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Journal of Investigative Medicine : the... Aug 2023The therapeutic response heterogeneity in acromegaly persists, despite the medical-surgical advances of recent years. Thus, personalized medicine implementation, which... (Review)
Review
The therapeutic response heterogeneity in acromegaly persists, despite the medical-surgical advances of recent years. Thus, personalized medicine implementation, which focuses on each patient, is justified. Metabolomics would decipher the molecular mechanisms underlying the therapeutic response heterogeneity. Identification of altered metabolic pathways would open new horizons in the therapeutic management of acromegaly. This research aimed to evaluate the metabolomic profile in acromegaly and metabolomics' contributions to understanding disease pathogenesis. A systematic review was carried out by querying four electronic databases and evaluating patients with acromegaly through metabolomic techniques. In all, 21 studies containing 362 patients were eligible. Choline, the ubiquitous metabolite identified in growth hormone (GH)-secreting pituitary adenomas (Pas) by in vivo magnetic resonance spectroscopy (MRS), negatively correlated with somatostatin receptors type 2 expression and positively correlated with magnetic resonance imaging T2 signal and Ki-67 index. Moreover, elevated choline and choline/creatine ratio differentiated between sparsely and densely granulated GH-secreting PAs. MRS detected low hepatic lipid content in active acromegaly, which increased after disease control. The panel of metabolites of acromegaly deciphered by mass spectrometry (MS)-based techniques mainly included amino acids (especially branched-chain amino acids and taurine), glyceric acid, and lipids. The most altered pathways in acromegaly were the metabolism of glucose (particularly the downregulation of the pentose phosphate pathway), linoleic acid, sphingolipids, glycerophospholipids, arginine/proline, and taurine/hypotaurine. Matrix-assisted laser desorption/ionization coupled with MS imaging confirmed the functional nature of GH-secreting PAs and accurately discriminated PAs from healthy pituitary tissue.
Topics: Humans; Acromegaly; Growth Hormone-Secreting Pituitary Adenoma; Magnetic Resonance Imaging; Metabolomics; Adenoma
PubMed: 37139720
DOI: 10.1177/10815589231169452 -
Pituitary May 2024This systematic review aims to examine the latest research findings and assess the impact of COVID-19 vaccination on the pituitary gland. (Review)
Review
PURPOSE
This systematic review aims to examine the latest research findings and assess the impact of COVID-19 vaccination on the pituitary gland.
METHOD
PubMed and Tripdatabase were searched from January 1st, 2020 to February 12th, 2024. Case reports, case series and reviews related to post COVID-19 vaccination pituitary disease were included. Eligible articles were tabulated and analysed in the attempt to provide an overview on the epidemiology, clinical presentation, imaging, treatment, outcomes and pathophysiological background of post COVID-19 vaccination pituitary disease.
RESULTS
Among the 23 case reports included in this review, post COVID-19 vaccination hypophysitis was reported in 9 patients, pituitary apoplexy (PA) in 6 cases, SIADH in 5 cases and Isolated ACTH deficiency in 2 cases. Additionally, precipitating adrenal crisis was registered in 7 patients and pituitary tumor enlargement in 1 patient after receiving COVID-19 vaccination.
CONCLUSION
Despite the rarity of these events, our research findings suggest an association between COVID-19 vaccination and the subsequent development of pituitary diseases. The most common manifestations include hypophysitis with ADH deficiency, PA and SIADH, with symptoms typically emerging shortly after vaccine administration. Potential pathogenetic mechanisms include molecular mimicry, vaccine adjuvants and vaccine-induced thrombotic thrombocytopenia (VITT), with the presence of ACE2 receptors in the hypothalamus-pituitary system contributing to the process. These findings can aid in diagnostic and treatment decisions for patients presenting with these syndromes. Nevertheless, given the rarity of these events, safety and efficacy of the currently available COVID-19 vaccines remain robust and we strongly advocate continuing pursuing vaccination efforts.
