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Frontiers in Endocrinology 2024Prolactinomas (PRLomas) constitute approximately half of all pituitary adenomas and approximately one-fifth of them are diagnosed in males. The clinical presentation of... (Review)
Review
Prolactinomas (PRLomas) constitute approximately half of all pituitary adenomas and approximately one-fifth of them are diagnosed in males. The clinical presentation of PRLomas results from direct prolactin (PRL) action, duration and severity of hyperprolactinemia, and tumor mass effect. Male PRLomas, compared to females, tend to be larger and more invasive, are associated with higher PRL concentration at diagnosis, present higher proliferative potential, are more frequently resistant to standard pharmacotherapy, and thus may require multimodal approach, including surgical resection, radiotherapy, and alternative medical agents. Therefore, the management of PRLomas in men is challenging in many cases. Additionally, hyperprolactinemia is associated with a significant negative impact on men's health, including sexual function and fertility potential, bone health, cardiovascular and metabolic complications, leading to decreased quality of life. In this review, we highlight the differences in pathogenesis, clinical presentation and treatment of PRLomas concerning the male sex.
Topics: Female; Male; Humans; Prolactinoma; Hyperprolactinemia; Quality of Life; Pituitary Neoplasms; Adenoma
PubMed: 38370355
DOI: 10.3389/fendo.2024.1338345 -
Pituitary Feb 2021Pathogenic variants in the aryl hydrocarbon receptor-interacting protein (AIP) gene are increasingly recognised as a cause of familial isolated pituitary adenoma....
Pathogenic variants in the aryl hydrocarbon receptor-interacting protein (AIP) gene are increasingly recognised as a cause of familial isolated pituitary adenoma. AIP-associated tumours are most commonly growth hormone (GH) producing. In our cohort of 175 AIP mutation positive patients representing 93 kindreds, 139 (79%) have GH excess, 19 have prolactinoma (17 familial and 2 sporadic cases) and out of the 17 clinically non-functioning tumours 4 were subsequently operated and found to be GH or GH & prolactin immunopositive adenoma. Here we report a family with an AIP variant, in which multiple family members are affected by prolactinoma, but none with GH excess. To our knowledge this is the first reported family with an AIP pathogenic variant to be affected solely by prolactinoma. These data suggest that prolactinoma families represent a small subset of AIP mutation positive kindreds, and similar to young-onset sporadic prolactinomas, AIP screening would be indicated.
Topics: Adenoma; Adult; Female; Genetic Testing; Growth Hormone-Secreting Pituitary Adenoma; Humans; Male; Middle Aged; Mutation; Pedigree; Pituitary Neoplasms; Prolactinoma
PubMed: 33010004
DOI: 10.1007/s11102-020-01085-5 -
Expert Review of Endocrinology &... May 2019Prolactinomas represent the most common pituitary adenomas encountered in the clinic. While a majority of these tumors will be successfully treated by dopamine agonist... (Review)
Review
INTRODUCTION
Prolactinomas represent the most common pituitary adenomas encountered in the clinic. While a majority of these tumors will be successfully treated by dopamine agonist (DA) such as cabergoline, their management becomes problematic since a resistance to DA can occur and/or if the tumor displays features of aggressiveness, two conditions that are closely related.
AREAS COVERED
Epidemiology and medical treatment of prolactinomas; resistance to DA and molecular basis of DA-resistance; therapeutical alternatives in case of DA-resistant Prolactinomas and therapies in development; summarizing conclusions.
EXPERT OPINION
The management of DA-resistant prolactinomas requires a multidisciplinary approach by an expert team. Along with discussions about surgery with or without gamma knife radiosurgery, genetic screening for multiple endocrine neoplasia type 1 (MEN1) syndrome is actively discussed in a case-by-case approach. In case of surgery, a careful analysis of the tumor sample can provide information about its aggressivity potential according to recent criteria. Ultimately, temozolomide can be indicated if the tumor is rapidly growing and/or threatening for the patient.
