The DOI matches its Crossref record; 29 of the 29 references it cites were found in a registry or an index.
Circulating Thyrotropin Bioactivity in Sporadic Central Hypothyroidism
Abstract
The etiopathogenesis of sporadic central hypothyroidism (CH) involves pituitary and hypothalamic lesions. Pituitary CH (pCH) implies a diminished number of functioning thyrotropes, accounting for the quantitative impairment of TSH secretion. Hypothalamic CH (hCH) is characterized by normal or even increased TSH concentrations and qualitative abnormalities of TSH secretion, including a decreased bioactivity of circulating TSH. However, controversy still exists about the actual occurrence of bioinactive TSH among CH patients, and no data are available in pCH. Therefore, we studied 41 CH patients with different hypothalamic-pituitary disorders. Immunoreactive TSH (TSH-I) ranged from 0.08-11.1 mU/L (normal, 0.24-4.0), free T4 (FT4) ranged from 0.6-8.8 pmol/L (normal, 9-18), and FT3 ranged from 1.2-5.4 pmol/L (normal, 4-8). A blunted TSH response to TRH (<4 mU/L), indicating prevalent pCH, was found in 56% of the patients, and a net TSH-I increment > or =4 mU/L, indicating prevalent hCH, was found in the remaining 44%. Net TSH-I increments showed significant correlation with basal FT4 (P < 0.02), indicating the relevance of pituitary TSH reserve in the pathogenesis of CH. Circulating TSH was immunoconcentrated and tested in bioassay and in ricin affinity chromatography. The ratio between biological (B) and immunological (I) activities of circulating TSH was reduced (n = 25; TSH B/I, 0.38+/-0.19) compared to the values recorded in normal subjects (n = 26; TSH B/I, 1.53+/-0.54; P < 0.001) and primary hypothyroid patients (n = 24; TSH B/I, 0.74+/-0.31; P < 0.001), but no difference between pCH (n = 9; 0.36+/-0.16) and hCH (n = 16; 0.39+/-0.20) was seen. TSH B/I values in CH patients showed a limited overlap with normal values (20%) and a highly significant correlation with the FT3 response to endogenous TRH-stimulated TSH (P < 0.005). The elevated sialylation degree of TSH molecules may explain part of these findings. In conclusion, the secretion of TSH molecules with reduced bioactivity is a common alteration in the patients with hypothalamic-pituitary lesions, contributing along with the impairment of pituitary TSH reserve to the pathogenesis of CH.
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In the citing paper
“TSH measurement alone is not sufficient for the diagnosis or treatment of patients with central hypothyroidism.”
In the citing paper
“(c) poor intrinsic biological activity of secreted TSH molecules [14-18].”
From 2018 European Thyroid Association (ETA) Guidelines on the Diagnosis and Management of Central Hypothyroidism (2018) · cites this paper as [17]
In the citing paper
“In these cases, TSH elevations are similar to those generally found in subclinical or mild primary hypothyroidism and may lead to misdiagnosis [14-17, 30, 42].”
From 2018 European Thyroid Association (ETA) Guidelines on the Diagnosis and Management of Central Hypothyroidism (2018) · cites this paper as [17]
In the citing paper
“Studies have suggested that 10-18% of high-risk pituitary patients have unrecognized CH with low-normal fT4 levels (77,79).”
From Hormonal Replacement in Hypopituitarism in Adults: An Endocrine Society Clinical Practice Guideline (2016) · cites this paper as [77]
In the citing paper
“Serum T3 or free T3 (fT3) levels are generally not helpful in diagnosing CH; most patients with CH have low fT3 levels, but there is considerable overlap between CH and non-CH patients with pituitary MAY 4, 2016 disease (75,77).”
From Hormonal Replacement in Hypopituitarism in Adults: An Endocrine Society Clinical Practice Guideline (2016) · cites this paper as [77]
In the citing paper
“Some investigators recommend following fT3 levels or peripheral indicators of thyroid function during L-T4 therapy, since elevated fT3 levels can indicate overtreatment, although studies have not validated this (33,77).”
From Hormonal Replacement in Hypopituitarism in Adults: An Endocrine Society Clinical Practice Guideline (2016) · cites this paper as [77]
In the citing paper
“CH patients receiving GC therapy do not appear to require L-T4 dose adjustments (77).”
From Hormonal Replacement in Hypopituitarism in Adults: An Endocrine Society Clinical Practice Guideline (2016) · cites this paper as [77]
In the citing paper
“Alexopoulou et al. reported that only men with CH required increased L-T4 doses after starting GH therapy (1.8 vs. 1.6 mcg/kg/day) (77).”
From Hormonal Replacement in Hypopituitarism in Adults: An Endocrine Society Clinical Practice Guideline (2016) · cites this paper as [77]
In the citing paper
“Estrogen therapy increased mean L-T4 dose requirements in patients with CH from 1.3 to 1.8 mcg/kg/day (77).”
From Hormonal Replacement in Hypopituitarism in Adults: An Endocrine Society Clinical Practice Guideline (2016) · cites this paper as [77]
In the citing paper
“The three mechanisms are frequently coexisting as a consequence of the expansive lesions of the sella region (16, 17).”
From The diagnosis and management of central hypothyroidism in 2018 (2019) · cites this paper as [17]
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Metadata
- Authors
- Persani, L.
- Corresponding author
- Persani, L.
- ORCID
- Persani, L.
- Venue
- Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2000-10-01
- Volume
- 85
- Issue
- 10
- Pages
- 3631-3635
- ISSN
- 0021-972X (ISSN-L)
- OpenAlex
- W4253282708
- Cited by
- 70
- References
- 0
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 2 · 2023: 2 · 2022: 4 · 2021: 5 · 2020: 1 · 2019: 3 · 2018: 5 · 2017: 4 · 2016: 3 · 2015: 3 · 2013: 2 · 2012: 5
- FWCI
- 1.26
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- IRIS Research product catalog (Sapienza University of Rome) (submittedVersion)
- 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, TSH receptor, TRH stimulation test, hypothalamic-pituitary dysfunction, free thyroxine, TSH secretion
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