The commonest causes are hereditary (two tall parents!), idiopathic (constitutional) or early development. It can occasionally be due to thyrotoxicosis. Other causes include chromosomal abnormalities (e.g. Klinefelter’s syndrome, Marfan’s syndrome) or metabolic abnormalities. G H excess is a very rare cause and is usually clinically apparent.
This is due to a pituitary tumour in almost all cases. Hyperplasia due to GHRH excess is rare.
Symptoms and signs of acromegaly . 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. diabetic, hypertension, dental, dermatology.
GH LEVELS are normally very low «1 mU litre:”) in adults except during stress or as occasional spikes but, unless levels are always below 1 mU litre “, one cannot exclude the diagnosis.
GLUCOSE TOLERANCE TEST is diagnostic. Acromegalies fail to suppress GH below 2 mU litre’:’ and some show a paradoxical rise; about 25% of acromegalies have a diabetic glucose tolerance test.
IGF-l LEVELS. A single plasma level of IGF-l reflects mean 24-hour GH levels and is useful in diagnosis.
LATERAL SKULL X-RAYS: abnormal in 90% as the tumours are relatively large.
VISUAL FIELDS: field defects are common.
HIGH-RESOLUTION CT SCANS are virtually never normal;
MRI often gives even better definition of tumour extent and anatomy, particularly where surgery is contemplated.
PITUITARY FUNCTION: partial or complete anterior hypopituitarism is common.
PROLACTIN: mild to moderate hyperprolactinaemia occurs in 30% of patients.
MANAGEMENT AND TREATMENT
Untreated acromegaly results in markedly reduced survival with most deaths from heart failure, coronary artery disease and hypertension related causes. Treatment is therefore indicated in all except the elderly or those with minimal abnormalities. The general pros and cons of surgery, radiotherapy and medical treatment.
Preferred treatment is controversial and complete cure is often slow, if possible at all. The choice lies between:
TRANS-SPHENOIDAL SURGERY with subsequent radiotherapy if excision is incomplete or if GH has not been normalized after surgery. Many authorities would give postoperative radiotherapy in nearly all cases, as the tumours frequently recur.
TRANS FRONTAL SURGERY for big tumours with pressure effects. Postoperative radiotherapy is again usually given as excision is virtually never complete.
EXTERNAL RADIOTHERAPY (takes 1-10+ years to be effective), possibly plus bromocriptine or octreotide.
OCTREOTI DE. The synthetic analogue of somatostatin (GHRIH, p.796) called octreotide is now the treatment of choice in resistant cases, and as a short-term treatment while other modalities become effective. It has to be given by subcutaneous injection in doses of 50-200 ILg 8-hourly but is associated with mild steatorrhoea and an increased incidence of gallstones. It is extremely expensive.
BROMOCRIPTINE ALONE, usually reserved for the elderly and frail. It can be given to shrink tumours prior to definitive therapy or to control symptoms and persisting GH secretion. It is probably only effective in mixed growth-hormone producing (somatotroph) and prolactin producing (mammotroph) tumours. The dose is 10-60 mg daily (higher than for prolactinomas) but should start slowly (see Hyperprolactinaemia). It has largely been replaced by octreotide. Progress can be assessed by mean GH levels and by IGF- 1 measurements. When present hypopituitarism should be corrected and concurrent diabetes and/or hypertension should be treated conventionally; both usually improve with treatment of the acromegaly. It is not yet clear by how much the cardiac prognosis is improved by energetic treatment. There appears to be an excess of large bowel carcinoma in acromegaly.