Recent advances in central congenital hypothyroidism
Open accessAbstract
Central congenital hypothyroidism (CCH) may occur in isolation, or more frequently in combination with additional pituitary hormone deficits with or without associated extrapituitary abnormalities. Although uncommon, it may be more prevalent than previously thought, affecting up to 1:16 000 neonates in the Netherlands. Since TSH is not elevated, CCH will evade diagnosis in primary, TSH-based, CH screening programs and delayed detection may result in neurodevelopmental delay due to untreated neonatal hypothyroidism. Alternatively, coexisting growth hormones or ACTH deficiency may pose additional risks, such as life threatening hypoglycaemia. Genetic ascertainment is possible in a minority of cases and reveals mutations in genes controlling the TSH biosynthetic pathway ( TSHB, TRHR , IGSF1 ) in isolated TSH deficiency, or early ( HESX1, LHX3, LHX4, SOX3, OTX2 ) or late ( PROP1, POU1F1 ) pituitary transcription factors in combined hormone deficits. Since TSH cannot be used as an indicator of euthyroidism, adequacy of treatment can be difficult to monitor due to a paucity of alternative biomarkers. This review will summarize the normal physiology of pituitary development and the hypothalamic–pituitary–thyroid axis, then describe known genetic causes of isolated central hypothyroidism and combined pituitary hormone deficits associated with TSH deficiency. Difficulties in diagnosis and management of these conditions will then be discussed.
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Progressive onset of thyrotrope defect beyond the critical neonatal period can be not infrequently seen in several genetic CeH cases.
“However, a progressive onset of the thyrotrope defect beyond the critical neonatal period can be not infrequently seen in several of these genetic CeH cases (3, 9, 28, 30).”
From The diagnosis and management of central hypothyroidism in 2018 (2019) · cites this paper as [28]
Acquired forms of CeH are usually sporadic and in most cases due to large pituitary macroadenomas with suprasellar extensions, craniopharyngiomas and suprasellar tumors, head trauma, vascular accident or cranial irradiation.
“Acquired forms of CeH are usually sporadic and in most cases due to large pituitary macroadenomas with a suprasellar extensions, craniopharyngiomas and suprasellar tumors, head trauma, vascular accident or cranial irradiation (1, 28, 33).”
From The diagnosis and management of central hypothyroidism in 2018 (2019) · cites this paper as [28]
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- Authors
- Schoenmakers, N., Alatzoglou, K. S., Chatterjee, V. K., & Dattani, M. T.
- Affiliations
- University of Cambridge (GB)
- Corresponding author
- Schoenmakers, Nadia
- Venue
- Journal of Endocrinology
- Publisher
- Bioscientifica
- Published
- 2015-09-28
- Volume
- 227
- Issue
- 3
- Pages
- R51-R71
- ISSN
- 0022-0795 (ISSN-L)
- 1479-6805
- PMC
- PMC4629398
- OpenAlex
- W1930524906
- Cited by
- 125
- References
- 17
- Citations by year
- 2026: 4 · 2025: 7 · 2024: 13 · 2023: 10 · 2022: 7 · 2021: 5 · 2020: 12 · 2019: 17 · 2018: 21 · 2017: 17 · 2016: 10 · 2015: 1 · 2014: 1
- FWCI
- 2.47
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Journal of Endocrinology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Apollo (University of Cambridge) (submittedVersion, cc-by)
- Funders
- Wellcome Trust (095564/Z/11/Z, 100585/Z/12/Z)
- National Institute for Health and Care Research (NF-SI-0508-10198, NF-SI-0514-10176)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pituitary Gland Disorders and Treatments
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Growth Hormone and Insulin-like Growth Factors
- Keywords
- TSH deficiency, combined pituitary hormone deficiency, neonatal hypothyroidism screening, neurodevelopmental delay, hypoglycemia, pituitary transcription factors, HESX1, LHX3, LHX4, SOX3, Otx2, PROP1, Pit-1, IGSF1, treatment monitoring, hypothalamic-pituitary-thyroid axis, pituitary development
- MeSH terms
- Congenital Hypothyroidism, Humans, Infant, Newborn, Pituitary Gland, Pituitary Hormones
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