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Diagnosis and Management of Acromegaly in 2012

elevated IGF-1 and normal GH value (i.e., suppressible with OGTT), the subject likely has early stage acromegaly.18

After diagnosis of acromegaly, a magnetic resonance imaging (MRI) scan of the sella should be obtained to determine tumour size, location and invasiveness.19

Visual field testing is performed if the

tumour is touching or compressing the optic chiasm. A thorough ophthalmological examination should be performed if the patient describes diplopia and the tumour is invading the cavernous sinus.


The goals of therapy for acromegaly are to control GH and IGF-1 activity, reduce tumour size and prevent local mass effects, reduce signs and symptoms of disease, prevent or improve medical co-morbidities, and prevent premature mortality. The primary mode of therapy is surgery. Medical therapy is mostly used in the adjuvant setting following surgery, although a role for primary medical therapy in selected patients with macroadenomas may be considered. Radiation therapy is largely relegated to an adjuvant role.


Surgery is highly useful to debulk or resect the somatotroph adenoma, decompress local mass effects, rapidly lower or normalise GH and IGF-1 values, and obtain pathological tissue for further anlaysis. Surgery is recommended for all subjects with microadenomas because approximately 80 % or more of microadenomas are curable.5

With an experienced surgeon,

surgical cure rates for macroadenomas are approximately 40–50 %, likely reflecting the high prevalence of extrasellar extension and parasellar invasion of the cavernous sinus.20–25

Surgery is

recommended for all patients who have macroadenomas with associated mass effects. In patients who have macroadenomas without mass effects and with low likelihood of surgical cure, a role for surgical debulking of macroadenomas to improve response to subsequent medical therapy has been advocated, as has the use of primary medical therapy alone.23

The transsphenoidal approach is

the most common procedure, with craniotomy reserved for select cases involving large, extrasellar lesions. Transnasal endoscopic procedures offer improved visibility and are rapidly replacing microscopic techniques.21

Surgical efficacy can be assessed as early as post-operative day one, as demonstrated by Krieger et al.26

where a fasting serum GH

less than 2 ng/ml was associated with both a normal IGF-1 value and clinical evidence of disease remission at five years. Because the stress of surgery may stimulate the remaining normal gland to elevate GH levels, there is concern that a post-operative serum GH may have more limited prognostic value. The biochemical evaluation at 12 weeks post-operatively, including an IGF-1 level and an OGTT, is considered more valid in assessing surgical result.27,28

In the post-operative setting, a lower nadir GH of less than

0.4 ng/ml has been suggested as a cut-off, although a 1.0 ng/ml value is generally used.14,29

If there are discordant results, such as

an elevated IGF-1 value but normal GH level, repeat testing may be warranted, particularly if there is a high clinical suspicion of persistent disease. Repeat imaging with an MRI scan is usually performed at least 12 weeks following surgery to allow for resolution of oedema and involution of Gelfoam® and fat packing.30 Repeat pituitary hormone studies are performed at this time as well to assess for residual function.

EUROPEAN ENDOCRINOLOGY Table 1: Diagnostic Tests in Acromegaly

Elevated serum IGF-1 (age- and gender-normalised) GH nadir >1.0 ng/ml after oral glucose

Random GH <0.4 ng/ml and normal IGF-1 makes the diagnosis highly unlikely Dedicated ‘pituitary’ MRI once there is biochemical confirmation

GH = growth hormone; IGF-1 = insulin-line growth factor 1; MRI = magnetic resonance imaging.

Is There a Role for Pre-operative Medical Therapy? A role for medical therapy, particulary with somatostatin analogues, to improve surgical remission has been conjectured. In a multicentre study, six-month pre-treatment with octreotide long-acting release (LAR) (20 mg/month) resulted in surgical remission in 50 % of subjects with macroadenomas, compared with 16 % of those who underwent surgery without pre-treatment (p=0.02).31

In a single-centre study,

98 subjects with macroadenomas were randomised to receive lanreotide for four months prior to surgery or to undergo surgery directly, and surgical remission was achieved in 49 % and 18 %, respectively (p=0.001).32

These randomised studies suggest that

pre-operative medical therapy may improve surgical remission rates. However, a limitation of both studies is the relatively low remission rates in the groups randomised to surgery alone. Further study is needed to determine whether medical therapy should be used routinely in the pre-operative setting.

Another consideration is the use of medical therapy pre-operatively to improve anaesthetic risk in the peri- and post-operative settings. Because intubation may be difficult and traumatic in up to 30 % of acromegagly patients, a role for medical therapy to reduce soft tissue swelling and reduce this risk has been considered.33


addition, subjects with acromegaly are at risk of cardiovascular disease, including hypertension and hypertrophic cardiomyopathy, with associated reduced ejection fraction.34

improve cardiovascular morbidities and surgical outcomes.35,36

Medical therapy may Use

of medical therapy to reduce surgical risk is an important topic that deserves further research.

Medical Therapy

Medical therapy is largely used in an adjuvant role for patients with residual disease following surgery. However, primary medical therapy may be considered in subjects with macroadenomas and extrasellar involvement (especially involving the cavernous sinus) but no evidence of local mass effects such as chiasmal compression. In this situation, surgery will unlikely be curative and primary medical therapy in lieu of surgery may be considered.37

In a recent study,

three-quarters of patients had at least 25 % tumour shrinkage following 12 months of somatostatin analogue administration.38 Primary medical therapy may also be considered in patients who are at high risk from surgery and according to patient preferences. In a subject who is undergoing primary medical therapy, surgery can always be reconsidered for tumour debulking to improve the response to medical therapy.23

For somatostatin analogue and dopamine agonist administration, serum GH and IGF-1 are the appropriate biochemical markers for following activity. Repeat testing is performed following dose changes at eight- to 12-week intervals.27

GH suppression following glucose

administration may be useful for monitoring the efficacy of medical therapy,39–41

although a recent study questioned the use of this test in 49

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