Galactorrhea: Rapid Evidence Review.

Galactorrhea is the production of breast milk that is not the result of physiologic lactation. Milky nipple discharge within one year of pregnancy and the cessation of breastfeeding is usually physiologic. Galactorrhea is more often the result of hyperprolactinemia caused by medication use or pituitary microadenomas, and less often hypothyroidism, chronic renal failure, cirrhosis, pituitary macroadenomas, hypothalamic lesions, or unidentifiable causes. A pregnancy test should be obtained for premenopausal women who present with galactorrhea. In addition to prolactin and thyroid-stimulating hormone levels, renal function should also be assessed. Medications contributing to hyperprolactinemia should be discontinued if possible. Treatment of galactorrhea is not needed if prolactin and thyroid-stimulating hormone levels are normal and the discharge is not troublesome to the patient. Magnetic resonance imaging of the pituitary gland should be performed if the cause of hyperprolactinemia is unclear after a medication review and laboratory evaluation. Cabergoline is the preferred medication for treatment of hyperprolactinemia. Transsphenoidal surgery may be necessary if prolactin levels do not improve and symptoms persist despite high doses of cabergoline and in patients who cannot tolerate dopamine agonist therapy.

Galactorrhea After Nipple-Sparing Mastectomy: Case Report, Review of the Literature, and Algorithmic Approach to Management.

ABSTRACT: Nipple discharge is a rare but possible occurrence after nipple-sparing mastectomy (NSM). This study presents the first case of galactorrhea in a female patient after NSM. Although milky discharge due to physiologic lactation related to pregnancy is more common, galactorrhea is still possible and should be worked up appropriately to ensure that all breast tissue has been removed and that there are no other more worrisome causes.

Venlafaxine-related galactorrhea in an adolescent female: A case report.

Hyperprolactinemia with galactorrhea is a well-documented adverse effect of some psychotropic medications. While advanced practice psychiatric nurses are likely familiar with hyperprolactinemia with galactorrhea as an adverse effect of antipsychotics, they may be less familiar with hyperprolactinemia with galactorrhea associated with antidepressants, an adverse effect that is far less common. Advanced practice psychiatric nurses must be able to identify hyperprolactinemia and galactorrhea in patients and must be able to evaluate and manage antidepressant-related hyperprolactinemia with galactorrhea. Thus, this case report describes hyperprolactinemia with galactorrhea in a teenage female prescribed venlafaxine for the treatment of major depressive disorder and posttraumatic stress disorder. To our knowledge, this is the first case report that describes galactorrhea related to a reuptake inhibitor (SNRI) in an adolescent.

Galactorrhea during antipsychotic treatment: results from AMSP, a drug surveillance program, between 1993 and 2015.

Galactorrhea is a well-known adverse drug reaction (ADR) of numerous antipsychotic drugs (APD) and is often distressing for those affected. Methodological problems in the existing literature make it difficult to determine the prevalence of symptomatic hyperprolactinemia in persons treated with APDs. Consequently, a large sample of patients exposed to APDs is needed for more extensive evaluation. Data on APD utilization and reports of galactorrhea caused by APDs were analyzed using data from an observational pharmacovigilance program in German-speaking countries-Arzneimittelsicherheit in der Psychiatrie (AMSP)-from 1993 to 2015. 320,383 patients (175,884 female inpatients) under surveillance were treated with APDs for schizophrenia and other indications. A total of 170 events of galactorrhea caused by APDs were identified (0.97 cases in 1000 female inpatient admissions). Most cases occurred during the reproductive age with the highest incidence among patients between 16 and 30 years (3.81 cases in 1000 inpatients). The APDs that were most frequently imputed alone for inducing galactorrhea were risperidone (52 cases and 0.19% of all exposed inpatients), amisulpride (30 resp. 0.48%), and olanzapine (13 resp. 0.05%). In three cases, quetiapine had a prominent role as a probable cause for galactorrhea. High dosages of the imputed APDs correlated with higher rates of galactorrhea. Galactorrhea is a severe and underestimated condition in psychopharmacology. While some APDs are more likely to cause galactorrhea, we identified a few unusual cases. This highlights the importance of alertness in clinical practice and of taking a patient's individual situation into consideration.

Prolactin Assay Interference by Macroprolactin.

