Genetic testing in endocrinology

2021 ◽  
pp. 787-808
Author(s):  
Márta Korbonits ◽  
Paul Newey
Keyword(s):  
Genetic Testing ◽  
Pituitary Adenoma ◽  
Pituitary Adenomas ◽  
Genetic Basis ◽  
Endocrine System ◽  
Potential Utility ◽  
Genetic Tests ◽  
Endocrine Disease ◽  
System P ◽  
Different Types

This chapter begins with describing the genetic basis of endocrine disease, and the potential utility for genetic testing (alongside consent). It then covers different types of genetic tests and their applications. There is a section on pituitary adenomas, MEN types 1 and 4, familial isolated pituitary adenoma, and various other genetic conditions related to the endocrine system.

scholarly journals A patient with a germline SDHB mutation presenting with an isolated pituitary macroprolactinoma

2018 ◽  
Vol 2018 ◽  
Author(s):  
Michelle Maher ◽  
Federico Roncaroli ◽  
Nigel Mendoza ◽  
Karim Meeran ◽  
Natalie Canham ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Pituitary Adenoma ◽  
Pituitary Adenomas ◽  
Biochemical Response ◽  
List Type ◽  
Factor X ◽  
Loss Of Function ◽  
Variable Response ◽  
Sdhb Mutation ◽  
Tumour Shrinkage

Summary Symptomatic pituitary adenomas occur with a prevalence of approximately 0.1% in the general population. It is estimated that 5% of pituitary adenomas occur in a familial setting, either in isolated or syndromic form. Recently, loss-of-function mutations in genes encoding succinate dehydrogenase subunits (SDHx) or MYC-associated factor X (MAX) have been found to predispose to pituitary adenomas in co-existence with paragangliomas or phaeochromocytomas. It is rare, however, for a familial SDHx mutation to manifest as an isolated pituitary adenoma. We present the case of a pituitary lactotroph adenoma in a patient with a heterozygous germline SDHB mutation, in the absence of concomitant neoplasms. Initially, the adenoma showed biochemical response but poor tumour shrinkage in response to cabergoline; therefore, transsphenoidal surgery was performed. Following initial clinical improvement, tumour recurrence was identified 15 months later. Interestingly, re-initiation of cabergoline proved successful and the lesion demonstrated both biochemical response and tumour shrinkage. Our patient’s SDHB mutation was identified when we realised that her father had a metastatic paraganglioma, prompting genetic testing. Re-inspection of the histopathological report of the prolactinoma confirmed cells with vacuolated cytoplasm. This histological feature is suggestive of an SDHx mutation and should prompt further screening for mutations by immunohistochemistry and/or genetic testing. Surprisingly, immunohistochemistry of this pituitary adenoma demonstrated normal SDHB expression, despite loss of SDHB expression in the patient’s father’s paraganglioma. Learning points: Pituitary adenomas may be the presenting and/or sole feature of SDHB mutation-related disease. SDHx mutated pituitary adenomas may display clinically aggressive behaviour and demonstrate variable response to medical treatment. Histological evidence of intracytoplasmic vacuoles in a pituitary adenoma might suggest an SDH-deficient tumour and should prompt further screening for SDHx mutations. Immunohistochemistry may not always predict the presence of SDHx mutations.

Tartan Buddhists

2012 ◽  
Vol 7 (1) ◽  
pp. 8-28 ◽  
Author(s):  
John McKenzie
Keyword(s):  
Potential Utility ◽  
Tibetan Buddhist ◽  
The West ◽  
Dependent Relationship ◽  
Different Types

The purpose of this article is to provide a sociological typology for understanding the different types of practitioners within the Tibetan Buddhist organization, Rokpa International, in Scotland. It will be argued that the empirically derived criteria and Weber’s (1978) sociological concepts of authority, power and status allow us to understand the tensions and mutually dependent relationship between the different types. In conclusion, it will be argued that, while this typology is not presented as a challenge to existing typologies, this article demonstrates the potential utility of these sociological concepts for understanding the practice and development of Buddhism in the West.

