symptomatology of acromegaly and glucose tolerance more than 50 years ago. Selective estrogen receptor modulators (SERMs) mimic the effects of estrogen in bone, liver and the cardiovascular system, but function as an anti-estrogen in endometrial and breast tissue. In this study, we evaluated hormonal effects of a SERM, tamoxifen, in active acromegalic patients with particular emphasis on its use in males.

Design

We studied 15 men and 2 post-menopausal women with biochemically-active acromegaly despite the fact that other modalities were ineffective in normalizing their insulin-like growth factor-1 (IGF-1) levels. All patients were treated with tamoxifen 20–40 mg daily for 2–11 months (median of 4 months).

Methods

IGF-1 and growth hormone (GH) levels were assessed immediately before the beginning of treatment and at 2–4 monthly intervals thereafter. Baseline and treatment levels of total and bioavailable testosterone were measured in men.

Results

Tamoxifen did not affect basal GH secretion, but it decreased circulating IGF-I in 14 patients (82 %) by an average of 90 ± 4 mcg/L, (p = 0.005), and normalized plasma IGF-I in 8 patients (47 %). Total and bioavailable testosterone levels increased in all evaluable men (n = 8). Tamoxifen was well tolerated.

Conclusion

Tamoxifen might be useful in the treatment of patients with biochemically-mild active acromegaly, but longer term studies are warranted.
Literature
1.
go back to reference Melmed S, Colao A, Barkan A, Molitch M, Grossman AB, Kleinberg D, Clemmons D, Chanson P, Laws E, Schlechte J, Vance ML, Ho K, Giustina A (2009) Acromegaly consensus group. Guidelines for acromegaly management: an update. J Clin Endocrinol Metab 94:1509–1517PubMedCrossRef Melmed S, Colao A, Barkan A, Molitch M, Grossman AB, Kleinberg D, Clemmons D, Chanson P, Laws E, Schlechte J, Vance ML, Ho K, Giustina A (2009) Acromegaly consensus group. Guidelines for acromegaly management: an update. J Clin Endocrinol Metab 94:1509–1517PubMedCrossRef
2.
go back to reference Murray RD, Melmed S (2008) A critical analysis of clinically available somatostatin analog formulations for therapy of acromegaly. J Clin Endocrinol Metab 93:2957–2968PubMedCrossRef Murray RD, Melmed S (2008) A critical analysis of clinically available somatostatin analog formulations for therapy of acromegaly. J Clin Endocrinol Metab 93:2957–2968PubMedCrossRef
3.
go back to reference Cozzi R, Attanasio R, Barausse M, Dallabonzana D, Orlandi P, Da Re N, Branca V, Oppizzi G, Gelli D (1998) Cabergoline in acromegaly: a renewed role for dopamine agonist treatment? Eur J Endocrinol 139:516–521PubMedCrossRef Cozzi R, Attanasio R, Barausse M, Dallabonzana D, Orlandi P, Da Re N, Branca V, Oppizzi G, Gelli D (1998) Cabergoline in acromegaly: a renewed role for dopamine agonist treatment? Eur J Endocrinol 139:516–521PubMedCrossRef
4.
go back to reference Buchfelder M, Schlaffer S, Droste M, Mann K, Saller B, Bru¨bach K, Stalla GK, Strasburger CJ (2009) German pegvisomant observational study. The German ACROSTUDY: past and present. Eur J Endocrinol 161(Suppl 1):S3–S10PubMedCrossRef Buchfelder M, Schlaffer S, Droste M, Mann K, Saller B, Bru¨bach K, Stalla GK, Strasburger CJ (2009) German pegvisomant observational study. The German ACROSTUDY: past and present. Eur J Endocrinol 161(Suppl 1):S3–S10PubMedCrossRef
5.
go back to reference Albright F, Reifenstein EG Jr et al (1946) Effect of estrogens in acromegaly. Trans Conf Metab Asp Conval 12–13:102–122 Albright F, Reifenstein EG Jr et al (1946) Effect of estrogens in acromegaly. Trans Conf Metab Asp Conval 12–13:102–122
6.
go back to reference McCullagh EP, Beck JC, Schaffenburg CA (1955) Control of diabetes and other features of acromegaly following treatment with estrogens. Diabetes 4:13–23PubMed McCullagh EP, Beck JC, Schaffenburg CA (1955) Control of diabetes and other features of acromegaly following treatment with estrogens. Diabetes 4:13–23PubMed
