Acromegaly
Acromegaly, meaning ‘large extremities’ in Greek, is almost
exclusively caused by a GH-secreting pituitary tumour. Patients have often had
acromegaly for many years before the diagnosis is considered. The increased
detection of incidental pituitary tumours can lead to early diagnosis if
appropriate tests are performed. Untreated acromegaly can lead to disfiguring
features and premature death, predominantly from cardiovascular disease.
Clinical features
Acromegaly is associated with a classic constellation of
clinical features (Figure 3.1). Increased size of hands and feet occur
commonly, and rings may need to be cut off as they become too tight. Facial
features become coarser over time, with frontal bossing of the forehead,
protrusion of the chin (prognathism) and widely spaced teeth (Figure 3.2). The
diagnosis is often made after the first consultation with a new healthcare
professional. Soft tissue swelling leads to enlargement of the tongue and soft
palate, snoring and sleep apnoea, and puffiness of the hands with carpal tunnel
syndrome. Other specific features of GH hypersecretion include sweating,
headaches, hypertension and diabetes mellitus, which may resolve after
treatment.
Comparison with old photographs can show when acromegalic
features started to develop (Figure 3.3). Patients with large pituitary tumours
may present with visual field disturbance resulting from optic chiasm
compression and hypopituitarism. If acromegaly occurs before puberty, gigantism
occurs. Organomegaly, cardiomyopathy and increased risk of colon cancer can
occur in association with acromegaly.
Investigation
Oral glucose tolerance test and IGF-1
It is relatively easy to confirm or refute a diagnosis of
acromegaly once it is considered. An oral glucose tolerance test (OGTT) with 75
g glucose causes suppression of GH to <1 µg/L in patients who do not have
acromegaly. Failure to suppress suggests autonomous GH secretion and a
diagnosis of acromegaly. Typically, IGF-1 levels are elevated in acromegaly,
reflecting increased GH activity. Some tumours co-secrete both GH and prolactin
as they share the same cell origin, therefore prolactin may be simultaneously
elevated.
Imaging
Pituitary MRI will reveal either a macro-adenoma or a
microadenoma. Typically, large tumours are associated with higher GH and
IGF-1 levels. Patients with cavernous sinus invasion are likely to need
additional treatment because this area is relatively inaccessible surgically.
Management
Surgery is the most appropriate initial treatment for most
patients as this is the only modality that offers the chance of permanent cure.
With micro-adenomas, there is a high likelihood (>80%) of surgical
remission, while remission is only achieved in approximately 60% of patients
with macro-adenomas, hence additional treatment may be needed to achieve
acceptable GH and IGF-1 levels.
Medical treatment
Somatostatin analogues (e.g. octreotide, lanreotide and
pasireotide) can improve symptoms and control GH and IGF-1 levels. These drugs
are usually given as monthly injections. GH receptor blockers (pegvisomant) can
control IGF-1 levels in patients with aggressive acromegaly although treatment
is expensive and not widely available. Dopamine agonists can control GH in
certain patients with acromegaly, although less effective in patients with very
high levels of GH secretion.
In patients with significant residual tumour bulk and
disease activity, additional treatment may be needed. External beam or
stereotactic (‘gamma knife’ or radio-surgery) radiotherapy can be used. External
beam radiotherapy is more established treatment with more published outcome
data, but requires daily visits to hospital for administration over several
weeks. Stereotactic radiotherapy provides a more targeted treatment at higher
dosage and is increasingly used, but is only suitable for lesions well away
from the optic chiasm. Radiotherapy can take many years to lower GH. Long-term
side effects of radiotherapy include gradual-onset hypopituitarism because of
damage to the normal pituitary, and possible cerebrovascular disease.
Monitoring disease activity
After initial surgery, repeat OGTT will indicate if there
is persistent disease. Long-term follow-up is important to ensure adequate
control of GH and IGF-1 levels, and exclude recurrence. Surveillance of disease
status is by clinical assessment, IGF-1 measurement and a measure of GH
activity (random GH, nadir GH to OGTT or mean GH from a GH day series). The
target is GH <1 μg/L and normal IGF-1 although this is often difficult to
achieve in practice. There may be a discrepancy between GH and IGF-1 levels in
up to 30% of patients. Clinical assessment is important in such patients in
deciding whether to treat or monitor. Because of the association of acromegaly
with risk of neoplasia colonoscopy should also be considered.
