The DOI matches its Crossref record; 136 of the 140 references it cites were found in a registry or an index.
Central hypothyroidism — a neglected thyroid disorder
Abstract
Central hypothyroidism is a rare and heterogeneous disorder that is characterized by a defect in thyroid hormone secretion in an otherwise normal thyroid gland due to insufficient stimulation by TSH. The disease results from the abnormal function of the pituitary gland, the hypothalamus, or both. Moreover, central hypothyroidism can be isolated or combined with other pituitary hormone deficiencies, which are mostly acquired and are rarely congenital. The clinical manifestations of central hypothyroidism are usually milder than those observed in primary hypothyroidism. Obtaining a positive diagnosis for central hypothyroidism can be difficult from both a clinical and a biochemical perspective. The diagnosis of central hypothyroidism is based on low circulating levels of free T 4 in the presence of low to normal TSH concentrations. The correct diagnosis of both acquired (also termed sporadic) and congenital (also termed genetic) central hypothyroidism can be hindered by methodological interference in free T 4 or TSH measurements; routine utilization of total T 4 or T 3 measurements; concurrent systemic illness that is characterized by low levels of free T 4 and normal TSH concentrations; the use of the sole TSH-reflex strategy, which is the measurement of the sole level of TSH, without free T 4, if levels of TSH are in the normal range; and the diagnosis of congenital hypothyroidism based on TSH analysis without the concomitant measurement of serum levels of T 4. In this Review, we discuss current knowledge of the causes of central hypothyroidism, emphasizing possible pitfalls in the diagnosis and treatment of this disorder.
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“In comparison with primary hypothyroidism, there is a higher frequency for such conditions because of the persistent impact from rhGH (reviewed in [63]).”
From 2018 European Thyroid Association (ETA) Guidelines on the Diagnosis and Management of Central Hypothyroidism (2018) · cites this paper as [63]
In the citing paper
“Acquired forms of CeH are usually sporadic and in most cases due to large pituitary macroadenomas with a suprasellar extensions, craniopharyngiomas and suprasellar tumors, head trauma, vascular accident or cranial irradiation (1, 28, 33).”
From The diagnosis and management of central hypothyroidism in 2018 (2019) · cites this paper as [33]
In the citing paper
“the introduction of these replacement therapies often requires an uptitration of L-T4”
From The diagnosis and management of central hypothyroidism in 2018 (2019) · cites this paper as [33]
In the citing paper
“Both estrogens and GH influence thyroid hormone transport and/or metabolism and consequently interfere CeH management (33, 60).”
From The diagnosis and management of central hypothyroidism in 2018 (2019) · cites this paper as [33]
In the citing paper
“Sex steroid and GH deficiencies can mask an underlying CeH”
From The diagnosis and management of central hypothyroidism in 2018 (2019) · cites this paper as [33]
Citations
Cites
A mutation in the human leptin receptor gene causes obesity and pituitary dysfunction
Clément, K., Vaisse, C., Lahlou, N., Cabrol, S., Pelloux, V., Cassuto, D., Gourmelen, M., Dina, C., Chambaz, J., Lacorte, J.-M., et al. (1998) · Nature · doi:10.1038/32911 · Cited by 2,346
Werner & Ingbar's the thyroid : a fundamental and clinical text
Werner, S. C., Ingbar, S. H., Braverman, L. E., & Utiger, R. D. (2012) · Lippincott-Raven eBooks · Cited by 1,016
Craniopharyngiomas in children and adults: systematic analysis of 121 cases with long-term follow-up
Karavitaki, N., Brufani, C., Warner, J. T., Adams, C. B. T., Richards, P., Ansorge, O., Shine, B., Turner, H. E., & Wass, J. A. H. (2005) · Clinical Endocrinology · doi:10.1111/j.1365-2265.2005.02231.x · Cited by 633
Hypothalamic-pituitary dysfunction after radiation for brain tumors
Constine, L. S., Woolf, P. D., Cann, D., Mick, G., McCormick, K., Raubertas, R. F., & Rubin, P. (1993) · New England Journal of Medicine · doi:10.1056/nejm199301143280203 · Cited by 619
Caturegli, P., Newschaffer, C. J., Olivi, A., Pomper, M. G., Burger, P. C., & Rose, N. R. (2005) · Endocrine Reviews · doi:10.1210/er.2004-0011 · Cited by 612
Karavitaki, N., Cudlip, S., Adams, C. B. T., & Wass, J. A. H. (2006) · Endocrine Reviews · doi:10.1210/er.2006-0002 · Cited by 514
Bunevičius, R., Kažanavičius, G., Žalinkevičius, R., & Prange, A. J. (1999) · New England Journal of Medicine · doi:10.1056/nejm199902113400603 · Cited by 482
Demers, L. M., & Spencer, C. A. (2003) · Clinical Endocrinology · doi:10.1046/j.1365-2265.2003.01681.x · Cited by 460
Szkudlinski, M. W., Fremont, V., Ronin, C., & Weintraub, B. D. (2002) · Physiological Reviews · doi:10.1152/physrev.00031.2001 · Cited by 458
Mechanisms behind the non-thyroidal illness syndrome: an update
Warner, M., & Beckett, G. J. (2009) · Journal of Endocrinology · doi:10.1677/joe-09-0412 · Cited by 438
