Evidence map›Paper›PMID 40813536›Full record

ArticlePituitary2025

Genetic evaluation of pediatric pituitary adenomas and USP8-related genotype-phenotype correlations in Cushing's disease.

Rida Zainab, Sukhvir Kaur, Justin Lack, Morgan Similuk, Mayank Tandon, Rajarshi Ghosh, Bryce A Seifert, Mari Tokita, Chelsi Flippo, Jia Yan and 3 more

2 registry-linked trialsAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Pituitary, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT00001595 recruitingnot on this map

A Clinical and Genetic Investigation of Pituitary and Hypothalamic Tumors and Related Disorders

TypeobservationalSponsorEunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)Ran1997Enrolled2,000ConditionsPanhypopituitarism, Gigantism/Acromegaly, Prolactinoma, Cushing DiseaseArmsTissue specimen collection, MRI
NCT03206099 recruitingnot on this map

NIAID Centralized Sequencing Protocol

TypeobservationalSponsorNational Institute of Allergy and Infectious Diseases (NIAID)Ran2017 to 2029Enrolled20,000ConditionsAtopy, Primary Immunodeficiency, Autoimmunity, Autoinflammation
3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Review
  2. Mammosomatotroph pituitary neuroendocrine tumour in a 7-year-old boy: case report.Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery · 2026
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors.

Rida ZainabUnit on Hypothalamic and Pituitary Disorders, Eunice Kennedy Shriver National Institute of Child Health, and Human Development (NICHD), National Institutes of Health, Bethesda, MD, USA.
Sukhvir KaurUnit on Hypothalamic and Pituitary Disorders, Eunice Kennedy Shriver National Institute of Child Health, and Human Development (NICHD), National Institutes of Health, Bethesda, MD, USA.
Justin LackCollaborative Bioinformatics Resource, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health, Bethesda, United States.
Morgan SimilukCentralized Sequencing Program, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health, Bethesda, MD, USA.
Mayank TandonCollaborative Bioinformatics Resource, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health, Bethesda, United States.
Rajarshi GhoshCentralized Sequencing Program, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health, Bethesda, MD, USA.
Bryce A SeifertCentralized Sequencing Program, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health, Bethesda, MD, USA.
Mari TokitaCentralized Sequencing Program, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health, Bethesda, MD, USA.
Chelsi FlippoDivision of Pediatric Endocrinology, Children's National Hospital, Washington, DC, USA.
Jia YanCentralized Sequencing Program, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health, Bethesda, MD, USA.
Magdalena WalkiewiczCentralized Sequencing Program, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health, Bethesda, MD, USA.
Prashant ChittiboinaNeurosurgery Unit for Pituitary and Inheritable Diseases, National Institute of Neurological Disorders and Stroke (NINDS), National Institutes of Health, Bethesda, MD, USA.
Christina TatsiUnit on Hypothalamic and Pituitary Disorders, Eunice Kennedy Shriver National Institute of Child Health, and Human Development (NICHD), National Institutes of Health, Bethesda, MD, USA. christina.tatsi3@nih.gov.ORCID http://orcid.org/0000-0002-2882-4584

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

purposePituitary adenomas (PAs) constitute a rare pediatric diagnosis and their pathogenetic mechanisms are not clearly understood. The aim of this study was to evaluate the prevalence of genetic defects in pediatric PAs through germline and tumor testing, and to describe genotype-phenotype correlations.

methodsFifty-four pediatric patients with PAs and available germline and/or tumor samples were studied. Germline and/or tumor sequencing were reviewed for variants in genes previously associated with pituitary tumorigenesis.

resultsGermline genetic testing revealed a pathogenic variant in AIP gene in 2 patients with growth hormone excess (GHE) and a likely pathogenic variant in CDKN2A in a patient with Cushing's disease (CD). Somatic gene sequencing identified pathogenic variants in GNAS in 4/7 patients (57.1%) with GHE. 6/38 patients (15.8%) with CD had pathogenic variants in USP8 gene, and in one tumor pathogenic variants in PRKAR1A, TP53 and MEN1 genes were identified. Overall, pathogenic/likely pathogenic germline or somatic variants were identified in 14/54 patients (25.9%). When evaluating the genotype-phenotype correlations in patients with CD, patients with somatic USP8 pathogenic variants had larger tumors (median size: 9.5 mm [6.5, 13.3] vs. 6 mm [4.0, 7.0], p = 0.048), trend towards higher incidence of cavernous sinus invasion (50% vs. 12.5%, p = 0.06), and higher risk of non-remission after surgery (33.3% vs. 0%, p = 0.021) compared to patients without USP8 variants.

conclusionsSomatic USP8 pathogenic variants correlate with worse tumor behavior and patient outcomes in pediatric-onset CD. Unlike GH-secreting PAs, the genetic basis of the majority of pediatric corticotroph PAs remains unclear. Further studies are needed to explore the genetic drivers of pediatric CD. CLINICALTRIALS: GOV ID: NCT00001595, NCT03206099.

Indexed as

AdenomaEndopeptidasesEndosomal Sorting Complexes Required for TransportPituitary ACTH HypersecretionPituitary NeoplasmsUbiquitin ThiolesteraseAdolescentChildChild, PreschoolChromograninsFemaleGenetic Association StudiesGenotypeGerm-Line MutationGTP-Binding Protein alpha Subunits, GsHumansChromograninsEndopeptidasesEndosomal Sorting Complexes Required for TransportGNAS protein, humanGTP-Binding Protein alpha Subunits, GsUbiquitin ThiolesteraseUSP8 protein, humanCorticotroph tumorCushingGigantismPediatric pituitary adenomasSomatotroph tumor

Identifiers

PMID40813536
PMCPMC12354490

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.