PTTG has a Dual Role of Promotion-Inhibition in the Development of Pituitary Adenomas

2019 ◽  
Vol 26 (11) ◽  
pp. 800-818
Author(s):  
Zujian Xiong ◽  
Xuejun Li ◽  
Qi Yang
Keyword(s):  
Cell Cycle ◽  
Pituitary Adenoma ◽  
Pituitary Adenomas ◽  
Cell Cycle Progression ◽  
Key Factors ◽  
Cycle Progression ◽  
Sister Chromatids ◽  
Regulation Of Cell Cycle ◽  
Late Stages

Pituitary Tumor Transforming Gene (PTTG) of human is known as a checkpoint gene in the middle and late stages of mitosis, and is also a proto-oncogene that promotes cell cycle progression. In the nucleus, PTTG works as securin in controlling the mid-term segregation of sister chromatids. Overexpression of PTTG, entering the nucleus with the help of PBF in pituitary adenomas, participates in the regulation of cell cycle, interferes with DNA repair, induces genetic instability, transactivates FGF-2 and VEGF and promotes angiogenesis and tumor invasion. Simultaneously, overexpression of PTTG induces tumor cell senescence through the DNA damage pathway, making pituitary adenoma possessing the potential self-limiting ability. To elucidate the mechanism of PTTG in the regulation of pituitary adenomas, we focus on both the positive and negative function of PTTG and find out key factors interacted with PTTG in pituitary adenomas. Furthermore, we discuss other possible mechanisms correlate with PTTG in pituitary adenoma initiation and development and the potential value of PTTG in clinical treatment.

scholarly journals Successful pregnancy after operation in an infertile woman caused by luteinizing hormone-secreting pituitary adenoma: case report and literature review

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Yi Zhang ◽  
Cheng Chen ◽  
Min Lin ◽  
Kan Deng ◽  
Huijuan Zhu ◽  
...  
Keyword(s):  
Case Report ◽  
Pituitary Adenoma ◽  
Literature Review ◽  
Pituitary Adenomas ◽  
Sella Turcica ◽  
Infertile Woman ◽  
Mass Treatment ◽  
Successful Pregnancy ◽  
Case Presentation ◽  
Transsphenoidal Resection

Abstract Background Functional gonadotroph adenomas (FGAs) are rare adenomas that most commonly secrete FSH. However, solitary LH-secreting pituitary adenomas are unusual. Case presentation A 30-year-old woman with elevated LH and normal FSH presented with inability to conceive. An MRI revealed an enlarged sella turcica and an intrasellar mass. Treatment with transsphenoidal resection led to normalization of LH and estradiol, as well as successful pregnancy. And we reviewed 6 cases of LH-secreting pituitary adenomas from 1981 to 2020. Conclusions Our case is unique because of the LH-secreting pituitary adenoma without FSH hypersecretion. This case indicates that pituitary adenoma should be considered when other diseases causing infertility have been excluded.

scholarly journals HIF-1α Inhibition Sensitized Pituitary Adenoma Cells to Temozolomide by Regulating Presenilin 1 Expression and Autophagy

2016 ◽  
Vol 15 (6) ◽  
pp. NP95-NP104 ◽  
Author(s):  
Zhang kun ◽  
Yang yuling ◽  
Wang dongchun ◽  
Xie bingbing ◽  
Li xiaoli ◽  
...  
Keyword(s):  
Pituitary Adenoma ◽  
Pituitary Adenomas ◽  
Ph Value ◽  
Hypoxia Inducible Factor ◽  
Presenilin 1 ◽  
Gh3 Cells ◽  
Lysosomal Ph ◽  
Hypoxia Inducible Factor 1Α ◽  
Anticancer Effects ◽  
Autophagy Induction

Pituitary adenomas usually develop temozolomide resistance, which could compromise the anticancer effects of temozolomide. Suppression of hypoxia-inducible factor 1α has been shown to sensitize glioblastoma cells to temozolomide treatment according to previous reports. However, whether and how the suppression of hypoxia-inducible factor 1α could sensitize pituitary adenomas to temozolomide treatment are still poorly understood. In the present study, using hypoxia-inducible factor 1α knockdown strategy, we demonstrated for the first time that hypoxia-inducible factor 1α knockdown could inhibit temozolomide-induced autophagy in rat pituitary adenoma GH3 cells and thus increase antitumor efficacy of temozolomide. Furthermore, we found hypoxia-inducible factor 1α knockdown could block autophagy process through neutralizing lysosomal pH value but not inhibiting autophagy induction. Finally, we found hypoxia-inducible factor 1α could regulate lysosomal pH value through regulating full length presenilin 1 expression, and exogenous reexpression of presenilin 1could restore lysosome acidic levels. Our data indicated hypoxia-inducible factor 1α knockdown could be a potential approach to improve the efficacy of temozolomide therapy for pituitary adenomas.

