-
Presse Medicale (Paris, France : 1983) Dec 2021Hyperprolactinemia, defined by a level of serum prolactin above the standard upper limit of normal range, is a common finding in clinical practice and prolactinomas are... (Review)
Review
Hyperprolactinemia, defined by a level of serum prolactin above the standard upper limit of normal range, is a common finding in clinical practice and prolactinomas are the main pathological cause. Prolactinomas lead to signs and symptoms of hormone oversecretion, such as galactorrhea and hypogonadism, as well as symptoms of mass effect, including visual impairment, headaches and intracranial hypertension. Diagnosis involves prolactin measurement and sellar imaging, but several pitfalls are involved in this evaluation, which may difficult the proper management. Treatment is medical in the majority of cases, consisting of dopamine agonists, which present high response rates, with a very favorable safety profile. Major adverse effects that should be monitored consist of cardiac valvulopathy and impulse control disorders. Other treatment options include surgery and radiotherapy. Temozolomide may be used for aggressive or malignant carcinomas. Finally, pregnancy outcomes are similar to general population even when dopamine agonist treatment is maintained.
Topics: Antineoplastic Agents, Alkylating; Disruptive, Impulse Control, and Conduct Disorders; Dopamine Agonists; Female; Galactorrhea; Humans; Hyperprolactinemia; Hypogonadism; Pituitary Neoplasms; Pregnancy; Prolactin; Prolactinoma; Sella Turcica; Temozolomide
PubMed: 34687915
DOI: 10.1016/j.lpm.2021.104080 -
The Journal of Clinical Endocrinology... Aug 2023Prolactinomas are the most common pituitary tumor histotype, with microprolactinomas being prevalent in women and macroprolactinomas in men. Hyperprolactinemia is among... (Review)
Review
Prolactinomas are the most common pituitary tumor histotype, with microprolactinomas being prevalent in women and macroprolactinomas in men. Hyperprolactinemia is among the most common causes of hypogonadotropic hypogonadism in both sexes, prompting medical advice for hypogonadism (infertility, oligo-amenorrhea, impotence, osteoporosis/osteopenia) in both sexes, and for signs and symptoms of mass effects (hypopituitarism, visual loss, optic chiasm compression, cranial nerve deficits, headaches) predominantly in men. Diagnostic workup involves a single prolactin measurement and pituitary imaging, but some laboratory artifacts (ie, the "hook effect" and macroprolactin) can complicate or delay the diagnosis. The treatment of choice for prolactinomas is represented by dopamine agonists, mainly cabergoline, which are able to induce disease control, restore fertility in both sexes, and definitively cure one-third of patients, thus permitting treatment discontinuation. Pregnancy and menopause may promote spontaneous prolactin decline and anticipate cabergoline discontinuation in women. Surgery and/or radiotherapy are indicated in case of resistance to cabergoline not overcome by the increase in drug dose up to the maximally tolerated or the patient's personal choice of surgery. The evidence of resistance to cabergoline in invasive and proliferative tumors may indicate biological aggressiveness, thus requiring alternative therapeutic approaches mainly based on temozolomide use as monotherapy or combined with radiotherapy. In uncontrolled patients, new medical approaches (alternative hormonal treatments, cytotoxic drugs, peptide receptor radionuclide therapy, mTOR/Akt inhibitors, tyrosine kinase inhibitors, or immunotherapy) may be offered but the experience collected to date is still very scant. This article reviews different facets of prolactinomas and discusses approaches to the condition in more common clinical situations.
