The presentation of prolactinoma is based on the hormonal effects secondary to hyperprolactinemia and the space-occupying effects of the growing tumor. The major clinical features, which vary according to the duration and degree of the pathological condition and the age and sex of the patient, usually include:

• Menstrual disturbance and/or infertility (especially in reproductive-aged females) [14]
• Spontaneous galactorrhea which appears evident upon squeezing of the nipples
• Signs of hypogonadism in men, like decreased libido and erectile dysfunction
• Deficiencies in the secretion of one or more hormones produced by the pituitary gland (due to the compressing effect of the prolactinoma itself over the surrounding pituitary cells)

The following related effects also occur with a certain frequency:

• Headache, as a result of the physical stress of the pain-sensitive elements within the pituitary gland
• Visual problems due to the encroachment of surrounding tissues. These range from mild symptoms such as hemianopsia, which is very common in the majority of the cases, to very severe ones such as total vision loss due to the physical compression of cranial nerves
• The space-occupying effects of the growing tumor, which tend to be more evident and frequent in women or men in advanced age.

• Galactorrhea

  She no longer had galactorrhea. MRI of the brain showed a microadenoma of the pituitary. [rainbow.coop]

  […] prolactinoma [ pro-lak″tĭ-no´mah ] pro·lac·tin-·pro·duc·ing ad·e·no·ma a pituitary adenoma composed of prolactin-producing cells; it gives rise to symptoms of nonpuerperal amenorrhea and galactorrhea (Forbes-Albright syndrome) in women and to impotence [medical-dictionary.thefreedictionary.com]

  Synonyms of Prolactinoma amenorrhea-galactorrhea, nonpuerperal Forbes-Albright syndrome galactorrhea-amenorrhea syndrome nonpuerperal galactorrhea General Discussion A prolactinoma is a benign tumor of the pituitary gland (adenoma) that produces an excessive [rarediseases.org]

  This disorder is also known by the following names: Galactorrhea-Amenorrhea Syndrome Amenorrhea-Galactorrhea, Nonpuerperal Forbes-Albright Syndrome Nonpuerperal Galactorrhea Prolactinoma ICD9 Code The ICD9 code for this disorder is 253.1. [hxbenefit.com]

  Galactorrhea, amenorrhea and infertility were next highest reported symptoms. Results of the tumour size on initial MRI showed macroprolactinomas 52.9% (36), microprolactinomas in 33.8% (23), and giant prolactinomas in 13.3 % (9) patients. [ncbi.nlm.nih.gov]

• Pallor

  Question a 21 yr old man ,presented with headache for 6 monhs and RT eye decreased vision for 6 months .on ophthalmological evalutation found to have both eyes temporal pallor,bitemporal field defect more in the rt eye.MRI brain was done suggestive of [endotext.org]

• Arthritis

  […] including diagnostic tests, consultations with fee-approved specialists and specialist treatment – including radiotherapy and chemotherapy What you're not covered for Chronic conditions We cannot cover incurable long-term illnesses such as diabetes, arthritis [aviva.co.uk]

• Hirsutism

  Case: A 21-year-old woman was admitted to internal medicine outpatient clinic for irregular menses and hirsutism for 2 years. Physical examination, revealed hirsutism (Ferrimann-Gallwey score 12 points). [endocrine-abstracts.org]

  This 33-year-old woman was admitted to the internal medicine outpatient clinic for irregular menses, obesity, hirsutism and infertility, and hyperprolactinemia. [ncbi.nlm.nih.gov]

  Irregular menstrual periods (oligomenorrhea) or no menstrual periods (amenorrhea) Milky discharge from the breasts (galactorrhea) when not pregnant or breast-feeding Painful intercourse due to vaginal dryness Acne and excessive body and facial hair growth (hirsutism [mayoclinic.org]

  A 42-year-old obese woman with type 2 diabetes, diabetic retinopathy, hypertension, and hirsutism presents to discuss an elevated prolactin level of 144.8 ng/mL (normal range, 4.8 to 23.3 ng/mL) found by her Ob-Gyn two months ago. [mdedge.com]