7.
go back to reference Mintz DH, Finster JL, Josimovich JB (1967) Effect of estrogen therapy on carbohydrate metabolism in acromegaly. J Clin Endocrinol Metab 27:1321–1327PubMedCrossRef Mintz DH, Finster JL, Josimovich JB (1967) Effect of estrogen therapy on carbohydrate metabolism in acromegaly. J Clin Endocrinol Metab 27:1321–1327PubMedCrossRef
8.
go back to reference Leung KC, Johannsson G, Leong GM, Ho KK (2004) Estrogen regulation of growth hormone action. Endocr Rev 25:693–721PubMedCrossRef Leung KC, Johannsson G, Leong GM, Ho KK (2004) Estrogen regulation of growth hormone action. Endocr Rev 25:693–721PubMedCrossRef
9.
go back to reference Leung KC, Doyle N, Ballesteros M, Sjogren K, Watts CK, Low TH, Leong GM, Ross RJ, Ho KK (2003) Estrogen inhibits GH signaling by suppressing GH-induced JAK2 phosphorylation, an effect mediated by SOCS-2. Proc Natl Acad Sci USA 100:1016–1021PubMedCentralPubMedCrossRef Leung KC, Doyle N, Ballesteros M, Sjogren K, Watts CK, Low TH, Leong GM, Ross RJ, Ho KK (2003) Estrogen inhibits GH signaling by suppressing GH-induced JAK2 phosphorylation, an effect mediated by SOCS-2. Proc Natl Acad Sci USA 100:1016–1021PubMedCentralPubMedCrossRef
10.
go back to reference Fournier B, Gutzwiller S, Dittmar T, Matthias G, Steenbergh P, Matthias P (2001) Estrogen receptor (ER)-alpha, but not ER-beta, mediates regulation of the insulin-like growth factor I gene by antiestrogens. J Biol Chem 276:35444–35449PubMedCrossRef Fournier B, Gutzwiller S, Dittmar T, Matthias G, Steenbergh P, Matthias P (2001) Estrogen receptor (ER)-alpha, but not ER-beta, mediates regulation of the insulin-like growth factor I gene by antiestrogens. J Biol Chem 276:35444–35449PubMedCrossRef
11.
go back to reference Cozzi R, Attanasio R, Oppizzi G, Orlandi P, Giustina A, Lodrini S, Da Re N, Dallabonzana D (1997) Effects of tamoxifen on GH and IGF-I levels in acromegaly. J Endocrinol Invest 20:445–451PubMedCrossRef Cozzi R, Attanasio R, Oppizzi G, Orlandi P, Giustina A, Lodrini S, Da Re N, Dallabonzana D (1997) Effects of tamoxifen on GH and IGF-I levels in acromegaly. J Endocrinol Invest 20:445–451PubMedCrossRef
12.
go back to reference Metzger DL, Kerrigan JR (1994) Estrogen receptor blockade with tamoxifen diminishes growth hormone secretion in boys: evidence for a stimulatory role of endogenous estrogens during male adolescence. J Clin Endocrinol Metab 79:513–518PubMed Metzger DL, Kerrigan JR (1994) Estrogen receptor blockade with tamoxifen diminishes growth hormone secretion in boys: evidence for a stimulatory role of endogenous estrogens during male adolescence. J Clin Endocrinol Metab 79:513–518PubMed
13.
go back to reference Lahti EI, Knip M, Laatikainen TJ (1994) Plasma insulin-like growth factor I and its binding proteins 1 and 3 in postmenopausal patients with breast cancer receiving long term tamoxifen. Cancer 74:618–624PubMedCrossRef Lahti EI, Knip M, Laatikainen TJ (1994) Plasma insulin-like growth factor I and its binding proteins 1 and 3 in postmenopausal patients with breast cancer receiving long term tamoxifen. Cancer 74:618–624PubMedCrossRef
14.
go back to reference Corsello SM, Rota CA, Putignano P, Della Casa S, Barnabei A, Migneco MG et al (1998) Effect of acute and chronic administration of tamoxifen on GH response to GHRH and on IGF-I serum levels in women with breast cancer. Eur J Endocrinol 139:309–313PubMedCrossRef Corsello SM, Rota CA, Putignano P, Della Casa S, Barnabei A, Migneco MG et al (1998) Effect of acute and chronic administration of tamoxifen on GH response to GHRH and on IGF-I serum levels in women with breast cancer. Eur J Endocrinol 139:309–313PubMedCrossRef
15.
