ESA-SRB 2013* A 26 year-old man with refractory acromegaly (#354)
Introduction
Treatment of acromegaly requires control of the pituitary mass and normalisation of Insulin-like Growth Factor-1 (IGF-1). Failure to normalise IGF-1 is associated with increased mortality.(1)
Case
PJ is a 26 year-old man with refractory acromegaly. At age 22, he underwent transphenoidal resection of a 2.3×2.7cm pituitary macroadenoma displacing the optic chiasm and extending into the right cavernous sinus. Immunohistochemical staining was strongly positive for GH and weakly positive for prolactin.
Due to residual tumour and failure to achieve biochemical control, at age 24 PJ underwent a second transphenoidal debulking procedure followed by stereotactic radiotherapy. Following radiotherapy lanreotide autogel (ATG)® 60mg monthly was commenced.
Two years later, PJ continues to have active disease. He has hypopituitarism with deficiencies of the adrenal, thyroidal and gonadal axes (Table).
Current medications: lanreotide ATG 60mg monthly; cabergoline 0.5mg weekly, hydrocortisone 30mg/d in divided doses; and thyroxine 100mcg/d.
Options for achieving biochemical control
Dose escalation of lanreotide and cabergoline
Lanreotide can be prescribed in doses of 60-120mg monthly. In an open-label study, titrated lanreotide was more effective than fixed dose in controlling GH and IGF-1 at 12 months.(2) Doses of cabergoline have ranged from 0.5-7mg per week in acromegaly studies, but there is little evidence that higher doses are more effective.(3)
Pasireotide
Pasireotide is hypothesised to be more effective than lanreotide in treating acromegaly, because if its broader somatostatin receptor binding profile.(4) In phase II studies, pasireotide has been shown to be effective and safe in treating acromegaly for up to 12 months.(4,5) There are no reports comparing pasireotide to lanreotide in patients with refractory disease. Pasireotide is not approved for use by the Therapeutic Goods Administration (TGA).
Pegvisomant
Guidelines support the use of pegvisomant for refractory disease.(6) A trial of 56 patients with inadequately controlled acromegaly following surgery, radiotherapy, and 6 months of long-acting octreotide were randomized to pegvisomant alone or pegvisomant plus continued octreotide. Fourteen of 25 patients (56%) in the pegvisomant monotherapy group and 16/26 (62%) in the combination group met the primary end-point of normal IGF-1 concentration at week 40, but there was no placebo group.(7) Pegvisomant is TGA-approved.
- Dekkers OM, Biermasz NR, Pereira AM, Romijn JA, Vandenbroucke JP. Mortality in acromegaly: a metaanalysis. J. Clin. Endocrinol. Metab. 2008 Jan;93(1):61–7.
- Caron P, Bex M, Cullen DR, Feldt-Rasmussen U, Pico Alfonso AM, Pynka S, et al. One-year follow-up of patients with acromegaly treated with fixed or titrated doses of lanreotide AutogelR. Clin Endocrinol. 2004 Jun;60(6):734–40.
- Sandret L, Maison P, Chanson P. Place of Cabergoline in Acromegaly: A Meta-Analysis. J. Clin. Endocrinol. Metab. 2011 May 4;96(5):1327–35.
- Petersenn S, Farrall AJ, Block C, Melmed S, Schopohl J, Caron P, et al. Long-term efficacy and safety of subcutaneous pasireotide in acromegaly: results from an open-ended, multicenter, Phase II extension study. Pituitary. 2013 Mar 26.
- Petersenn S, Schopohl J, Barkan A, Mohideen P, Colao A, Abs R, et al. Pasireotide (SOM230) Demonstrates Efficacy and Safety in Patients with Acromegaly: A Randomized, Multicenter, Phase II Trial. J. Clin. Endocrinol. Metab. 2010 Jun 4;95(6):2781–9.
- Melmed S, Colao A, Barkan A, Molitch M, Grossman AB, Kleinberg D, et al. Guidelines for Acromegaly Management: An Update. J. Clin. Endocrinol. Metab. 2009 May 6;94(5):1509–17.
- Trainer PJ, Ezzat S, D’Souza GA, Layton G, Strasburger CJ. A randomized, controlled, multicentre trial comparing pegvisomant alone with combination therapy of pegvisomant and long-acting octreotide in patients with acromegaly. Clin Endocrinol. 2009 Sep 7;71(4):549–57.