PubMed: 38761322
DOI: 10.1007/s11102-024-01402-2 -
Anti-cancer Drugs Jan 2022To date, there are no standardized systemic treatment options for patients with metastatic pituitary carcinoma progressed to chemo and radiation therapy....
To date, there are no standardized systemic treatment options for patients with metastatic pituitary carcinoma progressed to chemo and radiation therapy. Immune-checkpoint inhibitors (ICIs) have been successfully assessed in other solid malignancies and could be a concrete hope for these patients. We performed a critical review of the literature aimed to evaluate studies assessing ICIs in pituitary malignancies. We also conducted research about published translational data assessing immune-contexture in these malignancies. Some preliminary reports reported a successful administration of pembrolizumab or the combination between nivolumab and ipilimumab in patients with metastatic ACTH-secreting pituitary carcinomas. Translational data suggest that adenomas secreting growth hormone and ACTH have a suppressed immune-microenvironment, which could be more likely to benefit from ICIs. Immune-checkpoint inhibitors can be an effective treatment in patients with pituitary carcinoma and maybe also recurrent adenoma. Tumors secreting growth hormone and ACTH are more likely to benefit from ICIs due to a different immune-microenvironment.
Topics: Adrenocorticotropic Hormone; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Growth Hormone; Humans; Immune Checkpoint Inhibitors; Ipilimumab; Neoplasm Metastasis; Nivolumab; Pituitary Neoplasms; Tumor Microenvironment
PubMed: 34348358
DOI: 10.1097/CAD.0000000000001157 -
Pituitary Jun 2022To evaluate the association between acromegaly and pregnancy in terms of disease activity, maternal and fetal outcomes. (Meta-Analysis)
Meta-Analysis
PURPOSE
To evaluate the association between acromegaly and pregnancy in terms of disease activity, maternal and fetal outcomes.
METHODS
This systematic review was conducted according to the Joanna Briggs Institute methodology for systematic reviews of etiology and risk. We focused on observational studies that included pregnant women with acromegaly. The outcomes were acromegaly activity, preterm birth, gestational diabetes, hypertension, eclampsia/preeclampsia, miscarriage, perinatal mortality, low birthweight, small for gestational age, and congenital malformations. Embase, Medline, LILACS, and CENTRAL were our source databases. To perform proportional meta-analyses, we used Stata Statistical Software 17.
RESULTS
Nineteen studies were included encompassing a total of 273 pregnancies in 211 women with acromegaly. The overall frequency of control of acromegaly during pregnancy was 62%, and of tumor growth was 9%. No fetal or maternal deaths were reported. The overall frequency of worsening of previous diabetes or development of gestational diabetes was 9%, and of previous hypertension or preeclampsia/eclampsia was 6%. The overall frequency of premature labor was 9% [from 17 studies of 263 pregnancies; 95% confidence interval (CI), 5-13%]; of spontaneous miscarriage was 4% (from 19 studies of 273 pregnancies; 95% CI, 2-11%); of small for gestational age was 5% (from 15 studies of 216 newborns; 95% CI, 3-9%); and of congenital malformations was 1% (from 18 studies of 240 newborns; 95% CI, 0-7%).
CONCLUSION
Pregnancy in women with acromegaly is frequently associated with disease control and is safe in relation to fetal and maternal outcomes, as in women without acromegaly.
Topics: Abortion, Spontaneous; Acromegaly; Diabetes, Gestational; Eclampsia; Female; Humans; Hypertension; Infant, Newborn; Pre-Eclampsia; Pregnancy; Pregnancy Outcome; Premature Birth
PubMed: 35098440
DOI: 10.1007/s11102-022-01208-0 -
Endocrine-related Cancer May 2022Once temozolomide has failed, there is no recommended treatment option for pituitary carcinomas and aggressive pituitary tumors. Immune-checkpoint inhibitors (ICIs)...