MICROSURGICAL ANATOMY OF THE DIAPHRAGMA SELLAE AND ITS ROLE IN DIRECTING THE PATTERN OF GROWTH OF PITUITARY ADENOMAS

Neurosurgery ◽  
2008 ◽  
Vol 62 (3) ◽  
pp. 717-723 ◽  
Author(s):  
Alvaro Campero ◽  
Carolina Martins ◽  
Alexandre Yasuda ◽  
Albert L. Rhoton
Keyword(s):  
Pituitary Adenoma ◽  
Cavernous Sinus ◽  
Dura Mater ◽  
Pituitary Adenomas ◽  
Potential Role ◽  
Pituitary Tumors ◽  
Microsurgical Anatomy ◽  
Suprasellar Region ◽  
Lateral Distance ◽  
Diaphragma Sellae

Abstract OBJECTIVE To evaluate the anatomic aspects of the diaphragma sellae and its potential role in directing the growth of a pituitary adenoma. METHODS Twenty cadaveric heads were dissected and measurements were taken at the level of the diaphragma sellae. RESULTS The diaphragma sellae is composed of two layers of dura mater. There is a remarkable variation in the morphology of the diaphragm opening. The average anteroposterior distance of the opening was 7.26 mm (range, 3.4–10.7 mm) and the average lateral-to-lateral distance was 7.33 mm (range, 2.8–14.1 mm). CONCLUSION The variability in the diameter of the opening of the diaphragma sellae could explain the growth of pituitary tumors toward the cavernous sinus or toward the suprasellar region.

scholarly journals How do non-geneticist physicians deal with genetic tests? A qualitative analysis

2021 ◽  
Author(s):  
Laurent Pasquier ◽  
Guy Minguet ◽  
Sylvie Moisdon-Chataigner ◽  
Pascal Jarno ◽  
Philippe Denizeau ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Social Issues ◽  
Clinical Skills ◽  
Rapid Development ◽  
Genomic Medicine ◽  
Genetic Tests ◽  
Simple Fact ◽  
Medical Specialties ◽  
Management Procedure ◽  
Testing Practices

AbstractGenetic testing is accepted to be a common practice in many medical specialties. These genetic tests raise issues such as respect for basic rights, how to handle results and uncertainty and how to balance concerns for medical confidentiality with the rights of third parties. Physicians need help to deal with the rapid development of genomic medicine as most of them have received no specific training on the medical, ethical, and social issues involved. Analyzing how these professionals integrate genetic testing into the patient-provider relationship is essential to paving the way for a better use of genomics by all. We conducted a qualitative study comprising a series of focus groups with 21 neurologists and endocrinologists about their genetic testing practices in the western part of France. The interviews were transcribed and analyzed for major themes. We identified an automated care management procedure of genetic testing that affects patient autonomy. The simple fact of having a written consent cannot justify a genetic test given the stakes associated with the results. We also suggest orienting practices toward a systemic approach using a multidisciplinary team or network to provide resources for dealing with uncertainties in interpreting results or situations that require additional technical or clinical skills and, if necessary, to allow for joint consultations with both a geneticist and a non-geneticist medical specialist.

scholarly journals Pediatric Pituitary Adenoma: Case Series, Review of the Literature, and a Skull Base Treatment Paradigm

