Excess of β-Subunit of Thyrotropin (TSH) in Patients with Idiopathic Central Hypothyroidism due to the Secretion of TSH with Reduced Biological Activity*

Faglia, G.; Beck‐Peccoz, Paolo; Ballabio, Maria; Nava, C

doi:10.1210/jcem-56-5-908

Cited by 46 publications

(18 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These data suggest that the osmoreceptors or the input from the osmoreceptors to AVP-synthesizing neurons, usually controlling AVP release, were damaged by iron accumulation in the hypothalamus. On the other hand, it is reported that the TSH release response to TRH is delayed, exaggerated or prolonged (21), and that T3 release response to TRH does not increase (22) in patients with hypothalamic disorders, demonstrating the secretion of biologically inactive TSH (23). In the present case, TRH loading test resulted in a delayed response of TSH and a blunted response of T3, suggesting the existence of hypothalamic hypothyroidism.…”

Section: Discussioncontrasting

confidence: 52%

Central Diabetes Insipidus and Hypothalamic Hypothyroidism Associated with Aceruloplasminemia

et al. 2010

View full text Add to dashboard Cite

Aceruloplasminemia is a rare autosomal recessive disease first reported by Miyajima et al. (Neurology 37: 761-767, 1987); it is clinically characterized by diabetes mellitus, retinal degeneration and neurological abnormalities, such as cerebellar ataxia, extrapyramidal signs and dementia. Aceruloplasminemia is caused by mutations in the ceruloplasmin gene, which results in the absence of serum ceruloplasmin and iron overload in the brain, liver, pancreas and other organ tissues. However, little is known about endocrine diseases associated with aceruloplasminemia. We report herein a case of aceruloplasminemia accompanied by central diabetes insipidus and hypothalamic hypothyroidism.

show abstract

Section: Discussioncontrasting

confidence: 52%

Central Diabetes Insipidus and Hypothalamic Hypothyroidism Associated with Aceruloplasminemia

et al. 2010

View full text Add to dashboard Cite

show abstract

“…This in vivo indirect evidence should be confirmed by in vitro bioassay, although they are highly suggestive of a less-bioactive TSH. The serum T3 response to TRH was reduced in some patients with central hypothyroidism, whose basal TSH was slightly elevated and less bioactive (Faglia et al 1983). Mice lacking TRH had slightly higher serum TSH, low serum T3 and T4, and showed diminished T3 response to endogenous TSH after TRH stimulation, which was considered as evidence of reduction in TSH bioactivity (Yamada et al 1997).…”

Section: Discussionmentioning

confidence: 99%

Disruption of neuromedin B receptor gene results in dysregulation of the pituitary–thyroid axis

Oliveira¹,

Ortiga-Carvalho²,

Cabanelas³

et al. 2006

Journal of Molecular Endocrinology

View full text Add to dashboard Cite

The level of thyrotropin (TSH) secretion is determined by the balance of TSH-releasing hormone (TRH) and thyroid hormones. However, neuromedin B (NB), a bombesin-like peptide, highly concentrated in the pituitary, has been postulated to be a tonic inhibitor of TSH secretion. We studied the pituitary-thyroid axis in adult male mice lacking NB receptor (NBR-KO) and their wild-type (WT) littermates. At basal state, NBR-KO mice presented serum TSH slightly higher than WT (18%, P,0·05), normal intra-pituitary TSH content, and no significant changes in and TSH mRNA levels. Serum thyroxine was normal but serum triiodothyronine (T3) was reduced by 24% (P,0·01) in NBR-KO mice. Pituitaries of NBR-KO mice exhibited no alteration in prolactin mRNA expression but type I and II deiodinase mRNA levels were reduced by 53 and 42% respectively (P,0·05), while TRH receptor mRNA levels were importantly increased (78%, P,0·05). The TSH-releasing effect of TRH was significantly higher in NBR-KO than in WT mice (7·1-and 4·0-fold respectively), but, while WT mice presented a 27% increase in serum T3 (P,0·05) after TRH, NBR-KO mice showed no change in serum T3 after TRH. NBR-KO mice did not respond to exogenous NB, while WT showed a 30% reduction in serum TSH. No compensatory changes in mRNA expression of NB or other bombesin-related peptides and receptors (gastrin-releasing peptide (GRP), GRP-receptor and bombesin receptor subtype-3) were found in the pituitary of NBR-KO mice. Therefore, the data suggest that NB receptor pathways are importantly involved in thyrotroph gene regulation and function, leading to a state where TSH release is facilitated especially in response to TRH, but probably with a less-bioactive TSH. Therefore, the study highlights the important role of NB as a physiological regulator of pituitary-thyroid axis function and gene expression.