BACKGROUND: Macroprolactinemia is a common presentation especially in gynecology and fertility clinics. However, with this clinical condition, there is a potential for misdiagnosis and unnecessary investigations/treatments due to lack of awareness of its prevalence and diagnostic approaches amongst trainees and physicians. METHODS: In this paper, we discuss the causes of hyperprolactinemia, its pathobiology, and an approach to macro-prolactinemia including relevant clinical chemistry methods and their limitations through the case of a 45-year-old female with a history of irregular menstrual cycles, who was seen in the endocrine clinic. RESULTS: Patient did not have a history of infertility, galactorrhea, visual-disturbance, or headaches. Her physical examination and routine clinical chemistry investigations were unremarkable. Her initial prolactin level was 4,836 mIU/L (109 - 557) with subsequent results demonstrating diminishing levels of prolactin a month apart (1,023 mIU/L). Polyethylene glycol (PEG) precipitation test demonstrated the presence of macroprolactin with a 3% post-PEG recovery of prolactin and 111 mIU/L post-PEG prolactin concentration. CONCLUSIONS: Patient's post-PRL results and clinical course confirmed the presence of macroprolactin to be the cause of factitious hyperprolactinemia. A sound approach to macroprolactinemia is critical in clinical and laboratory practices.

Efficacy and safety in the treatment of hyperprolactinemia: A systematic review and network meta-analysis.

WHAT IS KNOWN AND OBJECTIVE: Hyperprolactinemia is a neuroendocrine disease that is responsible for a quarter of cases of secondary amenorrhea, which can lead to infertility in women. Dopaminergic agonists (bromocriptine, cabergoline, quinagolide) can be used in the treatment. However, there is a lack of secondary studies that compare their efficacy and safety, especially through a network meta-analysis. Thus, to contribute to the decision-making, a systematic review and network meta-analyses (NMA) were performed to evaluate the efficacy and safety of dopaminergic agonists in the treatment of hyperprolactinemia. METHODS: Randomized clinical trials (RCT) were retrieved through PubMed, Web of Science and Scopus databases. The efficacy and safety of the drugs were compared, considering the following outcomes: prolactin (PRL) levels, number of patients with galactorrhoea, menstrual irregularities and adverse drug reactions. NMA was built for each outcome. Results were reported as odds ratios (OR) with 95% credibility intervals. Ranking probabilities were calculated by surface under the cumulative ranking analysis (SUCRA) and Stochastic multicriteria acceptability analysis (SMAA). RESULTS AND DISCUSSION: Seventeen RCTs were included in the systematic review and fifteen in the meta-analyses. The drugs had similar efficacy, considering the PRL levels. The SUCRA analysis showed that quinagolide (0.075 and 0.05 mg/day) was superior for reducing irregular menstruation, whereas bromocriptine was the best (97%) for galactorrhoea. Cabergoline proved to be the safest drug, except for abdominal pain at a dose of 1 mg/week. The SMAA demonstrated similar results to SUCRA. WHAT IS NEW AND CONCLUSION: This is the first network meta-analysis that evaluated the efficacy and safety of dopaminergic agonists in the treatment of hyperprolactinemia. The results of this review revealed that these drugs have similar efficacy, but cabergoline has a better safety profile.

Galactorrhea/Galactocele After Breast Augmentation: A Systematic Review.

AIMS: To review cases of galactorrhea and galactocele postbreast augmentation, determine possible risk factors and consider management strategies of this rare complication. METHODS: A systematic literature review was conducted in July 2019 searching Pubmed, Embase, and Google Scholar. RESULTS: The searches revealed 19 articles (17 case reports/series and 2 retrospective chart reviews) collectively comprising 38 women. The average age was 28 years, 42% were on oral contraceptives, whereas a quarter were nulliparous. The most common incision was periareolar (48%) followed by transaxillary (24%). The most common implant location was subglandular (57%) followed by subpectoral (37%). The average time to symptom onset was 61 days (range, 3-912 days) but only 3 cases presented more than a month after implant insertion. Twenty-one patients had galactorrhea, 7 had galactocele, whereas 10 women had both. Bilateral symptoms were present in 72% of cases, whereas hyperprolactinemia was present in only 62%. Management strategies included simple surveillance, antibiotics, dopamine agonists, leukotriene receptor antagonists, estrogenic agents, surgical washout, and implant removal (8 patients). The mean time to symptom resolution was 22.6 days. CONCLUSIONS: The numbers are too small for definitive conclusions but there is a weak suggestion that periareolar incisions, subglandular implants, prior hormonal contraceptive use, gravidity, and recent history of breastfeeding (<1 year) may be risk factors for galactorrhea/galactocele. Symptom onset is usually within 3 months. Treatments providing the fastest response (2 days) comprised of a composite approach (antibiotics, dopamine agonist, surgical drainage, and implant removal), whereas the use of estrogenic medications appeared to confer little benefit.