2018 ◽  
Vol 79 (01) ◽  
pp. 091-114 ◽  
Author(s):  
Avital Perry ◽  
Christopher Graffeo ◽  
Christopher Marcellino ◽  
Bruce Pollock ◽  
Nicholas Wetjen ◽  
...  
Keyword(s):  
Systematic Review ◽  
Pituitary Adenoma ◽  
Skull Base ◽  
Pituitary Adenomas ◽  
Pediatric Population ◽  
Csf Leak ◽  
Persistent Disease ◽  
Treatment Paradigm ◽  
Surgical Cure

Background Pediatric pituitary adenoma is a rare skull base neoplasm, accounting for 3% of all intracranial neoplasms in children and 5% of pituitary adenomas. Compared with pituitary tumors in adults, secreting tumors predominate and longer disease trajectories are expected due to the patient age resulting in a natural history and treatment paradigm that is complex and controversial. Objectives The aims of this study were to describe a large, single-institution series of pediatric pituitary adenomas with extensive long-term follow-up and to conduct a systematic review examining outcomes after pituitary adenoma surgery in the pediatric population. Methods The study cohort was compiled by searching institutional pathology and operative reports using diagnosis and site codes for pituitary and sellar pathology, from 1956 to 2016. Systematic review of the English language literature since 1970 was conducted using PubMed, MEDLINE, Embase, and Google Scholar. Results Thirty-nine surgically managed pediatric pituitary adenomas were identified, including 15 prolactinomas, 14 corticotrophs, 7 somatotrophs, and 4 non-secreting adenomas. All patients underwent transsphenoidal resection (TSR) as the initial surgical treatment. Surgical cure was achieved in 18 (46%); 21 experienced recurrent/persistent disease, with secondary treatments including repeat surgery in 10, radiation in 14, adjuvant pharmacotherapy in 11, and bilateral adrenalectomy in 3. At the last follow-up (median 87 months, range 3–581), nine remained with recurrent/persistent disease (23%).Thirty-seven publications reporting surgical series of pediatric pituitary adenomas were included, containing 1,284 patients. Adrenocorticotropic hormone (ACTH)-secreting tumors were most prevalent (43%), followed by prolactin (PRL)-secreting (37%), growth hormone (GH)-secreting (12%), and nonsecreting (7%). Surgical cure was reported in 65%. Complications included pituitary insufficiency (23%), permanent visual dysfunction (6%), chronic diabetes insipidus (DI) (3%), and postoperative cerebrospinal fluid (CSF) leak (4%). Mean follow-up was 63 months (range 0–240), with recurrent/persistent disease reported in 18% at the time of last follow-up. Conclusion Pediatric pituitary adenomas are diverse and challenging tumors with complexities far beyond those encountered in the management of routine adult pituitary disease, including nuanced decision-making, a technically demanding operative environment, high propensity for recurrence, and the potentially serious consequences of hypopituitarism with respect to fertility and growth potential in a pediatric population. Optimal treatment requires a high degree of individualization, and patients are most likely to benefit from consolidated, multidisciplinary care in highly experienced centers.

Cancer specialists in the VA as early adopters of clinical genetic services.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 11029-11029
Author(s):  
Maren Theresa Scheuner ◽  
Paloma Sales ◽  
Mary Whooley ◽  
Katherine Hoggatt ◽  
Michael Kelley
Keyword(s):  
Risk Assessment ◽  
Genetic Testing ◽  
Genetic Test ◽  
Primary Care Providers ◽  
Precision Oncology ◽  
Genetic Tests ◽  
The Past ◽  
Cancer Specialists ◽  
Genetics Referral ◽  
Test Ordering

