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Enrolling by invitationNCT07544290IPER6Updated Apr 22, 2026

Autoimmune Hyperthyroidism in Prepubertal Children

An observational study in Autoimmune Hyperthyroidism and Children, sponsored by IRCCS Ospedale San Raffaele. Enrolling by invitation at 1 site in Italy. Open to participants aged 2 Years to 18 Years. Per ClinicalTrials.gov, last updated 2026-04-22.

Sponsored by IRCCS Ospedale San Raffaele · Observational

Study type
Observational
Model
Case-control
Time perspective
Retrospective
Enrollment
100
Ages
2 Years to 18 Years
Sex
All
01

Study summary

The investigators propose a multicenter retrospective study to assess clinical, biochemical, and auxological characteristics at diagnosis and during follow-up in a cohort of Caucasian pediatric patients diagnosed with autoimmune hyperthyroidism before puberty. These prepubertal patients will be compared with a control group of post-pubertal patients with Graves' disease.

This study aims to enhance the understanding of autoimmune hyperthyroidism in prepubertal patients by providing a detailed evaluation of disease onset, therapeutic response, and growth-related outcomes. The inclusion of a carefully matched post-pubertal control group will allow for robust comparative analysis and identification of age-dependent clinical patterns and prognostic indicators, ultimately supporting more tailored and effective management strategies in pediatric populations at this particular age.

Read the detailed description

There are only few studies in literature focusing on the analysis of cohorts of patients with autoimmune hyperthyroidism with onset exclusively in early childhood. The investigators therefore propose this study with the aim of retrospectively assessing characteristics at onset and during follow-up in a cohort of Caucasian hyperthyroid subjects diagnosed with the disease before puberty.

OBJECTIVES AND ENDPOINTS

  • Primary Objective To evaluate the clinical and biochemical features at the onset of autoimmune hyperthyroidism in patients diagnosed in prepubertal age Secondary Objectives

    1. To evaluate of biochemical parameters during medical therapy
    2. To evaluate of auxological parameters at diagnosis and during follow-up
    3. To compare the previous data with the clinical and biochemical features at diagnosis and during the follow-up in patients diagnosed with Graves during the pubertal age (> Tanner 2)

      Inclusion Criteria 1. Subjects with autoimmune hyperthyroidism 2. Prepubertal stage (Tanner 1) at diagnosis Exclusion Criteria 3. Subjects with hyperthyroidism not of autoimmune aetiology 4. Pubertal stage (>Tanner 2) at diagnosis

      Sample size:

  • 50 hyperthyroid subjects diagnosed with the disease before puberty
  • 50 hyperthyroid subjects diagnosed with the disease during and post puberty

The data will then be analyzed using PRISM software. The principal investigator will verify the completeness, correctness, consistency and congruence of the reported data.

02

Conditions studied

  • Autoimmune Hyperthyroidism
  • Children

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Keywords

  • pubertal age
  • autoimmune hyperthyroidism
  • graves
  • prepubertal age
  • antithyroid drugs
03

Who can participate

Ages eligible
2 Years to 18 Years
Sexes eligible
All
Accepts healthy volunteers
No
Sampling method
Non-probability sample

Study population

We enrolled all patients affected by autoimmune hyperthyroidism in prepubertal age and pubertal age to compare 2 groups

Inclusion criteria

-Subjects with autoimmune hyperthyroidism

Exclusion criteria

Exclusion Criteria:

  • Subjects with hyperthyroidism not of autoimmune aetiology
04

Study design

Observational model
Case-control
Time perspective
Retrospective
Enrollment
100 participants (estimated)
Patient registry
No

Groups and cohorts

  • 50 patients affected by autoimmune hyperthyroidism in prepubertal age

    Other: restrospective observational study

  • 50 patients affected by autoimmune hyperthyroidism in pubertal age

    Other: restrospective observational study

Interventions

  • Otherrestrospective observational study

    we collect clinical, hormonal and follow up data and compare data in prepubertal and pubertal patients affected by autoimmune hyperthyroidism

05

What researchers measure

Primary outcomes

  1. Number of clinical signs of hyperthyroidism at diagnosis

    Total number of clinical signs (including goiter, exophthalmos, and tachycardia) present at diagnosis, recorded as a count per patient.

