The DOI matches its Crossref record; 36 of the 39 references it cites were found in a registry or an index.
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.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“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]
The cited source says what the claim attributes to it.
In the citing paper
“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]
The cited source says what the claim attributes to it.
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]
The check wasn’t confident either way, so it gives no verdict — never disputed.
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]
Experimental — accuracy not yet measuredThe check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“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]
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
JOURNAL OF CLINICAL ENDOCRINOLOGY AND METABOLISM
Hoskins, R. G. (1953) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem-13-4-473 · Cited by 3,780
Clinical longitudinal standards for height and height velocity for North American children
Tanner, J. M., & Davies, P. S. W. (1985) · The Journal of Pediatrics · doi:10.1016/s0022-3476(85)80501-1 · Cited by 1,088
Andersen, S., Pedersen, K. M., Bruun, N. H., & Laurberg, P. (2002) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.87.3.8165 · Cited by 686
Mutations in PROP1 cause familial combined pituitary hormone deficiency
Wu, W., Cogan, J. D., Pfäffle, R. W., Dasen, J. S., Frisch, H., O’Connell, S. M., Flynn, S. E., Brown, M. R., Mullis, P. E., Parks, J. S., et al. (1998) · Nature Genetics · doi:10.1038/ng0298-147 · Cited by 562
Bunevičius, R., Kažanavičius, G., Žalinkevičius, R., & Prange, A. J. (1999) · New England Journal of Medicine · doi:10.1056/nejm199902113400603 · Cited by 482 · cited 1×
“It remains to be determined whether adding small doses of T3 would be beneficial in CH patients, as has been proposed in primary hypothyroidism ( 22 ).”
BackgroundFish, L. H., Schwartz, H. L., Cavanaugh, J., Steffes, M. W., Bantle, J. P., & Oppenheimer, J. H. (1987) · New England Journal of Medicine · doi:10.1056/nejm198703263161302 · Cited by 353
Ain, K. B., MORI, Y., & Refetoff, S. (1987) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem-65-4-689 · Cited by 310
Increased need for thyroxine in women with hypothyroidism during estrogen therapy
Arafah, B. M. (2001) · New England Journal of Medicine · doi:10.1056/nejm200106073442302 · Cited by 267
Collu, R., Tang, J., Castagné, J., Lagacé, G., Masson, N., Huot, C., Deal, C., Delvin, E., Faccenda, E., Eidne, K. A., et al. (1997) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.82.5.3918 · Cited by 207
FAGLIA, G., BITENSKY, L., PINCHERA, A., FERRARI, C., PARACCHI, A., BECK-PECCOZ, P., AMBROSI, B., & SPADA, A. (1979) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem-48-6-989 · Cited by 197
JøRGENSEN, J. O. L., PEDERSEN, S. A., LAURBERG, P., WEEKE, J., SKAKKEBÆK, N. E., & CHRISTIANSEN, J. S. (1989) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem-69-6-1127 · Cited by 192
Jørgensen, J. O. L., Møller, J., Laursen, T., Ørskov, H., Christiansen, J. S., & Weeke, J. (1994) · Clinical Endocrinology · doi:10.1111/j.1365-2265.1994.tb01826.x · Cited by 162
Hypothyroidism in the Elderly*
ROBUSCHI, G., Safran, M., Braverman, L. E., GNUDI, A., & Roti, E. (1987) · Endocrine Reviews · doi:10.1210/edrv-8-2-142 · Cited by 140
Diagnosis of Hidden Central Hypothyroidism in Survivors of Childhood Cancer1
Rose, S. R., Lustig, R. H., Pitukcheewanont, P., Broome, D. C., Burghen, G. A., Li, H., Hudson, M. M., Kun, L. E., & Heideman, R. L. (1999) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.84.12.6097 · Cited by 139
Ferretti, E., Persani, L., Jaffrain-Rea, M.-L., Giambona, S., Tamburrano, G., & Beck-Peccoz, P. (1999) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.84.3.5553 · Cited by 134
A circulating, biologically inactive thyrotropin caused by a mutation in the beta subunit gene.
