Hyperprolactinaemia

Serum prolactin should only be measured in patients with a pituitary mass or the clinical symptoms and signs of hyperprolactinaemia.
Hyperprolactinaemia can cause galactorrhoea and impair reproductive function.
Most prolactinomas are microprolactinomas.
- They usually do not grow sufficiently to cause hypopituitarism or visual field loss.
Patients with a prolactinoma are usually successfully treated with a dopamine agonist such as cabergoline.

Physiology

Prolactin is a Protein synthesized and secreted by Lactotrophs (acidophil cells) in the anterior pituitary
1. Stimulation (releasing factors)
  1. Vasoactive intestinal polypeptide (VIP)
  2. Thyroid Releasing Hormone (TRH, short-term factor only)
  3. Estrogen
2. Inhibition
  1. Hypothalamic Dopamine (Prolactin Inhibiting Factor or PIF)
Prolactin Effects
Prolactin increases with infant Breast Feeding
1. Increases with each Breast Feeding episode
2. Prolactin levels gradually level off after the first few months of regularly Breast Feeding
3. Prolactin decreases to normal within 1-2 months of stopping Breast Feeding
Prolactin stimulates milk secretion into the Breast alveoli in pregnancy and Lactation
Oxytocin stimulates myoepithelial cells to contract, expressing Breast Milk from the nipple
Prolactin response assumes prior Breast development
1. Breast ducts, fat and stroma develop with Estrogen exposure
2. Breast glands, alveoli and secretory tissues develop with Progesterone exposure

	Examples
Physiological (transient hyperprolactinaemia) – These increases are transient, and usually do not exceed twice the upper limit of normal reference ranges.	Pregnancy Lactation Exercise Coitus Chest wall/nipple stimulation Stress Seizure
Macroprolactinaemia – arises when immunoglobulins in serum bind prolactin to create high-molecular-weight forms of prolactin. – As clearance of these macroprolactin molecules is slower than monomeric prolactin, the serum prolactin concentration increases. – Macroprolactin is largely biologically inactive, so most patients with macroprolactinaemia are asymptomatic.	Immunoglobulin (IgG) binding prolactin
Hypothalamic/ pituitary lesions	Prolactinoma Non-functioning masses: – adenoma – craniopharyngioma – meningioma – Rathke’s cleft cyst Inflammatory/infiltrative lesions: – lymphocytic hypophysitis – Langerhan’s cell histiocytosis
Other illness	Hypothyroidism Chronic renal failure
Drugs	Antipsychotics (risperidone, amisulpride, paliperidone, haloperidol) Antiemetics (metoclopramide, domperidone) SSRI Opioids Oestrogens Antihypertensives (verapamil)

	Women	Men
Breast	Galactorrhoea	Gynaecomastia Galactorrhoea
Reproductive	Oligo-amenorrhoea Infertility Osteopenia/osteoporosis	Erectile dysfunction Infertility Osteopenia/osteoporosis

Confirm Hyperprolactinemia

Evaluate for Physiologic Cause
1. History
  1. Breast stimulation or Lactation
  2. Sexual Intercourse temporally related to lab test
  3. Excessive Eating, Exercise, Sleep or Stress
2. Labs
  1. Thyroid Stimulating Hormone (Hypothyroidism)
    - In primary hypothyroidism, such as Hashimoto’s thyroiditis, there is an increase in serum TRH levels, which stimulates hyperprolactinaemia, as well as TSH secretion.
    - Reduced metabolic clearance in patients is also believed to contribute to high serum prolactin levels.
    - Therefore, it is always good practice to correct abnormalities in thyroid biochemistry in women with galactorrhoea to see if symptoms resolve.
  2. Urine Pregnancy Test
  3. Comprehensive Metabolic Panel (Electrolytes, Serum Creatinine, hepatic panel)
    1. Evaluate for liver disease and renal disease
  4. Consider reproductive Hormone levels if Hypogonadism is present
    1. Serum Estrogen
    2. Serum Testosterone
    3. Follicle Stimulating Hormone
    4. Luteinizing Hormone
3. MRI of the pituitary
  - pituitary mass more than 1 cm in diameter should have investigations assessing other pituitary hormones and have visual field testing.
4. bone mineral density
  - in hypogonadal patients.

Some patients do not require treatment.
Patients with physiological hyperprolactinaemia, macroprolactinaemia, asymptomatic microprolactinoma or drug-induced hyperprolactinaemia usually do not require treatment.
If hyperprolactinaemia is secondary to hypothyroidism, treating the patient with thyroxine should normalise prolactin.

In patients with symptomatic drug-induced hyperprolactinaemia the first consideration is whether the drug can be withdrawn, or replaced with an alternative that does not cause hyperprolactinaemia.
If the risks of stopping the drug are greater than the potential benefits, any hypogonadism can be treated with appropriate sex hormone replacement.
Occasionally patients with galactorrhoea can be prescribed a dopamine agonist, but this may impair the primary action of the drug which has caused the hyperprolactinaemia.
- For example, prescribing a dopamine agonist to a patient taking an antipsychotic drug could exacerbate their psychiatric condition.

first-line treatment of a prolactinoma: dopamine agonist
- Cabergoline and Bromocriptine
- recommended in all patients with a macroprolactinoma and most patients with a symptomatic microprolactinoma
- Cabergoline normalises prolactin in up to 95% of patients, reduces tumour size in about 90% and controls symptoms in the majority of patients.
- It can be extremely effective, even in a patient with a giant prolactinom
Correction of sex hormone deficiency also improves bone mineral density, although bisphosphonate therapy can occasionally be required.
Thyroid dysfunction–induced hyperprolactinaemia should resolve with thyroxine use.