Once temozolomide has failed, there is no recommended treatment option for pituitary carcinomas and aggressive pituitary tumors. Immune-checkpoint inhibitors (ICIs) represent the most recent therapeutic avenue, having raised hope with the publication of the first successful case in 2018. Here, we present an overview of immunotherapy in pituitary carcinomas and aggressive pituitary tumors, starting with the rationale for using ICIs and the implications of tumor-infiltrating lymphocytes in anterior pituitary tumors, followed by a systematic review of all published cases, analyzing both treatment response and potential predictors of response and finishing with research and clinical perspectives. Seven corticotroph and four lactotroph tumors have been so far treated with ICIs. Corticotroph tumors showed radiological partial response in 57% of cases, followed by stable disease in 29% of cases, which was accompanied by biochemical partial or complete response in 83% of cases. Half of lactotroph tumors showed radiological complete or partial response, accompanied by biochemical complete response in 33% of the cases. In the case of a dissociate response, continuation of immunotherapy combined with local treatment represents a good option. At this time, a high tumor mutational burden appears to be the most promising predictive marker of response. MMR deficiency does not guarantee a response. Negative PD-L1 staining should not preclude ICIs administration. Therefore, ICIs are a promising option after temozolomide failure. This review highlights key clinical aspects that can already be implemented into practice and also discusses tumor biology concepts and perspectives expected to improve immunotherapy outcomes.
Topics: Carcinoma; Humans; Immune Checkpoint Inhibitors; Immunotherapy; Pituitary Neoplasms; Temozolomide
PubMed: 35521777
DOI: 10.1530/ERC-22-0037 -
American Journal of Otolaryngology 2022The larynx is the most common site of localized head and neck amyloidosis. Our study aimed to review the clinical features, treatments, and outcomes associated with... (Review)
Review
OBJECTIVE
The larynx is the most common site of localized head and neck amyloidosis. Our study aimed to review the clinical features, treatments, and outcomes associated with localized laryngeal amyloidosis (LA). We also compared these features between two different time periods to evaluate the evolution of LA management.
METHODS
A literature search using PubMed, CINAHL, Embase, and Cochrane Library identified cases of LA published between 1891 and 2021. Biopsy-proven cases of localized LA were included. Non-English studies, animal studies, and reviews were excluded.
RESULTS
282 patients (1891-1999: 142 patients, 2000-2021: 140 patients) from 129 studies were included. Results are reported as 1891-2000 vs. 2000-2021: Mean age was 48.5 years (range, 8-90 years) vs. 46.0 years (range, 9-84 years). The most common presenting symptoms were dysphonia (n = 30, 95 % vs. n = 127, 96 %) and difficulty breathing (n = 37, 27 % vs. n = 35, 27 %). A total of 62 (44 %) vs. 46 (33 %) lesions were found in the true vocal folds and 35 (25 %) vs. 59 (42 %) were found in the false vocal folds. 133 (94 %) vs. 137 (98 %) patients underwent surgical interventions to investigate and/or treat LA. Recurrent LA was reported in 27 (19 %) vs. 33 (24 %) patients with a mean time to recurrence of 25.4 months (range, 0.3-132 months) vs. 34.5 months (range, 0.8-144 months). Of cases reporting survival rate, 104 (97 %) vs. 107 (99 %) were alive at source study endpoints.
CONCLUSION
LA typically exhibits an indolent course; therefore, early intervention may address longstanding symptoms. Recurrent disease poses a clinical challenge in patients with LA.
