The essence in brief:
Prolactinomas are benign adenomas of the pituitary gland that produce excessive prolactin hormone. They can be treated with medications called dopamine agonists, such as bromocriptine, cabergoline, or quinagolide. These drugs selectively target the dopamine D2 receptor and help shrink the tumors. In most cases, microprolactinomas completely regress within one to two years of treatment, allowing the discontinuation of dopamine agonists. While significant reduction in tumor volume can be achieved for macroprolactinomas, complete disappearance is unlikely. After long-term treatment, only hormonally inactive remnants remain, enabling the discontinuation of medication without recurrence of hyperprolactinemia. Surgery is reserved for cases where medication is ineffective or not tolerated well. Cabergoline is preferred due to its lower side effect profile and is taken in low doses once or twice a week before bedtime.
Prolactinoma is the most common benign adenoma of the pituitary gland. It occurs five times more frequently in women than in men. Prolactinoma produces the hormone prolactin, which stimulates the growth of the mammary glands during pregnancy and maintains milk production during breastfeeding. Prolactin inhibits the pulsatile release of the gonadotropins LH and FSH. LH and FSH are necessary for the maturation of the egg (follicle). Therefore, prolactin suppresses ovulation and has a contraceptive effect during breastfeeding.
The release of prolactin is primarily stimulated by TRH and oxytocin. Stress, hypoglycemia, and hypothyroidism can also lead to an increase in prolactin levels.
When there is a clinical suspicion of prolactinoma, initially, a basal prolactin measurement is sufficient. Normal range: 2-25 ng/mL.
Prolactin levels in the gray area (25-200 ng/mL) can be caused by hypothyroidism, stress, mental disorders, protein-rich diet, increased beer consumption, and medications. In particular, antipsychotics and cannabis increase prolactin levels. Other adenomas in the pituitary gland can also cause hyperprolactinemia, known as accompanying hyperprolactinemia. Occasionally, it is difficult to differentiate between a hormonally inactive microadenoma and a small prolactinoma due to accompanying hyperprolactinemia.
Prolactin levels greater than 200 ng/mL indicate a high likelihood of a prolactinoma.
TRH and metoclopramide stimulate the release of prolactin. If there is an excessive increase above 200 ng/mL, it indicates a significant hyperprolactinemia. These tests are used to investigate hypogonadism and amenorrhea. They are usually not very helpful in confirming the diagnosis of prolactinoma.
Imaging: After clinical and laboratory suspicion of prolactinoma, an MRI of the pituitary gland is performed to determine the size of the pituitary adenoma.
Prolactinomas can be treated with medications called dopamine agonists. These drugs selectively act on the dopamine D2 receptor. Treatment with dopamine agonists leads to complete resolution of most microprolactinomas within one to two years, and the dopamine agonists can be discontinued. Significant reduction in tumor volume can be achieved with macroprolactinomas. However, complete disappearance of the adenoma is not achievable with large tumors. However, after several years of treatment, only hormonally inactive remnants remain, allowing discontinuation of dopamine agonists and preventing a recurrence of hyperprolactinemia. Surgery for prolactinoma is only necessary in cases of treatment resistance or severe intolerance to dopamine agonists.
Bromocriptine, cabergoline, or quinagolide are used for the treatment of prolactinomas. The Clinical Practice Guideline “recommends using cabergoline in preference to other dopamine agonists because it has higher efficacy in normalizing prolactin levels, as well as a higher frequency of pituitary tumor shrinkage has significantly fewer side effects than bromocriptine”. It is taken once or twice a week before bedtime in low dosage and is generally well tolerated.
During pregnancy, treatment with dopamine agonists should be discontinued. Measuring prolactin levels during pregnancy is not necessary. Women with a macroprolactinoma who do not respond to dopamine agonist therapy or cannot tolerate it should ideally undergo surgery before becoming pregnant.
If sudden headaches or visual field defects occur, visual field testing and MRI should be performed.
If treatment is required during pregnancy due to tumor growth, bromocriptine should be used. Bromocriptine has the most clinical experience in pregnancy. If bromocriptine is not tolerated, a trial with cabergoline may be considere
Diagnosis and Treatment of Hyperprolactinemia: An Endocrine Society Clinical Practice Guideline,
Shlomo Melmed, Felipe F. Casanueva, Andrew R. Hoffman, David L. Kleinberg, Victor M. Montori, Janet A. Schlechte, John A. H. Wass, The Journal of Clinical Endocrinology & Metabolism, Volume 96, Issue 2, 1 February 2011, Pages 273–288, https://doi.org/10.1210/jc.2010-1692