Hyper secretion of growth hormone due to a pituitary tumour.
Hyperplasia due to GHRH excess is very rare.
Overall incidence is approximately 3-4/million per year and prevalence 50-80/million.
Clinical features :
Symptoms result from mass effect of the adenoma or effect of the growth hormone.
One-third of patients present with changes in appearance,
One-quarter with visual field defects or headaches;
In the remainder the diagnosis is made by an alert observer in another clinic, e.g. GP, diabetic, hypertension, dental, dermatology.
Associations
1. Sleep apnea
2. Multiple skin tags
3. Adenomatus polyps
4. Hypercalcurea and renal stones
5. MEN I in 6%
Investigations :
1. GH levels may exclude acromegaly if undetectable but a detectable value is non-diagnostic. Normal adult levels are < 1 mU/L for most of the day except during stress or a 'GH pulse'.
2. The glucose tolerance test is diagnostic. Acromegalics fail to suppress GH below 1 mU/L and some show a paradoxical rise; about 25% of acromegalics have a diabetic glucose tolerance test.
3. IGF-1 levels are almost always raised in acromegaly - a single plasma level of IGF-1 reflects mean 24-hour GH levels and is useful in diagnosis.
4. Visual field defects are common.
5. MRI scan of pituitary - will almost always reveal the pituitary adenoma.
6. Pituitary function - partial or complete anterior hypopituitarism is common.
7. Prolactin - mild to moderate hyperprolactinaemia occurs in 30% of patients. In some, the adenoma secretes both GH and prolactin.
Management and treatment :
Untreated acromegaly results in markedly reduced survival with most deaths from heart failure, coronary artery disease and hypertension-related causes. In addition, there is an increase in deaths due to neoplasia, particularly large-bowel tumours.
Treatment is therefore indicated in all except the elderly or those with minimal abnormalities.
There is now consensus agreement that the aim of therapy should be to achieve a mean growth hormone level below 5 mU/L, which has been shown to reduce mortality to normal levels.
Complete cure is often slow, if possible at all.
The choice lies between :
→ trans-sphenoidal surgery,
→ pituitary radiotherapy,
→ somatostatin analogues,
→ Growth hormone agonists dopamine agonists.
Progress can be assessed by monitoring GH and IGF-1 levels..
When present, hypopituitarism should be corrected and concurrent DM and/or hypertension should be treated conventionally; both usually improve with treatment of the acromegaly
1-Surgery :
Trans-sphenoidal surgery is generally agreed as the appropriate first-line therapy.
It will result in clinical remission in a majority of cases (60-90%) with pituitary microadenoma, but in only 50% of those with macroadenoma.
Surgical success rates are variable and highly dependent upon experience, and a specialist pituitary surgeon is essential.
Transfrontal surgery is rarely required except for massive macroadenomas.
2-Pituitary radiotherapy :
External radiotherapy is normally used after pituitary surgery fails to normalize GH levels rather than as primary therapy.
It is often combined with medium-term treatment with a somatostatin analogue or a dopamine agonist because of the slow biochemical response to radiotherapy, which may take 10 years or more. Stereotactic radiotherapy is used in some centres.
3-Somatostatin analogues :
Octreotide and lanreotide are synthetic analogues of somatostatin which are the treatment of choice in resistant cases, and employed as a short-term treatment while other modalities become effective.
They reduce GH and IGF levels in most patients.
Both drugs are typically administered as monthly depot injections and are generally well tolerated but are associated with an increased incidence of gallstones and are expensive.
4-Dopamine agonists :
Dopamine agonists were the original medical therapy for acromegaly, and remain useful in some cases.
They can be given to shrink tumours prior to definitive therapy or to control symptoms and persisting GH secretion;
They are probably most effective in mixed growth-hormone-producing (somatotroph) and prolactin-producing (mammotroph) tumours.
The doses are bromocriptine 10-60 mg daily or cabergoline 0.5 mg daily (higher than for prolactinomas) but should be started slowly.
Given alone they reduce GH to 'safe' levels in only a minority of cases - but may be useful for mild residual disease or in combination with somatostatin analogues.
5-Growth hormone antagonists :
Pegvisomant (a genetically modified analogue of GH) is a GH receptor antagonist which has its effect by binding to and preventing dimerization of the GH receptor. It has been shown to normalize IGF-1 levels in 90% of patients. Its main role at the present time is treatment of patients in whom GH and IGF levels cannot be reduced to safe levels with somatostatin analogues alone, surgery or radiotheraphy.
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