CClinicalTrials.gg
Not yet recruitingNCT07126353IpoMetUpdated Aug 17, 2025

Metabolic Risk Assessment in Prepubertal Children With Congenital Hypothyroidism

An observational study in Congenital Hypothyroidism and Metabolic Syndrome, sponsored by Buzzi Children's Hospital. Not yet recruiting at 1 site in Italy. Open to participants aged 5 Years to 12 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2025-08-17.

Sponsored by Buzzi Children's Hospital · Observational

Study type
Observational
Model
Cohort
Time perspective
Prospective
Enrollment
170
Ages
5 Years to 12 Years
Sex
All
01

Study summary

We propose a multicenter prospective study to define the prevalence and severity score of metabolic syndrome in a prepubertal pediatric cohort with congenital hypothyroidism, compared to a healthy and normal-weight pediatric population. These data will help to define whether hypothyroidism can be considered a risk factor for the metabolic health of the pediatric population. The possible identification of an at-risk metabolic profile will provide useful information to optimize the diagnostic and monitoring pathway for affected children.

Read the detailed description

Primary congenital hypothyroidism is the most common endocrine disorder in childhood and can present in either a permanent or transient form. Prolonged thyroid hormone deficiency can cause widespread damage affecting multiple organs and systems. Exposure to thyroid hormone deficiency during fetal and/or neonatal life has particularly severe consequences on the central nervous system, leading to neurocognitive delay. Appropriate and timely hormone replacement therapy (L-thyroxine) can prevent such outcomes, provided it is initiated early.

Thyroid hormones play a crucial role not only in growth and organ development but also in metabolic homeostasis. Thyroid function lies at the crossroads of multiple metabolic pathways. They have multiple effects on glucose and lipid metabolism, specifically by increasing glucose levels, fatty acid oxidation in muscle and liver, and lipolysis in adipose tissue. They also contribute to blood pressure regulation, thereby influencing the prevalence of metabolic syndrome, which is itself a key predictor of type 2 diabetes, cardiovascular diseases, and neurodegenerative conditions.Thyroid function plays a central regulatory role at the intersection of key metabolic pathways. Although, the role of thyroid hormones in metabolic processes is well established, and a bidirectional relationship between metabolic dysfunction and thyroid hypofunction has been reported in the adult population, data on metabolic risk in pediatric patients with congenital hypothyroidism are currently lacking.

The primary aim of this multicenter project is to assess the prevalence of metabolic syndrome in patients with congenital hypothyroidism and to determine whether this population presents a higher metabolic risk profile compared to the general population. As secondary objectives, this prospective study aims to:

  1. Define the prevalence and severity score of metabolic syndrome in a prepubertal pediatric cohort with congenital hypothyroidism, compared to a pediatric population with obesity.
  2. Evaluate the correlations between individual metabolic dysfunction parameters and the clinical and hormonal profile (including thyroid hormone levels and thyroid hormone sensitivity indices).
  3. Assess the correlations between the metabolic profile and renal function.
  4. Assess the correlations between the hormonal profile and renal function. To achieve these objectives, auxological parameters, vital signs (including blood pressure and heart rate), and metabolic profile data (glucose and lipid profiles, renal function, and hormonal status - FT3, FT4, TSH and thyroid hormone resistence indices TSHI, TT4RI, TT3RI, TFQI, PTFQI) will be collected for each enrolled subject. These parameters will be evaluated on peripheral blood samples collected during routine blood monitoring already scheduled according to established follow up. The potential presence of metabolic syndrome will be evaluated in each enrolled patient. The severity of the metabolic disorder will be evaluated using the Metabolic Score (MetS).

Data analysis will be performed using the statistical packages R 4.0.5 (R Core Team, 2021) and STATA (version 15.1, 2017, Stata Corporation, College Station, Texas, USA).

02

Conditions studied

  • Congenital Hypothyroidism
  • Metabolic Syndrome

Keywords

  • Congenital hypothyroidism
  • metabolic syndrome
  • Obesity
03

Who can participate

Ages eligible
5 Years to 12 Years
Sexes eligible
All
Accepts healthy volunteers
Yes
Sampling method
Non-probability sample

Study population

We enrolled patients affected by permanent congenital hypothyroidism in prepubertal age and healthy childrens in prepubertal age to compare them with each other.

Inclusion criteria

  • Pubertal stage Tanner 1
  • Permanent congenital hypothyroidism
  • All ethnic groups
  • Informed consent signature

Exclusion criteria

Exclusion Criteria:

  • Age\< 5 years
  • Pubertal stage Tanner 2-5
  • Transient congenital hypothyroidism or other type of hypothyroidism
04

Study design

Observational model
Cohort
Time perspective
Prospective
Enrollment
170 participants (estimated)
Target follow-up
12 Months
Patient registry
Yes

Groups and cohorts

  • Permanent congenital hypothyroidism

    170 patients in prepubertal age.

    Other: prospective observational study (clinical, hormonal and auxological data)

  • Healthy childrens normal weight

    170 childrens in prepubertal age.

