Prolactinoma and Hyperprolactinaemia

Somatotroph adenomas of the pituitary secreting prolactin, and other conditions presenting with elevated serum prolactin levels. Diagnosis requires blood testing of prolactin levels, a full drug history and frequently MRI scanning.

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.

Erythrocyte sedimentation rate

This is recommended prior to ergot derived dopamine agonist therapy following recent reports of fibrotic tissue reactions.

Urea and electrolytes

Useful indicator of general health and underlying disease.

Hyperkalaemia and hyponatraemia may occur in glucocorticoid deficiency.

This is also recommended prior to ergot derived dopamine agonist therapy following recent reports of fibrotic tissue reactions.

Liver function test

This is also needed as baseline before starting medical treatments.

Bone profile

Hypercalcaemia is highly suggestive of multiple endocrine neoplasia 1 in a patient with a prolactinoma, though it can also occur with glucocorticoid deficiency.

Fasting glucose and lipids

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

Fasting glucose and lipids are essential for cardiovascular risk modification.

Baseline pituitary function


Prolactin

Serum prolactin is affected by many factors, for example stress, nipple stimulation, interfering medications and PCOS, and so should always be repeated on at least two occasions.

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


9am cortisol

Due to the circadian rhythm of ACTH release, cortisol is best assessed early morning (or on waking in patients with irregular hours, for example 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.

Ensure patients have stopped sex steroid therapy, for example HRT or the combined oral contraceptive pill for six weeks prior to test.

Estrogen replacement therapy leads to elevation of cortisol binding globulin and hence serum cortisol and so is difficult to interpret. 


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 hypopituitary patients.


Growth hormone, insulin like growth factor I 

Although GH release is pulsatile and so isolated levels are difficult to interpret, recent guidelines recommend that a normal GH and insulin like growth factor I (IGF-I) taken together form a useful screen for acromegaly. Elevation of either test taken with clinical suspicion mandates a formal GH suppression test with glucose tolerance testing.

Very low IGF-I levels alone are not diagnostic for GH deficiency but are a useful screen mandating a formal GH provocation test, for example insulin stress test or glucagon test.


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.

MRI pituitary

This should be performed in all cases with documented abnormality of pituitary function and urgently if there is visual field loss or optic disc pallor.

The primary role of the MRI scan in cases of hyperprolactinaemia is to rule out a non functioning pituitary adenoma, and to document the size of macroprolactinomas prior to starting dopamine agonist therapy.

Microadenomas are not necessarily visible on scanning, and do not require repeat scanning after diagnosis.

If possible, in the presence of offending drugs, the biochemical tests should be repeated six weeks after removing the putative causative agent as normalisation obviates the need for MRI scanning. In practise this is frequently not possible and an MRI is performed to rule out a large non functioning pituitary adenoma as the cause of the elevated prolactin.

Further investigations - selected cases only

Chest radiograph

All patients presenting with a new pituitary mass should have a chest radiograph performed as an assessment of general health and a simple screen for underlying malignancy.

This is also recommended prior to ergot derived dopamine agonist therapy following recent reports of fibrotic tissue reactions.

Electrocardiogram

This is usefully performed at presentation as it is required prior to starting dopamine agonist therapy or testing dynamic pituitary function if necessary.

Echocardiogram

This is recommended prior to (or within three months of starting) ergot derived dopamine agonist therapy following recent reports of cardiac valvulopathy with these agents.

Visual perimetry and acuity

Formal visual field testing is mandatory if there is clinical or MRI suspicion of chiasmal impingement.

Insulin stress test

Insulin tolerance testing should be performed if GH or ACTH deficiency is suspected but not yet confirmed subject to the usual safety exclusion criteria.

Glucagon test

Glucagon testing should be performed if GH or ACTH deficiency is suspected but not yet confirmed and the patient is unable to tolerate an insulin stress test.

Arginine-GHRH testing

 If GH deficiency is suspected, but an insulin stress test is contraindicated or unavailable, an Arginine-GHRH test is a suitable alternative to assess GH reserve. 

Bone densitometry scan

This should be considered in patients with long standing amenorrhoea, or other risk factors for osteoporosis.