Topics: Male; Pregnancy; Humans; Female; Prolactinoma; Cabergoline; Prolactin; Ergolines; Pituitary Neoplasms; Dopamine Agonists; Hypogonadism
PubMed: 36974474
DOI: 10.1210/clinem/dgad174 -
Medicina (Kaunas, Lithuania) Aug 2022Prolactinomas are the commonest form of pituitary neuroendocrine tumor (PitNET), representing approximately half of such tumors. Dopamine agonists (DAs) have... (Review)
Review
Prolactinomas are the commonest form of pituitary neuroendocrine tumor (PitNET), representing approximately half of such tumors. Dopamine agonists (DAs) have traditionally been the primary treatment for the majority of prolactinomas, with surgery considered the second line. The aim of this review is to examine the historical and modern management of prolactinomas, including medical therapy with DAs, transsphenoidal surgery, and multimodality therapy for the treatment of aggressive prolactinomas and metastatic PitNETs, with an emphasis on the efficacy, safety, and future directions of current therapeutic modalities. DAs have been the mainstay of prolactinoma management since the 1970s, initially with bromocriptine and more recently with cabergoline. Cabergoline normalizes prolactin in up to 85% of patients and causes tumor shrinkage in up to 80%. Primary surgical resection of microprolactinomas and enclosed macroprolactinomas performed by experienced pituitary neurosurgeons have similar remission rates to cabergoline. Aggressive prolactinomas and metastatic PitNETS should receive multimodality therapy including high dose cabergoline, surgery, radiation therapy (preferably using stereotactic radiosurgery where suitable), and temozolomide. DAs remain a reliable mode of therapy for most prolactinomas but results from transsphenoidal surgery in expert hands have improved considerably over the last one to two decades. Surgery should be strongly considered as primary therapy, particularly in the setting of microprolactinomas, non-invasive macroprolactinomas, or prior to attempting pregnancy, and has an important role in the management of DA resistant and aggressive prolactinomas.
Topics: Bromocriptine; Cabergoline; Dopamine Agonists; Female; Humans; Pituitary Neoplasms; Pregnancy; Prolactinoma; Treatment Outcome
PubMed: 36013562
DOI: 10.3390/medicina58081095 -
Neuroendocrinology 2019
Topics: Humans; Hyperprolactinemia; Pituitary Neoplasms; Prolactinoma
PubMed: 31167201
DOI: 10.1159/000500723 -
Neuroendocrinology 2019Prolactin-secreting adenomas (prolactinomas) are the most common secreting adenomas of the pituitary. Microprolactinomas (diameter <10 mm) are frequently diagnosed in... (Review)
Review
Prolactin-secreting adenomas (prolactinomas) are the most common secreting adenomas of the pituitary. Microprolactinomas (diameter <10 mm) are frequently diagnosed in women, whereas macroprolactinomas (maximum diameter ≥10 mm) are generally seen in men. Most macroprolactinomas measure between 10 and 40 mm. Giant prolactinomas, measuring >40 mm, are rare, accounting for only 1-5% of all prolactinomas. Although generally benign, giant prolactinomas are aggressive and invasive, extending into the suprasellar region and also involving the cavernous sinuses. The optic chiasm is frequently involved, which leads to visual damage, and patients occasionally suffer from ophthalmoplegia. Long-term (usually lifetime) therapy with high-dose dopamine agonists (cabergoline or bromocriptine), together with pituitary surgery in some cases and radiotherapy if required, can achieve biochemical remission, tumor control, and clinical improvement in most patients.
Topics: Female; Humans; Male; Pituitary Neoplasms; Prolactinoma
PubMed: 30404098
DOI: 10.1159/000495184 -
Pituitary Jun 2023A small subset of lactotroph adenomas is resistant to dopamine agonists (DA) and can also demonstrate aggressive or even malignant behavior. The implicated mechanisms... (Review)
Review
A small subset of lactotroph adenomas is resistant to dopamine agonists (DA) and can also demonstrate aggressive or even malignant behavior. The implicated mechanisms are not clearly defined. Management can be challenging and requires a multidisciplinary approach. In DA resistant prolactinomas, switching to another DA could be the first option to consider. Further strategies include surgery and radiotherapy used alone or in combination. In cases of aggressive or malignant prolactinomas, temozolomide could be offered. Immune checkpoint inhibitors have been also recently proposed as an alternative approach. The place of other treatments (e.g., metformin, selective estrogen modulators, somatostatin analogues, tyrosine kinase inhibitors, inhibitors of mammalian target of rapamycin and peptide radio-receptor therapy) remains to be carefully assessed.
