GH responsiveness to corticotropin-releasing hormone identifies corticotroph-like somatotroph adenomas in acromegaly

Itoh, Hirotaka; Mukai, Kosuke; Mitsui, Yuto; Umehara, Toru; Kijima, Noriyuki; Oshino, Satoru; Kohara, Masaharu; Morii, Eiichi; Fukuhara, Atsunori; Shimomura, Iichiro

doi:https://doi.org/10.1007/s11102-026-01714-5

GH responsiveness to corticotropin-releasing hormone identifies corticotroph-like somatotroph adenomas in acromegaly

Itoh, Hirotaka; Mukai, Kosuke; Mitsui, Yuto et al.

Pituitary, 2026, 29(4), 114

Number of Access:370（2026-09-29 08:33 Counts）

Identifier to cite or link to this item: https://hdl.handle.net/11094/106025

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Title	GH responsiveness to corticotropin-releasing hormone identifies corticotroph-like somatotroph adenomas in acromegaly
Creator	CreatorName Itoh, Hirotaka
	NRID 1000020815352 1000020815352 ORCID 0000-0002-9365-5561 0000-0002-9365-5561 researchmap permalink mukai mukai Scopus Author ID 55045414800 55045414800 CreatorName Mukai, Kosuke
	CreatorName Mitsui, Yuto
	NRID 1000020792469 1000020792469 researchmap permalink toru_umehara toru_umehara CreatorName Umehara, Toru
	NRID 1000080534627 1000080534627 ORCID 0000-0003-2103-1909 0000-0003-2103-1909 researchmap permalink kiji kiji Scopus Author ID 53463724600 53463724600 CreatorName Kijima, Noriyuki
	NRID 1000040403050 1000040403050 ORCID 0000-0002-4248-2322 0000-0002-4248-2322 researchmap permalink handai_ns_oshino handai_ns_oshino Scopus Author ID 6602717325 6602717325 CreatorName Oshino, Satoru
	NRID 1000000379257 1000000379257 ORCID 0009-0006-7636-5833 0009-0006-7636-5833 Scopus Author ID 22234528100 22234528100 CreatorName Kohara, Masaharu
	NRID 1000010283772 1000010283772 ORCID 0000-0001-8490-3650 0000-0001-8490-3650 researchmap permalink read0046454 read0046454 Scopus Author ID 7003914326 7003914326 CreatorName Morii, Eiichi
	NRID 1000000437328 1000000437328 ORCID 0000-0002-6289-3778 0000-0002-6289-3778 researchmap permalink AtsuF AtsuF Scopus Author ID 7003835710 7003835710 CreatorName Fukuhara, Atsunori
	NRID 1000060346145 1000060346145 ORCID 0000-0002-0851-9603 0000-0002-0851-9603 researchmap permalink shimomura_i shimomura_i Scopus Author ID 7006715546 7006715546 CreatorName Shimomura, Iichiro
Subject	Acromegaly
	Adrenocorticotropic hormone
	Corticotropin-releasing hormone
	Pituitary adenoma
	Somatotroph
	TPIT
Description	Itoh H., Mukai K., Mitsui Y., et al. GH responsiveness to corticotropin-releasing hormone identifies corticotroph-like somatotroph adenomas in acromegaly. Pituitary 29, 114 (2026); https://doi.org/10.1007/s11102-026-01714-5.
Description	The version of record of this article, first published in Pituitary, is available online at Publisher’s website: https://doi.org/10.1007/s11102-026-01714-5
Abstract	Purpose: Corticotropin-releasing hormone (CRH) induces an increase in growth hormone (GH) secretion in a subset of patients with acromegaly; however, the characteristics of these CRH responders remain poorly defined. Methods: 22 CRH responders were retrospectively compared with 43 nonresponders. Results: CRH responders exhibited significantly larger tumors and more frequent visual field impairment than nonresponders, despite comparable baseline GH and insulin-like growth factor 1 (IGF-1) levels, and disease duration. Tumor volume and diameter were positively correlated with the GH increase ratio in CRH test, whereas GH and IGF-1 per tumor volume or diameter were significantly lower in CRH responders, indicating reduced GH secretory capacity relative to tumor size. Immunohistochemical analyses revealed higher corticotropin-releasing hormone receptor 1 (CRHR1) and lower CRHR2 expression in CRH responders. In addition, T-box transcription factor (TPIT) and adrenocorticotropic hormone (ACTH) expression were significantly more frequent in adenomas from CRH responders, suggesting a corticotroph-like phenotype. GH responses to CRH were significantly correlated with those to luteinizing hormone–releasing hormone but not thyrotropin-releasing hormone or oral glucose tolerance testing. GH responses to CRH tended to be inversely correlated with somatostatin receptor subtype 2 expression as a predictor of first-generation somatostatin receptor ligand efficacy but not with octreotide response or MRI signal intensity. Conclusions: These findings support that GH responsiveness to CRH identifies a biologically distinct subset of somatotroph adenomas characterized by corticotroph-like features, larger tumor size, and reduced GH secretory capacity. GH responsiveness to CRH may serve as a noninvasive indicator of intrinsic tumor biology and behavior.
Publisher	Springer
Source Title	Pituitary
Volume (Issue)	29(4)
Page	114
Date of Issued	2026-08-01
Language	English
Handle URL	https://hdl.handle.net/11094/106025
PISSN	1386341X
eISSN	15737403
Relation.isIdenticalTo	DOI (Publisher Version) https://doi.org/10.1007/s11102-026-01714-5
Access Rights	open access
CopyRight	This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
oaire:version	Version of Record
Category	学術雑誌論文 Journal Article

