This page contains a Flash digital edition of a book.
Trainer_US Endo_Cardiology_book_temp 22/12/2009 10:49 Page 110
Pituitary Disorders
Figure 2: Treatment Algorithm for Acromegaly difficult. Although there are limited data in support, it seems likely that
these factors increase surgical morbidity, which might be reversible with
pre-operative medical therapy. Retrospective studies are conflicting, with
Diagnosis of acromegaly
some reporting no effect,
21,22
while others report a modest benefit.
23,24
The
only prospective, randomized study demonstrated a modest but significant
Surgery contraindicated
Surgery
or refused difference in IGF-I normalization following surgery in patients with
macroadenomas pre-treated with octreotide for six months compared
with those not pre-treated (13/26 versus 4/25), although there was no
difference if mean GH levels were used as criteria for cure. Pre-operative
Successful surgery Failed surgery
SSA did not improve the complication rates and there was a suggestion
that cure rates may actually be worse in patients with microadenomas.
25
Somatostatin
An interesting aside that probably reflects the reality of surgery for most
analogues or
patients, and not inconsistent with Colao et al., is that only 23% of patients
dopamine agonists
were cured by surgery.
IGF-I elevated or
SSAs are safe, well-tolerated, and the gold standard of post-surgical
adverse events
medical therapy. The plethora of studies addressing the use of
pre-operative or primary medical therapy suggest this may have a place in
the acromegaly treatment algorithm, particularly in the short term, as an
Pegvisomant monotherapy Consider
or combination treatment stereotactic radiotherapy
adjunct to surgery for macroadenomas or where there is limited surgical
expertise. However, there are considerable cost implications for long-term
primary medical therapy, and careful consideration is required in terms of
Evidence of continued tumour growth –
Control of IGF-I achieved intended duration of treatment.
external-beam radiotherapy
Dopamine Agonists
Monitor patient
DAs, of which cabergoline is the preferred agent, are relatively ineffective
in achieving the modern standards of biochemical control for acromegaly,
If tumor growth is evident following initial surgery, consideration should be given to repeat
but have the virtues of being relatively inexpensive and oral. Cabergoline is
surgery or conventional radiotherapy. IGF = insulin-like growth factor.
Adapted from Clemmons et al., J Clin Endocrinol Metab, 2003;88:4759–67.
not licensed for the treatment of acromegaly and systematic dose-finding
studies have never been undertaken. The largest retrospective study
medical therapy patients with uncontrolled GH and IGF-I should proceed demonstrated reductions in IGF-I and GH of 30–40%, sufficient to normalize
to surgery or alternative medications. A recent randomized, open-label, IGF-I and GH in around 30% of patients.
26
They are particularly useful in
prospective trial comparing primary SSA therapy with surgery highlights patients with milder disease (serum IGF-I <130% of the upper limit of
this matter, with 13 out of 40 patients who were uncontrolled on octreotide normal) and those co-secreting prolactin
27,28
or in combination with
LAR at 28 weeks opting for surgical intervention.
18
SSAs.
29,30
Most clinicians do not exceed a dose of 1mg per day, although
there are isolated reports of the successful use of higher doses. The future
The disappointing results of the only study to randomize patients to either use of ergot-derived DAs, such as cabergoline, is in question because of
primary medical therapy or surgery raises the question of whether SSAs concerns surrounding irreversible cardiac valve disease seen in patients
are more likely to achieve biochemical control after non-curative debulking with Parkinson’s disease, who are treated with high doses up to six times
surgery. As already discussed, pre-treatment GH, and IGF-I levels are the the dose used for acromegaly.
31,32
The mechanism is activation at the
main determinant of the prospect of biochemical remission with an SSA. 5-HT2B receptor, as seen in the carcinoid syndrome. Patients treated with
Petrossians et al.
19
reported in a retrospective analysis of 24 patients that cabergoline require close monitoring by echocardiogram, and these
pre-operative SSA treatment achieved control of IGF-I in 29 and 45%, concerns may lead to a reduction in cabergoline use despite the lack of
respectively. After non-curative surgery, the control rates in the same evidence of increased risk at the doses used in acromegaly.
patients rose to 54 and 78%, respectively. Similar results have been
reported by Colao et al.
20
and make a compelling argument that even if Pegvisomant
tumor size (or the choice of surgeon) makes the prospect of cure unlikely, The GH-receptor antagonist pegvisomant is licensed in Europe for
the probability of subsequent biochemical remission with an SSA is treatment of acromegaly in patients unresponsive to other forms of
improved by surgical debulking. treatment. It is a pegylated GH analog that acts as a competitive receptor
antagonist at the GH receptor. As it does not lower serum GH levels, the
Another way of approaching primary SSA therapy is as a precursor rather primary marker of disease activity is serum IGF-I. Pegvisomant at doses
than an alternative to surgery. The notion here is that SSA-induced tumor ≤40mg per day can reduce IGF-I to within the reference range in 97% of
shrinkage may improve the prospect of surgical cure or reduce its patients with active, treated acromegaly,
33
indicating that it should be
complications. Active acromegaly causes hypertension, diabetes, and possible with adequate dose titration to achieve a normal serum IGF-I in
reduced cardiac function, which increase surgical risk. It is also associated virtually every patient. Although generally well-tolerated and effective at
with hypertrophy of structures in the pharyngeal region, making intubation correcting the metabolic defects associated with acromegaly, careful
110 US ENDOCRINOLOGY
Page 1  |  Page 2  |  Page 3  |  Page 4  |  Page 5  |  Page 6  |  Page 7  |  Page 8  |  Page 9  |  Page 10  |  Page 11  |  Page 12  |  Page 13  |  Page 14  |  Page 15  |  Page 16  |  Page 17  |  Page 18  |  Page 19  |  Page 20  |  Page 21  |  Page 22  |  Page 23  |  Page 24  |  Page 25  |  Page 26  |  Page 27  |  Page 28  |  Page 29  |  Page 30  |  Page 31  |  Page 32  |  Page 33  |  Page 34  |  Page 35  |  Page 36  |  Page 37  |  Page 38  |  Page 39  |  Page 40  |  Page 41  |  Page 42  |  Page 43  |  Page 44  |  Page 45  |  Page 46  |  Page 47  |  Page 48  |  Page 49  |  Page 50  |  Page 51  |  Page 52  |  Page 53  |  Page 54  |  Page 55  |  Page 56  |  Page 57  |  Page 58  |  Page 59  |  Page 60  |  Page 61  |  Page 62  |  Page 63  |  Page 64  |  Page 65  |  Page 66  |  Page 67  |  Page 68  |  Page 69  |  Page 70  |  Page 71  |  Page 72  |  Page 73  |  Page 74  |  Page 75  |  Page 76  |  Page 77  |  Page 78  |  Page 79  |  Page 80  |  Page 81  |  Page 82  |  Page 83  |  Page 84  |  Page 85  |  Page 86  |  Page 87  |  Page 88  |  Page 89  |  Page 90  |  Page 91  |  Page 92  |  Page 93  |  Page 94  |  Page 95  |  Page 96  |  Page 97  |  Page 98  |  Page 99  |  Page 100  |  Page 101  |  Page 102  |  Page 103  |  Page 104  |  Page 105  |  Page 106  |  Page 107  |  Page 108  |  Page 109  |  Page 110  |  Page 111  |  Page 112  |  Page 113  |  Page 114  |  Page 115  |  Page 116  |  Page 117  |  Page 118  |  Page 119  |  Page 120  |  Page 121  |  Page 122  |  Page 123  |  Page 124
Produced with Yudu - www.yudu.com