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Cited by 135Thyroid Disorders and TreatmentsPituitary Gland Disorders and TreatmentsGrowth Hormone and Insulin-like Growth Factors

Clinical and hormonal characteristics of central hypothyroidism at diagnosis and during follow-up in adult patients

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Alexopoulou, O, Beguin, C, De Nayer, P, Maiter, D·2004·European Journal of Endocrinology
DOI 10.1530/eje.0.1500001
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Abstract

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 CeH patients, serum TSH concentrations are rapidly suppressed in a large portion during L-T4 administration.

    “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]

    The ‘Last evaluation under T4 therapy’ section reports that 75% of patients had low or undetectable TSH while receiving L-T4. It does not establish how rapidly TSH fell after treatment began, so the word ‘rapidly’ is unsupported. (LLM, conf=0.87)

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  • 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.

    “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]

    The ‘Last evaluation under T4 therapy’ section (page unavailable) reports mean L-T4 doses of 1.60 μg/kg/day overall and 1.48 μg/kg/day in adulthood-onset patients, consistent with part of the stated range. But the Discussion says only about 54% had fT4 in the upper half of the reference interval and that the remainder were probably undertreated. The paper therefore does not judge these doses sufficient for a large majority. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • Manifestations of central hypothyroidism are similar to those of primary hypothyroidism, but they can be masked by coexistent multiple pituitary hormone deficiency.

    “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]

  • Overt central hypothyroidism is most frequently indicated by the combined findings of low FT4 with low or normal TSH concentrations.

    “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]

  • Younger CeH patients require higher L-T4 doses than older CeH patients.

    “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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3 of the 39 references couldn’t be matched to a known paper.

Research works printed but not linked: 4

  1. [7]7. Andersen S, Pedersen KM, Bruun NH & Laurberg P. Narrow indi- vidual variations in serum T4 and T3 in normal subjects: a clue to understanding of subclinical thyroid disease. Journal of Clinical Endocrinology and Metabolism 2002 87 1068 -1072.
  2. [10]10. Rose SR, Lustig RH, Pitukcheewanont P, Broome DC, Burghen GA, Li H et al. Diagnosis of hidden central hypothyroidism in survivors of child cancer. Journal of Clinical Endocrinology and Metabolism 1999 84 4472-4479.
  3. [12]12. Eds LE Braverman & RD Utiger. Philadelphia: Lippincott, 1996.
  4. [25]25. Eds LJ DeGroot & JL Jameson. Philadelphia: Saunders, 2001.

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Authors
Alexopoulou, O., Beguin, C., De Nayer, P., & Maiter, D.
Affiliations
  • Cliniques Universitaires Saint-Luc (BE)
  • UCLouvain (BE)
Corresponding author
Maiter, D
ORCID
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
DOI
10.1530/eje.0.1500001
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
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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