Topics: Humans; Prolactinoma; Pituitary Neoplasms; Dopamine Agonists; Temozolomide; Somatostatin
PubMed: 36928728
DOI: 10.1007/s11102-023-01305-8 -
Endocrine, Metabolic & Immune Disorders... 2023This guideline (GL) is aimed at providing a reference for the management of prolactin (PRL)-secreting pituitary adenoma in adults. However, pregnancy is not considered.
INTRODUCTION
This guideline (GL) is aimed at providing a reference for the management of prolactin (PRL)-secreting pituitary adenoma in adults. However, pregnancy is not considered.
METHODS
This GL has been developed following the methods described in the Manual of the Italian National Guideline System. For each question, the panel appointed by Associazione Medici Endocrinologi (AME) has identified potentially relevant outcomes, which have then been rated for their impact on therapeutic choices. Only outcomes classified as "critical" and "important" have been considered in the systematic review of evidence and only those classified as "critical" have been considered in the formulation of recommendations.
RESULTS
The present GL provides recommendations regarding the role of pharmacological and neurosurgical treatment in the management of prolactinomas. We recommend cabergoline (Cab) vs. bromocriptine (Br) as the firstchoice pharmacological treatment to be employed at the minimal effective dose capable of achieving the regression of the clinical picture. We suggest that medication and surgery are offered as suitable alternative first-line treatments to patients with non-invasive PRL-secreting adenoma, regardless of size. We suggest Br as an alternative drug in patients who are intolerant to Cab and are not candidates for surgery. We recommend pituitary tumor resection in patients 1) without any significant neuro-ophthalmologic improvement within two weeks from the start of Cab, 2) who are resistant or do not tolerate Cab or other dopamine-agonist drugs (DA), 3) who escape from previous efficacy of DA, and 4) who are unwilling to undergo a chronic DA treatment. We recommend that patients with progressive disease notwithstanding previous tumor resection and ongoing DA should be managed by a multidisciplinary team with specific expertise in pituitary diseases using a multimodal approach that includes repeated surgery, radiotherapy, DA, and possibly, the use of temozolomide.
CONCLUSION
The present GL is directed to endocrinologists, neurosurgeons, and gynecologists working in hospitals, in territorial services or private practice, and to general practitioners and patients.
Topics: Adult; Humans; Bromocriptine; Cabergoline; Dopamine Agonists; Ergolines; Pituitary Neoplasms; Prolactin; Prolactinoma
PubMed: 37171003
DOI: 10.2174/1871530323666230511104045 -
Nature Communications May 2020The genetic basis and corresponding clinical relevance of prolactinomas remain poorly understood. Here, we perform whole genome sequencing (WGS) on 21 patients with...
The genetic basis and corresponding clinical relevance of prolactinomas remain poorly understood. Here, we perform whole genome sequencing (WGS) on 21 patients with prolactinomas to detect somatic mutations and then validate the mutations with digital polymerase chain reaction (PCR) analysis of tissue samples from 227 prolactinomas. We identify the same hotspot somatic mutation in splicing factor 3 subunit B1 (SF3B1) in 19.8% of prolactinomas. These patients with mutant prolactinomas display higher prolactin (PRL) levels (p = 0.02) and shorter progression-free survival (PFS) (p = 0.02) compared to patients without the mutation. Moreover, we identify that the SF3B1 mutation causes aberrant splicing of estrogen related receptor gamma (ESRRG), which results in stronger binding of pituitary-specific positive transcription factor 1 (Pit-1), leading to excessive PRL secretion. Thus our study validates an important mutation and elucidates a potential mechanism underlying the pathogenesis of prolactinomas that may lead to the development of targeted therapeutics.
