Pituitary lactotroph adenomas resistant to dopamine agonist treatment: histological and immunohistochemical characteristics

Федорова, Наталья Сергеевна; Abrosimov, Alexander; Dzeranova, Larisa; Pigarova, Ekaterina; Дедов, И И

doi:10.17116/patol201880334-39

Cited by 6 publications

(5 citation statements)

References 26 publications

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“…Lu et al found that the preoperative PRL levels in the Ki-67 index >3% group remained significantly higher compared to those in patients with the Ki-67 index <3% group (p < 0.05) (44). Fedorova et al (45) and Zielinski et al (46) confirmed a positive correlation between the Ki-67 index and preoperative prolactin concentration in patients with prolactinoma. Li et al proposed that ethanol altered hypothalamic neurotransmitter levels and stimulated anterior pituitary cell proliferation, which further increased the prolactin level in cells and the secretory output of prolactin (47).…”

Section: Discussionmentioning

confidence: 86%

A Nomogram for Preoperatively Predicting the Ki-67 Index of a Pituitary Tumor: A Retrospective Cohort Study

et al. 2021

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BackgroundThe Ki-67 index is an indicator of proliferation and aggressive behavior in pituitary adenomas (PAs). This study aims to develop and validate a predictive nomogram for forecasting Ki-67 index levels preoperatively in PAs.MethodsA total of 439 patients with PAs underwent PA resection at the Department of Neurosurgery in Jinling Hospital between January 2018 and October 2020; they were enrolled in this retrospective study and were classified randomly into a training cohort (n = 300) and a validation cohort (n = 139). A range of clinical, radiological, and laboratory characteristics were collected. The Ki-67 index was classified into the low Ki-67 index (<3%) and the high Ki-67 index (≥3%). Least absolute shrinkage and selection operator algorithm and uni- and multivariate logistic regression analyses were applied to identify independent risk factors associated with Ki-67. A nomogram was constructed to visualize these risk factors. The receiver operation characteristic curve and calibration curve were computed to evaluate the predictive performance of the nomogram model.ResultsAge, primary-recurrence subtype, maximum dimension, and prolactin were included in the nomogram model. The areas under the curve (AUCs) of the nomogram model were 0.694 in the training cohort and 0.658 in the validation cohort. A well-fitted calibration curve was also generated for the nomogram model. A subgroup analysis revealed stable predictive performance for the nomogram model. A correlation analysis revealed that age (R = −0.23; p < 0.01), maximum dimension (R = 0.17; p < 0.01), and prolactin (R = 0.16; p < 0.01) were all significantly correlated with the Ki-67 index level.ConclusionsAge, primary-recurrence subtype, maximum dimension, and prolactin are independent predictors for the Ki-67 index level. The current study provides a novel and feasible nomogram, which can further assist neurosurgeons to develop better, more individualized treatment strategies for patients with PAs by predicting the Ki-67 index level preoperatively.

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Section: Discussionmentioning

confidence: 86%

A Nomogram for Preoperatively Predicting the Ki-67 Index of a Pituitary Tumor: A Retrospective Cohort Study

et al. 2021

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“…In clinical practice, patients with prolactinomas are administered bromocriptine as the first line of treatment. Once resistance occurs, fulvestrant alone is usually administrated as an alternative therapeutic strategy; however, the response is often unsatisfactory 6 , 7 , 23 , 27 . Fulvestrant is a synthetic estrogen receptor antagonist, fulvestrant binds competitively to estrogen receptors and results in estrogen receptor deformation and decreased estrogen binding.…”

Section: Discussionmentioning

confidence: 99%

“…Prolactinomas are the most predominant type of functional pituitary adenoma, constituting ~40% of total pituitary adenomas globally 4 , 5 . Over the past decades, there have been substantial breakthroughs in the understanding and management of prolactinomas; bromocriptine is the first line treatment for prolactinomas, yet 30% of patients ultimately develop resistance 3 , 6 , 7 . These clinical phenomena highlight an urgent requirement for alternative treatment strategies.…”

Section: Introductionmentioning

confidence: 99%

Estrogen receptor α/prolactin receptor bilateral crosstalk promotes bromocriptine resistance in prolactinomas

Zhang¹,

Yang²,

Zhang³

et al. 2020

Int. J. Med. Sci.