Topics: Amyloidosis; Hoarseness; Humans; Laryngeal Diseases; Larynx; Vocal Cords
PubMed: 35917657
DOI: 10.1016/j.amjoto.2022.103550 -
Journal of Child and Adolescent... Sep 2022Antipsychotic-related prolactin changes may expose children and adolescents to severe adverse reactions (ARs) related to pubertal development and growth. We therefore... (Meta-Analysis)
Meta-Analysis Review
Antipsychotic-related prolactin changes may expose children and adolescents to severe adverse reactions (ARs) related to pubertal development and growth. We therefore aimed to assess the effects of antipsychotics on prolactin levels and associated somatic ARs in children and adolescents. We systematically searched PubMed and CENTRAL for placebo-controlled randomized trials of antipsychotics in children and adolescents aged ≤18 years, reporting prolactin levels and related ARs. We conducted a random-effect meta-analysis and assessed risk of bias version 2 (ROB2). Thirty-two randomized controlled trials with an average trial duration of 6 weeks, covering 4643 participants with an average age of 13 years and a male majority of 65.3%. Risk of bias across domains was low or unclear. The following antipsychotic compounds: aripiprazole ( = 810), asenapine ( = 506), lurasidone ( = 314), olanzapine ( = 179), paliperidone ( = 149), quetiapine ( = 381), risperidone ( = 609), and ziprasidone ( = 16) were compared with placebo ( = 1658). Compared with placebo, statistically significant higher prolactin increase occurred with risperidone (mean difference [MD] = 28.24 ng/mL), paliperidone (20.98 ng/mL), and olanzapine (11.34 ng/mL). Aripiprazole significantly decreased prolactin (MD = -4.91 ng/mL), whereas quetiapine, lurasidone, and asenapine were not associated with significantly different prolactin levels than placebo. Our results on ziprasidone are based on a single study, making it insufficient to draw strong conclusions. On average, 20.8% of patients treated with antipsychotic developed levels of prolactin that were too high (hyperprolactinemia), whereas only 1.03% of patients reported prolactin-related ARs. Data were highly limited for long-term effects. In children and adolescents, risperidone, paliperidone, and olanzapine are associated with significant prolactin increase, whereas aripiprazole is associated with significant decrease. Despite the significant changes in prolactin level, few ARs were reported. Study protocol on PROSPERO: CRD42018116451.
Topics: Adolescent; Antipsychotic Agents; Aripiprazole; Child; Dibenzocycloheptenes; Humans; Hyperprolactinemia; Lurasidone Hydrochloride; Male; Olanzapine; Paliperidone Palmitate; Piperazines; Prolactin; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Risperidone; Schizophrenia; Thiazoles
PubMed: 36074098
DOI: 10.1089/cap.2021.0140 -
World Neurosurgery Jun 2022In this systematic review and meta-analysis, we review the literature regarding patients with Cushing's disease (CD) with negative or inconclusive magnetic resonance... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
In this systematic review and meta-analysis, we review the literature regarding patients with Cushing's disease (CD) with negative or inconclusive magnetic resonance imaging (MRI).
METHODS
A quantitative systematic review was performed. Article selection was performed by searching MEDLINE (using PubMed), EMBASE, and Cochrane electronic bibliographic databases.
RESULTS
28 articles described surgical management of inconclusive MRI or MRI-negative CD. A total of 858 patients underwent surgery for their Cushing adenoma. Different types of surgery, including endoscopic endonasal transsphenoidal surgery (EETS) (190 cases) and microscopic endonasal transsphenoidal surgery (METS) (488 cases), were performed on patients with MRI-negative CD. 7 studies, which included 164 patients, did not describe any surgery. EETS and METS are conducted to achieve selective adenomectomy (231 cases), partial adenomectomy (80 cases), total adenomectomy (13 cases), hemihypophysectomy (15 cases), or enlarged adenomectomy (48 cases). Based on available data on these studies, the remission rate, persistence rate, and recurrence rate after different types of surgeries on patients with MRI-negative CD were 72.97%, 27.03%, and 12.05%, respectively. There was no statistically significant difference between EETS and METS in the subanalysis regarding recurrence rate, remission rate, and persistence rate. However, the recurrence rate in the METS group is almost 3 times higher than in the EETS group.
CONCLUSIONS
Surgery has a good prognosis in patients with MRI-negative CD in terms of remission, and EETS has a lower rate of disease recurrence than METS; therefore, EETS seems to be the potential recommended treatment technique, while to confirm the therapeutic method of choice, further investigations should be done.
