Acromegaly

The syndrome of growth hormone excess caused by somatotroph adenomas of the pituitary. Also known as gigantism in childhood. Diagnosis is confirmed with failure of suppression of a glucose tolerance test.

Random GH and IGF-I normal


Reassure and discharge

If clinical review is reassuring and GH and IGF-I are normal, acromegaly can be excluded.

Clinically suspicious or elevated GH or IGF-I


Proceed to OGTT

If there is a strong clinical suspicion, or if either screening tests are elevated, a formal GH suppression test should be undertaken.

OGTT shows failure of GH suppression


Acromegaly confirmed, proceed to further investigations

Failure of GH suppression on an OGTT confirms biochemical acromegaly, and so disease localisation and severity then need to be assessed. MRI pituitary, formal visual perimetry and baseline pituitary function are required urgently. Dynamic pituitary function testing should be performed if baseline cortisol is suboptimal.

Arrange CXR, ECG, echocardiogram, and offer a baseline colonoscopy.

Consider cardiology review if cardiomyopathy, valve disease or rhythm disturbance have been detected.

Consider referral to sleep specialist if there is clinical suspicion of obstructive sleep apnoea.


Review results and MRI scan at multidisciplinary meeting

The management of acromegaly is complex and a multidisciplinary approach is optimal.

Consider immediate surgical referral

Surgical cure is most likely to be achieved with microadenomas.

Surgical referral is mandatory if there is visual field loss or chiasmal compression on MRI scan.

Consider starting depot somatostatin analogue

Surgical cure is unlikely to be achieved with macroadenomas, and good tumour shrinkage as well as biochemical control may be achieved with somatostatin analogue therapy.

Consider trial of dopamine agonist

Dopamine agonists may be used as an alternative or adjunctive treatment to somatostatin analogues, and particularly if serum prolactin is elevated. These are effective only in a small proportion of patients, but are cheap, given orally, and are generally well tolerated, so a trial of therapy may be appropriate in various situations.

Consider pegvisomant in resistant cases

This is not a first line treatment and does not control local disease but is highly effective at controlling severe biochemical disease. Its role is largely confined to patients not acheiving biochemical control despite dual therapy with somatostatin and dopamine agonists after non curative surgery.

Conventional radiotherapy

This is not generally considered a first line treatment but is useful in cases where the disease is not cured surgically. It is also useful where the patient cannot tolerate, or responds poorly to medical treatments.

Clinical review with repeat IGF-I and OGTT at three months

Timing of repeat MRI should be determined after discussion at multidisciplinary meeting.

It is standard practise to repeat an OGTT three months post surgery to determine response. Cure is defined by suppression of GH<0.4ng/ml with a normal age and gender related IGF-I.

For patients not acheiving a primary cure, medical treatment should be started, and treatment titrated upwards if necessary. Although previously OGTT was used to assess control, latest guidance suggests that normalised life expectancy is acheived if a random GH is below 1ng/ml. Biochemical control is therefore now defined as a random GH <1ng/ml on a modern ultrasensitive assay with a normalised age and gender related IGF-I. Further assessment on medical treatment may be performed using a GH day curve combined with an IGF-I. 

Further clinical review with repeat IGF-I and GH every six months until GH controlled, then annually life long

Uptitrate treatment whenever necessary to achieve normalisation of IGF-I and GH <1ng/ml. OGTT is required to diagnose acromegaly, and to define cure post surgery. However, response to treatment with somatostatin analogues and dopamine agonists is best determined by GH and IGF-I, and response to GH receptor antagonists with IGF-I alone.

Medical treatment

Somatostatin analogue dose may be uptitrated, or dopamine agonists added.

Patients not responding or not fully controlled by standard treatments may be considered for pegvisomant treatment.

Surgery and radiotherapy

Conventional radiotherapy or repeat surgery may also be considered if the patient is not biochemically controlled or if there is poor tumour shrinkage post primary surgery.

Radiosurgery

Consider gamma knife radiosurgery in patients more than 24 months post conventional radiotherapy, who are not biochemically controlled or are poorly tolerating medical treatment. Radiosurgery is also considered as an alternative to conventional radiotherapy in some centres.

Lifelong follow up

All patients with acromegaly require lifelong follow up. Cardiovascular risk assessment, investigation and treatment of complications such as obstructive sleep apnoea, osteoarthritis, diabetes and cardiomyopathy, and screening for colon, prostate and other cancers should all be considered annually.

MRI should typically be repeated three to six months post surgery or treatment initiation, and subsequently at 12 months in all patients. Selected cases with extensive residual disease will require further scanning at two years, then every three years if stable, depending on multidisciplinary discussion. Cases with good biochemical control and minimal residual disease may not require ongoing imaging.

Biochemical reassessment with repeat IGF-I and OGTT should initially be performed pre-clinic annually to confirm cure. Long term, annual assessment with IGF-I and random GH will usually be sufficient to confirm on going biochemical control or to assess response to on going medical treatment.

Basal pituitary function and existing pituitary replacement therapy should also be reveiwed annually, and dynamic pituitary function should be repeated every two years post radiotherapy in patients who are not panhypopituitary.