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Prolactinomas are the most common type of functional pituitary adenoma. Although bromocriptine is the preferred first line treatment for prolactinoma, resistance frequently occurs, posing a prominent clinical challenge. Both the prolactin receptor (PRLR) and estrogen receptor α (ERα) serve critical roles in the development and progression of prolactinomas, and whether this interaction between PRLR and ERα contributes to bromocriptine resistance remains to be clarified. In the present study, increased levels of ERα and PRLR protein expression were detected in bromocriptine-resistant prolactinomas and MMQ cells. Prolactin (PRL) and estradiol (E2) were found to exert synergistic effects on prolactinoma cell proliferation. Furthermore, PRL induced the phosphorylation of ERα via the JAK2-PI3K/Akt-MEK/ERK pathway, while estrogen promoted PRLR upregulation via pERα. ERα inhibition abolished E2-induced PRLR upregulation and PRL-induced ERα phosphorylation, and fulvestrant, an ERα inhibitor, restored pituitary adenoma cell sensitivity to bromocriptine by activating JNK-MEK/ERK-p38 MAPK signaling and cyclin D1 downregulation. Collectively, these data suggest that the interaction between the estrogen/ERα and PRL/PRLR pathways may contribute to bromocriptine resistance, and therefore, that combination treatment with fulvestrant and bromocriptine (as opposed to either drug alone) may exert potent antitumor effects on bromocriptine-resistant prolactinomas.

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“…Учитывая высокую встречаемость пролактин-секретирующих аденом, значительный вклад данного заболевания в уменьшение репродуктивного потенциала популяции и снижение качества жизни, решение проблемы гиперпролактинемии является важным аспектом общественного здоровья и позитивного тренда демографической ситуации [ 9 ][ 10 ]. В настоящее время возможности применения альтернативных методов лечения у пациентов, резистентных к агонистам дофамина, ограничены: лучевая терапия малоэффективна [ 11 ][ 12 ], радикальная операция в большинстве случаев невозможна в связи с тенденцией пролактин-секретирующих аденом гипофиза к параселлярному распространению и экспансивному росту [ 6 ]. Таким образом, наиболее перспективным направлением в ведении резистентных пациентов является применение медикаментозной терапии, в том числе — сочетанной и комбинированной.…”

Section: Discussionunclassified

Overcoming therapy resistance in prolactinomas: from perspectives to real clinical practice

Shutova,

Pigarova,

Lepeshkina

et al. 2024

Probl Endokrinol (Mosk)

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Основной метод лечения пролактин-секретирующих аденом гипофиза — терапия агонистами дофамина, в большинстве случаев позволяющая нормализовать уровень пролактина и уменьшить размеры аденомы. Однако значительная часть пациентов — около 20% неудовлетворительно реагируют даже на высокие дозы агонистов дофамина, что обусловлено резистентностью к терапии. Одной из причин развития резистентности к стандартному лечению является наличие ряда фармакодинамических характеристик. Клинические проявления персистирующей гиперпролактинемии обусловлены двумя патологическими факторами: гормональной гиперпродукцией и масс-эффектом аденомы гипофиза. Предотвращение необратимых изменений возможно только при своевременном выявлении резистентности и определении оптимального персонализированного алгоритма лечения. Нами описан клинический случай опухолевой гиперпролактинемии, резистентной к терапии агонистами дофамина. Назначение комбинированного лечения тамоксифеном и агонистами дофамина позволило достичь улучшения состояния здоровья пациентки, нормопролактинемии и уменьшения размеров аденомы гипофиза. Гиперпролактинемия, обусловленная пролактин-секретирующей аденомой гипофиза, и ассоциированные с ней патологические проявления представляют собой значимую проблему, неблагоприятно влияющую на качество жизни отдельного пациента и демографическую ситуацию в целом. Это подчеркивает важность изучения причин и выявления предикторов резистентности. Результаты проводимого исследования, иллюстрированные клиническим примером, представлены в настоящей работе.

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Pituitary lactotroph adenomas resistant to dopamine agonist treatment: histological and immunohistochemical characteristics

Cited by 6 publications

References 26 publications

A Nomogram for Preoperatively Predicting the Ki-67 Index of a Pituitary Tumor: A Retrospective Cohort Study

A Nomogram for Preoperatively Predicting the Ki-67 Index of a Pituitary Tumor: A Retrospective Cohort Study

Estrogen receptor α/prolactin receptor bilateral crosstalk promotes bromocriptine resistance in prolactinomas

Overcoming therapy resistance in prolactinomas: from perspectives to real clinical practice

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