Congenital HypothyroidismNCT04734457
Final Height in Patients With CH Diagnosed by the Screening
An observational study of Congenital Hypothyroidism, run by Ain Shams University at 1 site in Egypt.
Trial summary
The aim of this study is to evaluate longitudinal growth and final height in patients with Congenital Hypothyroidism detected by neonatal screening and factors affecting it. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Congenital Hypothyroidism
- What is being tested?
- Levothyroxin
- How many people
- 60 participants
- Where
- 1 siteEgypt
- Study dates
- 2 Nov 2021to 1 Apr 2022
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: All the patients suffering from CH diagnosed by Egyptian neonatal screening program and have a documented history of CH who received treatment at endocrinology clinic, Children's Hospital, Ain Shams University.
Who may be able to join
- Patients having a documented history of CH diagnosed by Egyptian neonatal screening program.
- Patients receiving L-thyroxine (L-T4) since the diagnosis is established.
Who cannot join
- Patients who are non-compliant on L-thyroxine (L-T4) and failed to follow up at the clinic on regular basis.
- Patients who were missed from diagnosis by neonatal screening.
- Patients with associated hormonal disorders affecting same parameters concerned in the study.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Final Height in Patients With Congenital Hypothyroidism Diagnosed by Neonatal Screening
The aim of this study is to evaluate longitudinal growth and final height in patients with Congenital Hypothyroidism detected by neonatal screening and factors affecting it.
Read the detailed description
Linear growth and final height are reported as rather normal in patients with CH diagnosed through the screening and the target height is the most important factor determining linear growth. Data on final height in patients with CH suggest that adult height is significantly correlated with parental height and the mean L-Thyroxine daily dose administered over the first 6 months of treatment. The lowest recommended dose during this period is 8.5μg/kg/day. Periodical adjustments of L-Thyroxine daily dose should be guided by clinical observation and serum free T4 levels.
To our knowledge this is the first study from our center to assess final height in patients with congenital hypothyroidism diagnosed through the Egyptian neonatal screening program.
A complex network of endocrine signals stimulates the process of longitudinal growth including growth hormone, insulin-like growth factor-1, glucocorticoids, thyroid hormone, estrogen, androgens, vitamin D and leptin.
Thyroid hormones are essential for development and normal bone growth. Biochemical studies have shown that thyroid hormones can affect the expression of various bone markers in the serum, reflecting changes in bone remodeling which involves both osteoblastic and osteoclastic activities.
Thyroid hormones act through chondrocytes bearing thyroid hormone receptors (TRs) to modulate growth plate proliferation, differentiation and vascular invasion. Several mechanisms mediate these functions including direct action on the chondrocytes, osteoblasts and mast cells. It also works through interaction with other hormones and growth factors acting in endocrine, paracrine and autocrine fashions.
Overall, T3 acts via TRα in chondrocytes and osteoblasts to regulate intramembranous and endochondral ossification and control the rate of linear growth, bone maturation and mineralization,T4 induces the expression of both type II and X collagen and chondrocyte hypertrophy.
Hypothyroidism in children causes growth arrest, delayed bone maturation, and epiphyseal dysgenesis that can result in short stature and delayed closure of the epiphyses.
In severe undiagnosed cases, complete post-natal growth arrest and skeletal dysplasia occurs with characteristic X-ray features including stippled epiphyses reflecting epiphyseal dysgenesis, congenital hip dislocation, vertebral immaturity, scoliosis, patent fontanelles and sutures and delayed eruption of teeth.
Prompt treatment of patients suffering from CH with thyroid hormone replacement induces a period of rapid catch-up growth in which skeletal maturation and bone age are also accelerated. Ultimately, normal adult height can be expected.
It is controversial whether factors as the degree of hypothyroidism at diagnosis, the timing of the onset of treatment and the doses of replacement L-thyroxine (L-T4) affect linear growth in children with congenital hypothyroidism, detected by screening and treated from early infancy
- Conditions
- Congenital Hypothyroidism
- Being tested
- Levothyroxin
- Keywords
- Final Height, Neonatal screening
- Medical subject headings
- Congenital Hypothyroidism
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LevothyroxinDrug
Also called neonatal screening
We assess the effect of early diagnosis of CH by neonatal screening and start of treatment on the final height of the patients
What is being measured
The primary outcome is the main question the study is designed to answer.
Assessment of change of Final Height in patients with Congenital Hypothyroidism diagnosed by neonatal screening
The investigators assess the effect of early diagnosis and early levothyroxine start on the change in longitudinal growth in patients with Congenital Hypothyroidism.
