Hyperprolactinaemia is a condition of elevated serum prolactin (PRL). Normal PRL levels in women and men are <1087 picomol/L (25 micrograms/L or 500 milliunits/L) and 870 picomol/L (20 micrograms/L or 400 milliunits/L), respectively.
Hyperprolactinaemia is the most common endocrine disorder of the hypothalamus-pituitary axis. The prevalence of hyperprolactinaemia ranges from 0.4% in an unselected normal adult population to 5% in a family planning clinic. It increases to 9% in women with amenorrhoea and occurs in 25% of those with galactorrhoea. Among women presenting with concomitant amenorrhoea and galactorrhoea, 70% are hyperprolactinaemic. The condition also accounts for 5% of men who present with impotence or infertility. Although uncommon, hyperprolactinaemia can also present in children.
The hormone PRL is a 199-amino acid peptide synthesised and secreted by lactotroph cells in the anterior pituitary gland; 80% of circulating PRL exists as a 23 kilodalton (kD) monomer. Dimeric PRL (also known as big PRL) has a molecular weight of 50 kD to 60 kD and accounts for 10% to 15%; the remainder is macroprolactin (also known as big-big PRL), a high molecular weight (>150 kD) complex of monomeric PRL and IgG. PRL is also produced by numerous extrapituitary tissues, including various brain regions, lymphocytes, mammary epithelial cells, and tumours, as well as the decidua, myometrium, lacrimal gland, thymus, and spleen. Although it derives from an ancestral hormone common to growth hormone and human placental lactogen, PRL displays little structural homology with these hormones.
The main action of PRL is to stimulate breast epithelial cell proliferation and induce milk production. In addition to its lactogenic role, PRL promotes the formation and action of the corpus luteum and suppresses the pulsatile secretion of gonadotrophin-releasing hormone (GnRH). Suppression of GnRH by prolactin results in decreased levels of follicle-stimulating hormone and luteinising hormone. Moreover, prolactin plays a direct inhibitory role in spermatogenesis and steroidogenesis, as its receptors have been detected in Sertoli and Leydig cells in the testes.
PRL secretion is pulsatile and controlled predominantly by the inhibitory effect of dopamine released from the hypothalamus. Dopamine acts through its D2 receptors on lactotroph cells. Other inhibitory factors are endothelin peptides, tumour growth factor-beta 1, and calcitonin. Oestrogens stimulate the proliferation of lactotroph cells, resulting in an increased quantity of these cells in pre-menopausal women, especially during pregnancy. PRL production is also stimulated by thyrotropin-releasing hormone, vasoactive intestinal peptide, and oxytocin.
- Primary hypothyroidism
- Drug-induced hyperprolactinaemia
- Hypothalamic mass compressing pituitary stalk
- Multiple endocrine neoplasia syndrome type I (MEN I)
- Traumatic sectioning of pituitary stalk
- Lymphocytic hypophysitis
- Granulomatous hypophysitis
- Polycystic ovary syndrome
- Chronic kidney disease
- Chest wall trauma or surgery
- Ectopic hyperprolactinaemia
- Idiopathic hyperprolactinaemia
Panagiotis Anagnostis, MD, MSc, PhD, FRSPH
Department of Internal Medicine
Aristotle University of Thessaloniki
PA declares that he has no competing interests.
Dr Panagiotis Anagnostis would like to gratefully acknowledge Professor Faidon Harsoulis, a previous contributor to this topic.
FH declared that he had no competing interests.
Subhash Kini, MD, FRCS
Mount Sinai Medical Center
SK declares that he has no competing interests.
John C. Marshall, MD, PhD
Professor of Medicine
Center for Research in Reproduction
University of Virginia Health System
JCM has received NIH funding of over 6 figures USD. JCM declares that he has no competing interests.
- Diagnosis and treatment of hyperprolactinemia: an Endocrine Society clinical practice guideline
- Guidelines of the Pituitary Society for the diagnosis and management of prolactinomas
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