Idiopathic hyperprolactinemia - A challenge for primary care.

Hyperprolactinemia is a condition of elevated serum prolactin, which usually occurs in women as compared to men. Most patients present to primary care clinics with a history of galactorrhoea, oligomenorrhea, amenorrhoea or infertility. Literature search reveals that there were few idiopathic causes of hyperprolactinemia, which resolved by itself without specific pharmacological or surgical treatment. This case is of a 39-year-old woman presented with amenorrhea for four months after Implanon removal and concomitantly noted to have galactorrhoea for four years without any medical attention. The condition persisted after cessation of breastfeeding. After undergoing several investigations including imaging studies, the underlying cause of hyperprolactinemia was noted to be idiopathic. Due to the unclear cause of its aetiology, this case caused various challenges to the primary care. Exhaustive physiological and pathological causes of hyperprolactinemia have been ruled out. Nevertheless, with adequate treatment, she gained her normal menstrual and resolved galactorrhoea symptoms.

NEUROLOGICAL MANIFESTATIONS OF PROLACTINOMA (CASE REPORT).

This article describes a clinical case of prolactinoma, the onset of which was diagnosed after long-term use of eglonil, after the appearance of such side effects as galactorrhea. This clinical case is a unique one because of the peculiarities of diagnostic search. The first complaints of the patient were anxiety and fear, fatigue, frequent mood swings, memory disoders. She was examined by a family physician and prescribed eglonil (sulpiride) 200mg for 7 days. Because of the positive effect the patient decided on her own to continue treatment for another several weeks. But suddenly she revealed a leakage of milk from the mammary glands. The family physician assessed galactorrhea as a side effect of long-term use of eglonil, and cancelled this prescription. Simultaneously the family doctor canceled COCs, that the patient used for the last several years, because of pregnancy planning. But three months later the mensis didn't occur. The menstrual cycle did not resume and pregnancy did not occur even 6 months later. Thus the doctor started to perform complete examination of the patient. Unfortunately, during the diagnostic search the patient rejected to do the contrast and primarily was performed MRI without contrast. The doctor revealed abnormal prolactin level - 423 ng/ml (normal range <25 ng/ml). Finally MRI of the pitutary including dynamic contrast was done. It has demonstrated an 8 x 11 mm mass in pituitary gland. The patient was prescribed conservative treatment according to the protocol. As a result, subsequent monthly control laboratory tests of prolactin levels in blood indicated gradual decrease of its level. Thus the first symptoms of prolactinoma may be atypical and can be detected only by a detailed survey and observation of the patient. It is also known that the severity of symptoms depends on the size of prolactinomas. Large prolactinomas cause symptoms of central nervous system lesion: headaches, depression, anxiety, irritability, emotional instability but in our clinical case, the prolactinoma was small but manifests with severe symptoms of the central nervous system lesion (according to the results of HADScale and MoCA scale). The presence of concomitant pathology can mask or distort the symptoms of another disease that complicates the diagnosis. On the other hand, treatment of one of the comorbidities and improving its course leads to a reduction in the manifestations of the others.

Very late recurrence of B-cell acute lymphoblastic leukemia masquerading as a pituitary tumor.

Involvement of the pituitary gland by leukemic infiltration is exceedingly rare. Here, we describe a very late recurrence of B-cell acute lymphoblastic leukemia masquerading as a pituitary tumor and review the literature for previously reported cases. Our female patient presented 13 years after completion of therapy for B-ALL with headache, amenorrhea, galactorrhea and a pituitary mass. Subsequent studies revealed recurrence of her leukemia, and the pituitary lesion resolved after induction chemotherapy. Our case highlights the importance of considering leukemic infiltrate in the differential diagnosis of pituitary mass, particularly in a patient with a history of hematologic malignancy, sparing unnecessary surgical intervention and informing endocrine evaluation. In addition, the case also highlights difficulties with characterizing this recurrence as a very late relapse or clonal evolution of the original leukemia.

VENUS BY BOTTICELLI AND HER PITUITARY ADENOMA.

