Prolactinoma

Overview 
Theory 
Diagnosis 
Management 
Follow up 
Resources 

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer

ONGOING

premenopausal women

asymptomatic microprolactinoma, normal menstrual cycle, and who do not desire pregnancy

1st line – observation

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1st line –

observation

Women who are asymptomatic and have normal menstrual cycles may be monitored and do not require treatment.[11]

symptomatic microprolactinomas who do not desire pregnancy

1st line – dopamine agonist

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1st line –

dopamine agonist

Medical treatment with dopamine agonists is considered the first-line therapy for prolactinomas.[11]

Even in women who do not desire pregnancy, dopamine agonists are considered initially to treat other symptoms (e.g., troublesome galactorrhea).

The patient should be aware that treatment may result in return of fertility and alternative forms of contraception may be required.

Treatment usually starts at low doses to avoid adverse effects, with a gradual dose escalation during the first months upon achieving control of the hyperprolactinemia and tumor shrinkage.

A trial of dopamine agonist withdrawal is most likely to be successful if attempted in patients in whom there has been restoration of normal serum prolactin, significant reduction in tumor size on magnetic resonance imaging, maintenance of normal serum prolactin using a low dose of dopamine agonist, and a treatment duration of at least 2 years.[11][28]

Cabergoline is the recommended first-line dopamine agonist due to superior efficacy in normalizing serum prolactin and reducing tumor size, better tolerability, and more convenient dosing regimen.[11][16]

Primary options

cabergoline: 0.25 mg orally twice weekly or 0.5 mg orally once weekly initially, increase by 0.5 mg/dose increments every 4 weeks, increase dose gradually until desired reduction in prolactin levels and/or tumor

Secondary options

bromocriptine: 1.25 to 2.5 mg/day orally initially, increase by 2.5 mg/day increments every 2-7 days, increase dose gradually until desired reduction in prolactin levels and/or tumor

2nd line – combined oral contraceptive

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2nd line –

combined oral contraceptive

There are no controlled trials to compare the use of dopamine agonists and the combined oral contraceptive pill in women with microprolactinomas and oligo-/amenorrhea. If women with microadenomas have no symptoms beside menstrual irregularities and do not desire pregnancy, then estrogen with cyclical progesterone therapy may be considered (e.g., estrogen/progesterone combined oral contraceptive pill), without dopamine agonist therapy. Besides providing contraception, this treatment is used to achieve menstrual regularity.

3rd line – transsphenoidal surgery

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3rd line –

transsphenoidal surgery

Transsphenoidal surgery may be considered for those who do not tolerate dopamine agonists or whose symptoms are not responding to dopamine agonists.[11][21]

Transsphenoidal surgery may be complicated and result in anterior pituitary failure and/or diabetes insipidus requiring permanent hormonal replacement, although this is more likely in cases of large and invasive macroadenomas.

Dopamine agonist therapy may need to be continued following surgery if symptomatic hyperprolactinemia persists.

4th line – sellar radiation therapy

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4th line –

sellar radiation therapy

Radiation therapy is rarely used and is reserved for situations where medical and surgical treatments have failed, and for the rare cases of malignant prolactinomas.[11]

Both conventional radiation therapy and stereotactic radiation therapy do not achieve more than 20% to 40% prolactin normalization rate in patients with prolactinomas.[20] Thus, most prolactin-secreting adenomas are radioresistant, and this mode of therapy is not an acceptable primary treatment for prolactinomas.

Pituitary radiation therapy is associated with significant long-term morbidity, including hypopituitarism (up to 50% after 10-20 years), cerebrovascular accidents, optic nerve damage, cognitive deterioration, and secondary radiation-induced brain malignancies.

microprolactinomas who desire pregnancy, or macroprolactinomas

1st line – dopamine agonist

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1st line –

dopamine agonist

Medical treatment with dopamine agonists is considered the first-line therapy for prolactinomas in women.[11]

Treatment usually starts at low doses to avoid adverse effects, with a gradual dose escalation during the first months with the aim of achieving control of the hyperprolactinemia and tumor shrinkage.

Macroprolactinomas usually require higher doses of dopamine agonist compared with microprolactinomas.

There is minimal risk of microprolactinoma enlargement in pregnancy and therefore dopamine agonists can be stopped once pregnancy is confirmed.[11] Because risk of enlargement of macroprolactinomas in pregnancy is greater (20% to 30%), dopamine agonists may be continued throughout pregnancy or recommenced if visual fields deteriorate.[18] Prolactin increases in pregnancy and therefore serum prolactin measurements are not useful in monitoring prolactinoma patients during pregnancy. Both bromocriptine and cabergoline have been shown to be safe in pregnancy.[17][18]

A trial of dopamine agonist withdrawal is most likely to be successful if attempted in patients in whom there has been restoration of normal serum prolactin, significant reduction in tumor size on magnetic resonance imaging, low maintenance doses of dopamine agonists, and a treatment duration of at least 2 years.[11][28]

Remission of hyperprolactinemia in patients with prolactinoma following dopamine agonist withdrawal varies between studies, with greater success in microprolactinomas (approximately 40%) compared with macroprolactinomas (approximately 30%).[28] Therefore, in a woman with a prolactinoma who is planning pregnancy, it may be sensible to defer plans for a trial of dopamine agonist withdrawal until she has completed her family.

