The multiple genetic causes of central hypothyroidism

Persani, Luca; Bonomi, Marco

doi:10.1016/j.beem.2017.04.003

Cited by 46Thyroid Disorders and TreatmentsPituitary Gland Disorders and TreatmentsGrowth Hormone and Insulin-like Growth Factors

The multiple genetic causes of central hypothyroidism

Persani, Luca, Bonomi, Marco·2017·Best Practice & Research Clinical Endocrinology & Metabolism

DOI 10.1016/j.beem.2017.04.003

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Abstract

An insufficient stimulation by thyrotropin (TSH) of an otherwise normal thyroid gland represents the cause of Central Hypothyrodism (CeH). CeH is about 1000-folds rarer than Primary Hypothyroidism and often represents a real challenge for the clinicians, mainly because they cannot rely on adequately sensitive parameters for diagnosis or management, as it occurs with circulating TSH in PH. Therefore, CeH diagnosis can be frequently missed or delayed in patients with a previously unknown pituitary involvement. A series of genetic defects have been described to account for isolated CeH or combined pituitary hormone defects (CPHDs) with variable clinical characteristics and degrees of severity. The recently identified candidate gene IGSF1 appears frequently involved. This review provides an updated illustration of the different genetic defects accounting for CeH.

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The most frequently identified mutations associated with multiple pituitary hormone deficiency are in PROP1.
“The most frequently identified mutations associated with MPHD are in PROP1 [27, 34-37].”
From 2018 European Thyroid Association (ETA) Guidelines on the Diagnosis and Management of Central Hypothyroidism (2018) · cites this paper as [36]
Mental retardation can be particularly severe in case of delay in diagnosis of isolated congenital CeH associated with biallelic TSHβ mutations, due to false-negative results of neonatal TSH screening for primary thyroid defects.
“Mental retardation can be particularly severe in case of delay in the diagnosis of isolated congenital CeH associated with biallelic TSHβ mutations, due to the false-negative results of the neonatal TSH screening for primary thyroid defects (3, 20, 21, 22, 23, 24, 25).”
From The diagnosis and management of central hypothyroidism in 2018 (2019) · cites this paper as [3]
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 [3]

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Authors: Persani, L., & Bonomi, M.
Affiliations: University of Milan (IT)
Corresponding author: Persani, Luca
ORCID: Persani, Luca
Bonomi, Marco
Venue: Best Practice & Research Clinical Endocrinology & Metabolism
Publisher: Elsevier BV
Published: 2017-03
Volume: 31
Issue: 2
Pages: 255-263
ISSN: 1521-690X (ISSN-L)
DOI: 10.1016/j.beem.2017.04.003
OpenAlex: W2607142792
Cited by: 46
References: 47
Citations by year: 2026: 4 · 2025: 4 · 2024: 4 · 2023: 3 · 2022: 8 · 2021: 2 · 2020: 4 · 2019: 6 · 2018: 7 · 2017: 3 · 2015: 1
FWCI: 0.80
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
Locations: Best Practice & Research Clinical Endocrinology & Metabolism (publishedVersion)
PubMed (publishedVersion)
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: central hypothyroidism, thyroid-stimulating hormone, TSH deficiency, combined pituitary hormone deficiency, genetic disorders, IGSF1, pituitary disorders
MeSH terms: Diagnosis, Differential, Humans, Hypothyroidism, Pituitary Diseases, Pituitary Gland, Thyrotropin, Genetic Heterogeneity

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The multiple genetic causes of central hypothyroidism

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