Topics: Disease Management; Dopamine Agonists; Drug Resistance, Neoplasm; Humans; Pituitary Neoplasms; Prolactinoma; Signal Transduction; Treatment Outcome
PubMed: 30913932
DOI: 10.1080/17446651.2019.1596024 -
BMJ (Clinical Research Ed.) Nov 1988
Topics: Humans; Hyperprolactinemia; Pituitary Neoplasms; Prolactinoma; Tomography, X-Ray Computed
PubMed: 3145081
DOI: 10.1136/bmj.297.6658.1268-c -
Nutricion Hospitalaria Nov 2015prolactinomas are pituitary adenomas that express and secrete prolactin. These patients are overweight and the mechanisms are being studied.
INTRODUCTION
prolactinomas are pituitary adenomas that express and secrete prolactin. These patients are overweight and the mechanisms are being studied.
GOALS
assess nutritional and metabolic status of overweight patients with and without hyperprolactinemia caused by prolactinoma and compare them.
MATERIALS AND METHODS
cross-sectional study, patients with body mass index (BMI) ≥ 25 kg/m2 with and without prolactinoma: 1) 20 normoprolactinemic (NPrl) with prolactinoma; 2) 23 hyperprolactinemic (HPrl) with prolactinoma; 3) 28 controls without prolactinoma or alterations in prolactin levels. Evaluated through anthropometric, dietetics, and biochemical assessment.
RESULTS
of the 71 patients evaluated, most were obese women with macroprolactinomas. All three groups had diets with low caloric and monounsaturated fatty acid (MUFA) intake, the NPrl group had low carbohydrate (CHO) intake and high lipid (LIP) and saturated fatty acid (SFA) intake, and the NPrl and HPrl groups had appropriate intake of polyunsaturated fatty acids (PUFA). The HPrl group had elevated total cholesterol. HDL cholesterol was below the recommended threshold for most patients. No statistically significant differences were found in anthropometric and biochemical variables among the groups.
CONCLUSIONS
most patients with prolactinomas and controls are obese and metabolically similar regardless of prolactin levels. All groups presented low caloric and MUFA intake. Protein, LIP, SFA, and cholesterol were significantly different among the groups, the NPrl group ingested less amount of protein and greater of fat. Snacking between meals and changes of food consumption on weekends was reported by most patients. This is the first study comparing patients with prolactinomas and controls, both with overweight, regarding food consumption and feeding behavior.
Topics: Adult; Aged; Cross-Sectional Studies; Diet; Eating; Feeding Behavior; Female; Humans; Hyperprolactinemia; Male; Middle Aged; Nutrition Assessment; Nutritional Status; Obesity; Overweight; Pituitary Neoplasms; Prolactinoma
PubMed: 26545657
DOI: 10.3305/nh.2015.32.5.9673 -
Neurosurgical Review May 2023Initial treatment for prolactinoma is usually conservative with dopamine agonists. However, the duration of treatment is often lifelong and can be associated with...