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- Hulle, S. V. et al. Delayed adrenarche may be an additional feature of immunoglobulin super family member 1 deficiency syndrome. J. Clin. Res. Pediatr. Endocrinol. 8, 86–91 (2016). · DOI
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Items 101–140 of 140
Salce, N., Giovannelli, E., Graziani, V., Cozzolino, M., Mazzatenta, D., Zucchelli, M., & Marchetti, F. (2021) · Medico e Bambino - Pagine Elettroniche · doi:10.53126/mebxxiv210
Cosmo, C. D., & Tonacchera, M. (2018) · Endocrinology · doi:10.1007/978-3-319-29195-6_11-1
Radiation Therapy for Sinonasal and Skull Base Tumors
McDonald, M. W., Rudra, S. F., & Remick, J. S. (2022) · Springer eBooks · doi:10.1007/978-3-030-97618-7_8
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Krude, H., & Grüters‐Kieslich, A. (2018) · Springer Reference Medizin · doi:10.1007/978-3-662-52794-8_27-1
Smith, C. L., Harrison, P. M., & Bernard, D. J. (2022) · PLoS ONE · doi:10.1371/journal.pone.0267744
A practical approach to the management of thyroid dysfunction during pregnancy
Moretti, C., Lazzarin, N., Vaquero, E., Lago, A. D., Campagnolo, L., & Valensise, H. C. C. (2022) · Gynecological Endocrinology · doi:10.1080/09513590.2022.2154337 · Cited by 1
Hypothalamo-pituitary Disorders in Childhood and Adolescence
Cerbone, M., Dattani, M., Maghnie, M., & Patti, G. (2023) · Endocrinology · doi:10.1007/978-3-030-18901-3_2-1
Fu, C., Luo, J., Su, J., Zhang, S., Yang, Q., & Zhang, Y. (2023) · International Journal of General Medicine · doi:10.2147/ijgm.s421382
Long-Term Effects of Cancer Treatment
McNerney, K. P., & Jasim, S. (2023) · Springer eBooks · doi:10.1007/978-3-031-37275-9_10
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Quarde, A. (2023) · Wiley eBooks · doi:10.1002/9781119863564.ch9
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Shareef, S. A., Allami, R. H., & Al-Ezzy, R. M. (2024) · IOP Conference Series Earth and Environmental Science · doi:10.1088/1755-1315/1325/1/012024 · Cited by 1
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Clinical guidelines “Congenital hypothyroidism”
Peterkova, V. A., Bezlepkina, O. B., Nagaeva, E. V., Shiryaeva, T., Чикулаева, О. А., Вадина, Т. А., Shreder, E. V., Bashnina, E. B., Belyashova, E. Y., Bolotova, N. V., et al. (2024) · Clinical and experimental thyroidology · doi:10.14341/ket12799
Role of neonatal screening in the diagnosis of congenital hypothyroidism in newborns
Zaryankina, A. I., Sergeichik, L. S., Kozik, E. A., & Tselekhovich, O. P. (2025) · Health and Ecology Issues · doi:10.51523/2708-6011.2024-21-4-17
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Tan, H., Liu, Y., & Cholekho, S. (2025) · IntechOpen eBooks · doi:10.5772/intechopen.1005432
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Hoermann, R., & Dietrich, J. W. (2025) · Springer eBooks · doi:10.1007/978-981-96-3682-2_7
Casiraghi, A., Cattoni, A., & Persani, L. (2025) · Journal of Endocrinological Investigation · doi:10.1007/s40618-025-02659-5
Thyroid profile in acute lymphoblastic leukemia: prognostic role of thyrotropin-releasing hormone
Fares, H., Moustafa, N., Ibrahim, N., Ali, B. S. M., & Rakha, N. M. (2025) · Forum of Clinical Oncology · doi:10.2478/fco-2024-0018
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Kawauchi, Y., Sasaki, S., Matsushita, A., Nakamura, H. M., Yamashita, M., Kakizawa, K., Ohba, K., Tsuriya, D., Tanaka, T., & Suda, T. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms27010119
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Buyandalai, B., Takamizawa, T., Horiguchi, K., Sekiguchi, S., Yoshikawa, M., Watanabe, T., Watanuki, Y., Ishida, E., Yoshino, S., Matsumoto, S., et al. (2026) · Pituitary · doi:10.1007/s11102-026-01751-0
Sapia, R. D., Bera, A., Mamad, O., Mills, J. D., Villasana‐Salazar, B., Lavigna, G., Micotti, E., Conticello, M., Alam, A., Chiesa, R., et al. (2026) · Epilepsia · doi:10.1002/epi.70453
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Metadata
- Authors
- Beck-Peccoz, P., Rodari, G., Giavoli, C., & Lania, A.
- Affiliations
- Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico (IT)
- Humanitas University (IT)
- Venue
- Nature Reviews Endocrinology
- Published
- 2017-05-26
- Volume
- 13
- Issue
- 10
- Pages
- 588-598
- ISSN
- 1759-5029 (ISSN-L)
- 1759-5037
- OpenAlex
- W2616986899
- Cited by
- 140
- References
- 140
- Citations by year
- 2026: 12 · 2025: 22 · 2024: 15 · 2023: 8 · 2022: 19 · 2021: 17 · 2020: 13 · 2019: 16 · 2018: 14 · 2017: 3
- FWCI
- 1.83
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Reviews Endocrinology (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 › Adrenal Hormones and Disorders
- Keywords
- central hypothyroidism, TSH deficiency, pituitary dysfunction, hypothalamic dysfunction, free thyroxine, pituitary hormone deficiency, thyroid hormone secretion, treatment
- MeSH terms
- Female, Humans, Hypothalamus, Hypothyroidism, Male, Pituitary Gland, Thyroid Function Tests, Thyroid Gland, Thyroid Hormones, Thyroxine, Treatment Outcome, Risk Assessment, Rare Diseases, Neglected Diseases
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