    Time frame: Day 0 (retrospective assessment at diagnosis)

  2. Number of clinical symptoms at diagnosis

    Total number of symptoms per patient, categorized as none (0), mild (1-2), moderate (3-5), or severe (\>5).

    Time frame: Day 0

  3. Serum free triiodothyronine (FT3) levels at diagnosis

    Measurement of serum FT3 (pmol/L) at diagnosis.

    Time frame: Day 0

  4. Serum free thyroxine (FT4) levels at diagnosis

    Measurement of serum FT4 (pmol/L) at diagnosis.

    Time frame: Day 0

  5. Serum thyroid-stimulating hormone (TSH) levels at diagnosis

    Measurement of serum TSH (mIU/L) at diagnosis.

    Time frame: Day 0

  6. Serum TSH receptor antibody (TRAb) levels at diagnosis

    Measurement of TRAb levels (IU/L) at diagnosis.

    Time frame: Day 0

  7. Thyroid autoantibody positivity at diagnosis (TPOAb and TgAb)

    Presence or absence of thyroid autoantibodies (TPOAb and TgAb), reported as positive/negative.

    Time frame: Day 0

Secondary outcomes

  1. Duration of antithyroid drug therapy

    Time in months from initiation of antithyroid drug therapy to treatment discontinuation or switch to definitive therapy, whichever occurs first.

    Time frame: Baseline (treatment initiation) to treatment discontinuation (up to 24 months)

  2. Remission rate after antithyroid drug therapy

    Proportion of patients achieving sustained normalization of thyroid function (TSH, FT3, FT4) for at least 12 months after discontinuation of therapy.

    Time frame: At 24 months after treatment initiation

  3. Rate of definitive treatment (thyroidectomy or radioactive iodine therapy)

    Proportion of patients requiring definitive treatment, defined as thyroidectomy or radioactive iodine therapy.

    Time frame: Baseline to 24 months

  4. Serum TSH receptor antibody (TRAb) levels at time of the definitive treatment

    Measurement of serum TRAb levels (IU/L) at the time of transition to definitive therapy.

    Time frame: At time of definitive treatment (up to 24 months)

  5. Time to normalization of thyroid function

    Time in weeks from initiation of antithyroid therapy to normalization of FT3, FT4, and TSH levels.

    Time frame: Baseline to normalization (up to 12 months)

  6. Aauxological parameters at diagnosis and during follow-up

    delta target height

    Time frame: day 0, diagnosis; at 6 months; at 12 months

  7. Number of antithyroid drug discontinuation attempts

    Number of attempts to discontinue antithyroid therapy per patient, categorized as successful or unsuccessful based on biochemical remission.

    Time frame: Baseline to 24 months

  8. Annual growth velocity during follow-up

    Change in height per year (cm/year).

    Time frame: Baseline to 24 months

  9. Bone age during follow-up

    Bone age assessed using Greulich and Pyle method.

