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The Pituitary Foundation: Acromegaly

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The Pituitary Foundation

Acromegaly

Incidence: 4-6 New Cases per million per year Prevalence: 60 per million

Acromegaly

Acromegaly is the result of Growth hormone (GH) hypersecretion by a pituitary macro- or microadenoma. Many of the actions of GH are mediated by Insulin-like Growth Factor-1 (IGF-1), which is secreted from the liver and other organs under the regulation of GH. GH levels fluctuate over the day. Plasma IGF-1 levels, in contrast, fluctuate little during the day and can be used, along with GH, as a measure of disease activity. Up to a third of tumours co-secrete Prolactin.

Acromegaly most often occurs in adults aged 30-50 years. Presentation before the growing ends of bones have fused (usually around 18 years of age) is rare and is the cause of pituitary Gigantism. Elevated GH levels are associated with changes in appearance, headaches, sweating and tiredness. Acromegaly affects a number of body systems and is associated with a two-fold increase in mortality, particularly from cardiovascular disease.

If left untreated, acromegaly is associated with increased mortality, primarily due to cardivascular complications.

Presenting symptoms

Excessive GH secretion produces a gradual change in appearance (not usually noticed by those living or working with the patient) due to its effects on cartilage and soft tissues. Symptoms have often been present for a decade beefore the diagnosis is made. The patient may notice enlargement of the hands and feet and may experience growth of the jaw. Nerve compression symptoms may occur, particularly Carpal Tunnel Syndrome. Premature and widespread osteoarthritis of the weight-bearing joints is also characteristic. Obstructive Sleep apnoea may be present, especially in men, leading to daytime sleepiness.

The main features are:

  • coarsening of facial features
  • enlarged hands and feet
  • carpal tunnel syndrome
  • excessive sweating and oily skin
  • headaches
  • vision disturbance
  • sleep apnoea
  • general tiredness

There should be a low threshold for referral for any patient with any suspicion of acromegaly as the greatest challenge in the diagnosis of acromegaly is thinking of the disease. Once suspected biochemical confirmation or exclusion of the disease is usually straightforward.

We strongly recommend all referrals be to an endocrinoogist rather than neurosurgeon or others. Please see 'Who and When to Refer' (factsheet 14).

Investigations

Biochemical investigations of the diagnosis is rarely difficult once the diagnosis has been suggested. Investigations will include a GH series and an analysis of the GH response to a glucose load (Glucose Tolerance Test), as well as measurement of prolactin and other pituitary function tests. An MRI scan will be carried out and visual field tests may be performed to determine the size and position of the adenoma.

Treatment possibilities

Epidemiological evidence suggests that with mormalisation of GH and IGF-1 levels life expectancy can be restored to normal. The treatment recommended by the consultant will depend on the size and activity of the adenoma and also on the age of the patient. Transsphenoidal surgery is the treatment of choice in most cases and can be dramatically effective, especially for microadenomas. However, some patients may need medical treatment or Radiotherapy after surgery to reduce GH levels. Some GH-secreting adenomas are treatable by long-term medical therapy with or without radiotherapy. The consultant may offer the patient a choice between long-term medical treatment, involving injections, or surgery.

Medical Therapy

Some patients may need long-term medical treatment to maintain acceptable GH levels and IGF-1 levels. High levels of GH, even when the patient has no symptoms, are associated with a 2-3 fold increase in mortality.

Stabilisation of GH may be achieved with a dopamine agonist, particularly if the tumour also secretes prolactin. Bromocriptine is the only dopamine agonist licensed for the treatment of acromegaly but has been superseded by cabergoline which is more potent and causes few side effects. However, the Somatostatin analogues Octreotide and Lanreotide, which act by inhibiting GH release from the pituitary, are more effective in reducing GH and IGF-1 to acceptable levels. Octreotide is available as a short-acting preparation that requres to be injected subcutaneously 3 times daily, although most patients prefer the alternative longer-acting preparations that are administered monthly (Sandostatin LAR and Lanreotide Autogel). Normalisation of GH and IGF-1 can be achieved in between half and two-thirds of patients. Somastostatin analogues also cause tumour shrinkage in most cases, particularly when used as primary treatment when they improve surgical resuults. Some patients suffer gastrointestinal side effects with these drugs and there is some risk of developing gallstones. Pegvisomant is a GH receptor antagonist that blocks GH action by preventing GH from binding to its receptor. Unlike other forms of treatment, it does not attempt to inhibit GH release from the pituitary and as GH levels do not fall with treatment, disease activity is judged by measuring IGF-1.

