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.
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.
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.
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.
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.
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.