Objective: Simonetta Vespucci, considered the most beautiful woman of the Renaissance, is the inspiration and face of one of the most famous paintings of all times, "The Birth of Venus," by Botticelli. She died in 1476 at the age of 23 years. We postulate she suffered from a pituitary-secreting tumor progressing to pituitary apoplexy. The goals of this study were 3-fold: (i) verify that the subject depicted by Botticelli in different paintings represents the same woman; (ii) identify the facial traits affected by the progression of a growth hormone- and prolactin-secreting tumor; and (iii) confirm that the observed changes of the face traits observed in the portraits of Simonetta Vespucci are compatible with the facial traits changes identified earlier. Methods: Comparison among face traits was based on the analysis of the face regions measured by means of fiducial points and their distances, and after pose compensation based on three-dimensional head modelling. Results: In favor of the hypothesis that Simonetta suffered from a pituitary growth hormone- and prolactin-secreting tumor stands changes of her lineaments, a feature which becomes evident over the years and particularly manifest in the Allegorical Lady, where galactorrhea is depicted. Conclusion: We conclude that sufficient evidence is presented to suggest that Simonetta Vespucci, the Venus depicted by Botticelli, suffered from pituitary adenoma secreting prolactin and growth hormon with parasellar expansion. The current interpretation of the Venus strabism should be revisited according to this finding. Abbreviation: GH = growth hormone.

A registry of acromegaly patients and one year following up in Taiwan.

BACKGROUND/PURPOSE: The objectives of this study were to describe epidemiological data, treatment outcomes, and quality of life (QOL) of patients with acromegaly in Taiwan. METHODS: From 2013 to 2015, subjects with acromegaly were recruited through five medical centers. After enrollment, each patient was kept on observation for 1 year. RESULTS: The analyzed cohort included 272 acromegalic subjects (117 males, 155 females) with a mean age of 51.4 ± 12.9 years. Their mean age at diagnosis was 41.8 ± 12.1 years. About 83.8% patients presented symptoms of facial changes. Galactorrhea was noted at the earliest age of 32.7 ± 9.1 years. The duration between the onset of symptoms/signs and diagnosis was 6.9 ± 8.1 years. Around 70.3% patients harbored a macroadenoma. At enrollment, percentages of patients ever received surgical intervention, radiotherapy, somatostatin analogs, and dopamine agonists were 94.8%, 27.9%, 64%, and 30%, respectively. At the final following-up visit, the random growth hormone (GH), nadir GH after oral glucose tolerance test, and the insulin-like growth factor 1 levels were 2.7 ± 4.9 µg/L, 2.4 ± 6.1 µg/L, and 291.5 ± 162.4 ng/mL, respectively. The remission rate assessed by random GH level (≦2 µg/L) was 63.8%. The mean AcroQoL scores for the total 22 items were 64.0 ± 19.7. About 42.8% patients never sensed or felt discomfort about their changes in appearance. CONCLUSION: This study described the profiles of acromegaly in Taiwan. It is important to enhance early diagnosis and timely commencement of treatment to prevent serious complications of acromegaly.

Galactocele After Aesthetic Breast Augmentation with Silicone Implants: An Uncommon Presentation.

BACKGROUND: Breast augmentation is one of the most frequently performed esthetic operations. Galactorrhea and galactocele formation are both very rare complications. The real cause still remains unknown, but various risk factors have been well reported in the literature. This report concerns a case of postoperative galactocele following bilateral breast augmentation via the inframammary approach with dual-plane insertion of implants, which is usually considered a protective approach in terms of risk factors for induction of postoperative galactorrhea. METHODS: The patient had no significant surgical, gynecological or medical history, including galactorrhea or hyperprolactinemia, and did not present any chest wall abnormalities. There has been no use of oral contraceptives or any other drugs. After the surgical procedure, the patient presented with infection-like symptoms, for which galactorrhea or galactocele was initially not considered, mainly for the absence of specific risk factors. RESULTS: After antibiotic and bromocriptine therapy, her breast returned to normal, with no pain, inflammation, enlargement or esthetic alterations. After 6 months of follow-up, the patient did not present any abnormality and she was satisfied with the result. CONCLUSION: With our report, we want to underline that galactorrhea and galactocele cannot be ruled out, even in patients with no risk factors and with procedures considered as "protective." With a fast diagnosis and a specific therapy, implants and final result can be rescued. Level of Evidence V This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

SUCCESSFUL TREATMENT OF A PROLACTINOMA (CASE REPORT).

Currently, lots of young couples are facing infertility. One of the relatively rare causes of female infertility is prolactinoma - hormonally active pituitary tumor that secretes excessive quantity of prolactin. Excessive prolactin production is leading to anovulation and women infertility. We propose for your attention a case report management of patient with prolactinoma. Long and adequate administration of inhibitors of prolactin secretion leads to regression of the tumor size up to its complete disappearance, which allows patients with prolactinoma not only to get pregnant, but also to nurse and give birth to healthy children.