Initial treatment for prolactinoma is usually conservative with dopamine agonists. However, the duration of treatment is often lifelong and can be associated with significant side effects. Surgical outcomes are usually favorable and treatment complications low, raising the question whether surgical therapy should be included earlier in the treatment of prolactinoma. The aim of this study was to analyze the outcome of surgical resection of prolactinomas at our institution, to compare it with other published surgical and conservative series and to discuss the role of surgery in modern prolactinoma therapy. The authors reviewed a database of single-center consecutively operated prolactinoma cases and analyzed the extent of resection (EOR), endocrinological and neurological outcomes, and complications. Thirty patients were analyzed. Mean patient age was 37.2 ± 15.5 years (range 16-76) and consisted of 17 (56.7%) females and 13 (43.3%) males. Twenty-one patients (70%) failed medical therapy, the main reasons being intolerable side effects in 11 cases (52.4%) and insufficient response in 10 cases (47.6%). Nine patients (30%) received no medical treatment prior to surgery, of which five (55.6%) were operated because of pituitary apoplexy, two (22.2%) because of acute visual deterioration and two (22.2%) refused medical treatment and opted for surgery as first-line treatment. Of the 30 operated tumors, 56.7% (n = 17) were microadenomas, 30% (n = 9) were macroadenomas (≥ 10 mm), and 13.3% (n = 4) were giant adenomas (≥ 40 mm). GTR was achieved in 75% (n = 21) of cases. The overall remission rate was 63.3%. MRI showed a residual tumor in seven patients (25%), typically with invasive growth. Postoperative CSF leaks did not occur. Mean follow-up was 34.9 ± 60.3 months (range 0-246 months). Endocrine remission was defined as a morning fasting basal PRL level of 22.3 < ng/mL and measured at the last available follow-up. Postoperative Prolactine levels were missing in three patients. Our analysis describes a highly selected sample with a disproportionate number of larger, invasive tumors and emergency cases. Nevertheless, the results are satisfactory and comparable with other published series. The consistently good results of transphenoidal surgery, especially for microprolactinomas, have led to a greater acceptance of surgery in the treatment of prolactinomas in recent years. The timing of surgery in each individual case must be determined by a multidisciplinary team to ensure the best possible outcome.
Topics: Male; Female; Humans; Adolescent; Young Adult; Adult; Middle Aged; Aged; Prolactinoma; Pituitary Neoplasms; Treatment Outcome; Adenoma; Magnetic Resonance Imaging; Retrospective Studies
PubMed: 37249700
DOI: 10.1007/s10143-023-02033-0 -
Endocrine Reviews Aug 2006Prolactinomas account for approximately 40% of all pituitary adenomas and are an important cause of hypogonadism and infertility. The ultimate goal of therapy for... (Review)
Review
Prolactinomas account for approximately 40% of all pituitary adenomas and are an important cause of hypogonadism and infertility. The ultimate goal of therapy for prolactinomas is restoration or achievement of eugonadism through the normalization of hyperprolactinemia and control of tumor mass. Medical therapy with dopamine agonists is highly effective in the majority of cases and represents the mainstay of therapy. Recent data indicating successful withdrawal of these agents in a subset of patients challenge the previously held concept that medical therapy is a lifelong requirement. Complicated situations, such as those encountered in resistance to dopamine agonists, pregnancy, and giant or malignant prolactinomas, may require multimodal therapy involving surgery, radiotherapy, or both. Progress in elucidating the mechanisms underlying the pathogenesis of prolactinomas may enable future development of novel molecular therapies for treatment-resistant cases. This review provides a critical analysis of the efficacy and safety of the various modes of therapy available for the treatment of patients with prolactinomas with an emphasis on challenging situations, a discussion of the data regarding withdrawal of medical therapy, and a foreshadowing of novel approaches to therapy that may become available in the future.
Topics: Adolescent; Animals; Child; Combined Modality Therapy; Contraceptives, Oral, Hormonal; Dopamine Agonists; Drug Resistance; Female; Humans; Hypogonadism; Male; Models, Biological; Pituitary Neoplasms; Pregnancy; Prolactinoma; Therapies, Investigational; Withholding Treatment
PubMed: 16705142
DOI: 10.1210/er.2005-9998 -
Neuroendocrinology 2019The discovery of dopamine inhibitory effects on prolactin secretion has led to an era of successful dopaminergic therapy for prolactinomas. Herein we provide an overview... (Review)
Review
The discovery of dopamine inhibitory effects on prolactin secretion has led to an era of successful dopaminergic therapy for prolactinomas. Herein we provide an overview of the evolution of dopamine agonists and their use in patients with PRL-secreting pituitary tumors, starting from the 1970s up to today, highlighting that normalization of PRL levels, restoration of eugonadism, and reduction of tumor mass can be achieved in the majority of patients by treatment with dopamine agonists.
Topics: Dopamine Agonists; Humans; Pituitary Neoplasms; Prolactinoma
PubMed: 30852578
DOI: 10.1159/000499470 -
Journal of Cellular and Molecular... Dec 2018Metformin (MET) is a diabetes drug that activates AMP-activated protein kinase (AMPK), and is suggested to have anticancer efficacy. Here, we investigated the role of...
