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Pituitary Disorders
Combination Therapy Controversy remains in terms of the role of primary medical therapy
Pegvisomant is indicated for patients unresponsive to SSA, and in that with SSAs, particularly in centres without adequate neurosurgical
scenario the choice is whether to add it to ongoing SSA or substitute expertise. We would certainly recommend pre-operative medical
pegvisomant in place of SSA. Van der Lely’s group have described the therapy in patients with complications such as sleep apnoea or
successful addition of weekly pegvisomant to monthly SSA.
37,38
This is cardiomyopathy. There is a lack of data to show that pre-treatment of
an attractive option as a means of maintaining any tumour shrinkage macroadenomas improves surgical complications or remission rates,
that has occurred with an SSA. The only reported study to randomise and we feel the currently available data in terms of long-term
patients unresponsive to SSA to either combination therapy or morbidity and mortality are insufficient to recommend it replace TSS,
pegvisomant monotherapy found similar rates of IGF-I normalisation in but it should be an option for patients who are not fit for surgery or
both groups, with patients on pegvisomant monotherapy requiring on under special circumstances.
average 5mg per day more than those on combination therapy
39
– the
implication being that there is little difference in the price of the two Conventional radiotherapy should be reserved for patients with
options, which is contrary to previous claims that combination continued tumour growth despite surgical and medical therapy.
treatment was significantly less expensive. The decision to use However, stereotactic radiotherapy may have a specific role in those
monotherapy or combination treatment depends on individual patient patients with a well-defined area of residual disease at least 5mm away
circumstances; for example, good tumour shrinkage with SSA would from the optic chiasm post-debulking surgery.
be a reason for combination treatment, while deteriorating glucose
tolerance argues for monotherapy. Despite these interventions, the majority of patients will require
medical therapy. SSAs provide the mainstay of medical treatment, with
Novel Treatments DA being an option in those with mild elevations of IGF-I and
Pasireotide (SOM230) is a novel multireceptor ligand SSA with high co-secreting prolactin. In Europe, pegvisomant is limited to patients
binding affinity to SSTR-1, -2, -3 and -5 and up to 40-fold greater affinity who remain uncontrolled on maximum-dose SSA or who are intolerant
for SST5 than octreotide. It may have a role in the treatment of various of SSAs due to side effects. Combination treatments of SSAs and
types of pituitary tumour, including those secreting GH. A phase II study pegvisomant are increasingly being used as there is some evidence of
has demonstrated effective IGF-I and GH suppression with a significant a synergistic effect of the two medications and benefit in those
reduction in tumour volume, but there are concerns in terms of uncontrolled on either drug alone. The management of acromegaly is
deteriorating glucose tolerance.
40
The future role of pasireotide in the complex, but with improved surgical and radiotherapy techniques and
treatment of acromegaly remains to be determined, but it will probably multiple medical options, biochemical control should be achievable in
have a role in the treatment of octreotide-resistant tumours, all patients. As new medications and techniques evolve, the treatment
particularly large adenomas. Another multireceptor ligand, the chimeric paradigm will almost certainly change, and patients should be followed
molecule BIM-23A760, that has activity at both somatostatin (SSTR 2 closely and re-evaluated on a regular basis. n
and 5) and dopamine receptors (DA2) is in clinical trials following
encouraging in vitro results.
41
Claire E Higham is a Diabetes and Endocrinology
Specialist Registrar in the Department of Endocrinology
Optimal Management Regimen at The Christie Hospital in Manchester. Her research
The treatment regimen for acromegaly should be individually tailored
interests include pituitary disorders, particularly
acromegaly and the metabolic consequences of
based on informed patient choice and the defined biochemical and
endocrine conditions.
clinical goals of treatment. Treatment decisions will take into
consideration the desire to achieve biochemical control, relieve
symptoms and signs, preserve pituitary function and control tumour
Peter J Trainer is a Consultant Endocrinologist and
size (see Figure 2).
Professor of Endocrinology in the Department of
Endocrinology at The Christie Hospital in Manchester.
We would advocate that first-line treatment for the great majority of
His research interests are pituitary and adrenal disease,
particularly Cushing’s syndrome, acromegaly and
patients remains TSS performed by an experienced surgeon.
glucocorticoid receptors.
Microadenomas should be cured and debulking of macroadenomas will
relieve pressure on structures such as the optic chiasm, and will also
improve the likelihood of remission with secondary medical therapy.
1. Holdaway IM, et al., J Clin Endocrinol Metab, 2004;89:667–74. 15. Colao A, et al., Clin Endocrinol (Oxf), 2006;64:342–51. 30. Selvarajah D, et al., Eur J Endocrinol, 2005;152:569–74.
2. Abosch A, et al., J Clin Endocrinol Metab, 1998;83:3411–18. 16. Cozzi R, et al., J Clin Endocrinol Metab, 2006;91:1397–1403. 31. Schade R, et al., N Engl J Med, 2007;356:29–38.
3. Tindall GT, et al., J Neurosurg, 1993;78:205–15. 17. Bevan JS, et al., J Clin Endocrinol Metab, 2002;87:4554–63. 32. Zanettini R, et al., N Engl J Med, 2007;356:39–46.
4. Bates PR, et al., Clin Endocrinol, 2008;68:136–42. 18. Colao A, et al., Clin Endocrinol, 2009;70:757–68. 33. van der Lely AJ, et al., Lancet, 2001;358:1754–9.
5. Ciric I, et al., Neurosurgery, 1997;40:225–36 19. Petrossians P, et al., Eur J Endocrinol, 2005;152:61–6. 34. Schreiber I, et al., Eur J Endocrinol, 2007;156:75–82.
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8. Losa M, et al., J Clin Endocrinol Metab, 2008;93:2546–52. 22. Abe T, Ludecke DK, Eur J Endocrinol, 2001;145:137–45. 37. Feenstra J, et al., Lancet, 2005; 365:1644–6.
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10. Freda PU, et al., J Clin Endocrinol Metab, 2005;90:4465–73. 24. Barkan AL, et al., J Clin Endocrinol Metab, 1988;67:1040–48. 39. Trainer PJ, et al., Clin Endocrinol (Oxf), 2009 (Epub ahead of print).
11. Murray RD, Melmed S, J Clin Endocrinol Metab, 25. Carlsen SM, et al., J Clin Endocrinol Metab, 2008;93:2984–90. 40. Farrall AJ, et al., Pasireotide (SOM230) effectively reduces
2008;93:2957–68. 26. Abs R, et al., J Clin Endocrinol Metab 1998;83:374–6. pituitary tumour volume in patients with active acromegaly:
12. Bevan JS, et al., Clin Endocrinol (Oxf), 2008;68:343–9. 27. Colao A, et al., J Clin Endocrinol Metab, 1997;82:518–23. results from a phase II trial, OR53-4, proceedings of the
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