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12.10.2023 | Original Article

The mystery of transient pregnancy-induced cushing’s syndrome: a case report and literature review highlighting GNAS somatic mutations and LHCGR overexpression

verfasst von: Yufei Li, Jianfan Lin, Shien Fu, Li Li, Zhenxing Huang, Haiyan Yang, Xinghuan Liang, Yingfen Qin, Jia Zhou, Deyun Liu, Zuojie Luo

Erschienen in: Endocrine | Ausgabe 2/2024

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Abstract

Purpose

Transient pregnancy-induced Cushing’s syndrome is a rare condition characterized by the manifestation of symptoms solely during pregnancy, which typically resolve spontaneously following delivery or miscarriage. While it has been established that GNAS is associated with adrenal tumors, its specific role in the pathogenesis of pregnancy-induced Cushing’s syndrome remains uncertain.This work aims to examine the association between GNAS mutation and pregnancy-induced Cushing’s syndrome.

Methods

DNA was extracted from patients’ peripheral blood and tumor tissues for whole-exome sequencing (WES) and Sanger sequencing. We used AlphaFold to predict the protein structure of wild-type and mutant GNAS and to make functional predictions, and immunohistochemistry was used to detect disease-associated protein expression. A review and summary of reported cases of transient pregnancy-induced Cushing’s syndrome induced by pregnancy was conducted.

Results

Using WES, we identified a somatic mutation in GNAS (NM_000516, c.C601T, p.R201C) that was predicted to have a deleterious effect using computational methods, such as AlphaFold. Human chorionic gonadotropin (hCG) stimulation tests had weakly positive results, and immunohistochemical staining of adrenal adenoma tissue also revealed positivity for luteinizing hormone/chorionic gonadotropin receptor (LHCGR) and cytochrome P450 family 11 subfamily B member 1 (CYP11B1). We reviewed 15 published cases of transient Cushing’s syndrome induced by pregnancy. Among these cases, immunohistochemical staining of the adrenal gland showed positive LHCGR expression in 3 case reports, similar to our findings.

Conclusion

Transient pregnancy-induced Cushing’s syndrome may be associated with somatic GNAS mutations and altered adrenal pathology due to abnormal activation of LHCGR.

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Titel: The mystery of transient pregnancy-induced cushing’s syndrome: a case report and literature review highlighting GNAS somatic mutations and LHCGR overexpression
verfasst von: Yufei Li
Jianfan Lin
Shien Fu
Li Li
Zhenxing Huang
Haiyan Yang
Xinghuan Liang
Yingfen Qin
Jia Zhou
Deyun Liu
Zuojie Luo
Publikationsdatum: 12.10.2023
Verlag: Springer US
Erschienen in: Endocrine / Ausgabe 2/2024
Print ISSN: 1355-008X
Elektronische ISSN: 1559-0100
DOI: https://doi.org/10.1007/s12020-023-03549-7

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The mystery of transient pregnancy-induced cushing’s syndrome: a case report and literature review highlighting GNAS somatic mutations and LHCGR overexpression