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QJM : Monthly Journal of the... Jun 2024
Topics: Humans; Prolactinoma; Female; Pituitary Neoplasms; Pregnancy; Pregnancy Complications, Neoplastic; Adult; Magnetic Resonance Imaging; Prolactin
PubMed: 38336882
DOI: 10.1093/qjmed/hcae027 -
Problemy Endokrinologii Jan 2024The main treatment option of prolactin-secreting pituitary adenomas is dopamine agonist therapy, which demonstrates prolactin level normalizing and reducing the size of...
The main treatment option of prolactin-secreting pituitary adenomas is dopamine agonist therapy, which demonstrates prolactin level normalizing and reducing the size of an adenoma in the majority of cases. However, significant amount of patients - about 20% - poorly responds even to high doses of dopamine agonists that is explained by the resistance to therapy. The occurrence of pharmacodynamic characteristics is one of the causes responsible for the development of resistance to typical therapy. Clinical manifestations of persistent hyperprolactinemia are due to following pathological factors: hormonal hypersecretion and the mass-effect of pituitary adenoma. Prevention of irreversible changes is possible only with timely detection of resistance and determination of the optimal personalized treatment algorithm.We report a clinical case of dopamine-agonist resistant microprolactinoma. Patient's health stabilisation, normal level of prolactin and reduction in size of adenoma were achieved due to administration of combined treatment with tamoxifen and dopamine agonists. Hyperprolactinaemia occurring because of prolactin-secreting pituitary adenoma and associated adverse effects are significant problem, decreasing quality of life and demographics in general. This underlines the importance of figuring out causes and identifying predictors of the therapy resistance.The results of the study, illustrated by a clinical example, are presented in the present paper.
Topics: Humans; Prolactinoma; Dopamine Agonists; Prolactin; Quality of Life; Pituitary Neoplasms; Hyperprolactinemia; Adenoma
PubMed: 38311996
DOI: 10.14341/probl13351 -
Endocrine Practice : Official Journal... May 2024Cosecreting thyroid stimulating hormone (TSH) or prolactin (PRL) in patients with pituitary growth hormone (GH) adenomas has been rarely reported. Our study aimed to...
OBJECTIVE
Cosecreting thyroid stimulating hormone (TSH) or prolactin (PRL) in patients with pituitary growth hormone (GH) adenomas has been rarely reported. Our study aimed to elucidate their clinical characteristics.
METHODS
We retrospectively collected data of 22 cases of cosecreting GH and TSH pituitary adenomas [(GH+TSH)oma] and 10 cases of cosecreting GH and PRL pituitary adenomas [(GH+PRL)oma] from Beijing Tiantan Hospital, Capital Medical University between January 2009 and January 2023. The clinical manifestation, preoperative hormone levels, imaging features, pathologic characteristics, and biochemical remission rates were compared among 335 patients with solo-secreting GH adenomas (GHoma) and 49 patients with solo-secreting TSH adenoma (TSHoma). Patients with (GH+TSH)oma and (GH+PRL)oma were grouped according to biochemical remission to explore the risk factors leading to biochemical nonremission.
RESULTS
Cosecreting pituitary GH adenomas had various clinical manifestations and a larger tumor volume and were more likely to invade the cavernous sinus bilaterally and compress the optic chiasm. GH and TSH levels were lower in (GH+TSH)oma than in GHoma or TSHoma. Solo part remission was observed both in (GH+TSH)oma and (GH+PRL)oma. Cavernous sinus invasion was an independent risk factor for biochemical nonremission in patients with (GH+TSH)oma and (GH+PRL)oma.
CONCLUSIONS
The clinical manifestation of (GH+TSH)oma and (GH+PRL)oma may be atypical. When screening for pituitary adenomas, a comprehensive evaluation of all pituitary target gland hormones is needed. Cosecreting pituitary GH adenomas are more aggressive and surgery is often unable to completely remove the tumor, requiring pharmacologic or radiological treatment if necessary. Clinicians should give high priority to biochemical remission, although solo part remission may occur.
Topics: Adult; Aged; Female; Humans; Male; Middle Aged; Young Adult; Adenoma; Case-Control Studies; Growth Hormone-Secreting Pituitary Adenoma; Human Growth Hormone; Pituitary Neoplasms; Prolactin; Prolactinoma; Retrospective Studies; Thyrotropin; Child, Preschool; Child; Adolescent
PubMed: 38307455
DOI: 10.1016/j.eprac.2024.01.013 -
AACE Clinical Case Reports 2024To report a case of adenomyosis in a woman with hyperprolactinemia which resolved after initiation of dopamine agonist therapy.
BACKGROUND/OBJECTIVE
To report a case of adenomyosis in a woman with hyperprolactinemia which resolved after initiation of dopamine agonist therapy.
