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Endocrine-related Cancer May 2023The purpose of this work was toinvestigate the clinicopathological characteristics at the initial diagnosis of the pituitary tumor and at pituitary carcinoma (PC)...
PURPOSE
The purpose of this work was toinvestigate the clinicopathological characteristics at the initial diagnosis of the pituitary tumor and at pituitary carcinoma (PC) diagnosis, alongside with the management and outcomes of PCs, and identify potential prognostic factors and therapeutic strategies associated with the clinical outcome.
METHODS
PubMed was searched in May 2021 for articles in English and French reporting PCs, the diagnosis of which was made on the presence of metastases. The cases without histological proof and with either another cancer present or an atypical history for a pituitary tumor were excluded.
RESULTS
One hundred and eighty-one articles reporting 207 cases were included, which included 38% corticotroph and 29% lactotroph carcinomas. An initial Ki67 index ≥10% was associated with shorter survival after the initial diagnosis (P = 0.01). Cases with early metastases were associated with both higher initial Ki67 index (P = 0.01) and shorter survival after PC diagnosis (P = 0.001). Interestingly, cases with short survival after PC diagnosis were associated with shorter time between the initial diagnosis and PC diagnosis (P = 0.0006) and had both higher initial Ki67 index (P = 0.003) and higher Ki67 index of the metastasis (P = 0.03). In addition, cases with long survival after PC diagnosis had received more frequently both systemic treatment after PC diagnosis (P = 0.0005) and local treatment for metastases (P < 0.0001).
CONCLUSIONS
An initial Ki67 index ≥10% is associated with worse outcome and appears as a promising early marker of future metastasis. Its presence should lead to an intensified surveillance and to a more timely management. Clinicians should not hesitate to use local treatment, independent of whether systemic treatment is used.
Topics: Humans; Pituitary Neoplasms; Prognosis; Ki-67 Antigen
PubMed: 36852675
DOI: 10.1530/ERC-22-0338 -
Journal of Clinical Medicine Mar 2022: Reports on clinical and biochemical differences between adrenocorticotropic hormone (ACTH)-secreting pituitary microadenomas and macroadenomas are limited and...
: Reports on clinical and biochemical differences between adrenocorticotropic hormone (ACTH)-secreting pituitary microadenomas and macroadenomas are limited and inconsistent. Compare clinical and biochemical characteristics of patients with corticotroph microadenomas and macroadenomas and assess predictive factors for biochemical response to dynamic testing for Cushing's disease (CD) in a clinical trial and a systematic review. A second aim was to evaluate differences between macroadenomas with and without cavernous and sphenoid sinus invasion. Retrospective charts review of patients with CD, treated at Rabin Medical Center between 2000 and 2020 or at Maccabi Healthcare Services in Israel between 2005 and 2017. Clinical and biochemical factors were compared between patients with corticotroph microadenomas and macroadenomas. We have also performed a systematic review of all studies (PRISMA guidelines) comparing corticotroph microadenomas with macroadenomas up to 31 November 2021. : The cohort included 105 patients (82 women, 78%; mean age, 41.5 ± 14.5 years), including 80 microadenomas (mean size, 5.2 ± 2.2 mm) and 25 macroadenomas (mean size, 18.0 ± 7.7 mm). Other baseline characteristics were similar between groups. Most common presentation suggestive for hypercortisolemia among patients with both micro- and macroadenomas were weight gain (46.3% vs. 48.0%, = NS) and Cushingoid features (27.5% vs. 20.0%, = NS). Mean 24 h urinary free cortisol (5.2 ± 5.4 × ULN vs. 7.8 ± 8.7 × ULN) and serum cortisol following low-dose dexamethasone (372.0 ± 324.5 vs. 487.6 ± 329.8 nmol/L), though higher for macroadenomas, were not significant. Levels of ACTH were greater for macroadenomas (1.9 ± 1.2 × ULN vs. 1.3 ± 0.8 × ULN, respectively, = 0.01). Rates of recurrent/persistent disease were similar, as were rates of post-operative adrenal insufficiency and duration of post-operative glucocorticoid replacement. Macroadenomas with sphenoid or cavernous sinus invasion were associated with higher ACTH, 24 h free urinary cortisol, and serum cortisol following low-dose dexamethasone, compared with suprasellar or intrasellar macroadenomas. While ACTH-secreting macroadenomas exhibit higher plasma ACTH than microadenomas, there was no association between tumor size with cortisol hypersecretion or clinical features of hypercortisolemia. Though overall rare, increased awareness is needed for patients with CD with tumor extension in the cavernous or sphenoid sinus, which displays increased biochemical burden, highlighting that extent/location of the adenoma may be more important than size per se. Our systematic review, the first on this topic, highlights differences and similarities with our study.
