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.

Baseline investigations - all patients

Full blood count

Useful indicator of general health and underlying disease. 

Normocytic normochromic anaemia and eosinophilia may be seen with glucocorticoid deficiency.

Urea and electrolytes

Useful indicator of general health and underlying disease.

Hyperkalaemia and hyponatraemia may occur in glucocorticoid deficiency.

Liver function test

Liver function should be assessed as a baseline before starting medical treatments. It is frequently abnormal due to fatty infiltration of the liver or diabetes.

Bone profile

Hypercalcaemia may occur with glucocorticoid deficiency, though an elevated calcium is also suggestive of possible multiple endocrine neoplasia type 1.

Glycosylated Haemoglobin, fasting glucose and lipids

Hypopituitary patients have an elevated mortality due to an excess of cardiovascular deaths.

Screening for diabetes and assessment of fasting lipids are essential for cardiovascular risk modification.

Baseline pituitary function


Growth hormone

GH release is pulsatile and so isolated levels are difficult to interpret. However, recent guidelines recommend that a normal GH and IGF-I taken together are useful for screening.

Elevation of either test taken with clinical suspicion mandates a formal GH suppression test with glucose tolerance testing.


Insulin like growth factor I

Insulin like growth factor I (IGF-I) alone is not a diagnostic test for acromegaly but taken with a GH level is a useful screen. An elevated level mandates a formal GH suppression test.


Prolactin

Hyperprolactinaemia may occur in multiple pituitary pathologies. In acromegaly, tumours may co-secrete prolactin and growth hormone. Elevated prolactin also occurs with macroadenomas due to loss of dopaminergic inhibition.

Serum prolactin is also affected by many other factors, for example stress, interfering medications and PCOS.

Elevated prolactin levels should also prompt the PEG precipitation test to determine whether this is biologically active or the inactive ‘macroprolactin’.


9am cortisol

Estrogen replacement therapy leads to elevation of cortisol binding globulin, hence serum cortisol is also elevated and difficult to interpret. Before testing serum cortisol, ensure patients have stopped sex steroid therapy, for example HRT or the combined oral contraceptive pill, for at least six weeks. Also ensure that patients are not taking any steroid containing medications that might cross react with the assay, or interfere with the hypothalamo-pituitary-adrenal axis.

Due to the circadian rhythm of ACTH release, cortisol is best assessed early morning (or on waking in patients with irregular hours such as shift workers).

Levels above 590nmol/l exclude glucocorticoid deficiency. Patients with levels below this require formal assessment for ACTH reserve, for example with an insulin stress test or glucagon test.


Thyroid stimulating hormone, free thyroxine

It is essential to assess levels of both thyroxine and thyroid stimulating hormone (TSH) in pituitary patients since a normal TSH level is frequently associated with loss of thyroid function in this patient group.

Levels of both TSH and thyroxine are typically low-normal in hypo-pituitary patients.


Luteinising hormone, follicle stimulating hormone

In the presence of pituitary disease both luteinising hormone and follicle stimulating hormone are typically low, or not elevated in post menopausal women.

This may be due to pituitary failure or a specific consequence of hyperprolactinaemia.


Estrodiol/testosterone, sex hormone binding globulin

These should be assessed early morning, and in the early follicular phase and off the contraceptive pill in women.

Sex hormone binding globulin is necessary to calculate free androgen index in some cases, for example where the decision to start testosterone replacement is not clear cut.

Oral glucose tolerance test

Formal OGTT should be performed if clinical suspicion persists and the random GH or IGF-I are elevated.

Further investigations - selected patients only

Growth hormone day curve

The day curve is an alternative means of assessing disease severity although this is not a diagnostic test. Particularly helpful to assess response to treatment with long acting somatostatin analogues.

MRI pituitary

This should only be performed if the biochemical diagnosis of acromegaly has been confirmed.

Visual fields

Formal visual perimetry should be performed once the biochemical diagnosis of acromegaly has been confirmed.

This is particularly important if the tumour is a macroadenoma (above 1cm diameter on the MRI scan), though restriction of the superior fields may reflect expansion of the supraorbital ridges.

Chest radiograph

If acromegaly is confirmed, a baseline chest radiograph is important to assess for cardiac failure.

Electrocardiograph

If acromegaly is confirmed, a baseline ECG is required due to the increased risk of acromegalic cardiomyopathy and rhythm disturbance.

Echocardiogram

If acromegaly is confirmed, baseline echocardiography is required to seek evidence of cardiomyopathy.

Colonoscopy

After the diagnosis of acromegaly has been confirmed, a colonoscopy should be arranged due to the increased risk of colonic polyps and malignancy.

Colonoscopy should be performed by an experienced endoscopist due to the frequency of a tortuous megacolon.

Timing of future colonoscopies will depend on biochemical disease control, the findings of previous colonoscopies, and the availability of local colorectal cancer screening programmes, for example feacal occult blood screening.

 Sleep studies

Patients with acromegaly are at extremely high risk of developing obstructive sleep apnoea which will elevate their operative and cardiovascular risk. Referral for formal sleep studies should be considered in all patients at baseline.