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Pituitary Disorders
Advances in Our Understanding of Acromegaly—
Is There an Optimal Management Regimen?
Claire E Higham, DPhil, MRCP
1
and Peter J Trainer, MD, FRCP
2
1. Diabetes and Endocrinology Specialist Registrar; 2. Consultant Endocrinologist, Department of Endocrinology, Christie Hospital, Manchester
Abstract
The two- to three-fold increased mortality associated with active acromegaly can be significantly decreased and even normalized with effective
treatment to reduce growth hormone (GH) and insulin-like growth factor-I (IGF-I) levels to within normal limits. This article addresses the
advances in surgical techniques, new approaches in radiotherapy, and the choice of medical treatments that make it possible to achieve
biochemical remission and improve signs and symptoms of disease in almost every patient with acromegaly. The literature is reviewed in terms
of the relative merits of each treatment method, recent controversies such as the role of radiotherapy and primary octreotide therapy are
discussed and a treatment algorithm is proposed to provide a guide to management.
Keywords
Acromegaly, trans-sphenoidal surgery, radiotherapy, dopamine agonist, somatostatin analog, pegvisomant, treatment algorithm
Disclosure: Claire E Higham, DPhil, MRCP, has no conflicts of interest to declare. Peter J Trainer, MD, FRCP, has received research support from Pfizer, Ipsen, Novartis, and Novo Nordisk.
Received: May 6, 2009 Accepted: July 16, 2009
Correspondence: Claire E Higham, DPhil, MRCP, Department of Endocrinology, Christie Hospital, Manchester, M20 4BX, UK. E: cehigham@doctors.org.uk
Active acromegaly is associated with a two- to three-fold increase in centres from 20 to 68%.
4
As well as the compelling evidence that
mortality that can be reduced to that of the background population with complication rates are lower with experienced surgeons,
5
this means it is
effective treatment to decrease growth hormone (GH) and insulin-like critical that optimal surgical management is performed in a dedicated
growth factor-I (IGF-I) levels to within normal limits.
1
Advances in surgical regional centre with small numbers of surgeons operating on a sufficient
techniques, new approaches in radiotherapy, and a choice of medical caseload to maintain expertise. Other determinants of surgical outcomes
treatments make it possible to achieve biochemical remission in almost are tumor characteristics such as size, local invasion, and extrasellar
every patient with acromegaly. However, controversy persists around the extension.
2
Large macroadenomas with extension into surrounding
optimal order and combination of modalities to achieve control of GH and tissues are very unlikely to be amenable to surgical cure, and it has been
IGF-I while at the same time relieving symptoms and preserving pituitary argued that such patients would be better served by avoiding the risks
function. In particular, the place of surgery as first-line treatment has been for surgery, such as hypopituitarism, and receiving a somatostatin analog
challenged by increasing interest and evidence that primary medical (SSA) as first-line treatment. The combination of the recognition that
therapy can bring disease control without risking hypopituitarism and the some macroadenomas cannot be surgically cured and the variable
other complications of surgery. standards of surgeons have been the major forces driving the interest in
primary medical therapy with SSAs.
Surgery
Even with the increasing popularity of primary medical therapy, the Radiotherapy
majority of patients with acromegaly will undergo trans-sphenoidal Radiotherapy treatment is effective at controlling GH secretion and tumor
surgery (TSS) as it offers the prospect of rapid, cost-effective correction growth, with up to 80% of patients achieving a GH <5mU/l at 15 years.
6
of tumor mass effect and elevated circulating GH levels. The results of Historically, in the UK fractionated three-field external-beam radiotherapy
surgery continue to improve as a consequence of innovations such as at a dose of 4,500cGy was used as second-line adjunctive therapy in
the endoscope and intra-operative imaging. In the most successful patients with acromegaly not cured by surgery. However, it has fallen out
series, 70–80%
2,3
of patients achieve remission; however, the success of of favor principally because of concerns about the consequences of
surgery is operator-dependent and unfortunately, as most patients are hypopituitarism and evidence of an increased risk for a cerebrovascular
operated on by less experienced surgeons, the reality is not published by accident (CVA).
7
Stereotactic radiotherapy in the form of proton beam,
the leading centres. A recent analysis of the UK national acromegaly Linac, or Gamma Knife
©
are developing as techniques for focusing
registry reported that, overall, 56% of patients with a microadenoma high-dose radiation to well-defined residual tumor volume in a single
achieved remission (GH <5mU/l); however, the rates varied between session, while minimising scatter to the brain and surrounding tissues.
108 © TOUCH BRIEFINGS 2009
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