Hyperprolactinaemia

Physiology of Prolactin

  • Produced in the anterior pituitary by lactotroph cells
  • Dual regulation by hypothalamic hormones (negative feedback loop)
    • The difference between prolactin and other anterior pituitary hormones is that the main (tonic) regulatory signals are inhibitory (cf with other hormones that are regulated by predominantly stimulatory hormones)
      • Dopamine is the main inhibiting neurotransmitter (TRH is the main stimulating hormone)
  • The main function of prolactin is to induce and maintain lactation in the breast, as well as to aid the formation of the corpus luteum and maintain it within the womb.

Epidemiology

  • Most common pituitary hormone imbalance, thought to have a prevalence of 0.4% of the population (higher in women with reproductive problems)
  • Prolactinoma is thought to occur in around 5 per 100,000; much more common in women than men (8.7:1.4)

Causes of hyperprolactinaemia

  • Physiological
    • Pregnancy and puerperium (post-natally)
    • Breast stimulation (including breast feeding)
    • Stress (including physical e.g. excessive exercise or psychological)
    • Macroprolactinaemia
      • Circulation of prolactin of high molecular mass, thought to be bound to immunoglobulin proteins- which is biologically inactive
  • Intracranial causes
    • Prolactinoma- prolactin secreting pituitary adenoma
      • Most commonly microadenoma (90%- 10% are macroadenoma)
      • May be associated with tumour syndrome- MEN1
    • Other pituitary macroadenomas may also cause hyperprolactinaemia by compressing the pituitary stalk and thus decreasing the amount of dopamine able to suppress normal prolactin secretion
    • Head injury (injury of the pituitary stalk)
      • Brain surgery
      • Radiotherapy
    • Occasionally post-ictal
  • Endocrine/Metabolic
    • Hypothyroid (increased TRH)
    • Cushing’s syndrome
    • Chronic renal failure
    • Severe liver disease
    • PCOS
  • Drugs
    • Dopamine receptor antagonists- Anti-emetics e.g. domperidone; metoclopramide, antipsychotics
    • Dopamine depleting agents e.g. methyldopa
    • Antidepressants (TCAs, SSRIs, MAOIs)
    • Verapamil
    • Opiates
    • H2-receptor antagonists, omeprazole
    • Oestrogens/anti-androgens
    • (NB Cimetidine can be associated with gynaecomastia rather than hyperprolactinaemia)

I.e. The P’s (Pregnancy; prolactinoma; physiological; polycystic ovarian syndrome; primary hypothyroidism; phenothiazines; metoclopramide and domperidone)

Presentation

  • Female
    • Amenorrhoea/Oligomenorrhea
    • Galactorrhoea
    • Ask about infertility
    • Ask about hirsutism
    • Loss of libido
    • Hypogonadism
  • Men
    • Reduced libido
    • Erectile dysfunction
    • Gynaecomastia
  • Occasionally, where there is a macroadenoma, there may also be symptoms of tumour effect e.g. visual disturbance, headache, facial nerve palsies,
    • Also signs of other hormone deficiencies e.g. hypothyroidism

Investigations

  • TFTs and pregnancy test
  • Serum prolactin
    • NB Prolactin can be raised under stress or after nipple stimulation.  Therefore, ideally, levels should be measured twice on two separate occasions for a true reading (however, a single level can be sufficient for diagnosis if the patient is clearly symptomatic)
  • Imaging (usually brain MRI)
  • Complete pituitary function
    • Insulin stress test (growth hormone and cortisol)
      • Dose of insulin after fasting to reduce blood sugar to significantly low levels such to stimulate hormone production
    • TRH test (thyroxine/TSH)
    • LHRH test (LH/FSH)

Management

  • Patients should be only be treated if they are symptomatic and or if there is a concern about symptoms (either from the patient or the physician)
  • First line treatment is medical-
    • Dopamine agonists e.g. cabergoline or bromocriptine
      • Reduce prolactin, reduce tumour size (in 75% and 80% respectively)
      • Generally used long-term but treatment can be reviewed after 3 years (most still require treatment)
      • NB relatively contraindicated in patients with existing lung/cardiac fibrosis as a side-effect of long-term use is fibrosis (this should be monitored for on follow-up.  Others include sleepiness and hypotension (initially)
  • Surgery and/or radiotherapy may also be used to reduce tumour size in macroadenoma.  (Microadenoma may also be treated surgically too, although only if the patient is intolerant of dopamine agonists and/or oral-contraceptive pill- which can also be used to treat hyperprolactinaemia)
  • In drug-induced hyperprolactinaemia, withdrawal of the drug is recommended.  If this is not possible, then a trial of hormone (contraceptive) or dopamine agonist may be used.
    • NB In men, testosterone is rarely used.

Follow-up

NB In most women, tumours will regress after the menopause.  Need for treatment should be reviewed.

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