Adjunct Aripiprazole Reduces Prolactin and Prolactin-Related Adverse Effects in Premenopausal Women With Psychosis: Results From the DAAMSEL Clinical Trial.

PURPOSE/BACKGROUND: Prolactin-related adverse effects contribute to nonadherence and adverse health consequences, particularly in women with severe mental illness. Treating these adverse effects may improve treatment acceptability, adherence, and long-term outcomes. METHODS/PROCEDURES: Premenopausal women with a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision diagnosis of schizophrenia, schizoaffective disorder, or bipolar disorder were recruited for a randomized, double-blind, placebo-controlled 16-week trial of adjunct aripiprazole (5-15 mg/d). Participants had elevated prolactin (>24 ng/mL) and were experiencing galactorrhea, amenorrhea, oligomenorrhea, or sexual dysfunction on a prolactin-elevating antipsychotic. Participants were evaluated biweekly for prolactin elevation and galactorrhea and completed a menstrual diary review. Psychiatric symptoms and adverse effects were closely monitored. FINDINGS/RESULTS: Forty-six women were randomized (n = 25 aripiprazole, n = 21 placebo). Thirty-seven completed at least 8 weeks of the study (n = 20 [80%] aripiprazole and n = 17 [81%] placebo). Aripiprazole (mean dose, 11.7 ± 2.4 mg/d) was effective for lowering prolactin relative to placebo (P = 0.04). In addition, 45% (9/20) of the aripiprazole group had a normalized prolactin (<24 mg/mL) compared with 12% (2/17) of the placebo group (P = 0.028). Galactorrhea resolved in 77% (10/13) of the aripiprazole-treated participants compared with 33% (4/12) in the placebo group (P = 0.028). Normalization of sexual function (<16 on the Arizona Sexual Experience Scale) occurred in 50% on aripiprazole (7/14) versus 9% (1/11) on placebo (P = 0.030). No differences between groups in symptoms or adverse effects were noted. Overall, women rated a mean score of 4.6 ± 0.6 on a 5-point Likert scale for sexual function improvement, suggesting their particular satisfaction with improvement in this domain. IMPLICATIONS/CONCLUSIONS: Building upon prior studies, this rigorous evaluation confirms the utility of adjunctive aripiprazole as a strategy for improving prolactin and managing prolactin-related adverse effects in premenopausal women with psychosis.

Impact of macroprolactin on galactorrhea and the rate of patients possibly affected by macroprolactin.

The clinical influence of macroprolactin (MPRL) is not clearly understood and the rate of patients potentially affected by MPRL is unknown. We investigated the influence of MPRL on the onset of galactorrhea and estimated the rate of patients with a proportion of MPRL fraction that may possibly affect galactorrhea. Data of patients with obstetric or gynecological symptoms who had undergone PRL fractionation testing were retrospectively analyzed. To evaluate factors influencing galactorrhea, a multivariate logistic regression analysis was performed and the adjusted odds ratios of MPRL for galactorrhea were calculated. Cutoff values for the total PRL level and the proportion of MPRL fractions for galactorrhea were determined by ROC analysis using a multivariate logistic model. The prevalence of patients with a proportion of MPRL fraction greater than or equal to the cutoff value for galactorrhea was estimated. The median proportion of MPRL fraction was 30.1% and increased as PRL level increased. Total PRL and MPRL had a significant influence on the onset of galactorrhea and the adjusted odds ratio was 1.09 in total PRL and 0.94 in MPRL. The rate of patients with a proportion of MPRL fraction that may possibly affect galactorrhea was estimated to be 33.5% of the study population, and thus found to be twelve times or more the number of macroprolactinemia patients. Future prospects for hyperprolactinemia may require diagnostic criteria using free prolactin levels and so MPRL fraction measurement is important for the diagnosis and treatment of patients with obstetric and gynecological symptoms.

Paraneoplastic Galactorrhea in Childhood T-ALL: An Evaluation of Tumor-derived Prolactin.

T-cell acute lymphoblastic leukemia (T-ALL) comprises 15% of childhood leukemia. Although multiagent pulse chemotherapy has improved event-free survival in recent decades, the lack of reliable prognosticators and high rate of relapse remain a challenge. Described is a novel discovery of tumor-derived hyperprolactinemia in childhood T-ALL through a case associated with paraneoplastic galactorrhea. Prolactin production by tumor cells, although a rare phenomenon, is previously demonstrated in several adult cancers and 2 pediatric malignancies with unknown implications. This is the first report demonstrating tumor-derived prolactin in pediatric T-ALL and offers potential as a disease marker and therapeutic drug target.