• Nipple Discharge

  However, 3 years later he presented with blood stained nipple discharge, the cytology of which was negative for cancer. Ultrasound scan of his right breast revealed a single dilated mammary duct. Microdochectomy was performed. [ncbi.nlm.nih.gov]

  Case report The patient is a 23-year-old male who was seen initially in our clinic because of bilateral nipple discharge. [f1000research.com]

• Large Breast

  PROLACTINOMA A curable brain tumor can cause women to have irregular periods, be infertile or have milk in their breasts without being pregnant, and men to be impotent, infertile, and have no sexual desire, or have large breasts. [drmirkin.com]

• Headache

  He went to the ED reporting 2 months of worsening intermittent and severe, squeezing occipital headaches that occurred two to 10 times daily. [healio.com]

  CONCLUSION: Most of the prolactinoma patients were females and the common the most frequent presenting complaint was headache. [ncbi.nlm.nih.gov]

  […] tumor may include: Headache Lethargy Nasal drainage Nausea and vomiting Problems with the sense of smell Vision changes, such as double vision, drooping eyelids or visual field loss There may be no symptoms, especially in men. [nlm.nih.gov]

• Amenorrhea

  […] prolactinoma [ pro-lak″tĭ-no´mah ] pro·lac·tin-·pro·duc·ing ad·e·no·ma a pituitary adenoma composed of prolactin-producing cells; it gives rise to symptoms of nonpuerperal amenorrhea and galactorrhea (Forbes-Albright syndrome) in women and to impotence [medical-dictionary.thefreedictionary.com]

  Here, we present a 48-year-old female patient who had a recurrent episode of major depressive disorder (MDD) and amenorrhea. Hyperprolactinemia (167 ng/ml), low estrogen (15.31 pg/ml) and a pituitary prolactinoma were found by MRI. [ncbi.nlm.nih.gov]

  When she first came to the women’s clinic, she had a history of infrequent menstrual periods leading to amenorrhea (absence of periods). Her breasts began producing milk, although she was not pregnant (galactorrhea.) [rainbow.coop]

  Symptoms In pre-menopausal women, the elevated prolactin causes suppression of LH and FSH, then estrogen and progesterone levels, resulting in irregular or complete cessation of menses (amenorrhea). [ccpd.ucsf.edu]

• Vaginal Dryness

  Other symptoms may include reduced sex drive, impotence, vaginal dryness, infertility, headaches, disturbed vision, brittle bones ( osteoporosis ), mood changes and depression. Causes and Risk Factors Prolactinomas can occur in both men and women. [cedars-sinai.edu]

  Vaginal dryness may also occur, as estrogen is important for vaginal lubrication. Some women with prolactinomas have trouble becoming pregnant. A man with a prolactinoma might develop erectile dysfunction. [issm.info]

  The low levels of estrogen mimic menopause and can result in diminished libido, osteoporosis, and vaginal dryness. Even mild elevations in prolactin have been associated with infertility. [ccpd.ucsf.edu]

  dryness Acne Excess growth in body and facial hair Prolactinoma in men may cause: Erectile dysfunction Enlargement of the breasts Decreased muscle mass Decreased facial and body hair If you develop signs or symptoms associated with prolactinoma and/or [medstarwashington.org]

  For women, typical symptoms of a small tumor include: Irregular menstrual periods Lack of menstrual periods Low sex drive Painful intercourse (caused by vaginal dryness ) Problems with fertility Unusual production of breast milk Because changes in a woman's [webmd.com]

• Oligomenorrhea

  Her past medical history was significant for having oligomenorrhea and a depressive syndrome since her mother's death. She also had a breast cancer gene 1 (BRCA1) mutation and a family history of breast cancer. [ncbi.nlm.nih.gov]

