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Prolactinoma and Hyperprolactinaemia

Prolactinoma and Hyperprolactinaemia
Hyperprolactinaemia is commo actice, occurring more commonly in women than men. Demonstration of persistent hyperprolactinaemia is important because repeat prolactin measurement may be normal. Pregnancy is a common cause of hyperprolactinaemia, and should be considered before further investigation. A full drug history is required because dopamine antagonists such as anti-emetics and antipsychotics commonly cause an elevation in prolactin. Classic features of hyperprolactinaemia include menstrual disturbance, reduced fertility and galactorrhoea. Profound hypothyroidism can cause hyperprolactinaemia by TRH-driven prolactin secretion. Polycystic ovary syndrome is commonly associated with mild hyperprolactinaemia, with prolactin levels typically <1000 miU/L together with symptoms of androgen excess. In large pituitary tumours, a prolactin level >5000 iU/L suggests a macro-prolactinoma rather than a non-functioning adenoma.

Clinical presentation
These are the most common pituitary tumours and are more frequently seen in women than men. Micro-prolactinomas are <1 cm, and typically present with menstrual disturbance and galactorrhoea, although infertility may be the only feature (Figure 6.1). Migrainous headaches can be a feature, probably because of endocrine disturbance in individuals predisposed to migraine, rather than mass effect. Polycystic ovary syndrome is distinguished from prolactinomas by the presence of androgenic symptoms, less elevated prolactin levels (typically <1000 miU/L) and the absence of a pituitary lesion on MRI. Occasionally, micro-prolactinomas can be so small that they are not seen on MRI.

By definition these are >1 cm and can be very large. They are more common in men than women, and patients typically present with mass symptoms of visual field loss and headache, particularly if there is cavernous sinus invasion. Prolactin levels are typically >5000 miU/L and can be in the hundreds of thousands, which is virtually diagnostic of a macro-prolactinoma (Figure 6.1). When levels of prolactin are extremely high, the immunoassay can give inaccurately low results for methodological reasons (called the hook effect) so it may be necessary to dilute the sample to achieve a more accurate result.
Prolactinomas are treated with dopamine (D2) agonists, most commonly cabergoline and bromocriptine (Figure 6.1). Cabergoline is given once or twice weekly and is better tolerated than bromocriptine, which is given daily. Common side effects include nausea and postural hypotension, and rarely psychiatric disturbance. Bromocriptine is preferable to cabergoline in women who are trying to conceive.
Macro-prolactinomas are treated medically even if they are very large, usually with good reduction in prolactin and tumour bulk (Figure 6.2). In 10% of macro-prolactinomas, cerebrospinal fuid (CSF) leak occurs as a result of the rapid reduction in the size of the lesion. This is important to recognise as it is a potential source of meningitis.

Surveillance and long-term follow-up
The aim of treatment is resolution of symptoms and normalisation of prolactin using the lowest possible dose of dopamine agonist medication. Micro-prolactinomas are usually treated with dopamine agonists for 2–3 years and then discontinued to see if there is remission. A convenient time for discontinuing treatment is after menopause, because prolactinomas are oestrogen-driven. Macro-prolactinomas require higher doses of dopamine agonists and commonly recur so treatment time is longer. A high cumulative dose of dopamine agonist can lead to cardiac valve abnormalities, although this is not a concern in the usual dosage needed to treat micro-prolactinomas.

Pituitary incidentaloma
Approximately 1 in 10 people have an incidental pituitary lesion, which may be of no clinical significance. Increased access to MRI scans has led to an increase in their detection. The majority of incidentalomas are micro-adenomas. Serum prolactin should be checked and if there are signs of acromegaly, Cushing’s or hypopituitarism, appropriate basal and dynamic tests should be performed. If there is thickening of the pituitary stalk on MRI, serum and urine osmolalities should be checked to exclude diabetes insipidus, especially if there is polyuria and polydipisia. Local protocols will guide further imaging, but patients can often be reassured and event if there is no growth detected on serial scans.