Final Height in Patients With CH Diagnosed by the Screening

NCT ID: NCT04734457

Last Updated: 2021-10-05

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Total Enrollment

60 participants

Study Classification

OBSERVATIONAL

Study Start Date

2021-11-02

Study Completion Date

2022-04-01

Brief Summary

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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

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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

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Congenital Hypothyroidism

Study Design

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Observational Model Type

COHORT

Study Time Perspective

RETROSPECTIVE

Interventions

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Levothyroxin

We assess the effect of early diagnosis of CH by neonatal screening and start of treatment on the final height of the patients

Intervention Type DRUG

Other Intervention Names

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neonatal screening

Eligibility Criteria

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Inclusion Criteria

* Patients having a documented history of CH diagnosed by Egyptian neonatal screening program.
* Patients receiving L-thyroxine (L-T4) since the diagnosis is established.

Exclusion Criteria

* 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.
Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Ain Shams University

OTHER

Sponsor Role lead

Responsible Party

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Mohamed Nader

Principal Investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Wessam Mouharram, PhD

Role: STUDY_DIRECTOR

Ain Shams University

Rana Mahmoud, PhD

Role: STUDY_DIRECTOR

Ain Shams University

Locations

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Ain Shams University

Cairo, Abbasiya, Egypt

Site Status

Countries

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Egypt

Central Contacts

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Mohamed Nader, M.B., B.Ch.

Role: CONTACT

+201014397938

References

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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.

Reference Type BACKGROUND
PMID: 12218379 (View on PubMed)

Bassett 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.

Reference Type RESULT
PMID: 17932107 (View on PubMed)

Bauer 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.

Reference Type RESULT
PMID: 31350727 (View on PubMed)

Cole 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.

Reference Type RESULT
PMID: 7639544 (View on PubMed)

Dickerman 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.

Reference Type RESULT
PMID: 9497870 (View on PubMed)

Huffmeier 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.

Reference Type RESULT
PMID: 17433800 (View on PubMed)

Nilsson 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.

Reference Type RESULT
PMID: 16205094 (View on PubMed)

Salerno 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.

Reference Type RESULT
PMID: 11580992 (View on PubMed)

Tanner 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.

Reference Type RESULT
PMID: 5491878 (View on PubMed)

Whitney 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.

Reference Type RESULT
PMID: 28548569 (View on PubMed)

Williams 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.

Reference Type RESULT
PMID: 25036648 (View on PubMed)

Williams 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.

Reference Type RESULT
PMID: 28853052 (View on PubMed)

Other Identifiers

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Final height in CH patients

Identifier Type: -

Identifier Source: org_study_id

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