  In females, prolactinoma can cause: Irregular menstrual periods (oligomenorrhea) or no menstrual periods (amenorrhea) Milky discharge from the breasts (galactorrhea) when not pregnant or breast-feeding Painful intercourse due to vaginal dryness Acne and [mayoclinic.org]

  Clinical Manifestations• Hormonal Effect : • Women : infertility, oligomenorrhea, amenorrhea or rarely galactorrhea .• Men : decreased libido, impotence, infertility, gynecomastia, or rarely galactorrhea. 7. [slideshare.net]

  Such alterations appear in adolescent females as delayed puberty (48% in our experience), primary amenorrhea (14–41%), secondary amenorrhea (29–45%) and oligomenorrhea (up to 29%) [ 14, 18 ]. [karger.com]

• Sexual Dysfunction

  The most common clinical manifestations included sexual dysfunction (47.4%), headache (55.9%), and visual disturbance (46.7%). Serum prolactin levels ranged from 150 to 204,952 ng/mL. Tumor size varied from 6 to 70 mm. [ncbi.nlm.nih.gov]

  dysfunction; women may become symptomatic while on OCs; menses may stop when OCs are discontinued; prolactinomas may grow during pregnancy and be diagnosed postdelivery. [medical-dictionary.thefreedictionary.com]

  Men may present with sexual dysfunction, hypogonadism and sometimes gynaecomastia, all related to the hyperprolactinaemia. Premenopausal women present earlier due to menstrual irregularity and hence usually have microprolactinomas. [bestpractice.bmj.com]

  High levels of prolactin in individuals who are neither pregnant nor breast-feeding, however, can lead to unexpected milk production, irregular periods, sexual dysfunction, and other symptoms. [weillcornellbrainandspine.org]

  Keywords prolactin, sexual dysfunction Corresponding authors: Ranjith Ramasamy, Larry Lipshultz Competing interests: No competing interests were disclosed. [f1000research.com]

• Secondary Amenorrhea

  In women of reproductive age, the symptoms are typically oligomenorrhea or secondary amenorrhea, galactorrhea, and sterility, followed by decreased libido, dry vaginal mucosa due to a deficiency in estrogen, weight gain, and psychological symptoms such [ncbi.nlm.nih.gov]

  These certainly include serum prolactine (PRL) levels, which should not be measured soon after pregnancy and always combined with pregnancy test in female patients, as pregnancy itself might be a cause of secondary amenorrhea. [symptoma.com]

  Such alterations appear in adolescent females as delayed puberty (48% in our experience), primary amenorrhea (14–41%), secondary amenorrhea (29–45%) and oligomenorrhea (up to 29%) [ 14, 18 ]. [karger.com]

  Furthermore, hyperprolactinemia in females may suppress and/or interfere with the menstrual cycle and result in primary or secondary amenorrhea and infertility. [pituitaryadenomas.com]

The workup of prolactinoma is largely based on laboratory studies and imaging tests.

The laboratory studies necessary to diagnose prolactinoma include several hormone tests [15] to analyze the major key hormones secreted by the pituitary gland. These certainly include serum prolactine (PRL) levels, which should not be measured soon after pregnancy and always combined with pregnancy test in female patients, as pregnancy itself might be a cause of secondary amenorrhea. The levels of thyroid-stimulating hormone should also be measured, since this compound might cause a marked increase in PRL levels. Other hormones to test are:

• Testosterone, especially in males showing signs of hypogonadism
• Cortisol, when adrenal insufficiency is suspected
• Insulinelike growth factor-1, in patients presenting with signs of acromegaly

To these other appropriate laboratory tests should be added, when there is the possibility of other systemic causes for hyperprolactemia as chronic renal failure and liver cirrhosis.

The most important imaging tests employed in the diagnosis of prolactinoma are MRI and CT scans, which are used to determine whether or not a tumor is present, its size, and the extent of its possible encroachment on the surrounding healthy structures. These scans should be repeated in the postoperative and follow-up phase, to follow the progress of the tumor and try to avoid further severe complications.

