Overview
A prolactinoma is a benign pituitary gland tumour that produces an excess of prolactin hormone. The pituitary gland is a pea-sized gland located at the base of the brain and is responsible for secreting multiple hormones. Prolactin is secreted by the anterior pituitary gland and is responsible for lactation, breast development, and many other functions that are responsible for homeostasis.
How prevalent is prolactinoma?
Prolactinoma is more common in people assigned female at birth (AFAB) (almost five times) but can affect individuals assigned male at birth (AMAB) too. According to the latest studies, prolactinomas are the most common pituitary tumours, with a recent epidemiological review estimating that this tumour makes up 53% of the cases.1 Recently, the prevalence of hyperprolactinemia has been increasing, probably as a result of the increased consumption of hyperprolactinaemic drugs.2
What causes prolactinoma?
Pituitary tumours (including prolactinoma) have been documented mainly as isolated pathology without any genetic background. However, the latest studies show the possibility of developing an adenoma as a result of genetic mutation. Prolactinoma may occur in families as part of a condition called the multiple endocrine neoplasia type 1 (MEN1) syndrome. The main error is a mutation in the AIP or MEN1 gene. The pituitary tumours, in response to these genetic mutations, show a positive family history, young age of the patient, aggressive clinical process, and resistance to treatment.3
How can we categorise symptoms of prolactinoma?
There are two categories of symptoms due to prolactinoma. Symptoms are due to excess prolactin levels, and second, which are due to the mass effect of the tumour.
An increase in prolactin secretion commonly results in reproductive and sexual dysfunctions, including:
- Infertility
- Menstrual irregularities
- Galactorrhoea(rarely seen in AMAB individuals)
- Erectile dysfunction
- Loss of libido
The symptoms related to the size of the tumour are usually seen in patients with macroprolactinomas and include:
- Headaches
- Vision loss
- Hypopituitarismand3
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Symptom differences between AMAB and AFAB individuals
Prolactinoma symptoms can vary widely; not all people will experience the same symptoms. Additionally, the severity and combination of symptoms may differ from person to person.
Symptoms of prolactinoma in AFAB individuals:
- Amenorrhoea (absence of menstruation)
- Infertility
- Oligomenorrhoea (infrequent menstruation).
- Heavy or irregular menstrual periods.
- Galactorrhoea: Milky discharge from breasts, unrelated to breastfeeding.
- Acne or hirsutism (excessive body hair).
- Osteoporosis: Weakening of bones, leading to increased fracture risk.
- Infertility: Difficulty conceiving or maintaining a pregnancy
Symptoms of Prolactinoma in AMAB individuals:
- Decreased Libido: Reduced sexual desire or function.
- Infertility: Impaired fertility or infertility.
- Galactorrhoea: Milky discharge from breasts (less common)
Common symptoms among most individuals:
- Headaches are caused by pressure on the optic nerve.
- Visual disturbances, such as blurred vision
- Loss of interest in sexual activity
- Unexplained weight gain, especially around the abdomen
- Mood Changes: Depression or anxiety
- Fatigue: Persistent fatigue and weakness3
How to diagnose prolactinoma?
Prolactinoma is diagnosed based on a high blood level of prolactin and evidence on imaging tests, such as magnetic resonance imaging (MRI) scan.
Blood test
The prolactin blood test: The normal prolactin level in blood is < 20 ng/ml. In most AFAB individuals level may rise to 30 – 300 ng/ml in small or microadenomas.
It is important to know that a moderate rise in prolactin (30 – 200 ng/ml) can occur as a result of several other causes, which must be ruled out before suspecting a pituitary tumour. The common causes of high prolactin are listed below:
- Stress (discomfort, exercise, low blood sugar)
- Hypothyroidism: low thyroid function
- Pregnancy or in the post-partum period
- Kidney failure
- Liver failure
- Medications (such as anti-ulcer, antihypertensive, antiemetics, and antidepressants and drugs used in Parkinson’s disease4
In AMAB people, however, the prolactinomas are usually not detected until they are large prolactinomas or macroadenomas. The level of prolactin may be as high as over 500 ng/ml. If the level of prolactin is too high, your doctor will order an imaging test to detect a possible tumour.