    Time frame: At baseline, 12 months, and 24 months

06

Study locations

1 site
  • IRCCS Ospedale San Raffaele
    Milan, Italy 20132, Italy
07

References and documents

Publications

  • Gu Y, Liang X, Liu M, Wu D, Li W, Cao B, Li Y, Su C, Chen J, Gong C. Clinical features and predictors of remission in children under the age of 7 years with Graves' disease. Pediatr Investig. 2020 Sep 27;4(3):198-203. doi: 10.1002/ped4.12219. eCollection 2020 Sep. PubMed 33150314 ↗
  • Chen J, Eng L & Lam L. MON-263 Graves' disease presenting as chronic diarrhea in a toddler. Journal of the Endocrine Society 2019
  • Jonak O, Polubok J, Barg E. Graves' disease in 2.5 years old girl - 6-years-long observation. Pediatr Endocrinol Diabetes Metab. 2016;22(2):76-79. doi: 10.18544/PEDM-22.02.0055. PubMed 28329777 ↗
  • Azova S, Rajabi F, Modi BP, Mansfield L, Jonas MM, Drobysheva A, Boyd TK, Wassner AJ, Smith JR. Graves' disease in a five-month-old boy with an unusual treatment course. J Pediatr Endocrinol Metab. 2020 Dec 15;34(3):401-406. doi: 10.1515/jpem-2020-0549. Print 2021 Mar 26. PubMed 33675208 ↗
  • Shulman DI, Muhar I, Jorgensen EV, Diamond FB, Bercu BB, Root AW. Autoimmune hyperthyroidism in prepubertal children and adolescents: comparison of clinical and biochemical features at diagnosis and responses to medical therapy. Thyroid. 1997 Oct;7(5):755-60. doi: 10.1089/thy.1997.7.755. PubMed 9349579 ↗
  • Lazar L, Kalter-Leibovici O, Pertzelan A, Weintrob N, Josefsberg Z, Phillip M. Thyrotoxicosis in prepubertal children compared with pubertal and postpubertal patients. J Clin Endocrinol Metab. 2000 Oct;85(10):3678-82. doi: 10.1210/jcem.85.10.6922. PubMed 11061522 ↗
  • Francis N, Francis T, Lazarus JH, Okosieme OE. Current controversies in the management of Graves' hyperthyroidism. Expert Rev Endocrinol Metab. 2020 May;15(3):159-169. doi: 10.1080/17446651.2020.1754192. Epub 2020 Apr 21. PubMed 32315207 ↗
  • Mooij CF, Cheetham TD, Verburg FA, Eckstein A, Pearce SH, Leger J, van Trotsenburg ASP. 2022 European Thyroid Association Guideline for the management of pediatric Graves' disease. Eur Thyroid J. 2022 Jan 1;11(1):e210073. doi: 10.1530/ETJ-21-0073. PubMed 34981748 ↗
  • Kaplowitz PB, Vaidyanathan P. Update on pediatric hyperthyroidism. Curr Opin Endocrinol Diabetes Obes. 2020 Feb;27(1):70-76. doi: 10.1097/MED.0000000000000521. PubMed 31789723 ↗
  • Leger J, Olivieri A, Donaldson M, Torresani T, Krude H, van Vliet G, Polak M, Butler G; ESPE-PES-SLEP-JSPE-APEG-APPES-ISPAE; Congenital Hypothyroidism Consensus Conference Group. European Society for Paediatric Endocrinology consensus guidelines on screening, diagnosis, and management of congenital hypothyroidism. Horm Res Paediatr. 2014;81(2):80-103. doi: 10.1159/000358198. Epub 2014 Jan 21. PubMed 24662106 ↗

Individual participant data

Plan to share: Undecided

08

Registry details

Key details

Study ID
NCT07544290
Lead sponsor
IRCCS Ospedale San Raffaele
Collaborators
University of Campania Luigi Vanvitelli, University of Genova, S. Anna Hospital, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Azienda Ospedaliero-Universitaria di Parma, Azienda Ospedaliero-Universitaria Consorziale Policlinico di Bari, Azienda Ospedaliera Universitaria Integrata Verona, Fondazione IRCCS San Gerardo dei Tintori, Azienda Ospedaliera Universitaria Policlinico "G. Martino", Azienda Ospedaliera SS. Antonio e Biagio e Cesare Arrigo di Alessandria, Università di Torino, Torino, Federico II University, Buzzi Children's Hospital
Responsible party
Vigone Maria Cristina (medical doctor - Specialist in Pediatrics Expert in Pediatric Endocrinology Head of the Thyroid Pathology Outpatient Clinic, IRCCS Ospedale San Raffaele) — Principal investigator
First posted
Apr 22, 2026
Start date
Jan 1, 2026
Primary completion
Jan 1, 2026
Completion
Dec 2026 (estimated)
Last update
Apr 22, 2026

Oversight

Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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