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ArticleAACE endocrinology and diabetes

Triphasic Adrenocorticotropic Hormone Dynamics During Immune Checkpoint Inhibitor Therapy in a Patient With Malignant Melanoma.

Natsumi Kuwata, Natsuko Ohashi, Maya Yonishi-Nakamura, Takashi Suzue, Kimihiro Nishimura, Koichiro Murata, Shogo Ida, Itsuko Miyazawa, Akira Shimatsu, Yutaka Takahashi and 1 more

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Article in AACE endocrinology and diabetes. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

11 authors.

Natsumi KuwataDepartment of Diabetes, Endocrinology and Nephrology, Shiga University of Medical Science, Otsu, Shiga, Japan.
Natsuko OhashiDepartment of Diabetes, Endocrinology and Nephrology, Shiga University of Medical Science, Otsu, Shiga, Japan.
Maya Yonishi-NakamuraDepartment of Diabetes, Endocrinology and Nephrology, Shiga University of Medical Science, Otsu, Shiga, Japan.
Takashi SuzueDepartment of Diabetes, Endocrinology and Nephrology, Shiga University of Medical Science, Otsu, Shiga, Japan.
Kimihiro NishimuraDepartment of Diabetes, Endocrinology and Nephrology, Shiga University of Medical Science, Otsu, Shiga, Japan.
Koichiro MurataDepartment of Diabetes, Endocrinology and Nephrology, Shiga University of Medical Science, Otsu, Shiga, Japan.
Shogo IdaDepartment of Diabetes, Endocrinology and Nephrology, Shiga University of Medical Science, Otsu, Shiga, Japan.
Itsuko MiyazawaDepartment of Diabetes, Endocrinology and Nephrology, Shiga University of Medical Science, Otsu, Shiga, Japan.
Akira ShimatsuAdvanced Medical Care Center, Omi Medical Center, Kusatsu, Shiga, Japan.
Yutaka TakahashiDepartment of Diabetes and Endocrinology, Nara Medical University, Kashihara, Nara, Japan.
Shinji KumeDepartment of Diabetes, Endocrinology and Nephrology, Shiga University of Medical Science, Otsu, Shiga, Japan.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Background/Objective: Immune checkpoint inhibitor (ICI)-related hypophysitis is generally considered to cause irreversible adrenocorticotropic hormone (ACTH) deficiency, requiring long-term glucocorticoid replacement. However, recent reports have described transient ACTH elevation before the onset of adrenal insufficiency. We report a patient with malignant melanoma who developed a previously unreported triphasic pattern of ACTH dynamics during ICI therapy. Case Presentation: A 74-year-old woman was treated with nivolumab monotherapy followed by combination therapy with nivolumab and ipilimumab. She initially presented with ACTH deficiency and an inadequate cortisol response to rapid ACTH stimulation. Plasma ACTH and serum cortisol levels then transiently increased, before declining again and progressing to persistent secondary adrenal insufficiency. Discussion: While transient functional suppression of corticotrophs prior to irreversible structural destruction may partly explain this course, the sequence of ICI exposure is likely to have played an important role in shaping the triphasic ACTH dynamics observed in this case. The temporal pattern of hormonal changes, differences in the typical onset of hypophysitis between antiprogrammed cell death 1 and anti-cytotoxic T-lymphocyte-associated antigen 4 antibodies, and imaging features characteristic of anticytotoxic T-lymphocyte-associated antigen 4-associated hypophysitis support the possibility of layered or overlapping inflammatory insults to the pituitary following sequential ICI exposure. Conclusion: This case highlights that transient ACTH elevation during ICI therapy should not be interpreted as recovery of pituitary function and may precede permanent ACTH deficiency. Careful hormonal monitoring is essential, particularly during sequential or combination ICI therapy. Accumulation of additional cases will help clarify the dynamic pathophysiology of ICI-related hypophysitis and improve clinical monitoring strategies.

Indexed as

adrenocorticotropic hormonehypophysitisimmune checkpoint inhibitorsecondary adrenal insufficiency

Identifiers

PMID42491697
PMCPMC13377964

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.