show abstract

“…Serum PRL, LH, and FSH levels were measured by commercial RIA kits (Biodata, Milan, Italy). Serum holo-TSH, a-sub, and TSH-|1 were measured by previously reported methods [22]. The «-sub and TSH-|i for iodination and standard curves, and corresponding antisera were a kind gift from the National Hormone and Pituitary Program (NIDDK, Baltimore, Md., USA).…”

Section: Methodsmentioning

confidence: 99%

“…Circulating TSH-|) derives only from thyrotroph secretion, but the low sensitivity of TSH-|1 RIA made difficull the assess ment of its responses to TRH, as well as to DA and antidopa minergic drug administration, except in hypothyroid patients [4,[17][18][19]21], However, the recent availability of a TSH-|i RIA with a sensitivity of 0.1 gg/l has allowed the detection of a slight increase in TSH-|) levels after TRH also in normal subjects [22].…”

mentioning

confidence: 99%

Thyrotropin Alpha- and Beta-Subunit Responses to Thyrotropin-Releasing Hormone and Domperidone in Normal Subjects and in Patients with Microprolactinomas

et al. 1991

Self Cite

View full text Add to dashboard Cite

Microprolactinoma is a particular pathological situation characterized by the presence of increased hypothalamic dopaminergic tone reactive to tumoral hyperprolactinemia. Since dopamine (DA) is a physiological regulating factor of the secretion of thyroid-stimulating hormone (TSH), we investigated the responses of serum TSH (holo-TSH) and its subunits (α-subunit: α-sub, and TSH-β) to thyrotropin-releasing hormone (TRH) and domperidone (DOM; an antidopaminergic drug acting outside the blood-brain barrier) in 36 euthyroid subjects (20 controls and 16 patients with microprolactinoma) in order to evaluate the possible in vivo effects of DA excess on TSH subunit secretion. No significant difference in serum TSH increase after TRH (200 µg i.v.) was observed between patients with microprolactinoma and controls (TSH net incremental area under the curve, nAUC: 146 ± 9, mean ± SE, and 143 ± 7.7 µg/1/60 min, respectively), while serum α-sub and TSH-β responses were markedly reduced in patients with microprolactinoma as compared to those found in normals (α-sub nAUC: 3.0 ± 0.5 vs. 19.8 ± 2.2 µg/1/60 min, p < 0.001; TSH-β nAUC: 5.0 ± 0.8 vs. 9.5 ± 0.9 µg/1/60 min, p < 0.05). Serum TSH response to DOM administration (10 mg i.v.) was significantly higher in patients with microprolactinoma than in controls (TSH nAUC: 76 ± 12.7 vs. 28 ± 8.3 µg/1/90 min, p < 0.001), while serum α-sub increase was similar in the two groups (α-sub nAUC: 8.7 ± 4.8 and 10.2 ± 4.7 µg/1/90 min, p = NS), and serum TSH-β did not show any increase in patients with microprolactinoma (TSH-β nAUC: 0.2 ± 0.1 vs. 6.0 ± 3.3 µg/1/90 min, p < 0.001). The present findings show that in normal subjects, α-sub and TSH-β are cosecreted along with holo-TSH in response to both TRH and dopaminergic receptor blockade by DOM. On the contrary, in patients with microprolactinoma, α-sub and TSH-β responses to the above stimulatory agents are definitely impaired. Such an impairment is particularly evident after DOM administration which caused a holo-TSH release 3-fold higher than in controls. The discrepancy between the secretory response of holo-TSH and that of both α-sub and TSH-β in the condition of increased hypothalamic dopaminergic tone suggests a preferential secretion of holo-TSH molecules in order to overcome the chronic dopaminergic inhibition and maintain normal thyroid stimulation.

show abstract

Excess of β-Subunit of Thyrotropin (TSH) in Patients with Idiopathic Central Hypothyroidism due to the Secretion of TSH with Reduced Biological Activity*

Cited by 46 publications

References 33 publications

Central Diabetes Insipidus and Hypothalamic Hypothyroidism Associated with Aceruloplasminemia

Central Diabetes Insipidus and Hypothalamic Hypothyroidism Associated with Aceruloplasminemia

Disruption of neuromedin B receptor gene results in dysregulation of the pituitary–thyroid axis

Thyrotropin Alpha- and Beta-Subunit Responses to Thyrotropin-Releasing Hormone and Domperidone in Normal Subjects and in Patients with Microprolactinomas

Contact Info

Product

Resources

About