Silent subtype 3 pituitary adenomas are not always silent and represent poorly differentiated monomorphous plurihormonal Pit-1 lineage adenomas.

Originally classified as a variant of silent corticotroph adenoma, silent subtype 3 adenomas are a distinct histologic variant of pituitary adenoma of unknown cytogenesis. We reviewed the clinical, biochemical, radiological, immunohistochemical and ultrastructural features of 31 silent subtype 3 adenomas to clarify their cellular origin. Among 25 with clinical and/or radiological data, all were macroadenomas; there was cavernous sinus invasion in 30% of cases and involvement of the clivus in 17% of cases. Almost 90% of patients were symptomatic; 67% had mass effect symptoms, 37% were hypogonadal and 8% had secondary adrenal insufficiency. Significant hormonal excess in 29% of cases included hyperthyroidism in 17%, acromegaly in 8% and hyperprolactinemia above 150 µg/l in 4%. Two individuals with hyperprolactinemia who were younger than 30 years had multiple endocrine neoplasia type 1. Immunohistochemically, all 31 tumors were diffusely positive for the pituitary lineage-specific transcription factor Pit-1. Although three only expressed Pit-1, others revealed variable positivity for one or more hormones of Pit-1 cell lineage (growth hormone, prolactin, thyroid-stimulating hormone), as well as alpha-subunit and estrogen receptor. Most tumors exhibited perinuclear reactivity for keratins with the CAM5.2 antibody; scattered fibrous bodies were noted in five (16%) tumors. The mean MIB-1 labeling index was 4% (range, 1-9%). Fourteen cases examined by electron microscopy were composed of a monomorphous population of large polygonal or elongated cells with nuclear spheridia. Sixty-five percent of patients had residual disease after surgery; after a mean follow-up of 48.4 months (median 41.5; range=2-171) disease progression was documented in 53% of those cases. These data identify silent subtype 3 adenomas as aggressive monomorphous plurihormonal adenomas of Pit-1 lineage that may be associated with hyperthyroidism, acromegaly or galactorrhea and amenorrhea. Our findings argue against the use of the nomenclature 'silent' for these tumors. To better reflect the characteristics of these tumors, we propose that they be classified as 'poorly differentiated Pit-1 lineage adenomas'.

Giant prolactinomas larger than 60 mm in size: a cohort of massive and aggressive prolactin-secreting pituitary adenomas.

OBJECTIVES: Prolactin (PRL)-secreting macroadenomas usually measure between 10 and 40 mm. Giant (adenoma size ≥40 mm) PRL-tumors are not common, and larger prolactinomas (maximal diameter ≥60 mm) are rare, and their management outcomes have not been well characterized. METHODS: We have identified 18 subjects (16 men, 2 females) with giant PRL-adenomas (size ≥60 mm; PRL > 1000 ng/ml) and summarized their characteristics and response to treatment. RESULTS: Mean age was 36.3 ± 13.5 years (range 12-59 years). Mean adenoma size was 71.8 ± 10.2 mm (60-92 mm). Complaints at presentation included headaches in 11 patients, visual deterioration in 9, sexual dysfunction in 9 males, and behavioral changes in two. Fourteen (78 %) had visual field defects. Mean PRL at presentation was 28,465 ng/ml (range 1300-270,000). All patients were treated with cabergoline (3.9 ± 2.0 mg/week), except for one who received bromocriptine. Treatment achieved PRL normalization in 11/18 patients within a median interval of 20 months. Visual improvement occurred in 12/14 patients with pre-treatment visual abnormalities. Nine patients underwent surgery (transsphenoidal, 7; transcranial, 2). None of the seven patients with elevated PRL before surgery achieved remission post-operatively. After a follow-up of 7.8 ± 5.1 years, 15/18 patients had significant adenoma shrinkage. Eleven patients are normoprolactinemic, 3 are partially controlled (PRL < 3 × ULN), and 4 remain with significantly elevated PRL. Most patients reported disappearance or improvement of their complaints. CONCLUSIONS: These enormous PRL-adenomas are invasive but respond fairly well to medical treatment. Long-term therapy with high dose cabergoline together with a pituitary surgery in some patients was the key for their successful management, achieving biochemical and clinical remission in most patients.