Topics: Adult; Female; Humans; Male; Mutation; Phosphoproteins; Progression-Free Survival; Prolactin; Prolactinoma; RNA Splicing Factors; Receptors, Estrogen; Transcription Factor Pit-1; Young Adult
PubMed: 32427851
DOI: 10.1038/s41467-020-16052-8 -
Neuroendocrinology 2022Dopamine agonists (DAs) are preferred for the treatment of prolactinomas and are usually very effective. Nonetheless, 20-30% of bromocriptine- and approximately 10% of... (Review)
Review
Dopamine agonists (DAs) are preferred for the treatment of prolactinomas and are usually very effective. Nonetheless, 20-30% of bromocriptine- and approximately 10% of cabergoline-treated individuals exhibit resistance to DAs. In addition, the mechanism underlying this phenomenon remains elusive. In this study, we summarize the major findings regarding the role of microRNAs (miRNAs) in the pathogenesis of DA-resistant prolactinoma (DARP). Currently available evidence suggests that miRNAs are usually dysregulated in DARP and that, although controversial, the dysregulated miRNAs target the transforming growth factor (TGF)-β, dopamine 2 receptor (D2R), or estradiol (E2)/estrogen receptor (ER) signaling pathways to mediate the therapeutic effect of DAs. These findings provide new incentives for research on innovative strategies for predicting patients' responsiveness to dopamine therapies and for developing treatment approaches. Unfortunately, recent studies tended to focus exclusively on the differential miRNA expression profiles between DARP and dopamine-sensitive prolactinoma, and no definitive consensus has been reached regarding the role of these miRNAs in the modulation mechanism. Therefore, current and future efforts should be directed toward the exploration of the mechanism underlying the dysregulation of miRNAs as well as of the target proteins that are affected by the dysregulated miRNAs. Furthermore, the modulation of the expression of dysregulated miRNAs, which target the D2R, TGF-β, or E2/ER signaling pathways, might be a promising alternative to treat patients with DARP and improve their prognosis.
Topics: Dopamine; Dopamine Agonists; Drug Resistance, Neoplasm; Humans; MicroRNAs; Pituitary Neoplasms; Prolactinoma
PubMed: 34034260
DOI: 10.1159/000517356 -
Neuroendocrinology 2019Prolactin-secreting tumors (prolactinomas) represent the most common pituitary tumor type, accounting for 47-66% of functional pituitary tumors. Prolactinomas are... (Review)
Review
Prolactin-secreting tumors (prolactinomas) represent the most common pituitary tumor type, accounting for 47-66% of functional pituitary tumors. Prolactinomas are usually benign and controllable tumors as they express abundant levels of dopamine type 2 receptor (D2), and can be treated with dopaminergic drugs, effectively reducing prolactin levels and tumor volume. However, a proportion of prolactinomas exhibit aggressive features (including invasiveness, relevant growth despite adequate dopamine agonist treatment, and recurrence potential) and few may exhibit metastasizing potential (carcinomas). In this context, the clinical, pathological, and molecular definitions of malignant and aggressive prolactinomas remain to be clearly defined, as primary prolactin-secreting carcinomas are similar to aggressive adenomas until the presence of metastases is detected. Indeed, standard molecular and histological analyses do not reflect differences between carcinomas and adenomas at a first glance and have limitations in prediction of the aggressive progression of prolactinomas, wherein the causes underlying the aggressive behavior remain unknown. Herein we present a comprehensive, multidisciplinary review of the most relevant epidemiological, clinical, pathological, genetic, biochemical, and molecular aspects of aggressive and malignant prolactinomas.
Topics: Female; Humans; Male; Pituitary Neoplasms; Prolactinoma
PubMed: 30677777
DOI: 10.1159/000497205