Peer-reviewedCC BY 4.0Hormone Research in Pædiatrics1 Oct 2026

The Transient Pubertal Free Thyroxine Dip Should Not Be Misinterpreted as Central Hypothyroidism: A Case Series

Mark R. Garrelfs^1,2
Jacquelien J. Hillebrand^2,3
Annemieke C. Heijboer^2,3,4
Christiaan F. Mooij^1,2
A.S. Paul van Trotsenburg^1,2
Nitash Zwaveling-Soonawala^1,2

4 affiliations

¹Department of Pediatric Endocrinology, Emma Children’s Hospital, Amsterdam University Medical Centers, University of Amsterdam and Vrije Universiteit, Amsterdam, The Netherlands
²Amsterdam Gastroenterology, Endocrinology and Metabolism, Amsterdam, The Netherlands
³Department of Laboratory Medicine, Endocrine Laboratory, Amsterdam University Medical Centers, University of Amsterdam and Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
⁴Amsterdam Reproduction and Development Research Institute, Amsterdam, The Netherlands

Abstract

Introduction: During puberty, free thyroxine (fT4) concentrations transiently decrease with a nadir around Tanner stage 3. Due to the interindividual variation in timing of pubertal onset, this transient fT4 dip occurs at different ages and becomes less apparent within an age-specific reference interval (RI). This may result in fT4 concentrations temporarily falling below the lower limit of the RI when age-specific instead of Tanner stage-specific RIs are used. As thyroid stimulating hormone (TSH) levels usually remain within the age-specific RI, the resulting biochemical profile resembles central hypothyroidism and frequently triggers extensive, but often unnecessary diagnostic work-ups.

Case Presentation: We present two cases of asymptomatic adolescents with low fT4 concentrations in combination with a normal TSH, in whom central hypothyroidism was initially suspected but subsequently excluded. In all cases, fT4 concentrations normalized later in puberty without intervention.

Conclusion: This phenomenon likely reflects increased peripheral conversion of T4 to tri-iodothyronine (T3) under the influence of growth hormone and sex steroids. Awareness of this physiological phenomenon is essential to avoid misdiagnosis, overtreatment, and undue psychological stress. Our findings highlight the need for Tanner stage-specific fT4 RIs to guide thyroid function interpretation in adolescents.

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Cite

BibTeX RIS

BibTeX

@article{garrelfs2026transient,
  title = {{The Transient Pubertal Free Thyroxine Dip Should Not Be Misinterpreted as Central Hypothyroidism: A Case Series}},
  author = {Mark R. Garrelfs and Jacquelien J. Hillebrand and Annemieke C. Heijboer and Christiaan F. Mooij and A.S. Paul van Trotsenburg and Nitash Zwaveling-Soonawala},
  journal = {Hormone Research in Pædiatrics},
  year = {2026},
  month = oct,
  doi = {10.1159/hrp/adaag031},
  url = {https://doi.org/10.1159/hrp/adaag031},
  note = {CC BY 4.0},
}

RIS

TY  - JOUR
TI  - The Transient Pubertal Free Thyroxine Dip Should Not Be Misinterpreted as Central Hypothyroidism: A Case Series
AU  - Mark R. Garrelfs
AU  - Jacquelien J. Hillebrand
AU  - Annemieke C. Heijboer
AU  - Christiaan F. Mooij
AU  - A.S. Paul van Trotsenburg
AU  - Nitash Zwaveling-Soonawala
PY  - 2026
DA  - 2026/10/01
JO  - Hormone Research in Pædiatrics
DO  - 10.1159/hrp/adaag031
UR  - https://doi.org/10.1159/hrp/adaag031
AB  - Introduction: During puberty, free thyroxine (fT4) concentrations transiently decrease with a nadir around Tanner stage 3. Due to the interindividual variation in timing of pubertal onset, this transient fT4 dip occurs at different ages and becomes less apparent within an age-specific reference interval (RI). This may result in fT4 concentrations temporarily falling below the lower limit of the RI when age-specific instead of Tanner stage-specific RIs are used. As thyroid stimulating hormone (TSH) levels usually remain within the age-specific RI, the resulting biochemical profile resembles central hypothyroidism and frequently triggers extensive, but often unnecessary diagnostic work-ups.  Case Presentation: We present two cases of asymptomatic adolescents with low fT4 concentrations in combination with a normal TSH, in whom central hypothyroidism was initially suspected but subsequently excluded. In all cases, fT4 concentrations normalized later in puberty without intervention.  Conclusion: This phenomenon likely reflects increased peripheral conversion of T4 to tri-iodothyronine (T3) under the influence of growth hormone and sex steroids. Awareness of this physiological phenomenon is essential to avoid misdiagnosis, overtreatment, and undue psychological stress. Our findings highlight the need for Tanner stage-specific fT4 RIs to guide thyroid function interpretation in adolescents.
SN  - 1663-2818
SN  - 1663-2826
ER  -

Abstract

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