Imaging test
The results of the imaging test usually will allow your doctor to confirm a diagnosis of prolactinoma and determine its size and exact location. Most prolactinomas can be detected through MRI or CT scans. The preferred test is the MRI scan because it can give more detailed images of soft tissues and the brain than a CT scan. But if you are a cardiac patient and using a pacemaker or other metallic implant, your doctor may order a computed tomography (CT) scan instead of the MRI.5
What are the treatment options?
The standard treatment of prolactinoma is taking medication and/or undergoing surgery.
Medical treatment with dopamine agonist
Medicines called dopamine agonists (which mimic the hormone dopamine in the brain), lower the level of prolactin and bring down the size of the tumour effectively. There are several dopamine agonists, but the most commonly used drugs are bromocriptine and cabergoline. Cabergoline is considered better than bromocriptine because it is more effective even in lower doses and has fewer side effects when compared with bromocriptine.6 Studies have shown that cabergoline is effective in almost 80% of prolactinoma patients. Not only this but in individuals who tend to have larger and resistant prolactinomas cabergoline has shown its efficacy in terms of return of sexual function and semen analysis.7
Side effects of dopamine agonists
Common side effects of dopamine agonists are as follows:
- Nausea
- Vomiting
- Headache
- Dizziness
- Orthostatic hypotension
- Cardiac arrhythmia
Side effects of long-term use of dopamine agonists include:
- Dystonic movements
- Cabergoline is associated with an increased incidence of cardiac valve regurgitation8
- Psychiatric disturbances: confusion, depression, hallucinations, delusions, and mania are some
- Impulse control disorders (e.g. Pathological gambling, hypersexuality, compulsive shopping, and binge eating)9
To avoid these side effects or lessen the intensity, dopamine agonists should always be taken with food. Starting treatment with a low dose and taking the medicine at bedtime can also reduce side effects.
The length of treatment with dopamine agonists
Individuals with prolactinoma need to monitor their prolactin levels. If prolactin is normal and there is no tumour detected on MRI then dopamine agonist may be stopped for a couple of years. However, the rise in prolactin level may recur, in that case, dopamine agonists may be resumed. If dopamine agonists fail to lower the prolactin level or there are intolerable side effects, the patient may consider surgical removal of this tumour.
Surgical treatment
Surgical resection is usually reserved for patients who are:
- Intolerant to dopamine therapy
- Resistant to dopamine therapy
- Individuals with large macroadenoma
- Individuals with prolactinomas who are considering pregnancy
- Surgical resection can be considered a primary treatment for patients with smaller tumours as an alternative to lifelong dopamine agonist treatment.6
Lifestyle and daily routine management
Living with prolactinomas requires a multidisciplinary approach involving endocrinologists and sometimes neurosurgeons. Individual experiences can differ, and personalised treatment plans are essential. Regular communication with healthcare providers and a proactive approach to managing symptoms contribute to a better quality of life for individuals with prolactinomas. A few features should be adopted as part of daily routine management:
- Consistency in taking prescribed medications is crucial for effective management.
- Regular medical check-ups with healthcare providers ensure that any changes in symptoms or hormone levels are promptly addressed.
- Stress can exacerbate symptoms, so incorporating stress-reducing activities such as meditation, yoga, or hobbies into daily life is beneficial.
- A healthy lifestyle, including regular exercise and a balanced diet, contributes to overall well-being and may help manage some symptoms.
- Building a support network, including friends, family, and healthcare professionals, can provide emotional support and assistance in managing the challenges associated with prolactinomas
How does prolactinoma affect pregnancy?
Infertility is an important consequence of prolactinoma, but dopamine agonists have been shown to restore pregnancy in 90% of individuals. Both dopamine agonists i.e., cabergoline and bromocriptine are safe during pregnancy for both mother and fetus.7,8,9 MRI without contrast is suggested for patients suspected to have enlargement of the tumour. Close monitoring should be done during prenatal visits, especially for visual field assessment each trimester.10
FAQs
Can you get pregnant if you have a prolactinoma?
Elevated levels of prolactin due to prolactinomas can interfere with the normal menstrual cycle and ovulation in AFAB individuals, leading to irregular or absent periods (amenorrhoea). This hormonal imbalance can make it difficult for AFAB patients to conceive. However, the impact of prolactinoma on fertility varies among individuals. Some AFAB patients with prolactinoma may still be able to conceive. Treatment options include dopamine agonist medications, such as bromocriptine or cabergoline, which help lower prolactin levels and restore normal menstrual function.8
Which foods decrease prolactin levels?
