{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T16:03:28Z","timestamp":1791821008198,"version":"4.3.4"},"reference-count":142,"publisher":"Bioscientifica","issue":"2","license":[{"start":{"date-parts":[[2019,2,1]],"date-time":"2019-02-01T00:00:00Z","timestamp":1548979200000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["ec.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2019,2]]},"abstract":"<jats:p>Central hypothyrodism (CeH) is a hypothyroid state caused by an insufficient stimulation by thyrotropin (TSH) of an otherwise normal thyroid gland. Several advancements, including the recent publication of expert guidelines for CeH diagnosis and management, have been made in recent years thus increasing the clinical awareness on this condition. Here, we reviewed the recent advancements and give expert opinions on critical issues. Indeed, CeH can be the consequence of various disorders affecting either the pituitary gland or the hypothalamus. Recent data enlarged the list of candidate genes for heritable CeH and a genetic origin may be the underlying cause for CeH discovered in pediatric or even adult patients without apparent pituitary lesions. This raises the doubt that the frequency of CeH may be underestimated. CeH is most frequently diagnosed as a consequence of the biochemical assessments in patients with hypothalamic\/pituitary lesions. In contrast with primary hypothyroidism, low FT4 with low\/normal TSH levels are the biochemical hallmark of CeH, and adequate thyroid hormone replacement leads to the suppression of residual TSH secretion. Thus, CeH often represents a clinical challenge because physicians cannot rely on the use of the \u2018reflex TSH strategy\u2019 for screening or therapy monitoring. Nevertheless, in contrast with general assumption, the finding of normal TSH levels may indicate thyroxine under-replacement in CeH patients. The clinical management of CeH is further complicated by the combination with multiple pituitary deficiencies, as the introduction of sex steroids or GH replacements may uncover latent forms of CeH or increase the thyroxine requirements.<\/jats:p>","DOI":"10.1530\/ec-18-0515","type":"journal-article","created":{"date-parts":[[2019,1,15]],"date-time":"2019-01-15T09:35:33Z","timestamp":1547544933000},"page":"R44-R54","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-10","source":"Crossref","is-referenced-by-count":57,"title":["The diagnosis and management of central hypothyroidism in 2018"],"prefix":"10.1530","volume":"8","author":[{"given":"Luca","family":"Persani","sequence":"first","affiliation":[{"name":"1Division of Endocrine and Metabolic Diseases, Istituto Auxologico Italiano IRCCS, Milan, Italy"},{"name":"2Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Biagio","family":"Cangiano","sequence":"additional","affiliation":[{"name":"1Division of Endocrine and Metabolic Diseases, Istituto Auxologico Italiano IRCCS, Milan, Italy"},{"name":"2Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Bonomi","sequence":"additional","affiliation":[{"name":"1Division of Endocrine and Metabolic Diseases, Istituto Auxologico Italiano IRCCS, Milan, Italy"},{"name":"2Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","reference":[{"key":"ref941","doi-asserted-by":"crossref","first-page":"2291","DOI":"10.1002\/j.1460-2075.1989.tb08355.x","article-title":"Thyroid-stimulating hormone (TSH) deficiency caused by a single base substitution in the CAGYC region of the 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