PubMed: 35329884
DOI: 10.3390/jcm11061558 -
Neurosurgery Jun 2023Craniopharyngiomas account for 1.2% to 4.6% of all intracranial tumors. Although age at presentation is distributed bimodally, with a pediatric peak occurring between 5... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Craniopharyngiomas account for 1.2% to 4.6% of all intracranial tumors. Although age at presentation is distributed bimodally, with a pediatric peak occurring between 5 and 15 years and an adult peak between 50 and 70 years, presentation, treatment, and outcome differences between these two craniopharyngioma populations have not been thoroughly characterized.
OBJECTIVE
To compare treatments and outcomes between adult and pediatric craniopharyngiomas.
METHODS
This is a systematic review and meta-analysis. Web of Science, MEDLINE, and Scopus databases were searched for primary studies reporting postoperative complications, functional outcomes, recurrence, and overall survival in patients with craniopharyngioma undergoing surgery.
RESULTS
The search yielded 1,202 unique articles, of which 106 (n=4,202 patients) met criteria for qualitative synthesis and 23 (n=735 patients) met criteria for meta-analysis. Compared with adult, pediatric craniopharyngiomas were less likely to present with visual defects (odds ratio [OR] 0.54, 95% CI 0.36-0.80) or cognitive impairment (OR 0.29, 95% CI 0.12-0.71) and more likely with headaches (OR 2.08, 95% CI 1.16-3.73). Children presented with significantly larger tumors compared with adults (standardized mean difference 0.68, 95% CI 0.38-0.97). Comparing functional outcomes, pediatric patients sustained higher rates of permanent diabetes insipidus (OR 1.70, 95% CI 1.13-2.56), obesity (OR 3.15, 95% CI 1.19-8.31), and cranial nerve and/or neurological defects (OR 4.87, 95% CI 1.78-13.31) than adults. No significant differences were found in rates of postoperative cerebrospinal fluid leak, overall or progression-free survival, or recurrence.
CONCLUSION
Adult and pediatric craniopharyngiomas seem to have fundamental differences in clinical presentation and functional outcomes. These patients frequently require multimodality treatment and are best managed with a multidisciplinary team and an individualized approach.
Topics: Adolescent; Adult; Child; Child, Preschool; Humans; Combined Modality Therapy; Craniopharyngioma; Diabetes Insipidus; Neurosurgical Procedures; Pituitary Neoplasms; Postoperative Complications; Treatment Outcome
PubMed: 36639856
DOI: 10.1227/neu.0000000000002346 -
Endocrine Nov 2020Recurrence after pituitary surgery in Cushing's disease (CD) is a common problem ranging from 5% (minimum) to 50% (maximum) after initially successful surgery,... (Review)
Review
PURPOSE
Recurrence after pituitary surgery in Cushing's disease (CD) is a common problem ranging from 5% (minimum) to 50% (maximum) after initially successful surgery, respectively. In this review, we give an overview of the current literature regarding prevalence, diagnosis, and therapeutic options of recurrent CD.
METHODS
We systematically screened the literature regarding recurrent and persistent Cushing's disease using the MESH term Cushing's disease and recurrence. Of 717 results in PubMed, all manuscripts in English and German published between 1980 and April 2020 were screened. Case reports, comments, publications focusing on pediatric CD or CD in veterinary disciplines or studies with very small sample size (patient number < 10) were excluded. Also, papers on CD in pregnancy were not included in this review.
RESULTS AND CONCLUSIONS
Because of the high incidence of recurrence in CD, annual clinical and biochemical follow-up is paramount. 50% of recurrences occur during the first 50 months after first surgery. In case of recurrence, treatment options include second surgery, pituitary radiation, targeted medical therapy to control hypercortisolism, and bilateral adrenalectomy. Success rates of all these treatment options vary between 25 (some of the medical therapy) and 100% (bilateral adrenalectomy). All treatment options have specific advantages, limitations, and side effects. Therefore, treatment decisions have to be individualized according to the specific needs of the patient.