    Other: prospective observational study (clinical, hormonal and auxological data)

  • Healthy childrens overweight/obese

    170 patients in prepubertal age

    Other: prospective observational study (clinical, hormonal and auxological data)

Interventions

  • Otherprospective observational study (clinical, hormonal and auxological data)

    We collect clinical, hormonal and auxological data and compare them between the two groups.

05

What researchers measure

Primary outcomes

  1. Metabolic syndrome (MS)

    Presence of at least 3 of the following parameters: 1. BMI z-score ≥ 2 and/or waist-to-height ratio (WHtR) \> 0.5 2. Fasting blood glucose ≥ 100 mg/dL and/or TryG index ≥ 7.88 3. Total cholesterol ≥ 200 mg/dL 4. HDL cholesterol \< 40 mg/dL and/or LDL cholesterol ≥ 130 mg/dL 5. Triglycerides (TG) ≥ 100 mg/dL for ages 0-9 years; ≥ 130 mg/dL for ages \>10 years 6. Systolic and/or diastolic blood pressure (SBP and/or DBP) ≥ 90th percentile for age and sex

    Time frame: At the time of enrollment

  2. Metabolic score (MeTs)

    Males MetS z-score = -4.931 + 0.2804 \* BMI z-score - 0.0257 \* HDL + 0.0189 \* SBP + 0.6240 \* log(triglycerides) + 0.0140 \* fasting glucose Females MetS z-score = -4.3757 + 0.4849 \* BMI z-score - 0.0176 \* HDL-C + 0.0257 \* SBP + 0.3172 \* log(triglycerides) + 0.0083 \* fasting glucose

