Hyperprolactinaemia

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Hyperprolactinaemia\: elevated blood prolactin levels; most common hypothalamic-pituitary dysfunction.
Normal prolactin levels\: \<400mU/L in males, \<500mU/L in females; cut-o
Causes\: physiological (stress, pregnancy), drug-related (antipsychotics, antidepressants), pathological (prolactinomas, CKD,
hypothyroidism).
Symptoms\: amenorrhoea, oligomenorrhoea, infertility, galactorrhoea, reduced libido, erectile dysfunction; headaches,
visual disturbances in macroprolactinomas.
Clinical
dysfunction (e.g., acromegaly, hypothyroidism).
Investigations\: serum prolactin, pregnancy test, thyroid function tests, urea & electrolytes, pituitary function tests; MRI
pituitary for adenomas.
Management\: address underlying cause; physiological/drug-related cases often don't need treatment; dopamine agonists
(cabergoline, bromocriptine) for prolactinomas.
Surgical management\: transsphenoidal surgery if resistant to or intolerant of dopamine agonists; radiotherapy for
refractory macroprolactinomas.
Complications\: hypogonadism (infertility, erectile dysfunction, osteoporosis), pituitary apoplexy (acute pituitary failure with
headache, visual disturbances, cranial nerve palsies).
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Introduction

Hyperprolactinaemia occurs when there is an elevated level of prolactin in the blood.
1
It is the most common type of hypothalamic-pituitary dysfunction and it is an important condition to consider in young
women with fertility issues or irregular menstruation.
2
Normal prolactin levels are generally \<400mU/L in males and \<500mU/L in females, but speci
local hospital clinical laboratories.
3

Aetiology

Normal physiology
Prolactin is secreted by lactotroph cells in the anterior pituitary gland.
2
Prolactin secretion is regulated by the hypothalamus, and this is predominantly under inhibitory control by hypothalamic
Conversely, thyrotropin-releasing hormone (TRH), serotonin and oestrogens can act to stimulate prolactin
dopamine. 1
release.
2,4
The primary function of prolactin is to stimulate breast tissue proliferation during pregnancy and breast milk production
post-partum. Prolactin also inhibits luteinising hormone (LH) and follicle-stimulating hormone (FSH) secretion.
5Causes of hyperprolactinaemia
There are many di
related and pathological causes.
1,5
Physiological causes
Physiological causes include stress, sexual intercourse, pregnancy, lactation and exercise. 6
temporary and do not normally exceed twice the upper limit of normal prolactin levels.
5
These increases are usually
Drug related causes
Numerous medications are associated with elevated prolactin levels. These include antipsychotics (e.g. risperidone,
haloperidol), antidepressants (SSRIs, MAO inhibitors and tricyclics) and certain antiemetics (domperidone and
metoclopramide).
Verapamil, phenytoin, opioids and oestrogens can also cause hyperprolactinaemia.
4,5
Pathological causes
Prolactinomas are tumours originating from the lactotroph cells of the anterior pituitary gland. They are the most common
cause of pathologically elevated prolactin. 2
Prolactinomas can be microprolactinomas (\<10mm size) or
macroprolactinomas (>10mm size).
1, 5
Other masses of the pituitary gland or hypothalamus can cause hyperprolactinaemia due to compression of the pituitary
stalk. These include meningiomas, craniopharyngiomas or a growth hormone-secreting pituitary adenoma, causing
acromegaly.
4
Several other disorders are known to cause hyperprolactinaemia. These include chronic kidney disease, cirrhosis,
polycystic ovarian disease, hypothyroidism, and sarcoidosis. 2,6
Epileptic seizures may also cause a transient
hyperprolactinaemia.
5