CASE REPORT
A 35-year-old woman with a history of Graves' disease was referred for evaluation of hyperthyroidism in March 2020. She was started on methimazole and thyroid function normalized. The patient also had a history of a pituitary microadenoma and was previously treated with cabergoline which was stopped after 12 months as she became pregnant.In July 2020, the patient began to have polymenorrhea. Hyperprolactinemia was thought to be an unlikely cause as it most often causes hypogonadotropic hypogonadism with amenorrhea. A pelvic ultrasound demonstrated a bulky uterus with adenomyosis. Gynecology recommended treating adenomyosis by lowering her prolactin levels. She was started on cabergoline 0.25 mg weekly in October 2021. Within 2 months of initiation of cabergoline, she had resolution of symptoms and radiological resolution of adenomyosis.
DISCUSSION
Prolactin has been implicated in the pathogenesis of adenomyosis, endometriosis and leiomyomas suggesting that a decrease in prolactin levels may suppress these lesions. The pathogenesis of adenomyosis has been related to direct prolactin effects in the promotion of gland/cell proliferation and function.
CONCLUSION
We conclude that prolonged elevation in prolactin may result in the development of adenomyosis and subsequent prolonged abnormal uterine bleeding. Dopamine agonists, like cabergoline, inhibit the synthesis and secretion of prolactin from the pituitary gland and may have a role in the management of adenomyosis in patients with hyperprolactinemia.
PubMed: 38303768
DOI: 10.1016/j.aace.2023.11.002 -
Operative Neurosurgery (Hagerstown, Md.) Feb 2024Invasive prolactinomas often require multimodal management including medical and surgical interventions. Here, we present the case of a 34-year-old man with a history of...
Invasive prolactinomas often require multimodal management including medical and surgical interventions. Here, we present the case of a 34-year-old man with a history of progressive visual disturbances. MRI unveiled a sella lesion with suprasellar and retrosellar extensions. Elevated prolactin levels (6125 ng/mL) confirmed the diagnosis of prolactinoma, leading to initiation of medical treatment, with gradual escalation to maximum dosing. The patient achieved only partial hormonal response and incomplete improvement of symptoms, and therefore, surgical intervention was pursued with objective of maximum safe resection. The patient consented to the procedure. An endonasal endoscopic approach was selected. Surgical procedures encompassed transsellar, transtuberculum, and transplanum approaches, extended laterally to expose the right parasellar carotid and the anterior wall of the cavernous sinus. Subsequent steps involved opening the sellar and suprasellar dura mater, anterior wall of the cavernous sinus, and transcavernous hemipituitary transposition for access to the retrosellar region.1-5 Debulking of the lesion was performed, followed by dissection of the retrosellar space and resection of tumor component within the interpeduncular cistern. Reconstruction employed dura substitute and vascularized nasoseptal flap. Histopathology confirmed diagnosis of prolactinoma. Postoperative MRI findings and significantly improved prolactin levels (50 ng/mL) were compatible with near total resection. The patient's postoperative course was uneventful, resulting in discharge on the second postoperative day. The patient was additionally started on cabergoline 0.5 mg 2x/week to achieve hormonal control. This case demonstrates the application of surgical anatomy and its translation in modern surgical techniques that allow improved resection of such complex tumors while ensuring optimal clinical outcomes.
PubMed: 38299803
DOI: 10.1227/ons.0000000000001075 -
Drug Resistance Updates : Reviews and... Mar 2024The treatment of dopamine agonists (DA) resistant prolactinomas remains a formidable challenge, as the mechanism of resistance is still unclear, and there are currently...
BACKGROUND
The treatment of dopamine agonists (DA) resistant prolactinomas remains a formidable challenge, as the mechanism of resistance is still unclear, and there are currently no viable alternative drug therapies available. This study seeks to investigate the mechanism of DA resistance in prolactinomas and identify new potentially effective drugs.
METHODS
To explore the mechanism of DA resistance in prolactinomas, this study conducted transcriptome sequencing analysis on 27 cases of DA-resistant prolactinomas and 10 cases of sensitive prolactinomas. In addition, single-cell sequencing analysis was performed on 3 cases of DA-resistant prolactinomas and 3 cases of sensitive prolactinomas. Furthermore, to screen for potential therapeutic drugs, the study successfully established an organoids model for DA-resistant prolactinomas and screened 180 small molecule compounds using 8 organoids. The efficacy of the identified drugs was verified through various assays, including CCK-8, colony formation, CTG, and flow cytometry, and their mechanisms of action were confirmed through WB and IHC. The effectiveness of the identified drugs was evaluated both in vitro and in vivo.