    Time frame: At the time of enrollment

06

Study locations

1 site
07

References and documents

Publications

  • Jostel A, Ryder WD, Shalet SM. The use of thyroid function tests in the diagnosis of hypopituitarism: definition and evaluation of the TSH Index. Clin Endocrinol (Oxf). 2009 Oct;71(4):529-34. doi: 10.1111/j.1365-2265.2009.03534.x. Epub 2009 Feb 18. PubMed 19226261 ↗
  • Iwamoto Y, Kimura T, Tatsumi F, Sugisaki T, Kubo M, Nakao E, Dan K, Wamata R, Iwamoto H, Takahashi K, Sanada J, Fushimi Y, Katakura Y, Shimoda M, Nakanishi S, Mune T, Kaku K, Kaneto H. Effect of Hyperglycemia-Related Acute Metabolic Disturbance on Thyroid Function Parameters in Adults. Front Endocrinol (Lausanne). 2022 May 12;13:869869. doi: 10.3389/fendo.2022.869869. eCollection 2022. PubMed 35634497 ↗
  • Dietrich JW, Landgrafe-Mende G, Wiora E, Chatzitomaris A, Klein HH, Midgley JE, Hoermann R. Calculated Parameters of Thyroid Homeostasis: Emerging Tools for Differential Diagnosis and Clinical Research. Front Endocrinol (Lausanne). 2016 Jun 9;7:57. doi: 10.3389/fendo.2016.00057. eCollection 2016. PubMed 27375554 ↗
  • Laclaustra M, Moreno-Franco B, Lou-Bonafonte JM, Mateo-Gallego R, Casasnovas JA, Guallar-Castillon P, Cenarro A, Civeira F. Impaired Sensitivity to Thyroid Hormones Is Associated With Diabetes and Metabolic Syndrome. Diabetes Care. 2019 Feb;42(2):303-310. doi: 10.2337/dc18-1410. Epub 2018 Dec 14. PubMed 30552134 ↗
  • Lakhani G, Patel P, Patel TC. A Cross-Sectional Study on the Prevalence of Subclinical Hypothyroidism in Metabolic Syndrome Patients at a Tertiary Care Hospital. Cureus. 2024 Aug 26;16(8):e67851. doi: 10.7759/cureus.67851. eCollection 2024 Aug. PubMed 39323691 ↗
  • Thakur R, Kumar S, Neeraj RK, Saleem M, Kumar C, Mohan L. Evaluation of the Association between Insulin Resistance and Subclinical Hypothyroidism Using Triglyceride-Glucose Index: a Cross-Sectional Study. Maedica (Bucur). 2024 Jun;19(2):255-259. doi: 10.26574/maedica.2024.19.2.255. PubMed 39188835 ↗
  • Verma DP, Chaudhary SC, Singh A, Sawlani KK, Gupta KK, Usman K, Reddy HD, Patel ML, Verma SK, Atam V. Hypothyroidism in Metabolic Syndrome. Ann Afr Med. 2024 Oct 1;23(4):717-722. doi: 10.4103/aam.aam_25_24. Epub 2024 Sep 14. PubMed 39279179 ↗
  • Xie H, Li N, Zhou G, He Z, Xu X, Liu Q, Wang H, Han J, Shen L, Yu P, Chen J, Chen X. The association between the thyroid feedback quantile-based index and serum uric acid in U.S. adults. Eur J Med Res. 2023 Jul 27;28(1):259. doi: 10.1186/s40001-023-01214-3. PubMed 37501165 ↗
  • Xie Y, Wang Z, Chen Z. Analysis of Subclinical Thyroid Dysfunction and Metabolic Abnormality in 28568 Healthy People. Int J Endocrinol. 2023 Oct 16;2023:5216945. doi: 10.1155/2023/5216945. eCollection 2023. PubMed 37876378 ↗
  • Zhong L, Liu S, Yang Y, Xie T, Liu J, Zhao H, Tan G. Metabolic syndrome and risk of subclinical hypothyroidism: a systematic review and meta-analysis. Front Endocrinol (Lausanne). 2024 Jun 25;15:1399236. doi: 10.3389/fendo.2024.1399236. eCollection 2024. PubMed 38982986 ↗
  • Di Bonito P, Corica D, Marzuillo P, Di Sessa A, Licenziati MR, Faienza MF, Calcaterra V, Franco F, Maltoni G, Valerio G, Wasniewska M. Sensitivity to Thyroid Hormones and Reduced Glomerular Filtration in Children and Adolescents with Overweight or Obesity. Horm Res Paediatr. 2024;97(4):383-387. doi: 10.1159/000534472. Epub 2023 Oct 9. PubMed 37812927 ↗
  • Calcaterra V, Mameli C, Macedoni M, De Silvestri A, Sgambetterra L, Nosenzo F, Redaelli FC, Petitti A, Bosetti A, Zuccotti G. Investigating the connection among thyroid function, sensitivity to thyroid hormones, and metabolic syndrome in euthyroid children and adolescents affected by type 1 diabetes. J Pediatr Endocrinol Metab. 2024 Mar 12;37(4):347-352. doi: 10.1515/jpem-2023-0565. Print 2024 Apr 25. PubMed 38462926 ↗
  • Calcaterra V, Gazzarri A, De Silvestri A, Madia C, Baldassarre P, Rossi V, Garella V, Zuccotti G. Thyroid function, sensitivity to thyroid hormones, and metabolic syndrome in euthyroid children and adolescents with Down syndrome. J Endocrinol Invest. 2023 Nov;46(11):2319-2325. doi: 10.1007/s40618-023-02086-4. Epub 2023 Apr 11. PubMed 37040064 ↗
  • Biondi B. Subclinical Hypothyroidism in Patients with Obesity and Metabolic Syndrome: A Narrative Review. Nutrients. 2023 Dec 27;16(1):87. doi: 10.3390/nu16010087. PubMed 38201918 ↗
  • Alwan H, Ribero VA, Efthimiou O, Del Giovane C, Rodondi N, Duntas L. A systematic review and meta-analysis investigating the relationship between metabolic syndrome and the incidence of thyroid diseases. Endocrine. 2024 May;84(2):320-327. doi: 10.1007/s12020-023-03503-7. Epub 2023 Sep 9. PubMed 37688711 ↗
  • Alsulami SS, Baig M, Albeladi AH, Alyoubi SB, Alsubaie SA, Albeladi SA, Ghamri KA, Alraiqi AMS, Alyoubi SM, Almutairi WA. Correlation between Subclinical Hypothyroidism and Metabolic Syndrome: A Retrospective Study. Saudi J Med Med Sci. 2023 Jul-Sep;11(3):250-256. doi: 10.4103/sjmms.sjmms_225_22. Epub 2023 Jul 15. PubMed 37533656 ↗
  • Abha P, Keshari JR, Sinha SR, Nishant K, Kumari R, Prakash P. Association of Thyroid Function With Lipid Profile in Patients With Metabolic Syndrome: A Prospective Cross-Sectional Study in the Indian Population. Cureus. 2023 Sep 5;15(9):e44745. doi: 10.7759/cureus.44745. eCollection 2023 Sep. PubMed 37809190 ↗

Individual participant data

Plan to share: Undecided

08

Registry details

Key details

Study ID
NCT07126353
Lead sponsor
Buzzi Children's Hospital
Collaborators
Federico II University, IRCCS Ospedale San Raffaele, Policlinico di Bari Giovanni XXIII, Azienda Ospedaliero Universitaria Policlinico Modena, Azienda Ospedaliero-Universitaria di Parma, Azienda Ospedaliera Ospedale Infantile Regina Margherita Sant'Anna, Azienda Ospedaliera Sant'Anna, University Hospital Perugia, University of L'Aquila, Clinica Pediatrica Università di Novara, Santobono-Pausilpon Hospital, Policlinico G . Martino, Messina Italy, IRCCS Azienda Ospedaliero-Universitaria di Bologna, University Hospital of Ancona
Responsible party
Valeria Calcaterra (Prof, Buzzi Children's Hospital) — Principal investigator
First posted
Aug 17, 2025
Start date
Sep 2025 (estimated)
Primary completion
Jul 2026 (estimated)
Completion
Oct 2026 (estimated)
Last update
Aug 17, 2025

Study contacts

Valeria Calcaterra, MD
Contact
valeria.calcaterra@unipv.it
+39 0263631

Oversight

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

Not currently enrolling

This study is not yet recruiting, as verified in Aug 2025. You cannot join it, but the record below documents what was studied.

Follow this study

Get an email when the registry record changes — status, dates, results — or when someone posts here.

Sign in to follow

Discussion

Questions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.

Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.

Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

Start the discussion