Clinical features

History
Typical symptoms associated with hyperprolactinaemia include\:
1,2
Symptoms due to the direct einfertility, galactorrhoea,
reduced libido, erectile dysfunction in men.
Symptoms due to tumour (usually macroprolactinomas)\: headache, visual disturbances +/- other pituitary de
or excess (e.g. growth hormone co-secretion)
Other important areas to cover in the history include\:
Obstetric history\: current or recent pregnancy; history of infertility
Menstrual history
History of hypothyroidism, renal or liver disease
Drug history\: to identify any drugs that may cause hyperprolactinaemia
Family history\: about 20% of patients with multiple endocrine neoplasia type 1 (MEN1) have prolactinomas.
1
Prolactinomas can also occur with familial isolated pituitary adenomas (FIPA).
2
Clinical examination
Typical clinical
1,2,5
Visual \: classically bitemporal hemianopia (caused by a pituitary adenoma compressing the optic chiasm)
Cranial nerve palsies
Gynaecomastia
Galactorrhoea
Clinical signs associated with concomitant dysfunction of other pituitary hormones (e.g. change in appearance and
interdental spacing in acromegaly)
Clinical signs of underlying systemic disorders (e.g. hair loss, bradycardia in hypothyroidism)Investigations
Laboratory investigations
Relevant laboratory investigations include\:
1
Serum prolactin\: to con
Pregnancy test\: to exclude pregnancy, a common physiological cause of hyperprolactinaemia
Thyroid function tests\: to identify hypothyroidism
Urea & electrolytes\: to identify reduced renal function (chronic kidney disease)
Pituitary function testing\: to assess pituitary function and possible hypopituitarism
Serum prolactin
A single measurement of serum prolactin with a level above the upper limit of normal con
6
However, repeated venepuncture attempts should be avoided as the stress from venepuncture can cause a mildly
raised prolactin. 1,4,5
If in doubt, prolactin levels should be repeated via an indwelling cannula after 30 minutes.
Imaging
An MRI pituitary is used to investigate for a pituitary adenoma or hypothalamic mass.

Management

Not all patients require treatment, but the underlying cause of hyperprolactinaemia should always be addressed if
possible.
Physiological and drug related hyperprolactinaemia do not typically require treatment. 5, 7
hyperprolactinaemia, stopping the causative drug should be considered.
6
In symptomatic drug-related
The main aim of treatment is to normalise prolactin levels, re-establishing normal ovulation in women and normal sexual
function and testosterone in men.
3
Management of prolactinomas
Medical management
Dopamine agonists are the
Dopamine agonists bind to dopamine receptors and are e1,3,7
lower prolactin levels, shrink tumour size and restore normal gonadal function.
These medications
The two most frequently used in practice are cabergoline and bromocriptine. Side e
dizziness and rarely, mood changes, impulse control disorders, CSF rhinorrhoea, and cardiac valvulopathy.
7
Surgical management
Transsphenoidal surgery is usually indicated for those patients who are resistant to dopamine agonists or cannot tolerate
the side e
3,4
Radiotherapy
This is sparingly used and reserved for patients with macroprolactinomas not responding to medical or surgical treatment.

Complications

Hypogonadism secondary to hyperprolactinaemia can lead to\:
6
Infertility and erectile dysfunction
Osteoporosis\: spinal bone density is decreased by roughly 25% in women with hyperprolactinemiaPatients with a pituitary mass causing elevated prolactin may su
infarction of the pituitary gland (pituitary apoplexy). This is characterised by a sudden onset of neurological symptoms
such as headache, visual disturbances and cranial nerve palsies.
1,4

References

Tidy C. H y p e r p r o l a c t i n a e m i a a n d P r o l a c t i n o m a . Patient.info. Published 2023. Available from\: Glezer A, Bronstein M. H y p e r p r o l a c t i n e m i a . Endotext. Published 2022. Available from\: [LINK]
BMJ Best Practice. P r o l a c t i n o m a . Published 2022. Available from\: [LINK]
[LINK]
Owen K, Turner H, Wass J. O x f o r d H a n d b o o k o f E n d o c r i n o l o g y a n d D i a b e t e s \: Oxford University Press; 2022.
Chen AX, Burt MG. H y p e r p r o l a c t i n a e m i a . Aust Prescr. 2017;40(6)\:220-4.
Melmed S, Casanueva FF, Ho
h y p e r p r o l a c t i n e m i a \: a n E n d o c r i n e S o c i e t y c l i n i c a l p r a c t i c e g u i d e l i n e . J Clin Endocrinol Metab. 2011;96(2)\:273-88.
Molitch M, Drummond J, Korbonits M. P r o l a c t i n o m a M a n a g e m e n t . Endotext. Published 2022. Available from\: [LINK]

Reviewer

Dr Gabriela Mihai
Clinical Lecturer in Endocrinology at Queen Mary University of London

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Contents

Introduction
Aetiology
Clinical features
Investigations
Management
ComplicationsSource\: geekymedics.com