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Clinical and hormonal characteristics of central hypothyroidism at diagnosis and during follow-up in adult patients
Open accessAbstract
OBJECTIVE: We studied the clinical and hormonal profiles of patients with central hypothyroidism (CH), the adequacy of levothyroxine (L-T4) treatment and the influence of other pituitary hormone replacement therapies. METHODS: We reviewed medical records of 108 adult patients with child-onset (CO; n=26) or adult-onset (AO; n=82) CH. RESULTS: At diagnosis, the most frequently reported symptoms were fatigue and headaches in AO patients, and growth retardation in CO patients. Serum TSH was normal in a majority of CH patients, low in 8% and elevated in 8%. Serum free thyroxine (fT(4)) was usually reduced, but remained within the low normal range in 28% of the study population (mostly CO patients). Similarly, serum total T(4) (tT(4)), total triiodothyronine (tT(3)) and free T(3) (fT(3)) were found to be within the normal range in significant subsets of patients. Interestingly, the clinical and biochemical characteristics of CH patients with normal f/t T(4) levels were not different from those of the patients with low fT(4) values. The thyroid hormonal profile was not influenced by gender, etiology or by the number of hormone deficiencies. At last evaluation, the mean dose of L-T(4) was 1.6+/-0.5 microg/kg/day and was negatively correlated to current age (P<0.001) but positively correlated to the number of hormone deficiencies (P<0.05). Treatment suppressed TSH in 75% of the patients, induced normal fT(4) in 94%, but normal fT(3) in only 49% of them. Male GH-treated patients and estrogen-treated females needed a higher L-T(4) dose compared with non-treated patients. CONCLUSIONS: fT(4) is clearly the best indicator of CH, but remains in the low normal range in a significant subset of patients, especially in those with CO disease. Adequacy of therapy is mostly reflected by the combination of upper normal fT(4) and low normal fT(3) levels. Pituitary hormone replacement therapy may require an adjustment of T(4) treatment, as female patients under estrogen treatment and male patients under GH treatment will need a higher T(4) dose in order to remain in the euthyroid range.
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“In particular, serum TSH concentrations are rapidly suppressed in a large portion of CeH patients during the administration of L-T4 [24, 25].”
From 2018 European Thyroid Association (ETA) Guidelines on the Diagnosis and Management of Central Hypothyroidism (2018) · cites this paper as [25]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Indeed, mean L-T4 daily doses of 1.2-1.6 μg/kg bw/day were judged sufficient in the large majority of adult CeH patients, with the main aim of achieving a more appropriate metabolic profile [24, 25, 55].”
From 2018 European Thyroid Association (ETA) Guidelines on the Diagnosis and Management of Central Hypothyroidism (2018) · cites this paper as [25]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“Manifestations of CeH are similar to those of primary hypothyroidism, but they can be masked by coexistent MPHD [1, 24, 25].”
From 2018 European Thyroid Association (ETA) Guidelines on the Diagnosis and Management of Central Hypothyroidism (2018) · cites this paper as [25]
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“Overt CeH is most frequently indicated by the combined findings of low FT4 with low or normal TSH concentrations [24, 25].”
From 2018 European Thyroid Association (ETA) Guidelines on the Diagnosis and Management of Central Hypothyroidism (2018) · cites this paper as [25]
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In the citing paper
“As in primary hypothyroidism [53], younger CeH patients require higher doses than the older ones [24, 25].”
From 2018 European Thyroid Association (ETA) Guidelines on the Diagnosis and Management of Central Hypothyroidism (2018) · cites this paper as [25]
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In the citing paper
“Since patients with primary hypothyroidism usually require high-normal or slightly elevated fT4 levels to normalize TSH levels (78), low-normal fT4 levels in hypopituitary patients may suggest the presence of CH.”
From Hormonal Replacement in Hypopituitarism in Adults: An Endocrine Society Clinical Practice Guideline (2016) · cites this paper as [78]
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“Clinicians are increasingly using newer liquid chromatography-mass spectrometric-based assays with suggested improved sensitivity and reduced interference.This is particularly true for steroids, namely E2, T (104,105), and thyroid and peptide hormones (78,106).”
From Hormonal Replacement in Hypopituitarism in Adults: An Endocrine Society Clinical Practice Guideline (2016) · cites this paper as [78]
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Metadata
- Authors
- Alexopoulou, O., Beguin, C., De Nayer, P., & Maiter, D.
- Affiliations
- Cliniques Universitaires Saint-Luc (BE)
- UCLouvain (BE)
- Corresponding author
- Maiter, D
- Venue
- European Journal of Endocrinology
- Publisher
- Oxford University Press (OUP)
- Published
- 2004-01-01
- Volume
- 150
- Issue
- 1
- Pages
- 1-8
- ISSN
- 0804-4643 (ISSN-L)
- 1479-683X
- OpenAlex
- W2115772710
- Semantic Scholar
- 49bc2de03a96150ced52a1e546d5b35e0ab26c7d
- Cited by
- 135
- References
- 39
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 6 · 2023: 7 · 2022: 8 · 2021: 6 · 2020: 4 · 2019: 12 · 2018: 10 · 2017: 7 · 2016: 7 · 2015: 8 · 2014: 5 · 2013: 7 · 2012: 6
- FWCI
- 3.31
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- European Journal of Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Digital Access to Libraries (Université catholique de Louvain (UCL), l'Université de Namur (UNamur) and the Université Saint-Louis (USL-B)) (submittedVersion, other-oa)
- 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, levothyroxine dose, free thyroxine, free triiodothyronine, TSH suppression, growth hormone therapy, estrogen therapy
- MeSH terms
- Adult, Aged, Fatigue, Female, Follow-Up Studies, Growth Disorders, Headache, Humans, Hypothyroidism, Male, Middle Aged, Retrospective Studies, Sexual Dysfunction, Physiological, Thyrotropin, Thyroxine, Age of Onset, Human Growth Hormone
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