RESULTS
The results of transcriptome sequencing and single-cell sequencing analyses showed that DA resistance in prolactinomas is associated with the upregulation of the Focal Adhesion (FA) signaling pathway. Additionally, immunohistochemical validation revealed that FAK and Paxillin were significantly upregulated in DA-resistant prolactinomas. Screening of 180 small molecule compounds using 8 organoids identified Genistein as a potentially effective drug for DA-resistant prolactinomas. Experimental validation demonstrated that Genistein inhibited the proliferation of pituitary tumor cell lines and organoids and promoted apoptosis in pituitary tumor cells. Moreover, both the cell sequencing results and WB validation results of the drug-treated cells indicated that Genistein exerts its anti-tumor effect by inhibiting the FA pathway. In vivo, experiments also showed that Genistein can inhibit subcutaneous tumor formation.
CONCLUSION
DA resistance in prolactinomas is associated with upregulation of the Focal Adhesion (FA) signaling pathway, and Genistein can exert its anti-tumor effect by inhibiting the expression of the FA pathway.
Topics: Humans; Pituitary Neoplasms; Dopamine Agonists; Prolactinoma; Prolactin; Genistein; Neuroendocrine Tumors; Drug Resistance, Neoplasm
PubMed: 38277755
DOI: 10.1016/j.drup.2024.101056 -
Journal of Neurological Surgery. Part... Feb 2024Pituitary tumor treatment is hampered by the relative rarity of the disease, absence of a multicenter collaborative platform, and limited translational-clinical...
Pituitary tumor treatment is hampered by the relative rarity of the disease, absence of a multicenter collaborative platform, and limited translational-clinical research partnerships. Prior studies offer limited insight into the formation of a multicenter consortium. The authors describe the establishment of a multicenter research initiative, Registry of Adenomas of the Pituitary and Related Disorders (RAPID), to encourage quality improvement and research, promote scholarship, and apply innovative solutions in outcomes research. The challenges encountered during the formation of other research registries were reviewed with those lessons applied to the development of RAPID. RAPID was formed by 11 academic U.S. pituitary centers. A Steering Committee, bylaws, data coordination center, and leadership team have been established. Clinical modules with standardized data fields for nonfunctioning adenoma, prolactinoma, acromegaly, Cushing's disease, craniopharyngioma, and Rathke's cleft cyst were created using a Health Insurance Portability and Accountability Act-compliant cloud-based platform. Currently, RAPID has received institutional review board approval at all centers, compiled retrospective data and agreements from most centers, and begun prospective data collection at one site. Existing institutional databases are being mapped to one central repository. The RAPID consortium has laid the foundation for a multicenter collaboration to facilitate pituitary tumor and surgical research. We sought to share our experiences so that other groups also contemplating this approach may benefit. Future studies may include outcomes benchmarking, clinically annotated biobank tissue, multicenter outcomes studies, prospective intervention studies, translational research, and health economics studies focused on value-based care questions.
PubMed: 38274483
DOI: 10.1055/a-1978-9380 -
Nature Reviews. Endocrinology May 2024
Topics: Humans; Prolactinoma; Pituitary Neoplasms; Prolactin
PubMed: 38253862
DOI: 10.1038/s41574-024-00954-4 -
Nature Reviews. Endocrinology May 2024
Topics: Humans; Prolactinoma; Pituitary Neoplasms; Prolactin
PubMed: 38253861
DOI: 10.1038/s41574-024-00953-5 -
Diagnostics (Basel, Switzerland) Jan 2024Plurihormonal pituitary neuroendocrine tumors (PitNETs) are rare forms of tumors that express more than one hormone. The most common association is between growth...
Plurihormonal pituitary neuroendocrine tumors (PitNETs) are rare forms of tumors that express more than one hormone. The most common association is between growth hormone (GH) and prolactin (PRL), but other unusual combinations have been reported, such as GH and ACTH. Usually, the clinical dominance in these cases is related to GH hypersecretion. In these cases, immunohistochemistry (IHC) of transcription factors (TFs) is very useful for an accurate diagnosis. We included 42 patients diagnosed with pituitary neuroendocrine tumors (PitNETs): 37 patients with a confirmed diagnosis of acromegaly, and 5 patients with prolactinomas. All patients underwent transsphenoidal surgical intervention. We correlated the immunohistochemical features of plurihormonal PitNETs with clinical, hormonal, and imaging data. Tumor specimens were histologically and immunohistochemically examined. Based on the 2022 WHO classification, using IHC, 13 patients exhibited positive staining for more than one hormone, while unusual combinations like GH + ACTH and PRL + ACTH were also identified in other cases. Unusual cell combinations that produce hormones unrelated histogenetically, biochemically, or through regulatory mechanisms can appear and may display aggressive behavior, persistent disease, and high recurrence. We have not identified a clear correlation with the prognosis of these rare PitNETs.
PubMed: 38248047
DOI: 10.3390/diagnostics14020170