Poster Presentation Annual Meetings of the Endocrine Society of Australia and Society for Reproductive Biology and Australia and New Zealand Bone and Mineral Society 2016

Two for the price of one: Tamoxifen for treatment of breast cancer in a patient with acromegaly normalised serum IGF-1 level (#417)

Chau Thien Tay 1 , Anthony Zimmermann 1 , Peak Mann Mah 1
  1. Lyell McEwin Hospital, Elizabeth Vale, SA, Australia

Introduction:

The Endocrine Society Clinical Practice Guidelines for Acromegaly recommends somatostatin analogue or pegvisomant as initial adjuvant therapy for patients with persistent disease following transsphenoidal surgery, or dopamine agonist in patients with modest elevation in insulin-like growth factor-1 (IGF-1)1. Oestrogen and selective oestrogen receptor modulators (SERMs) have been shown to reduce IGF-1 to normal but there is a lack of consensus surrounding their routine use in acromegaly2.

Case:

A 47-year-old woman with acromegaly had transsphenoidal resection of pituitary macroadenoma in May 2010. IGF-1 level decreased from 80nmol/l to 40 nmol/l (reference range 12-33). Growth hormone (GH) levels were suppressed on oral glucose tolerance test. Other anterior pituitary hormones were intact and MRI did not show tumour recurrence. IGF-1 levels normalised on cabergoline. Cabergoline was stopped after 18 months owing to intolerance and doubts regarding biochemical response. IGF-1 remained slightly above the normal range. In December 2014, she was diagnosed with hormone-receptor positive breast cancer. Following surgery, chemotherapy and radiation, she was started on tamoxifen. IGF-1 was 43 nmol/l a month before starting tamoxifen. Four months later, IGF-1 levels had normalised to 19nmol/l (reference range 7-24).

Discussion:

Oestrogens up-regulate liver-specific GH-receptor and GH-binding protein expression3. Oestrogens inhibit growth hormone signalling via the JAK-STAT pathway and suppress growth hormone dependent JAK-2 phosphorylation4. SERMs have agonistic or antagonistic properties on oestrogen receptors depending on the target organ4. In the liver, SERM have agonistic effects and is thought to function similarly to oestrogen by inhibiting GH receptor signalling, thereby decreasing hepatocellular synthesis of IGF-1.

Conclusion:

Tamoxifen may be an effective adjuvant treatment in acromegalic patients with residual disease and mild hypersecretion.

  1. Katznelson L, Laws E, Melmed S, Molitch M, Murad M, Utz A et al. Acromegaly: An Endocrine Society Clinical Practice Guideline. The Journal of Clinical Endocrinology & Metabolism. 2014;99(11):3933-3951.
  2. Stone J, Clark J, Cuneo R, Russell A, Doi S. Estrogen and selective estrogen receptor modulators (SERMs) for the treatment of acromegaly: a meta-analysis of published observational studies. Pituitary. 2014;17(3):284-295.
  3. Leung KC, Johannsson G, Leong GM, Ho KK. Estrogen regulation of growth hormone action. Endocrine Review. 2004; 25:693-721.
  4. Leung KC, Doyle N, Ballesteros M, Sjogren K, Watts CK, Low TH, Leong GM, Ross RH, Ho KK. Estrogen inhibits GH signalling by suppressing GH-induced JAK2 phosphorylation, an effect medicated by SOCS-2. Proceedings of the National Academy of Sciences USA. 2003; 100:1016-1021.
  5. Maiza J, Castillo-Ros S, Matta M, Bennet A, Caron P. Tamoxifen enhances the control of acromegaly treated with somatostatin analog lanreotide. Pituitary. 2012;15(S1):23-27.