Introduction

 

Prolactinomas are prolactin-secreting pituitary tumours.  This is the most common type of secreting tumour, and is usually benign.  Depending on their size they are classified as microprolactinomas (<10mm) or macroprolactinomas (>10mm).  The larger the tumour, the higher the blood prolactin concentration will be, resulting in hyperprolactinaemia.  However, hyperprolactinaemia is not necessarily caused by a pituitary prolactinoma, this will be discussed later.  

 

Background

 

The Pituitary Gland

  • Is located at the base of the brain, beneath the optic nerve in an area called the sella turcica (Image on the right- taken from www.uptodate.com)
  • Is regulated by the hypothalamus
  • Releases hormones into the blood stream
  • Is composed of two parts- anterior (adenohypophesis) and posterior (neurohypophesis)
  • Secretes different hormones that regulate growth, metabolism and reproduction (Image below- produced by author)
  • Because it is so close to optic nerve, enlargements of pituitary gland can sometimes press on the nerve causing visual disturbances. 
Image 1. Location of the pituitary gland, taken from  http://www.uptodate.com/contents/image?imageKe

Pituitary tumours

Pituitary tumours form as a result of cell hyperplasia, due to unknown reasons.  The tumour can be secreting or non-secreting.  Secreting tumours cause increased hormone production, resulting in hyperpituitarism.  The hormones released can be just of one type, or can be several types of hormones.  In non-secreting tumours the effect will be hypopituitarism, which is a low level of pituitary hormones. 

The tumour can be malignant or benign although malignancy is quite rare.

 

Prolactinomas

 

Normal physiology

The level of prolactin gradually increases towards the end of pregnancy, and remains high for about 6 weeks postpartum.  It is the elevated levels that initiate lactation of the mammary glands.  The infant’s tactile suckling action inhibits dopamine secretion by the hypothalamus, this results in unopposed release of prolactin, which maintains lactation. 

 

Epidemiology

  • Quite common in the general population
  • More males present with macroprolactinomas
  • More females present with microprolactinomas
  • Rarely present in children
  • Often asymptomatic unless affecting surrounding cranial structures

 

Causes

  • Hyperplasia of prolactin-producing cells in the pituitary gland results in higher levels of prolactin secretion, causing prolactinaemia (high plasma prolactin levels).  However the reason for the hyperplasia is unknown.
  • Prolactinomas are sporadic, and are therefore not passed on genetically.

 

Presentation

Prolactinomas are usually asymptomatic.  However symptomatic prolactinomas tend to present differently in men and women.  This is shown in the table below:

 

presentation

Women are likely to experience menstrual problems, which will encourage them to seek medical help, whereas male symptoms may not be as noticeable and the tumour can be left untreated.  This probably accounts for the reason why more males present with macroprolactinomas, due to continuous growth of the prolactinoma.  Complications can involve headaches and visual disturbances from extensive growth of the prolactinoma impinging on the optic nerve.  The common presentation for visual disturbances would be loss of both temporal visual fields (bitemporal hemianopia), due to compression of the optic nerve at the optic chiasm.  

 

Differential Diagnosis: Other causes of hyperprolactinaemia

 

Physiological

  • Pregnancy
  • Nipple stimulation and lactation

 

Drug induced

  • Dopamine antagonists
  • Oral contraceptive pill

 

Pathological

  • Disconnection hyperprolactinaemia (causing a disruption in dopamine’s effect on prolactin secretion)
  • Primary hypothyroidism
  • Polycystic ovarian syndrome
  • Hypothalamic disease
  • Ectopic sources 

 

Investigations

  • Pregnancy test (for women of reproductive age)
  • Serum prolactin level
  • Gonadal function test
  • TSH and T4 levels (primary hypothyroidism resulting in excessive release of TRH from the hypothalamus can elevate prolactin secretion)
  • MRI pituitary hypothalamic region to determine size of the tumour
  • Visual field testing

 

Management

Medical therapy:

Medical treatment is indicated if the prolactinoma is symptomatic.  Dopamine agonist drugs (Bromocriptine, Cabergoline, Quinagolide) will usually suppress prolactin secretion and can sometimes reduce the size of the prolactinoma. 

Surgery and radiotherapy:

Macroprolactinomas have a risk of causing complications such as compression of the optic nerve, and aggressive treatment is indicated.  If dopamine agonists fail to shrink the prolactinoma, the patient might need decompression surgery.  Radiotherapy is sometimes used to prevent regrowth of the tumour after dopamine agonists are stopped. 

 

Prognosis

Most microprolactinomas do not show rapid growth, therefore the patient will generally have excellent prognosis.  The prognosis for macroprolactinomas is dependant on the rate of their growth, which is difficult to predict.  Monitoring any changes to the patient’s clinical presentation and also following the adenoma growth with imaging techniques is required to maintain successful treatment.  

 

References and Further Reading

 

“Prolactin.” Encyclopaedia Britannica. Encyclopaedia Britannica Online, 2011. Web. 06 March 2011. http://www.britannica.com/EBchecked/topic/478570/prolactin

"Anatomy of the pituitary gland." UpToDate. UpToDate online version 18.3, 2011. Web. 06 March 2011. http://www.uptodate.com/contents/image?imageKey=ENDO/5134

Colledge NR, Walker BR, Ralston SH. 2010. Davidson’s Principles & Practice of Medicine 21st ed. Edinburgh; Churchill Livingstone, Elsevier.  

Schlechte JA. Clinical practice. Prolactinoma. N Engl J Med. Nov 20 2003;349(21):2035-41

 

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