Acromegaly

1. Epidemiology and aetiology

Epidemiology

Acromegaly is a rare condition occurring equally in males and females, most commonly in middle age. There is a prevalence of 40–60 cases per million people in the UK.

Aetiology

Acromegaly is caused by excessive secretion of growth hormone (GH) and insulin-like growth factor-1 (IGF-1). This results in enlargement of bone and soft tissues, in addition to cardiorespiratory and cerebrovascular complications.

Acromegaly may be difficult to identify in the initial stages due to its insidious onset, but its recognition is highly important.

If left untreated, the mortality rate in patients with acromegaly is double that of the normal population. Death is most commonly attributed to cardiovascular and cerebrovascular disease. Treatment is nowadays very successful.

In more than 99 per cent of cases, acromegaly is caused by a benign pituitary adenoma. These usually arise spontaneously and are not genetically inherited.

These tumours produce excess GH and, as they expand, may compress surrounding brain tissue and the optic nerves and alter production of other pituitary hormones. Most adenomas  grow slowly but they are more aggressive in the young.

Acromegaly may also occasionally occur as a result of hypersecretion of growth hormone releasing hormone (GHRH) from the hypothalamus or from an ectopic source for example, a carcinoid tumour.

2. Diagnosis

Symptoms develop insidiously and may difficult to identify early.

Investigations

Following an oral glucose tolerance test (OGTT), GH will normally be suppressed to <2 mU/l, but in acromegaly GH fails to suppress. A random GH of <1 mU/l excludes acromegaly.

IGF-1 is useful in addition to the OGTT. It can also be used to monitor the effects of treatment.

Imaging

MRI of the pituitary gland is required to identify the presence of a pituitary tumour and its size (75 per cent are macrodenomas, 25 per cent microadenomas).

Other tests

Pituitary function testing is important to determine any hormone deficiencies. There may also be excess prolactin due to co-secretion with GH or due to stalk compression. Visual fields must also be assessed to determine the mass effect of the tumour.

Serum calcium measurement may show hypercalcaemia. GHRH and imaging of the chest and abdomen may identify a carcinoid tumour.

Symptoms

  • Sweating. 
  • Headaches. 
  • Enlargement of hands and feet .
  • Lethargy.

Signs

  • Facial changes: frontal bossing, prognathism, interdental separation, macroglossia. 
  • Enlarged hands and feet. 
  • Compression neuropathies. 
  • Myopathy. 
  • Goitre.

Complications    

  • Hypertension, congestive cardiac failure, IHD, cerebrovascular disease.
  • Glucose intolerance.
  • Increased incidence of colonic polyps.
  • Osteoarthritis.

Local effects of pituitary tumour

  • Visual impairment.
  • Hypopituitarism.

Adapted from the Oxford Handbook of Endocrinology and Diabetes, 2006

3. Management

The goals of treatment are to reduce GH production to normal levels, to relieve the pressure of a pituitary tumour on surrounding brain tissue and to preserve normal pituitary function.

Treatment is essential for all patients, but the management strategy is determined by the tumour size and the individual patient.

Surgical treatment

Transphenoidal surgery is usually first-line treatment. It is rapid and effective, with reported cure rates of up to 90 per cent for microadenomas and 48 per cent for macroadenomas. If successful, facial appearance and soft tissue swelling improve within a few days. It is important an experienced neurosurgeon undertakes the surgery.

Preoperative octreotide treatment leads to some tumour shrinkage, and may lead to reduced operative morbidity and improve surgical results.

Postoperative ‘cure’ can be defined as a mean GH <5 mU/l. This GH level is associated with the same mortality as the normal population. If this level is achieved, annual GH and IGF-1 must be measured and patients carefully monitored for possible recurrence. If it is not achieved, medical or radiotherapy treatment may be required.

Medical treatment

Somatostatin analogues such as lanreotide SR, lanreotide autogel, octreotide LAR and dopamine agonists reduce both GH secretion and tumour size. They may be used as primary therapy when the tumour is not causing mass effects, but may also be used where surgery or radiotherapy have not been successful.

Patients may be complete responders with suppression of GH to <5 mU/l (in 50 per cent), or partial responders where GH is reduced but not to normal levels. The acute response of GH following injection of octreotide can be used to predict the long-term response.

In patients who do not respond adequately, radiotherapy can be offered.

Dopamine agonists (bromocriptine, cabergoline) are not as effective as somatostatin analogues (10–20 per cent success rate), but may be helpful if there is coexistent prolactin secretion. This may result in significant tumour shrinkage.

Pegvisomant is a new drug that acts as a GH antagonist. It reduces IGF-1 levels to normal in over 90 per cent of cases but it is very expensive.

Radiotherapy

This is usually reserved for patients in whom surgery has not resulted in cure, and is rarely used as a primary treatment. GH may take several years to normalise following radiotherapy (an average of six years to achieve mean GH <5 mU/l if starting mean GH >50 mU/l). Therefore adjunctive medical treatment will be required.

Assessment of a cure should be carried out annually using a GH day curve or OGTT and once a cure has been achieved, the medical treatment can be withdrawn. Other pituitary hormones should also be monitored because radiotherapy can cause gradual loss of these.

Colonoscopy

There is an increased incidence of colonic polyps (9–39 per cent) and colonic carcinoma (0–20 per cent) in acromegalic patients. Regular screening is therefore recommended, such as three-yearly routinely, and annually if polyps are present.

Echocardiogram

This is required due to the increased risk of congestive cardiac failure.

  • Acromegaly is due to excessive secretion of GH and IGF-1.
  • Acromegaly may be difficult to identify in the initial stages due to its insidious onset.
  • Recognition is very important.
  • Both medical and surgical options are very successful.

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