Patients may develop hypopituitarism (factsheet 6) after surgery, or several years after radiotherapy. Hormone replacement therapy will then be needed (factsheet 11).

Watchpoints

Urgent - refer to hospital

  • Deterioration of vision
  • Clear fluid dripping down the back of the throat or through the nose soon after surgery (CSF leak - factsheet 9 Surgery)

Non-urgent (but still very important)

  • If the patient is on Hydrocortisone, ensure that replacement therapy is increased when seriously ill or under major physical or psychological stress
  • Treat headaches (migraine)
  • Treat depression
  • Treat carpal tunnel syndrome
  • Treat osteoarthritis: refer for hip replacement if required
  • Ask about erectile function, 70% have problems. Treat this, reassure that it is part of the disease and that it can be treated
  • The patient is likely to have obstructive apnoea and to snore very loudly. It can be helped by treatment to lower GH, and by continuous positive airways pressure (CPAP)
  • Ask about change in bowel habit as some increased risk of colonic polyps and colonic carcinoma

Questions patients may ask

Why do my hands hurt?

Growth can occur in the connective tissue of the carpal tunnel compressing the median nerve.

Why do I wake up tired?

Growth hormone causes hypertrophy of the nasopharyngeal tissue and sleep apnoea (usually noticed by the partner).

Why am I getting headaches?

A large tumour may compress surrounding tissues.

Why can't I get my wedding ring on?

Hypertrophy of the soft tissues of the joints causes enlargement of hands and feet.

Why has my shoe size increased?

See above.

Why does my jaw ache when I eat an apple?

Growth of the mandible disturbs dental occlusion and puts increased strain on the temporomandibular joints.

Why do I keep biting my tongue?

GH promotes growth of the tongue.

Why do I have backache?

Growth of cartilaginous tissues cause musculoskeletal abnormalities and degenerative changes.

Why do I have such bad arthritis?

Growth and degenerative changes are common. One of the main aims of treatment is to prevent this.

Why do I sweat so much?

Not known but when GH levels are normal the problem disappears.

Have I inherited this, will my children get it?

In all but very exceptional circumstances there is no hereditary link.

Resources for patients

Please go to the Resource Library of this website to access resources for patients. Our library includes literuature, newsletters and articles available from The Pituitary Foundation as well as the contact information for other organisations who provide support and information. All of our patient leaflets are available to read as well as downloadable in PDF format from this website.

Resources for GPs

Endotext.org ‘Your Endocrine Source’
www.endotext.org (www.endotext.org/neuroendo/index.htm)

Oxford Handbook of Endocrinology OUP (2002) JAH Wass & H Turner (Eds).

More Specialist Resources

Management of Pituitary Tumors: The Clinician’s Practical Guide (2003) (Second Edition), Editors and authors Michael P. Powell, Stafford L. Lightman and Edward R. Laws. Humana Press, Totowa, New Jersey

Pituitary Tumours. Recommendations for service provision and guidelines for management of patients. Consensus statement of a working party (1997) RN
Clayton & JAH Wass (Eds) London: Royal College of Physicians

The Diagnosis and Treatment of Pituitary Insufficiency (1997) Lamberts SWJ (Ed) Bristol, UK: BioScientifica

Endocrinology (1997) Levy A & Lightman SL New York: Oxford University Press

Treating Acromegaly. (1994) Wass JAH (Ed) Bristol, UK: Society for Endocrinology

The Epidemiology, Pathogenesis and Management of Pituitary Tumours (1998) Webb SM (Ed) Bristol, UK: BioScientifica