Measured: Since the diagnosis is established by neonatal screening during first week of life height will be assessed every 6 months with follow up throughout the study period until the study subject reaches an average of 18 years of age( final height reached).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Feb 2021
- Study start2 Nov 2021 (estimated)
- Primary completion1 Mar 2022 (estimated)
- Study completion1 Apr 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (12)Papers the sponsor has linked to this study.
- Other trials for Congenital HypothyroidismStudies of the same condition, open and under way.
- More trials run by Ain Shams UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Retrospective
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Ain Shams University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Mohamed Nader, Ain Shams University
- Investigators
- Wessam Mouharram, PhD, Study director, Ain Shams UniversityRana Mahmoud, PhD, Study director, Ain Shams University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04734457
- Sponsor's protocol ID
- Final height in CH patients
- Status last verified
- Oct 2021
- First submitted
- 11 Jan 2021
- Last updated
- 5 Oct 2021
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Bain P, Toublanc JE. Adult height in congenital hypothyroidism: prognostic factors and the importance of compliance with treatment. Horm Res. 2002;58(3):136-42. doi: 10.1159/000064489.
PubMed 12218379Bassett JH, Williams AJ, Murphy E, Boyde A, Howell PG, Swinhoe R, Archanco M, Flamant F, Samarut J, Costagliola S, Vassart G, Weiss RE, Refetoff S, Williams GR. A lack of thyroid hormones rather than excess thyrotropin causes abnormal skeletal development in hypothyroidism. Mol Endocrinol. 2008 Feb;22(2):501-12. doi: 10.1210/me.2007-0221. Epub 2007 Oct 11.
PubMed 17932107Bauer AJ, Wassner AJ. Thyroid hormone therapy in congenital hypothyroidism and pediatric hypothyroidism. Endocrine. 2019 Oct;66(1):51-62. doi: 10.1007/s12020-019-02024-6. Epub 2019 Jul 26.
PubMed 31350727Cole TJ, Freeman JV, Preece MA. Body mass index reference curves for the UK, 1990. Arch Dis Child. 1995 Jul;73(1):25-9. doi: 10.1136/adc.73.1.25.
PubMed 7639544Dickerman Z, De Vries L. Prepubertal and pubertal growth, timing and duration of puberty and attained adult height in patients with congenital hypothyroidism (CH) detected by the neonatal screening programme for CH--a longitudinal study. Clin Endocrinol (Oxf). 1997 Dec;47(6):649-54. doi: 10.1046/j.1365-2265.1997.3181148.x.
PubMed 9497870Huffmeier U, Tietze HU, Rauch A. Severe skeletal dysplasia caused by undiagnosed hypothyroidism. Eur J Med Genet. 2007 May-Jun;50(3):209-15. doi: 10.1016/j.ejmg.2007.02.002. Epub 2007 Mar 12.
PubMed 17433800Nilsson O, Marino R, De Luca F, Phillip M, Baron J. Endocrine regulation of the growth plate. Horm Res. 2005;64(4):157-65. doi: 10.1159/000088791. Epub 2005 Oct 4.
PubMed 16205094Salerno M, Micillo M, Di Maio S, Capalbo D, Ferri P, Lettiero T, Tenore A. Longitudinal growth, sexual maturation and final height in patients with congenital hypothyroidism detected by neonatal screening. Eur J Endocrinol. 2001 Oct;145(4):377-83. doi: 10.1530/eje.0.1450377.
PubMed 11580992Tanner JM, Goldstein H, Whitehouse RH. Standards for children's height at ages 2-9 years allowing for heights of parents. Arch Dis Child. 1970 Dec;45(244):755-62. doi: 10.1136/adc.45.244.755.
PubMed 5491878Whitney GA, Kean TJ, Fernandes RJ, Waldman S, Tse MY, Pang SC, Mansour JM, Dennis JE. Thyroxine Increases Collagen Type II Expression and Accumulation in Scaffold-Free Tissue-Engineered Articular Cartilage. Tissue Eng Part A. 2018 Mar;24(5-6):369-381. doi: 10.1089/ten.TEA.2016.0533. Epub 2017 Jul 7.
PubMed 28548569Williams GR. Role of thyroid hormone receptor-alpha1 in endochondral ossification. Endocrinology. 2014 Aug;155(8):2747-50. doi: 10.1210/en.2014-1527. No abstract available.
PubMed 25036648Williams GR, Bassett JHD. Thyroid diseases and bone health. J Endocrinol Invest. 2018 Jan;41(1):99-109. doi: 10.1007/s40618-017-0753-4. Epub 2017 Aug 29.