Primary options

Secondary options

bromocriptine: 1.25 to 2.5 mg/day orally initially, increase by 2.5 mg/day increments every 2-7 days, increase dose gradually until desired reduction in prolactin levels and/or tumor

2nd line – transsphenoidal surgery

Back

2nd line –

transsphenoidal surgery

Transsphenoidal surgery may be considered for those who do not tolerate dopamine agonists or whose symptoms are not responding to dopamine agonists.[11][21]

Dopamine agonist therapy may need to be continued following surgery if symptomatic hyperprolactinemia persists.

3rd line – sellar radiation therapy

Back

3rd line –

sellar radiation therapy

Radiation therapy is rarely used and is reserved for situations where medical and surgical treatments have failed, and for the rare cases of malignant prolactinomas.[11]

postmenopausal women

microadenomas

1st line – observation

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1st line –

observation

Postmenopausal women with microadenoma or undetectable pituitary mass do not usually require any treatment.

Any galactorrhea usually improves when estrogens decrease postmenopausally.

macroadenomas

1st line – dopamine agonist

Back

1st line –

dopamine agonist

Medical treatment with dopamine agonists is considered the first-line therapy.[11]

Treatment usually starts at low doses to avoid adverse effects, with a gradual dose escalation during the first months with the aim of achieving control of the hyperprolactinemia and tumor shrinkage.

A trial of dopamine agonist withdrawal is most likely to be successful if attempted in patients in whom there has been restoration of normal serum prolactin, significant reduction in tumor size on magnetic resonance imaging, low maintenance doses of dopamine agonists, and a treatment duration of at least 2 years.[11][28]

Primary options

Secondary options

bromocriptine: 1.25 to 2.5 mg/day orally initially, increase by 2.5 mg/day increments every 2-7 days, increase dose gradually until desired reduction in prolactin levels and/or tumor

2nd line – transsphenoidal surgery

Back

2nd line –

transsphenoidal surgery

Transsphenoidal surgery may be considered for those who do not tolerate dopamine agonists or whose symptoms are not responding to dopamine agonists.[11][21]

Dopamine agonist therapy may need to be continued following surgery if symptomatic hyperprolactinemia persists.

3rd line – sellar radiation therapy

Back

3rd line –

sellar radiation therapy

Radiation therapy is rarely used and is reserved for situations where medical and surgical treatments have failed, and for the rare cases of malignant prolactinomas.[11]

men

microadenomas or macroadenomas

1st line – dopamine agonist

Back

1st line –

dopamine agonist

Medical treatment with dopamine agonists is considered the first-line therapy.[11]

Treatment usually starts at low doses to avoid adverse effects, with a gradual dose escalation during the first months with the aim of achieving control of the hyperprolactinemia and tumor shrinkage.

A trial of dopamine agonist withdrawal is most likely to be successful if attempted in patients in whom there has been restoration of normal serum prolactin, significant reduction in tumor size on magnetic resonance imaging, low maintenance doses of dopamine agonists, and a treatment duration of at least 2 years.[11][28]

Primary options

Secondary options

bromocriptine: 1.25 to 2.5 mg/day orally initially, increase by 2.5 mg/day increments every 2-7 days, increase dose gradually until desired reduction in prolactin levels and/or tumor

2nd line – transsphenoidal surgery

Back

2nd line –

transsphenoidal surgery

Transsphenoidal surgery may be considered for those who do not tolerate dopamine agonists or whose symptoms are not responding to dopamine agonists.[11][21]

Dopamine agonist therapy may need to be continued following surgery if symptomatic hyperprolactinemia persists.

3rd line – sellar radiation therapy

Back

3rd line –

sellar radiation therapy

Radiation therapy is rarely used and is reserved for situations where medical and surgical treatments have failed, and for the rare cases of malignant prolactinomas.[11]

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Prolactinoma

Treatment algorithm

premenopausal women

observation

dopamine agonist

Primary options

Secondary options

combined oral contraceptive

transsphenoidal surgery

sellar radiation therapy

dopamine agonist

Primary options

Secondary options

transsphenoidal surgery

sellar radiation therapy

postmenopausal women

observation

dopamine agonist

Primary options

Secondary options

transsphenoidal surgery

sellar radiation therapy

men

dopamine agonist

Primary options

Secondary options

transsphenoidal surgery

sellar radiation therapy