• Enlarged Sella

  X-ray of the skull showed an enlarged sella without any erosion. CT scanning and MRI of the brain revealed a tumor in the sella area mainly to right of the middle line extending into the homolateral cavernous sinus. [functionalneurology.com]

• Hyperprolactinemia

  There were five cases of hyperprolactinemia with no cases of macroprolactinoma of 14 790 patients in a general EH cohort. [ncbi.nlm.nih.gov]

  Prolactinoma causes a condition called hyperprolactinemia. Hyperprolactinemia is characterized by an increased production of the hormone prolactin. [medstarwashington.org]

  Progress in the management of hyperprolactinemia. N Engl J Med. 1994 Oct 6. 331(14):942-4. [Medline]. Rivera JL, Lal S, Ettigi P, et al. [emedicine.medscape.com]

• Prolactin Increased

  Causes of high prolactin levels in the blood: Primary Hypothyroidism : this is due to increased TRH levels which is known to stimulate prolactin levels Renal failure : prolactin is mainly excreted from the body from the kidneys. [houstonendocrine.com]

  A variety of hormones and endocrine disorders affect serum prolactin levels. Prolactin secretion is increased by the administration of estrogens. [pituitaryadenomas.com]

• Estrogen Decreased

  Prolactin high levels can reduce production of testosterone and estrogen,decreasing bone density and consequently increasing the risk of osteoporosis. Pregnancy complications. [flipper.diff.org]

The major goals of the treatment of prolactinoma are to bring the prolactin secretion back to normal levels, restore the pituitary gland function, reduce the tumor size as well as adjust the visual anomalies occurred during the tumor development. It is paramount to rule out any other cause for the elevation of prolactin levels, like stress which might easily be addressed by increasing the physical exercise.

The treatment of prolactinoma is largely based on the use of dopamine agonists, which appears to be effective in around 80% of the cases. Among these, bromocriptine and cabergoline are the most commonly used, even though they are frequently associated with serious side effects like nausea, dizziness, and hypertension, especially when the patients already have low blood pressure levels before starting the treatment itself. These side effects are less common and less severe with cabergoline than with bromocriptine, but as its half-life is quite long (4-7 days) it might inadvertently affect the ability of the patient to keep blood pressure within the correct physiological range, which in turn might cause discomfort and fainting. To reduce these side effects doctors are advised to start treatment very slowly.

Surgery might also be used in the treatment of prolactinoma, but only when medical treatment is not tolerated by the patients or when it fails to produce a positive outcome in terms of reduced prolactin levels, restored pituitary function, and reduced tumor size.

The patients affected by microprolactinoma usually have an excellent prognosis, since in 95% of the cases the tumor does not enlarge when monitored over a follow-up period of 4 to 6 years from the diagnosis.

On the contrary, the patients affected by macroprolactinoma have a worse prognosis due to the fact that their tumor tends to grow over time. Therefore, a much more aggressive treatment is required to avoid further complications, which should be regulated according to the tumor growth rate. The growth rate itself varies from individual to individual, and cannot be predicted with accuracy and in a reliable manner. In these cases, monitoring of clinical signs and measurements of serum prolactin levels are highly recommended [13].

Despite research, the cause of prolactinoma still remains largely unknown, although according to several studies, stress might play an pivotal role in its development as it can significantly increase prolactin levels. As all the pituitary adenomas, prolactinoma is monoclonal in origin [2], resulting from the uncontrolled proliferation of single mutated pituitary cells. Many genetic studies reveal that a great deal of mutations appear in the aryl hydrocarbon receptor-interacting protein (AIP) gene, which occur very early in life (less than 30 years of age), are invasive in nature, have a suprasellar extension and appear to be resistant to dopamine agonist treatment [3] [4]. Rarely prolactinomas occur in association with multiple endocrine neoplasia type 1 (MEN 1) syndrome.

