Evidence map›Paper›PMID 25972901›Full record

ArticleInternational journal of pediatric endocrinology2015

Patterns of thyroid hormone levels in pediatric medullary thyroid carcinoma patients on vandetanib therapy.

Maya Lodish, Alexandra Gkourogianni, Ethan Bornstein, Ninet Sinaii, Elizabeth Fox, Meredith Chuk, Leigh Marcus, Srivandana Akshintala, Frank Balis, Brigitte Widemann and 1 more

Registry-linked trialOpen access · diamondAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in International journal of pediatric endocrinology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00514046 (Phase I/II Trial of Vandetanib), which is not on this map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
1.6field-weighted citation impact, top 16% of its field
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.

NCT00514046 phase1 / phase2completednot on this map

Phase I/II Trial of Vandetanib (ZD6474, ZACTIMA) in Children and Adolescents With Hereditary Medullary Thyroid Carcinoma

TypeinterventionalSponsorNational Cancer Institute (NCI)Ran2007 to 2020Enrolled17ConditionsMedullary Thyroid Carcinoma, Multiple Endocrine Neoplasia Type 2A, Multiple Endocrine Neoplasia Type 2BArmsVandetanib
3 · Its place in the literature

Who cites it

4 citing papers in PubMed, 11 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Update on the treatment of hypothyroidism.Current opinion in oncology · 2016
    Review
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

11 authors at 4 institutions in 1 country.

Maya LodishNational Institute of Child Health & Human Development, National Institutes of Health (NIH), Building 10-CRC, room 1-3330 10 Center Drive, Bethesda, MD 20892 USA.
Alexandra GkourogianniNational Institute of Child Health & Human Development, National Institutes of Health (NIH), Building 10-CRC, room 1-3330 10 Center Drive, Bethesda, MD 20892 USA.
Ethan BornsteinNational Institute of Child Health & Human Development, National Institutes of Health (NIH), Building 10-CRC, room 1-3330 10 Center Drive, Bethesda, MD 20892 USA.
Ninet SinaiiEpidemiology & Biostatistics, CC, NIH BG 10 RM 2 N228 10 Center Drive, Bethesda, MD 20814 USA.
Elizabeth FoxThe Children's Hospital of Philadelphia, Colket Translational Research Building 4016, 3501 Civic Center Blvd, Philadelphia, PA 19104 USA.
Meredith ChukPediatric Oncology Branch, National Cancer Institute, NIH BG 10-CRC RM 1-5750 10 Center Dr., Bethesda, MD 20814 USA.
Leigh MarcusPediatric Oncology Branch, National Cancer Institute, NIH BG 10-CRC RM 1-5750 10 Center Dr., Bethesda, MD 20814 USA.
Srivandana AkshintalaPediatric Oncology Branch, National Cancer Institute, NIH BG 10-CRC RM 1-5750 10 Center Dr., Bethesda, MD 20814 USA.
Frank BalisThe Children's Hospital of Philadelphia, Colket Translational Research Building 4016, 3501 Civic Center Blvd, Philadelphia, PA 19104 USA.
Brigitte WidemannPediatric Oncology Branch, National Cancer Institute, NIH BG 10-CRC RM 1-5750 10 Center Dr., Bethesda, MD 20814 USA.
Constantine A StratakisNational Institute of Child Health & Human Development, National Institutes of Health (NIH), Building 10-CRC, room 1-3330 10 Center Drive, Bethesda, MD 20892 USA.
National Cancer Institute · USNational Institutes of Health · USChildren's Hospital of Philadelphia · USEunice Kennedy Shriver National Institute of Child Health and Human Development · US

Funding

Molecular Genetics of Endocrine Tumors and Related DisordersZIAHD008920 · NICHD · EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT · PI STRATAKIS, CONSTANTINE A. · 2012 to 2021
$25.8M
Therapies for patients with rare tumors and genetic tumor predispositionZIASC010354 · NCI · DIVISION OF CLINICAL SCIENCES - NCI · PI WIDEMANN, BRIGITTE · 2009 to 2025
$19.2M
6 · The paper itself

Abstract

backgroundTyrosine kinase inhibitors (TKIs) have been associated with elevated TSH as a drug class effect. Prior studies of vandetanib in adults with medullary thyroid carcinoma (MTC) described an increase in levothyroxine (LT) requirement. We studied TSH, free T4, and LT dosing in children and adolescents enrolled in the phase I/II trial of vandetanib for medullary thyroid cancer (MTC).

methodsData from 13 patients with multiple endocrine neoplasia type 2B (MEN 2B) and MTC were analyzed [6 M, 7 F, median age 13.0 y (9.1-17.3)] Eleven patients (85%) had undergone prior thyroidectomy and all received single-drug therapy with vandetanib for > 6 months. Confirmed compliance with vandetanib (67-150 mg/m(2)/day) and LT was a necessary inclusion criterion.

resultsWhile on vandetanib treatment, all 11 athyerotic patients exhibited significantly increased TSH levels. The baseline TSH level was 4.37 mclU/ml (0.08 - 23.30); in comparison, the first peak TSH concentration on vandetanib was 15.70 mclU/ml (12.50 - 137.00, p = 0.0010). The median time to reach the initial peak of elevated TSH was 1.8 months (0.3 - 9.3). Free T4 levels remained within the normal reference range. An increase from a baseline LT dose of 91 mcg/m(2)/day (±24) to 116 mcg/m(2)/day (±24) was required in order to resume normative TSH levels (p = 0.00005), equal to an increase of 36.6% (±16.56) in the dosage of LT in mcg/day. For the 2 patients with intact thyroid glands, free T4 and TSH remained normal over a combined 6 patient years of follow up.

conclusionsIn our cohort of pediatric MTC patients, athyreotic patients with preexisting hypothyroidism developed increased TSH and reduced free T4 during the first few months of treatment with vandetanib, necessitating an increase in LT dosage. Additional patients with normal thyroid function before treatment and intact glands (n = 2) maintained normal thyroid function tests during treatment. Elevated TSH in athyreotic patients may be due to an indirect effect of vandetanib on the metabolism of thyroid hormone, or to altered TSH sensitivity at the pituitary. Proper recognition and management of abnormal thyroid hormone levels is critical in growing children on TKIs.

trial registrationClinicalTrials.gov Identifier: NCT00514046.

Indexed as

Medullary thyroid carcinoma (MTC)Multiple Endocrine Neoplasia type 2 B (MEN2B)Tyrosine kinase inhibitor (TKIs)Vandetanib

Identifiers

PMID25972901
PMCPMC4429462
OpenAlexW2111371219

What OpenQuestion holds

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LicenceCC BY
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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.