go back to reference Ho GH, Ji CY, Phang BH, Lee KO, Soo KC, Ng EH (1998) Tamoxifen alters levels of serum insulin-like growth factors and binding proteins in postmenopausal breast cancer patients: a prospective paired cohort study. Ann Surg Oncol 5:361–367PubMedCrossRef Ho GH, Ji CY, Phang BH, Lee KO, Soo KC, Ng EH (1998) Tamoxifen alters levels of serum insulin-like growth factors and binding proteins in postmenopausal breast cancer patients: a prospective paired cohort study. Ann Surg Oncol 5:361–367PubMedCrossRef
16.
go back to reference Shupnik MA, Pitt LK, Soh AY, Anderson A, Lopes MB, Laws ER Jr (1998) Selective expression of estrogen receptor alpha and beta isoforms in human pituitary tumors. J Clin Endocrinol Metab 83:3965–3972PubMed Shupnik MA, Pitt LK, Soh AY, Anderson A, Lopes MB, Laws ER Jr (1998) Selective expression of estrogen receptor alpha and beta isoforms in human pituitary tumors. J Clin Endocrinol Metab 83:3965–3972PubMed
17.
go back to reference Chaidarun SS, Swearingen B, Alexander JM (1998) Differential expression of estrogen receptor-beta (ERbeta) in human pituitary tumors: functional interactions with ER alpha and a tumorspecific splice variant. J Clin Endocrinol Metab 83:3308–3315PubMed Chaidarun SS, Swearingen B, Alexander JM (1998) Differential expression of estrogen receptor-beta (ERbeta) in human pituitary tumors: functional interactions with ER alpha and a tumorspecific splice variant. J Clin Endocrinol Metab 83:3308–3315PubMed
18.
go back to reference Jaffe CA, Pan W, Brown MB, DeMott-Friberg R, Barkan AL (2001) Regulation of GH secretion in acromegaly: reproducibility of daily GH profiles and attenuated negative feedback by IGF-I. J Clin Endocrinol Metab 86:4364–4370PubMedCrossRef Jaffe CA, Pan W, Brown MB, DeMott-Friberg R, Barkan AL (2001) Regulation of GH secretion in acromegaly: reproducibility of daily GH profiles and attenuated negative feedback by IGF-I. J Clin Endocrinol Metab 86:4364–4370PubMedCrossRef
19.
go back to reference Manolopoulou J, Alami Y, Petersenn S, Schopohl J, Wu Z, Strasburger CJ, Bidlingmaier M (2012) Automated 22-kD growth hormone-specific assay without interference from Pegvisomant. Clin Chem 58(10):1446–1456PubMedCrossRef Manolopoulou J, Alami Y, Petersenn S, Schopohl J, Wu Z, Strasburger CJ, Bidlingmaier M (2012) Automated 22-kD growth hormone-specific assay without interference from Pegvisomant. Clin Chem 58(10):1446–1456PubMedCrossRef
20.
go back to reference Bajuk Studen K, Barkan A (2008) Assessment of the magnitude of growth hormone hypersecretion in active acromegaly: reliability of different sampling models. J Clin Endocrinol Metab 93(2):491–496PubMedCentralPubMedCrossRef Bajuk Studen K, Barkan A (2008) Assessment of the magnitude of growth hormone hypersecretion in active acromegaly: reliability of different sampling models. J Clin Endocrinol Metab 93(2):491–496PubMedCentralPubMedCrossRef
21.
go back to reference Dimaraki EV, Symons KV, Barkan AL (2004) Raloxifene decreases serum IGF-1 in male patients with active acromegaly. Eur J Endocrinol 150(4):481–487PubMedCrossRef Dimaraki EV, Symons KV, Barkan AL (2004) Raloxifene decreases serum IGF-1 in male patients with active acromegaly. Eur J Endocrinol 150(4):481–487PubMedCrossRef
22.
go back to reference Sandret L, Maison P, Chanson P (2011) Place of cabergoline in acromegaly: a meta-analysis. J Clin Endocrinol Metab 96(5):1327–1335PubMedCrossRef Sandret L, Maison P, Chanson P (2011) Place of cabergoline in acromegaly: a meta-analysis. J Clin Endocrinol Metab 96(5):1327–1335PubMedCrossRef
Metadata
Title
Tamoxifen as a therapeutic agent in acromegaly
Authors
Irida Balili
Ariel Barkan
Publication date
01-12-2014
Publisher
Springer US
Published in
Pituitary / Issue 6/2014
Print ISSN: 1386-341X
Electronic ISSN: 1573-7403
DOI
https://doi.org/10.1007/s11102-013-0534-9

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