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Cited by 114Thyroid Disorders and TreatmentsPituitary Gland Disorders and TreatmentsGrowth Hormone and Insulin-like Growth Factors

Mechanisms related to the pathophysiology and management of central hypothyroidism

Yamada, Masanobu, Mori, Masatomo·2008·Nature Clinical Practice Endocrinology & Metabolism
DOI 10.1038/ncpendmet0995
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Abstract

Central hypothyroidism (CH) is defined as hypothyroidism due to insufficient stimulation of the thyroid gland by TSH, for which secretion or activity can be impaired at the hypothalamic or pituitary levels. Patients with CH frequently present with multiple other pituitary hormone deficiencies. In addition to classic CH induced by hypothalamic-pituitary tumors or Sheehan syndrome, novel causes include traumatic brain injury or subarachnoid hemorrhage, bexarotene (a retinoid X receptor agonist) therapy, neonates being born to mothers with insufficiently controlled Graves disease, and lymphocytic hypophysitis. Growth hormone therapy, which may be used in children and adults, is now also recognized as a possible cause of unmasking CH in susceptible individuals. In addition, mutations in genes, such as TRHR, POU1F1, PROP1, HESX1, SOX3, LHX3, LHX4 and TSHB, have been associated with CH. The difficulty in making a clear diagnosis of CH is that the serum TSH levels can vary; values are normal in most cases, but in some might be low or slightly elevated. Levels of endogenous T(4) in serum might also be subnormal. Appropriate doses of levothyroxine for T(4) replacement therapy have not been confirmed, but might need to be higher than presently used empirically in patients with CH and should be adjusted according to age and other hormone deficiencies, to achieve free T(4) concentrations in the upper end of the normal range.

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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 [34]

  • Central hypothyroidism is diagnosed in 1:16,000 to about 1:100,000 of the general adult or neonatal populations and accounts for about 1 of 1000 hypothyroid patients.

    “Central hypothyroidism is diagnosed in 1: 16.000 to about 1: 100.000 of the general adult or neonatal populations (Persani et al., 2018) and accounts for about 1 of 1000 hypothyroid patients (Yamada and Mori, 2008).”

    From The hypothalamus-pituitary-thyroid (HPT)-axis and its role in physiology and pathophysiology of other hypothalamus-pituitary functions (2021) · cites this paper as Yamada and Mori, 2008

  • FT4 determination, more than TT4 or FT3, represents the parameter with highest diagnostic sensitivity and specificity in CeH.

    “Therefore, the FT4 determination, more than the TT4, which is influenced by the serum-binding protein variation (37, 38) or the FT3, which might be low in some nonthyroidal illness or deiodinase defect rather than in CeH, represents the parameter with the highest diagnostic sensitivity and specificity in this hormone defect (1, 39, 40, 41, 42).”

    From The diagnosis and management of central hypothyroidism in 2018 (2019) · cites this paper as [40]

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Authors
Yamada, M., & Mori, M.
Affiliations
Gunma University (JP)
Corresponding author
Yamada, Masanobu
ORCID
Yamada, Masanobu
Venue
Nature Clinical Practice Endocrinology & Metabolism
Publisher
Springer Science and Business Media LLC
Published
2008-10-21
Volume
4
Issue
12
Pages
683-694
ISSN
  • 1745-8366 (ISSN-L)
  • 1745-8374
DOI
10.1038/ncpendmet0995
OpenAlex
W2072763716
Cited by
114
References
70
Citations by year
2026: 6 · 2025: 7 · 2024: 4 · 2023: 1 · 2022: 5 · 2021: 3 · 2020: 4 · 2019: 7 · 2018: 11 · 2017: 11 · 2016: 6 · 2015: 6 · 2014: 8 · 2013: 3 · 2012: 11
FWCI
0.97
Type
journal article
Language
en
Open access
closed
Licence
www.springer.com/tdm (tdm)
Locations
  • Nature Clinical Practice Endocrinology & Metabolism (publishedVersion)
  • PubMed (publishedVersion)
Funders
Kementerian Pendidikan Nasional
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, TSH deficiency, hypothalamic-pituitary dysfunction, pituitary hormone deficiency, hypothalamic-pituitary tumors, Sheehan's syndrome, traumatic brain injury, subarachnoid hemorrhage, bexarotene, neonatal Graves' disease, lymphocytic hypophysitis, growth hormone therapy, Pit-1, PROP1, HESX1, SOX3, LHX3, LHX4, levothyroxine dose adjustment, free thyroxine
MeSH terms
Humans, Hypothyroidism, Infant, Newborn, Models, Biological, Thyrotropin, Thyroxine, Hormone Replacement Therapy

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