Topics: Adenoma; Humans; Magnetic Resonance Imaging; Neoplasm Recurrence, Local; Pituitary ACTH Hypersecretion; Pituitary Neoplasms; Retrospective Studies; Treatment Outcome
PubMed: 35338018
DOI: 10.1016/j.wneu.2022.03.076 -
Acta Endocrinologica (Bucharest,... 2023Pituitary adenomas are benign tumors, usually found in men in their 3 and 5 decades of life, representing 10-15% of all intracranial tumors. The clinical manifestations...
CONTEXT
Pituitary adenomas are benign tumors, usually found in men in their 3 and 5 decades of life, representing 10-15% of all intracranial tumors. The clinical manifestations include important endocrinological disturbances and visual impairment.
OBJECTIVE
This study aimed to determine the most suitable neurosurgical approach regarding the dimensions, extensions and invasiveness of tumor extensions.
DESIGN
This was a systematic review of the literature from 2002-2022, focused on clinical outcome, especially endocrinological state according to the surgical approach.
SUBJECTS AND METHODS
We performed an advanced search on Web of Science and PubMed databases on October 10, 2022. The literature showed 300 studies in the last 20 years, and after we applied the inclusion and exclusion criteria's, 19 studies were fully read and analyzed.
RESULTS
Postoperative complications were reviewed in each surgical approach group, including visual impairment, new endocrinological disturbances, diabetes insipidus and cerebrospinal fluid leakage. Analyze of the endocrinological findings did not determined differences in transcranial groups from transsphenoidal groups. Overall complications were identified in the transcranial cohorts, while cerebrospinal fluid leakage still represent the main problem in transsphenoidal groups. The majority of studies found included extended endoscopic transsphenoidal approach, which shows results of great potential.
CONCLUSIONS
For the surgical treatment of pituitary adenoma, transsphenoidal procedure with or without extended approaches is preferred, but they're cases when a craniotomy is mandatory for a feasible gross tumor resection. Combined "above and below" simultaneous procedure or a two-staged intervention is recommended for giant pituitary adenoma, to maximize tumor resection and lower the risk of cerebrospinal fluid leakage.
PubMed: 37908878
DOI: 10.4183/aeb.2023.228 -
Pituitary Oct 2023Pituitary carcinomas are a rare entity that respond poorly to multimodal therapy. Patients follow a variable disease course that remains ill-defined.
PURPOSE
Pituitary carcinomas are a rare entity that respond poorly to multimodal therapy. Patients follow a variable disease course that remains ill-defined.
METHODS
We present an institutional case series of patients treated for pituitary carcinomas over a 30-year period from 1992 to 2022. A systematic review was conducted to identify prior case series of patients with pituitary carcinomas.
RESULTS
Fourteen patients with a mean age at pituitary carcinoma diagnosis of 52.5 years (standard deviation [SD] 19.4) met inclusion criteria. All 14 patients had tumor subtypes confirmed by immunohistochemistry and hormone testing, with the most common being ACTH-producing pituitary adenomas (n = 12). Patients had a median progression-free survival (PFS) of 1.4 years (range 0.7-10.0) and a median overall survival (OS) of 8.4 years (range 2.3-24.0) from pituitary adenoma diagnosis. Median PFS and OS were 0.6 years (range 0.0-2.2) and 1.5 years (range 0.1-9.6) respectively upon development of metastases. Most patients (n = 12) had locally invasive disease to the cavernous sinus, dorsum sellae dura, or sphenoid sinus prior to metastasis. Common sites of metastasis included the central nervous system, liver, lung, and bone. In a pooled analysis including additional cases from the literature, treatment of metastases with chemotherapy or a combination of radiation therapy and chemotherapy significantly prolonged PFS (p = 0.02), while failing to significantly improve OS (p = 0.14).
CONCLUSION
Pituitary carcinomas are highly recurrent, heterogenous tumors with variable responses to treatment. Multidisciplinary management with an experienced neuro-endocrine and neuro-oncology team is needed given the unrelenting nature of this disease.
Topics: Humans; Pituitary Neoplasms; Neoplasm Recurrence, Local; Adenoma; ACTH-Secreting Pituitary Adenoma; Pituitary Gland
PubMed: 37523025
DOI: 10.1007/s11102-023-01341-4