11029 Background: Genetic testing has become essential to delivery of cancer treatment, risk assessment, surveillance, and prevention. We sought to understand the use of genetic tests by clinicians in the Department of Veterans Affairs (VA). Methods: We administered a web-based survey to clinicians at 20 VA facilities with precision oncology programs. We excluded respondents if they were: not at one of the 20 VA facilities; not seeing patients in VA; not a physician, nurse practitioner (NP), physician assistant (PA), or pharmacist; a medical geneticist or specialty was not reported; or if the survey was incomplete. Using multiple logistic regression, we assessed the association between genetic test ordering, genetics referral, and clinician characteristics. Results: There were 909 (909/11,442, 8%) eligible respondents with 61% women and 64% under age 55. There were 571 physicians (63%), 200 NPs (22%), 93 pharmacists (10%), and 45 PAs 5(%). There were 361 (40%) primary care providers (PCPs), 90 (10%) cancer specialists, and 458 (50%) non-cancer specialists. Only 21% of clinicians reported feeling prepared to use genetic tests in their practice. In the past year, only 8% had ordered at least one multi-gene cancer test (germline, tumor or both), 12% a pharmacogenetic test, and 0.2%, an exome. Compared to physicians, NPs were 60% less likely (OR = 0.42, 0.23-0.77, p = 0.005), pharmacists, 80% less likely (OR = 0.22, 0.08-0.62, p = 0.005), and PAs, 90% less likely (OR = 0.08, 0.01-0.58, p = 0.01) to have ordered a genetic test. Compared to PCPs, cancer specialists were almost 5 times more likely to order a genetic test (OR = 4.74, 2.57-8.73, p < 0.0001); there was no difference in genetic test ordering between PCPs and non-cancer specialists. Among clinicians (n = 72) who had ordered cancer genetic tests, only about two-thirds were confident in knowing the indications for testing; discussing the potential benefits, harms and limitations of testing; understanding the test report; and knowing implications of results on disease management and prevention. Clinicians (n = 106) who had ordered pharmacogenetic tests had lower frequencies of confidence in these tasks. About half (52%) of the cancer specialists had referred patients to genetics in the past year; they were 1.8 times more likely than PCPs to refer (OR = 1.82, 1.10-3.03, p = 0.02), and non-cancer specialists were about 50% less likely than PCPs to refer (OR = 0.46, 0.33-0.64, p < 0.0001). Conclusions: In the VA, cancer specialists are integrating genetic testing and genetics referral into their practice more than PCPs and other specialists. However, genetic testing is underutilized, and many clinicians remain unprepared to use genetic tests in their practice. These results will inform workforce planning, clinician education, and development of clinical decision support to facilitate genetic risk assessment, informed consent, and ordering of genetic tests.

Ki-67/MIB-1 and Recurrence in Pituitary Adenoma

2021 ◽  
Author(s):  
Kent Tadokoro ◽  
Colten Wolf ◽  
Joseph Toth ◽  
Cara Joyce ◽  
Meharvan Singh ◽  
...  
Keyword(s):  
Systematic Review ◽  
Pituitary Adenoma ◽  
Recurrence Rate ◽  
Pituitary Adenomas ◽  
Cellular Proliferation ◽  
Published Data ◽  
Ki 67 ◽  
Institutional Data ◽  
Mib 1

Abstract Objectives Ki-67/MIB-1 is a marker of cellular proliferation used as a pathological parameter in the clinical assessment of pituitary adenomas, where its expression has shown utility in predicting the invasiveness of these tumors. However, studies have shown variable results when using Ki-67/MIB-1 association with recurrence. The purpose of this study is to determine if a high Ki-67/MIB-1 labeling index (LI) is predictive of recurrence in pituitary adenomas. Methods A retrospective chart review was performed for patients undergoing pituitary adenoma resection with at least 1 year of follow-up. Additionally, systematic data searches were performed and included studies that correlated recurrence rate to Ki-67/MIB-1 LI. Our institutional data were included in a synthesis with previously published data. Results Our institutional review included 79 patients with a recurrence rate of 26.6%. We found that 8.8% of our patients had a high Ki-67/MIB-1 LI (>3%); however, high Ki-67/MIB-1 was not associated with recurrence. The systematic review identified 244 articles and 49 full-text articles that were assessed for eligibility. Quantitative analysis was performed on 30 articles including our institutional data and 18 studies reported recurrence by level of Ki-67/MIB-1 LI. Among studies that compared Ki-67/MIB-1 ≥3 vs. <3%, 10 studies reported odds ratios (OR) greater than 1 of which 6 were statistically significant. A high Ki-67/MIB-1 had higher odds of recurrence via the pooled odds ratio (OR = 4.15, 95% confidence interval [CI]: 2.31–7.42). Conclusion This systematic review suggests that a high Ki-67/MIB-1 should prompt an increased duration of follow-up due to the higher odds of recurrence of pituitary adenoma.

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