Foods high in zinc may lower prolactin levels. Examples of such food are shellfish, beef, turkey, and beans. It's also important to get plenty of B6, so foods like potatoes, bananas, wild salmon, chicken, and spinach can help boost those vitamin levels.9
Can prolactinoma be cured?
Prolactinomas are biologically different tumours, ranging from small microadenomas to large, invasive macroadenomas and rarely aggressive metastatic cancers. They are curable and most sensitive to medical therapy with the dopamine agonist. Advances in pituitary surgery have now reached the stage where this is an effective first-line treatment option for patients with microadenomas and women seeking pregnancy.7
Summary
Prolactinomas are the most common benign pituitary tumours and have been documented mainly as isolated pathologies. However, the latest studies show the possibility of developing prolactinoma due to a genetic mutation. The symptoms can vary widely, from infertility, galactorrhoea, and menstrual irregularities to headache and visual side effects. Its diagnosis is based on a high blood level of prolactin and evidence from MRI. Standard treatment options are taking dopamine agonist medications. Surgical treatment can be a primary option for patients with microadenomas and individuals seeking pregnancy. Regular medical checkups and a healthy lifestyle are important in managing this condition.
References
- Daly AF, Beckers A. The epidemiology of pituitary adenomas. Endocrinology and Metabolism Clinics of North America [Internet]. 2020 Sep [cited 2023 Nov 16];49(3):347–55. Available from: https://linkinghub.elsevier.com/retrieve/pii/S0889852920300256
- Soto‐Pedre E, Newey PJ, Bevan JS, Greig N, Leese GP. The epidemiology of hyperprolactinaemia over 20 years in the Tayside region of Scotland: the Prolactin Epidemiology, Audit and Research Study (PROLEARS). Clinical endocrinology. 2017 Jan;86(1):60-7. Available from: https://onlinelibrary.wiley.com/doi/10.1111/cen.13156
- Baba MS, Mir SU, Bhat MH, Laway BA, Misgar RA, Islam SU. Gender Disparities in Prolactinomas: Unravelling Clinical Patterns, Metabolic Variations, and Treatment Responses. Cureus. 2023 Aug 3;15(8). Available from: https://www.cureus.com/articles/173441-gender-disparities-in-prolactinomas-unravelling-clinical-patterns-metabolic-variations-and-treatment-responses#!/
- Wildemberg LE, Fialho C, Gadelha MR. Prolactinomas. La Presse Médicale. 2021 Dec 1;50(4):104080. Available from: https://www.sciencedirect.com/science/article/pii/S0755498221000191
- Fukuhara N, Nishiyama M, Iwasaki Y. Update in pathogenesis, diagnosis, and therapy of Prolactinoma. Cancers. 2022 Jul 24;14(15):3604. Available from: https://www.mdpi.com/2072-6694/14/15/3604
- Naz F, Malik A, Riaz M, Mahmood Q, Mehmood MH, Rasool G, Mahmood Z, Abbas M. Bromocriptine therapy: a review of mechanism of action, safety and tolerability. Clinical and Experimental Pharmacology and Physiology. 2022 Aug;49(8):903-22. Available from: https://onlinelibrary.wiley.com/doi/10.1111/1440-1681.13678
- Inder WJ, Jang C. Treatment of prolactinoma. Medicina. 2022 Aug 13;58(8):1095..Available from: https://www.mdpi.com/1648-9144/58/8/1095
- Tessier S, Lipton BA, Arastu MI, Curiale AM, Longo S, Nanda S. Long‐term low‐dose cabergoline usage: Another association with cardiac valvulopathy. Echocardiography. 2023;40(1):61-4. Available from: https://onlinelibrary.wiley.com/doi/10.1111/echo.15506
- Belhadj Slimane C, Oueslati I, Yazidi M, Kamoun E, Chihaoui M. De Novo Psychiatric Disorders in a Woman With Giant Prolactinoma Treated With Cabergoline. Clinical Medicine Insights: Case Reports. 2023 Jul;16:11795476231186062. Available from: https://journals.sagepub.com/doi/10.1177/11795476231186062
- Bachmeier CAE, Snell C, Morton A. Visual loss in pregnancy. BMJ Case Rep [Internet]. 2019 [cited 2024 Mar 21]; 12(5):e228323. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6506020/.