Representing around 40% of all tumors occurring in the pituitary gland, prolactinoma is undoubtedly the most common type of pituitary adenoma. Its prevalence is unknown in the US, but according to a study made in Belgium, this should be around 620 cases per million inhabitants [5].

This tumor appears much more frequently in women than men, with an estimated ratio of frequency between the two genders of 10:1 [6]. In women prolactinoma tends to occur especially during childbearing years, with a peak incidence between the second and third decades of life. This sex imbalance disappears in advanced ages, especially after the fifth decade of life, when the frequencies of prolactinoma occurrence in men and women become very similar [7]. Furthermore, women tend to be affected by microadenomas while men by macroadenomas.

The tumor transformation taking place in prolactinoma is the result of a neoplasmatic alteration which always occurs in the anterior pituitary lactotrophs, and, as previously mentioned, it is frequently linked to mutations appearing in the aryl hydrocarbon-interacting protein gene.

The outcome of this transformation is the elevated synthesis and secretion of the prolactin hormone, which in normal physiological conditions is regulated by hypothalamic factors. These can be divided in two major groups, prolactin-releasing factors (PRFs), like for example dopamine, and prolactin-inhibitory factors (PIFs), like thyrotropin-releasing hormone or vasoactive intestinal peptide. The concentrations of these compounds are constantly regulated, so that there is always a proper balance among them which keeps the prolactin levels in the serum within the correct physiological range. This balance is also influenced by a variety of neurohormonal factors which determine the pulsative secretion of prolactin from the pituitary gland. When a prolactinoma develops this balance is disrupted, to be replaced by an elevated secretion of prolactin in a condition known as hyperprolactinemia [8] [9] [10] [11] [12].

As the etiology of prolactinoma still remains largely unknown, no preventive measures can be suggested, apart from genetic testing in early age (less the 40 years of age) to detect any mutation in key genes such as hydrocarbon receptor-interacting protein (AIP) gene.

The pituitary gland is an endocrine gland situated at the bottom of the hypothalamus. It is also reffered to as hypophysis and is responsible for the secretion of a number of hormones regulating several aspects of the human body metabolism and functions, such as growth, blood pressure, lactation (formation of breast milk) and internal temperature regulation. One of the most important of these hormones, playing a pivotal role in lactation, is prolactin, which enables female mammals to produce milk in response to a variety of stimuli like eating, mating, ovulation, and nursing. Following a circular pattern, prolactin levels increase during pregnancy and childbirth and decrease once breastfeeding is discontinued. In men, prolactin is responsible for the sexual refractory period after having an orgasm, a temporary interval during which men cannot experience another orgasm despite receiving sexual stimulation.

According to the size, prolactinoma is classified as microprolactinoma, if the diameter of the tumor mass is lower than 10 mm, and as macroprolactinoma, if the diameter is higher than 10 mm.

Prolactinoma is the most common form of benign (non-cancerous) tumor of the pituitary gland. Despite research, the cause of prolactinoma still remains largely unknown, although according to several studies stress might play a role in its development. Representing around 40% of all tumors occurring in the pituitary gland, prolactinoma is undoubtedly the most common type of pituitary tumor.

The outcome of this tumor is an elevated production and secretion of the hormone prolactin, which in normal physiological conditions is regulated by hypothalamic factors. The signs and symptoms of prolactinoma are based on the hormonal effects of elevated prolactin and the space-occupying effects of the growing tumor itself, and the major clinical features include menstrual disturbance, infertility, spontaneous flow of milk from the breast, hypogonadism, as well as headache, dizziness and visual problems.

The treatment of prolactinoma is largely based on the use of dopamine agonists, which appears to be effective in around 80% of the cases. Surgery might be used in the treatment of prolactinoma, but only when medical treatment is not tolerated or when it fails to produce a positive outcome in terms of reduced prolactin levels, restored pituitary function, and reduced tumor size.

As the etiology of prolactionoma is mostly unknown, no preventive measure can be suggested, apart from genetic testing for the major mutations involved in its development.

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