Topics: ACTH-Secreting Pituitary Adenoma; Adrenalectomy; Adult; Child; Female; Humans; Neoplasm Recurrence, Local; Pituitary ACTH Hypersecretion; Pituitary Gland; Pregnancy; Recurrence; Treatment Outcome
PubMed: 32743767
DOI: 10.1007/s12020-020-02432-z -
Journal of Endocrinological... Jun 2022Cushing's disease (CD), 70% of endogenous hypercortisolism cases, is a rare disease caused by adrenocorticotropic hormone (ACTH)-secreting pituitary adenomas. To date,... (Meta-Analysis)
Meta-Analysis
PURPOSE
Cushing's disease (CD), 70% of endogenous hypercortisolism cases, is a rare disease caused by adrenocorticotropic hormone (ACTH)-secreting pituitary adenomas. To date, no systematic reviews and meta-analyses on its global epidemiology have been published. We provide a systematic review and meta-analysis of CD global epidemiology, also evaluating the quality of study reporting for the identified studies.
METHODS
MEDLINE and EMBASE databases were searched for studies on CD epidemiology from inception until November 30th, 2020, including original observational studies in English about CD prevalence and/or incidence for well-defined geographic areas. Two reviewers independently extracted data and assessed reporting quality. CD prevalence/incidence pooled estimates were derived from a random-effects meta-analysis. Reporting quality was assessed using a STrengthening the Reporting of OBservational studies in Epidemiology (STROBE) checklist adapted for observational studies on rare diseases, heterogeneity using the Cochran's Q-test and its derived measure of inconsistency (I).
RESULTS
Thirteen studies were included. The pooled CD prevalence was 2.2 [95% CI 1.1-4.8] per 100,000, while the incidence rate was 0.24 [95% CI 0.15-0.33] per 100,000 person-years. For both parameters, considerable between-studies heterogeneity was found (I = 78.8% and 87.8%, respectively). The quality of study reporting was rated as medium for 11 (84.6%) studies and as low for 2 (15.4%).
CONCLUSION
Overall, our systematic meta-analysis demonstrated CD epidemiology to be similarly reported across different areas of the world, with some exceptions regarding regional differences or observation period intervals. Keeping into account the methodological differences between each paper, large-scale studies on CD epidemiology are warranted. Setting up national specific registries, based on standardized diagnostic and clinical parameters, with clearly defined selection and analysis criteria, and a strong cooperation between the scientific national societies for endocrinology is crucial to exclude other causes of variability (i.e. geographical differences due to other factors like (epi)genetic changes), and to support public health decision making.
Topics: ACTH-Secreting Pituitary Adenoma; Adenoma; Humans; Incidence; Pituitary ACTH Hypersecretion; Prevalence
PubMed: 35133616
DOI: 10.1007/s40618-022-01754-1 -
AJNR. American Journal of Neuroradiology Mar 2023MR imaging is key in the diagnostic work-up of Cushing disease. The sensitivity of MR imaging in Cushing disease is not known nor is the prognostic significance of "MR...
BACKGROUND
MR imaging is key in the diagnostic work-up of Cushing disease. The sensitivity of MR imaging in Cushing disease is not known nor is the prognostic significance of "MR imaging-negative" disease.
PURPOSE
Our aim was to determine the overall sensitivity and prognostic significance of MR imaging localization of Cushing disease.
DATA SOURCES
We performed a systematic review of the MEDLINE and PubMed databases for cohort studies reporting the sensitivity of MR imaging for the detection of adenomas in Cushing disease.
STUDY SELECTION
This study included 57 studies, comprising 5651 patients.
DATA ANALYSIS
Risk of bias was assessed using the methodological index for non-randomized studies criteria. Meta-analysis of proportions and pooled subgroup analysis were performed.
DATA SYNTHESIS
Overall sensitivity was 73.4% (95% CI, 68.8%-77.7%), and the sensitivity for microadenomas was 70.6% (66.2%-74.6%). There was a trend toward greater sensitivity in more recent studies and with the use of higher-field-strength scanners. Thinner-section acquisitions and gadolinium-enhanced imaging, particularly dynamic sequences, also increased the sensitivity. The use of FLAIR and newer 3D spoiled gradient-echo and FSE sequences, such as spoiled gradient-echo sequences and sampling perfection with application-optimized contrasts by using different flip angle evolutions, may further increase the sensitivity but appear complementary to standard 2D spin-echo sequences. MR imaging detection conferred a 2.63-fold (95% CI, 2.06-3.35-fold) increase in remission for microadenomas compared with MR imaging-negative Cushing disease.