Metformin (MET) is a diabetes drug that activates AMP-activated protein kinase (AMPK), and is suggested to have anticancer efficacy. Here, we investigated the role of AMPK signalling in prolactinoma (PRLoma), with particular respect to MET and bromocriptine (BC) as a PRLoma treatment. We analysed AMPK phosphorylation, dopamine D2 receptor (D2R), and oestrogen receptor (ER) expression in both BC-sensitive and -resistant PRLoma samples; effects of the AMPK agonist MET (alone or with BC) on in vitro proliferation and apoptosis, xenograft growth and prolactin (PRL) secretion of BC-sensitive and -resistant cells, and ER expression in xenografts. Some BC-resistant PRLomas showed high D2R expression but extremely low AMPK activation. MET significantly inhibited proliferation of cultured PRLoma cells; MET + BC notably restrained their PRL secretion. MET + BC further decreased tumour growth and serum PRL levels in xenografts than BC treatment alone. ER was down-regulated after AMPK activation in both cultured cells and xenografts. Together, we propose that the AMPK signalling pathway down-regulates ERα and ERβ, and suppresses PRLoma growth as well as PRL secretion. Combined MET + BC is a potential treatment for PRLomas.
Topics: AMP-Activated Protein Kinase Kinases; Animals; Apoptosis; Bromocriptine; Cell Proliferation; Estrogen Receptor alpha; Estrogen Receptor beta; Female; Heterografts; Humans; Metformin; Mice; Phosphorylation; Pituitary Diseases; Prolactin; Prolactinoma; Protein Kinases; Receptors, Dopamine D2
PubMed: 30334324
DOI: 10.1111/jcmm.13963 -
International Journal of Molecular... Jan 2021As hyperprolactinemia is observed in patients with bromocriptine‑resistant prolactinoma, prolactin (PRL) has been implicated in the development of bromocriptine...
As hyperprolactinemia is observed in patients with bromocriptine‑resistant prolactinoma, prolactin (PRL) has been implicated in the development of bromocriptine resistance. Since PRL primarily mediates cell survival and drug resistance via the Janus kinase‑2 (JAK2)/signal transducer and activator of transcription 5A (STAT5) signaling pathway, the STAT5 inhibitor, pimozide, may inhibit cell proliferation and reverse bromocriptine resistance in prolactinoma cells. In the present study, compared with bromocriptine or pimozide alone, the combination of pimozide and bromocriptine exerted enhanced reduction in cell growth and proliferation, and increased apoptosis and cell cycle arrest in bromocriptine‑resistant prolactinoma cells. A reduction in phospho‑STAT5, cyclin D1 and B‑cell lymphoma extra‑large (Bcl‑xL) expression levels were observed in cells treated with the combination of drugs. In addition, pimozide suppressed spheroid formation of human pituitary adenoma stem‑like cells, and reduced the protein expression of the cancer stem cell markers, CD133 and nestin. Pimozide did not exert any additional antitumor activity in STAT5‑knockdown primary culture cells of human bromocriptine‑resistant prolactinomas. Furthermore, Pimozide combined with bromocriptine treatment significantly reduced human prolactinoma xenograft growth. Western blot and immunohistochemical analyses also demonstrated significant inhibition of cell proliferation and stem cell marker proteins in vivo. Collectively, these data indicated that pimozide treatment reduced prolactinoma growth by targeting both proliferating cells and stem cells, at least in part, by inhibiting the STAT5/Bcl‑xL and STAT5/cyclin D1 signaling pathways.
Topics: Animals; Bromocriptine; Cell Line, Tumor; Cyclin D1; Humans; Mice; Mice, Nude; Pimozide; Pituitary Neoplasms; Prolactinoma; Rats; STAT5 Transcription Factor; Signal Transduction; Xenograft Model Antitumor Assays; bcl-X Protein
PubMed: 33155660
DOI: 10.3892/ijmm.2020.4784