PubMed 28853052
Study at a glance
From the registry record, last updated by the sponsor on 5 Oct 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Final Height in Patients With Congenital Hypothyroidism Diagnosed by Neonatal Screening
- ClinicalTrials.gov ID
- NCT04734457
- Acronym / sponsor ID
- Final height in CH patients
- Conditions
- Congenital Hypothyroidism
- Keywords
- Final Height, Neonatal screening
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- Ain Shams UniversityUniversity, hospital or other
- Study start
- 2 Nov 2021 (estimated)
- Primary completion
- 1 Mar 2022 (estimated)
- Study completion
- 1 Apr 2022 (estimated)
- First posted
- 2 Feb 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The aim of this study is to evaluate longitudinal growth and final height in patients with Congenital Hypothyroidism detected by neonatal screening and factors affecting it.
Detailed description
Linear growth and final height are reported as rather normal in patients with CH diagnosed through the screening and the target height is the most important factor determining linear growth. Data on final height in patients with CH suggest that adult height is significantly correlated with parental height and the mean L-Thyroxine daily dose administered over the first 6 months of treatment. The lowest recommended dose during this period is 8.5μg/kg/day. Periodical adjustments of L-Thyroxine daily dose should be guided by clinical observation and serum free T4 levels.
To our knowledge this is the first study from our center to assess final height in patients with congenital hypothyroidism diagnosed through the Egyptian neonatal screening program.
A complex network of endocrine signals stimulates the process of longitudinal growth including growth hormone, insulin-like growth factor-1, glucocorticoids, thyroid hormone, estrogen, androgens, vitamin D and leptin.
Thyroid hormones are essential for development and normal bone growth. Biochemical studies have shown that thyroid hormones can affect the expression of various bone markers in the serum, reflecting changes in bone remodeling which involves both osteoblastic and osteoclastic activities.
Thyroid hormones act through chondrocytes bearing thyroid hormone receptors (TRs) to modulate growth plate proliferation, differentiation and vascular invasion. Several mechanisms mediate these functions including direct action on the chondrocytes, osteoblasts and mast cells. It also works through interaction with other hormones and growth factors acting in endocrine, paracrine and autocrine fashions.
Overall, T3 acts via TRα in chondrocytes and osteoblasts to regulate intramembranous and endochondral ossification and control the rate of linear growth, bone maturation and mineralization,T4 induces the expression of both type II and X collagen and chondrocyte hypertrophy.
Hypothyroidism in children causes growth arrest, delayed bone maturation, and epiphyseal dysgenesis that can result in short stature and delayed closure of the epiphyses.
In severe undiagnosed cases, complete post-natal growth arrest and skeletal dysplasia occurs with characteristic X-ray features including stippled epiphyses reflecting epiphyseal dysgenesis, congenital hip dislocation, vertebral immaturity, scoliosis, patent fontanelles and sutures and delayed eruption of teeth.
Prompt treatment of patients suffering from CH with thyroid hormone replacement induces a period of rapid catch-up growth in which skeletal maturation and bone age are also accelerated. Ultimately, normal adult height can be expected.
It is controversial whether factors as the degree of hypothyroidism at diagnosis, the timing of the onset of treatment and the doses of replacement L-thyroxine (L-T4) affect linear growth in children with congenital hypothyroidism, detected by screening and treated from early infancy
Study design
- Observational model
- Cohort
- Time perspective
- Retrospective
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- All the patients suffering from CH diagnosed by Egyptian neonatal screening program and have a documented history of CH who received treatment at endocrinology clinic, Children's Hospital, Ain Shams University.
Key inclusion criteria (2 listed)
- Patients having a documented history of CH diagnosed by Egyptian neonatal screening program.
- Patients receiving L-thyroxine (L-T4) since the diagnosis is established.
Key exclusion criteria (3 listed)
- Patients who are non-compliant on L-thyroxine (L-T4) and failed to follow up at the clinic on regular basis.
- Patients who were missed from diagnosis by neonatal screening.
- Patients with associated hormonal disorders affecting same parameters concerned in the study.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LevothyroxinAlso: neonatal screeningWe assess the effect of early diagnosis of CH by neonatal screening and start of treatment on the final height of the patients | Drug | – |
Primary outcome
Assessment of change of Final Height in patients with Congenital Hypothyroidism diagnosed by neonatal screening
Time frame: Since the diagnosis is established by neonatal screening during first week of life height will be assessed every 6 months with follow up throughout the study period until the study subject reaches an average of 18 years of age( final height reached).
The investigators assess the effect of early diagnosis and early levothyroxine start on the change in longitudinal growth in patients with Congenital Hypothyroidism.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Oct 2021.