LIMITATIONS
Pooled analysis is limited by heterogeneity among studies. We could not account for variation in image interpretation and tumor characteristics.
CONCLUSIONS
Detection on MR imaging improves the chances of curative resection of adenomas in Cushing disease. The evolution of MR imaging technology has improved the sensitivity for adenoma detection. Given the prognostic importance of MR imaging localization, further effort should be made to improve MR imaging protocols for Cushing disease.
Topics: Humans; Adenoma; Contrast Media; Magnetic Resonance Imaging; Pituitary ACTH Hypersecretion; Pituitary Neoplasms; Sensitivity and Specificity
PubMed: 36759141
DOI: 10.3174/ajnr.A7789 -
TouchREVIEWS in Endocrinology Nov 2023Pituitary tumours (PTs) are the second most common intracranial tumour. Although the majority show benign behaviour, they may exert aggressive behaviour and can be... (Review)
Review
Pituitary tumours (PTs) are the second most common intracranial tumour. Although the majority show benign behaviour, they may exert aggressive behaviour and can be resistant to treatment. The aim of this review is to report the recently identified biomarkers that might have possible prognostic value. Studies evaluating potentially prognostic biomarkers or a therapeutic target in invasive/recurrent PTs compared with either non-invasive or non-recurrent PTs or normal pituitaries are included in this review. In the 28 included studies, more than 911 PTs were evaluated. A systematic search identified the expression of a number of biomarkers that may be positively correlated with disease recurrence or invasion in PT, grouped according to role: (1) insensitivity to anti-growth signals: minichromosome maintenance protein 7; (2) evasion of the immune system: cyclooxygenase 2, arginase 1, programmed cell death protein 1 (PD-1)/programmed death ligand 2, cluster of differentiation (CD) 80/CD86; (3) sustained angiogenesis: endothelial cell-specific molecule, fibroblast growth factor receptor, matrix metalloproteinase 9, pituitary tumour transforming gene; (4) self-sufficiency in growth signals: epidermal growth factor receptor; and (5) tissue invasion: matrix metalloproteinase 9, fascin protein. Biomarkers with a negative correlation with disease recurrence or invasion include: (1) insensitivity to anti-growth signals: transforming growth factor β1, Smad proteins; (2) sustained angiogenesis: tissue inhibitor of metalloproteinase 1; (3) tissue invasion: Wnt inhibitory factor 1; and (4) miscellaneous: co-expression of glial fibrillary acidic protein and cytokeratin, and oestrogen receptors α36 and α66. PD-1/programmed cell death ligand 1 showed no clear association with invasion or recurrence, while cyclin A, cytotoxic T lymphocyte-associated protein 4, S100 protein, ephrin receptor, galectin-3 , neural cell adhesion molecule, protein tyrosine phosphatase 4A3 and steroidogenic factor 1 had no association with invasion or recurrence of PT. With the aim to develop a more personalized approach to the treatment of PT, and because of the limited number of molecular targets currently studied in the context of recurrent PT and invasion, a better understanding of the most relevant of these biomarkers by well-d esigned interventional studies will lead to a better understanding of the molecular profile of PT. This should also meet the increased need of treatable molecular targets.
PubMed: 38187082
DOI: 10.17925/EE.2023.19.2.12 -
Current Psychiatry Reports Nov 2023Despite clear evidence that sex differences largely impact the efficacy and tolerability of antipsychotic medication, current treatment guidelines for schizophrenia... (Review)
Review
PURPOSE OF REVIEW
Despite clear evidence that sex differences largely impact the efficacy and tolerability of antipsychotic medication, current treatment guidelines for schizophrenia spectrum disorders (SSD) do not differentiate between men and women. This review summarizes the available evidence on strategies that may improve pharmacotherapy for women and provides evidence-based recommendations to optimize treatment for women with schizophrenia.
