- Author
-
J.C. Naafs
- Title
- Central congenital hypothyroidism
- Subtitle
- Early diagnosis and clinical outcome during childhood and adolescence
- Supervisors
-
A.S.P. van Trotsenburg
E. Fliers - Co-supervisors
-
N. Zwaveling-Soonawala
A. Boelen - Award date
- 16 April 2021
- Number of pages
- 221
- ISBN
- 9789464165050
- Document type
- PhD thesis
- Faculty
- Faculty of Medicine (AMC-UvA)
- Abstract
-
This thesis focuses on improving the diagnostic process for central congenital hypothyroidism (CH) and describes the long-term outcome of early-detected patients. Central CH refers to thyroid hormone (thyroxine, T4) deficiency at birth due to insufficient hypothalamic-pituitary stimulation of the thyroid gland. It may occur in isolation or combined with multiple pituitary hormone deficiency (MPHD).
Diagnosing central CH in neonates is challenging, as this relies on a low serum free T4 (FT4) concentration only. We established age-specific reference intervals for FT4 and thyrotropin (TSH) and show that the neonatal FT4 lower limit is 3 pmol/L higher than in adults.
Although worldwide most neonatal screening programs do not detect central CH, the Dutch program does. We report clinical characteristics of the largest patient group described so far and show that most patients are not identified clinically, but only after receiving an abnormal screening result. A genetic diagnosis is established in most patients with isolated central CH.
In a systematic review we show that robust studies on cognitive outcome are lacking. In a cross-sectional study we show that full-scale IQ (FSIQ) in early-detected patients with isolated central CH does not differ from siblings. In MPHD patients, FSIQ is significantly lower compared with siblings. We also show that self-reported health-related quality of life (HRQoL) is similar in central CH patients and siblings. Parent-reported HRQoL is significantly lower in MPHD patients compared with siblings.
Finally, despite a high overall mortality among early-detected central CH patients, deaths due to pituitary insufficiency are rare. - Persistent Identifier
- https://hdl.handle.net/11245.1/32744297-2171-413f-ba6e-7b96682b1f45
- Downloads
-
Thesis (complete)
Front matter
Chapter 1: General introduction
Chapter 2: Age-specific reference intervals for plasma free thyroxine and thyroid stimulating hormone in term neonates during the first two weeks of life
Chapter 3: Clinical and genetic characteristics of Dutch children with central congenital hypothyroidism, early detected by neonatal screening
Chapter 4: Cognitive outcome in congenital central hypothyroidism: A systematic review with meta-analysis of individual patient data
Chapter 5: Cognitive and motor outcome in patients with early-detected central congenital hypothyroidism compared with siblings
Chapter 6: Health-related quality of life in patients with early-detected central congenital hypothyroidism
Chapter 7: Mortality in children with early-detected congenital central hypothyroidism
Chapter 8: General discussion and future perspectives
Summary; Nederlandse samenvatting; List of contributing authors; PhD portfolio; List of publications; Financial support; Dankwoord; About the author
- Supplementary materials
Disclaimer/Complaints regulations
If you believe that digital publication of certain material infringes any of your rights or (privacy) interests, please let the Library know, stating your reasons. In case of a legitimate complaint, the Library will make the material inaccessible and/or remove it from the website. Please Ask the Library, or send a letter to: Library of the University of Amsterdam, Secretariat, Singel 425, 1012 WP Amsterdam, The Netherlands. You will be contacted as soon as possible.