- Background: PubMed 12218379Bain P, Toublanc JE. Adult height in congenital hypothyroidism: prognostic factors and the importance of compliance with treatment. Horm Res. 2002;58(3):136-42. doi: 10.1159/000064489.
- Results publication: PubMed 17932107Bassett JH, Williams AJ, Murphy E, Boyde A, Howell PG, Swinhoe R, Archanco M, Flamant F, Samarut J, Costagliola S, Vassart G, Weiss RE, Refetoff S, Williams GR. A lack of thyroid hormones rather than excess thyrotropin causes abnormal skeletal development in hypothyroidism. Mol Endocrinol. 2008 Feb;22(2):501-12. doi: 10.1210/me.2007-0221. Epub 2007 Oct 11.
- Results publication: PubMed 31350727Bauer AJ, Wassner AJ. Thyroid hormone therapy in congenital hypothyroidism and pediatric hypothyroidism. Endocrine. 2019 Oct;66(1):51-62. doi: 10.1007/s12020-019-02024-6. Epub 2019 Jul 26.
- Results publication: PubMed 7639544Cole TJ, Freeman JV, Preece MA. Body mass index reference curves for the UK, 1990. Arch Dis Child. 1995 Jul;73(1):25-9. doi: 10.1136/adc.73.1.25.
- Results publication: PubMed 9497870Dickerman Z, De Vries L. Prepubertal and pubertal growth, timing and duration of puberty and attained adult height in patients with congenital hypothyroidism (CH) detected by the neonatal screening programme for CH--a longitudinal study. Clin Endocrinol (Oxf). 1997 Dec;47(6):649-54. doi: 10.1046/j.1365-2265.1997.3181148.x.
- Results publication: PubMed 17433800Huffmeier U, Tietze HU, Rauch A. Severe skeletal dysplasia caused by undiagnosed hypothyroidism. Eur J Med Genet. 2007 May-Jun;50(3):209-15. doi: 10.1016/j.ejmg.2007.02.002. Epub 2007 Mar 12.
- Results publication: PubMed 16205094Nilsson O, Marino R, De Luca F, Phillip M, Baron J. Endocrine regulation of the growth plate. Horm Res. 2005;64(4):157-65. doi: 10.1159/000088791. Epub 2005 Oct 4.
- Results publication: PubMed 11580992Salerno M, Micillo M, Di Maio S, Capalbo D, Ferri P, Lettiero T, Tenore A. Longitudinal growth, sexual maturation and final height in patients with congenital hypothyroidism detected by neonatal screening. Eur J Endocrinol. 2001 Oct;145(4):377-83. doi: 10.1530/eje.0.1450377.
- Results publication: PubMed 5491878Tanner JM, Goldstein H, Whitehouse RH. Standards for children's height at ages 2-9 years allowing for heights of parents. Arch Dis Child. 1970 Dec;45(244):755-62. doi: 10.1136/adc.45.244.755.
- Results publication: PubMed 28548569Whitney GA, Kean TJ, Fernandes RJ, Waldman S, Tse MY, Pang SC, Mansour JM, Dennis JE. Thyroxine Increases Collagen Type II Expression and Accumulation in Scaffold-Free Tissue-Engineered Articular Cartilage. Tissue Eng Part A. 2018 Mar;24(5-6):369-381. doi: 10.1089/ten.TEA.2016.0533. Epub 2017 Jul 7.
- Results publication: PubMed 25036648Williams GR. Role of thyroid hormone receptor-alpha1 in endochondral ossification. Endocrinology. 2014 Aug;155(8):2747-50. doi: 10.1210/en.2014-1527. No abstract available.
- Results publication: PubMed 28853052Williams GR, Bassett JHD. Thyroid diseases and bone health. J Endocrinol Invest. 2018 Jan;41(1):99-109. doi: 10.1007/s40618-017-0753-4. Epub 2017 Aug 29.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Wessam Mouharram, PhD study director
Ain Shams University
Rana Mahmoud, PhD study director
Ain Shams University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Congenital Hypothyroidism, run by Ain Shams University at 1 site in Egypt.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 5 Oct 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Egypt. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Mohamed Nader, M.B., B.Ch. (+201014397938, moh.nader90@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Assessment of change of Final Height in patients with Congenital Hypothyroidism diagnosed by neonatal screening (time frame: Since the diagnosis is established by neonatal screening during first week of life height will be assessed every 6 months with follow up throughout the study period until the study subject reaches an average of 18 years of age( final height reached).). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04734457, which also lists 12 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Oct 2021.