RECENT FINDINGS
We systematically searched PubMed and Embase for peer-reviewed studies on three topics: (1) sex differences in dose-adjusted antipsychotic serum concentrations, (2) hormonal augmentation therapy with estrogen and estrogen-like compounds to improve symptom severity, and (3) strategies to reduce antipsychotic-induced hyperprolactinemia. Based on three database studies and one RCT, we found higher dose-adjusted concentrations in women compared to men for most antipsychotics. For quetiapine, higher concentrations were specifically found in older women. Based on two recent meta-analyses, both estrogen and raloxifene improved overall symptomatology. Most consistent findings were found for raloxifene augmentation in postmenopausal women. No studies evaluated the effects of estrogenic contraceptives on symptoms. Based on two meta-analyses and one RCT, adjunctive aripiprazole was the best-studied and safest strategy for lowering antipsychotic-induced hyperprolactinemia. Evidence-based recommendations for female-specific pharmacotherapy for SSD consist of (1) female-specific dosing for antipsychotics (guided by therapeutic drug monitoring), (2) hormonal replacement with raloxifene in postmenopausal women, and (3) aripiprazole addition as best evidenced option in case of antipsychotic-induced hyperprolactinemia. Combining these strategies could reduce side effects and improve outcome of women with SSD, which should be confirmed in future longitudinal RCTs.
Topics: Female; Humans; Male; Aged; Antipsychotic Agents; Schizophrenia; Aripiprazole; Hyperprolactinemia; Raloxifene Hydrochloride; Estrogens
PubMed: 37864676
DOI: 10.1007/s11920-023-01460-6 -
Endocrine, Metabolic & Immune Disorders... 2021Coronaviruses are a big family of viruses that can infect mammalians and birds. In humans they mainly cause respiratory tract infections, with a large spectrum of...
Coronaviruses are a big family of viruses that can infect mammalians and birds. In humans they mainly cause respiratory tract infections, with a large spectrum of severity, from mild, self-limited infections to highly lethal forms as severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV) and Coronavirus Disease 2019 (COVID-19). Scanty data are reported for the involvement of endocrine glands in human coronaviruses, in particular SARS-CoV-2. In this review, we summarize endocrinological involvement in human coronaviruses, including data on animal coronaviruses. Avians, ferrets and bovine are affected by specific coronavirus syndromes, with variable involvement of endocrine glands. SARS-CoV and SARS-CoV-2 use angiotensin-converting enzyme 2 (ACE2) as a target receptor, so ACE2 plays a central role in viral transmission and initial organ involvement. Autoptic studies on SARS patients revealed that thyroid, parathyroid, pituitary gland, endocrine pancreas and especially adrenals and testis could be impaired by different mechanisms (direct damage by SARS-CoV, inflammation, vascular derangement and autoimmune reactions) and few clinical studies have evidenced functional endocrine impairment. Only few data are available for COVID-19 and gonads and endocrine pancreas seem to be involved. International endocrinological societies have brought some recommendations for the COVID-19 pandemic, but further studies need to be performed, especially to detect long-term hormonal sequelae.
Topics: Angiotensin-Converting Enzyme 2; Animals; COVID-19; Endocrine Glands; Endocrine System; Endocrine System Diseases; Humans; Middle East Respiratory Syndrome Coronavirus; SARS-CoV-2
PubMed: 32888287
DOI: 10.2174/1871530320666200905123332 -
Presse Medicale (Paris, France : 1983) Dec 2021Hypophysitis is defined as inflammation of the pituitary gland. It is a heterogeneous condition as it can originate from different parts of the pituitary gland, can be...
Hypophysitis is defined as inflammation of the pituitary gland. It is a heterogeneous condition as it can originate from different parts of the pituitary gland, can be caused by different pathophysiological processes, and can be isolated or the manifestation of a underlying systemic disease. Hypophysitis usually presents with endocrine deficiencies, including diabetes insipidus, with varying patterns. A subset of patients presents with mass effects. The last decades major progress has been made in the understanding of this disease. New forms are now recognized, new diagnostics are being developed, and specific treatments are proposed. This review provides an overview of the current knowledge on hypophysitis using an aetiology-based approach and provides the clinician with a stepwise approach to the patient with (suspected) hypophysitis.
Topics: Autoimmune Hypophysitis; Diabetes Insipidus; Endocrine System Diseases; Erdheim-Chester Disease; Histiocytosis, Langerhans-Cell; Humans; Hypophysitis; Immune Checkpoint Inhibitors; Immunoglobulin G; Immunoglobulin G4-Related Disease; Pituitary Gland; Symptom Assessment; Xanthomatosis
PubMed: 34687912
DOI: 10.1016/j.lpm.2021.104076