Prolactinoma
Prolactinoma

Prolactinoma

Prolactinomas are lactotroph adenomas in the pituitary. They are benign pituitary tumours that produce prolactin. It is the most common of all pituitary adenomas. You can read more about pituitary adenomas and pituitary tumours here.

🏃‍♀️ Physiology

Lactotropic cells are found in the anterior pituitary. They are involved in the production and secretion of prolactin. Prolactin production is regulated by thyrotropin-releasing hormone (TRH) and also by dopamine (also known as prolactin inhibiting factor).

Let’s look at how this works:

  1. The hypothalamus releases TRH into the anterior pituitary. This stimulates the production of prolactin from the anterior pituitary.
  2. The hypothalamus also releases dopamine which inhibits the production and secretion of prolactin. Dopamine is constantly being secreted and inhibits TRH’s effect, thus leading to no prolactin production normally.
  3. In pregnancy, oestrogen and progesterone production by the placenta suppress dopamine production and increase sensitivity of the mammary glands to prolactin.
  4. After pregnancy, suckling and breastfeeding continue the stimulation of prolactin and inhibit the effects of dopamine.

Prolactin itself inhibits gonadotropin releasing hormone (GnRH) and this means that luteinising hormone (LH) and follicle stimulating hormone (FSH) are also inhibited (meaning that breastfeeding women are in a state of anovulation).

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🔢 Classification

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Prolactinomas are categorised according to their size:

  1. Microadenomas - these are <10 mm diameter. This is the most common type in women. They rarely increase in size.
  2. Macroadenomas - these are ≥10 mm diameter. These are common in both men and post-menopausal women. They often present at a 4 cm diameter or larger. They are larger, and they usually invade the suprasellar and parasellar regions. This means that these are more likely to press on vital structures and lead to certain clinical symptoms which we will discuss below.

⚠️ Risk factors

  • Multiple endocrine neoplasia 1 (MEN-1) - multiple tumours throughout the endocrine system, most commonly in the parathyroid, pancreas and pituitary.
  • Familial isolated pituitary adenomas - hereditary condition with an autosomal dominant pattern of inheritance. Unlike MEN-1 and CNC, it solely affects the pituitary.
  • Premenopausal women
  • Oestrogen therapy

😷 Presentation

We will look at general symptoms that may be present in both sexes and then we’ll look at sex-specific symptoms:

  • Headaches
  • Visual disturbances - such as bitemporal hemianopia. This is because the pituitary gland sits beneath the optic chasm and the tumour can then compress the nasal retinal fibres (which correlate with the temporal visual fields). It initially begins with the inferior nasal retinal fibres and the superior temporal visual fields are lost. Later on there is progression to the superior nasal retinal fibres which correlates to loss of the inferior temporal visual fields.
  • Loss of libido
  • Osteoporosis
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Female-specific symptoms:
  • Oligomenorrhoea or amenorrhoea
  • Galactorrhoea
  • Infertility
  • Vaginal dryness
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Male-specific symptoms:
  • Erectile dysfunction
  • Reduced facial hair
  • Gynecomastia

🔍 Investigations

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  • 🥇 Serum prolactin - elevated prolactin levels
  • Visual field assessment - to see if there is compression of the optic chiasm.
  • 🏆 Brain MRI - gives visualisation of the tumour and its location.

🧰 Management

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Management of prolactinoma:
  • Microadenomas will require observation and watchful waiting unless symptomatic (or if there is a desire to get pregnant, for example).
  • Macrodenomas may be managed with the following approaches:
    • 🥇 Trans-sphenoidal hypophysectomy - this is the primary management option. It involves gaining access to the pituitary gland via the sphenoidal sinus and then removing the tumour.
    • Radiotherapy - this is implemented in situations where it is not possible to remove the entirety of the tumour or with recurrence.

      • Pharmacological options:

    • Dopamine agonists (bromocriptine and cabergoline) - as dopamine antagonises prolactin production it can be used in cases of prolactinoma. Cabergoline is preferred as it is needed once or twice a week. Bromocroptine is taken daily, and was historically the established therapy and therefore is preferred in pregnancy.

🚨 Complications

  • Hormonal imbalance
  • Tumour recurrence
  • Surgical and radiation risks
  • Osteoporosis
  • Infertility