Medeiros-Neto, G. A., Herodotou, D. T., Rajan, S. S., Kommareddi, S., de Lacerda, L., Sandrini, R., Boguszewski, M. C. D. S., Hollenberg, A. N., Radovick, S., & Wondisford, F. E. (1996) · Journal of Clinical Investigation · doi:10.1172/jci118540 · Cited by 130
Thyroxine Transport Proteins of Plasma. Molecular Properties and Biosynthesis
ROBBINS, J. J., Cheng, S.-Y., Gershengorn, M. C., Glinoer, D., CAHNMANN, H. J., & EDELNOCH, H. (1978) · Elsevier eBooks · doi:10.1016/b978-0-12-571134-0.50017-x · Cited by 123
Porretti, S., Giavoli, C., Ronchi, C. L., Lombardi, G., Zaccaria, M., Valle, D., Arosio, M., & Beck‐Peccoz, P. (2002) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.87.5.8479 · Cited by 112
Dall, R., Longobardi, S., Ehrnborg, C., Keay, N., Rosén, T., Jørgensen, J. O. L., Cuneo, R. C., Boroujerdi, M. A., Cittadini, A., Napoli, R., et al. (2000) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.85.11.6964 · Cited by 108
The Acute Effects of Human Growth Hormone Administration on Thyroid Function in Normal Men*
GRUNFELD, C., SHERMAN, B. M., & CAVALIERI, R. R. (1988) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem-67-5-1111 · Cited by 108
Archila, E. A., & De Castro Gómez, F. (1971) · PubMed · Cited by 83
Portes, E. S., Oliveira, J. H. A., Maccagnan, P., & Abucham, J. (2000) · Clinical Endocrinology · doi:10.1046/j.1365-2265.2000.01071.x · Cited by 81
Circulating Thyrotropin Bioactivity in Sporadic Central Hypothyroidism
Persani, L. (2000) · Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.85.10.3631 · Cited by 70
Monitoring Therapy in Patients Taking Levothyroxine
Helfand, M., & Crapo, L. M. (1990) · Annals of Internal Medicine · doi:10.7326/0003-4819-113-6-450 · Cited by 62
Cranial irradiation and central hypothyroidism
Rose, S. R. (2001) · Trends in Endocrinology & Metabolism · doi:10.1016/s1043-2760(00)00359-3 · Cited by 55
Rose, S. R., Manasco, P. K., PEARCE, S., & NISULA, B. C. (1990) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem-70-6-1750 · Cited by 53
Dall, R. (2000) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.85.11.4193 · Cited by 53
Gender Differences in rhGH-Induced Changes in Body Composition in GH-Deficient Adults
Span, J. P. T., PIETERS, G. F. F. M., Sweep, F. C. G. J., Hermus, A. R., & SMALS, A. G. H. (2001) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.86.9.7815 · Cited by 46
Patterns of Pulsatile Pituitary Glycoprotein Secretion in Central Hypothyroidism and Hypogonadism*
Samuels, M. H., Lillehei, K. O., Kleinschmidt-DeMasters, B. K., Stears, J. C., & Ridgway, E. C. (1990) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem-70-2-391 · Cited by 37
Levothyroxine Replacement Therapy in Central Hypothyroidism: A Practice Report
Carrozza, V., Csako, G., Yanovski, J. A., Skarulis, M. C., Nieman, L., Wesley, R., & Pucino, F. (1999) · Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy · doi:10.1592/phco.19.4.349.30940 · Cited by 36
Screening for central hypothyroidism is unjustified
Price, A., & Weetman, A. P. (2001) · BMJ · doi:10.1136/bmj.322.7289.798 · Cited by 34
Pfäffle, R. W., Parks, J. S., Brown, M. R., & Heimann, G. (1993) · Journal of Pediatric Endocrinology and Metabolism · doi:10.1515/jpem.1993.6.3-4.229 · Cited by 26
Lee, K.-O., Persani, L., Tan, M., Sundram, F. X., & Beck-Peccoz, P. (1995) · Journal of Endocrinological Investigation · doi:10.1007/bf03349814 · Cited by 25
The Etiology of Isolated Thyroid Stimulating Hormone Deficiency
Hashimoto, K. (1998) · Internal Medicine · doi:10.2169/internalmedicine.37.231 · Cited by 10
Stuck, L. M., & McFarland, K. F. (1991) · Postgraduate Medicine · doi:10.1080/00325481.1991.11701145 · Cited by 10
Fowler, P. B. S. (2001) · The Lancet · doi:10.1016/s0140-6736(00)05147-3 · Cited by 2
Research works printed but not linked: 4
- [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.
- [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.
- [12]12. Eds LE Braverman & RD Utiger. Philadelphia: Lippincott, 1996.
- [25]25. Eds LJ DeGroot & JL Jameson. Philadelphia: Saunders, 2001.
Cited by
Sorted by citations
Jonklaas, J., Bianco, A. C., Bauer, A. J., Burman, K. D., Cappola, A. R., Celi, F. S., Cooper, D. S., Kim, B. W., Peeters, R. P., Rosenthal, M. S., et al. (2014) · Thyroid® · doi:10.1089/thy.2014.0028 · Cited by 1,928
“6 lg/kg LT4 produced normal FT4 values in 94% of patients, but normal FT3 values in only 49% (394).”
Hormonal Replacement in Hypopituitarism in Adults: An Endocrine Society Clinical Practice Guideline
Fleseriu, M., Hashim, I. A., Karavitaki, N., Melmed, S., Murad, M. H., Salvatori, R., & Samuels, M. H. (2016) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2016-2118 · Cited by 945
Schmidt, M. E., Wiskemann, J., Armbrust, P., Schneeweiß, A., Ulrich, C. M., & Steindorf, K. (2014) · International Journal of Cancer · doi:10.1002/ijc.29383 · Cited by 324
Central Hypothyroidism: Pathogenic, Diagnostic, and Therapeutic Challenges
Persani, L. (2012) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2012-1616 · Cited by 295
Higham, C., Johannsson, G., & Shalet, S. M. (2016) · The Lancet · doi:10.1016/s0140-6736(16)30053-8 · Cited by 273
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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review