Resource Type	journal article
Local Type	Journal Article
DCMI Type	Text
DCTERMS.bibliographicCitation	Pituitary. 2026, 29(4), p. 114
DC.title	GH responsiveness to corticotropin-releasing hormone identifies corticotroph-like somatotroph adenomas in acromegaly
DC.creator	Itoh, Hirotaka
	Mukai, Kosuke
	Mitsui, Yuto
	Umehara, Toru
	Kijima, Noriyuki
	Oshino, Satoru
	Kohara, Masaharu
	Morii, Eiichi
	Fukuhara, Atsunori
	Shimomura, Iichiro
DC.publisher	Springer
DC.language' scheme='DCTERMS.RFC1766	English
DC.type' scheme='DCTERMS.DCMIType	Text
DCTERMS.issued' scheme='DCTERMS.W3CDTF	2026-08-01
DC.identifier	https://doi.org/10.1007/s11102-026-01714-5
DC.subject	Acromegaly
	Adrenocorticotropic hormone
	Corticotropin-releasing hormone
	Pituitary adenoma
	Somatotroph
	TPIT
DC.description	Itoh H., Mukai K., Mitsui Y., et al. GH responsiveness to corticotropin-releasing hormone identifies corticotroph-like somatotroph adenomas in acromegaly. Pituitary 29, 114 (2026); https://doi.org/10.1007/s11102-026-01714-5.
DC.description	The version of record of this article, first published in Pituitary, is available online at Publisher’s website: https://doi.org/10.1007/s11102-026-01714-5
DCTERMS.abstract	Purpose: Corticotropin-releasing hormone (CRH) induces an increase in growth hormone (GH) secretion in a subset of patients with acromegaly; however, the characteristics of these CRH responders remain poorly defined. Methods: 22 CRH responders were retrospectively compared with 43 nonresponders. Results: CRH responders exhibited significantly larger tumors and more frequent visual field impairment than nonresponders, despite comparable baseline GH and insulin-like growth factor 1 (IGF-1) levels, and disease duration. Tumor volume and diameter were positively correlated with the GH increase ratio in CRH test, whereas GH and IGF-1 per tumor volume or diameter were significantly lower in CRH responders, indicating reduced GH secretory capacity relative to tumor size. Immunohistochemical analyses revealed higher corticotropin-releasing hormone receptor 1 (CRHR1) and lower CRHR2 expression in CRH responders. In addition, T-box transcription factor (TPIT) and adrenocorticotropic hormone (ACTH) expression were significantly more frequent in adenomas from CRH responders, suggesting a corticotroph-like phenotype. GH responses to CRH were significantly correlated with those to luteinizing hormone–releasing hormone but not thyrotropin-releasing hormone or oral glucose tolerance testing. GH responses to CRH tended to be inversely correlated with somatostatin receptor subtype 2 expression as a predictor of first-generation somatostatin receptor ligand efficacy but not with octreotide response or MRI signal intensity. Conclusions: These findings support that GH responsiveness to CRH identifies a biologically distinct subset of somatotroph adenomas characterized by corticotroph-like features, larger tumor size, and reduced GH secretory capacity. GH responsiveness to CRH may serve as a noninvasive indicator of intrinsic tumor biology and behavior.
DC.rights	This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
DC.format	106025
citation_title	GH responsiveness to corticotropin-releasing hormone identifies corticotroph-like somatotroph adenomas in acromegaly
citation_author	Itoh, Hirotaka
	Mukai, Kosuke
	Mitsui, Yuto
	Umehara, Toru
	Kijima, Noriyuki
	Oshino, Satoru
	Kohara, Masaharu
	Morii, Eiichi
	Fukuhara, Atsunori
	Shimomura, Iichiro
citation_publisher	Springer
citation_language	English
citation_date	2026-08-01
citation_journal_title	Pituitary
citation_volume	29
citation_issue	4
citation_firstpage	114
citation_doi	https://doi.org/10.1007/s11102-026-01714-5
citation_public_url	https://hdl.handle.net/11094/106025

GH responsiveness to corticotropin-releasing hormone identifies corticotroph-like somatotroph adenomas in acromegaly

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