A Rare Case of Acromegaly and Prolactinoma in MEN4 Caused by a CDKN1B Mutation - Case Report

Sep 23, 2026

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Multiple endocrine neoplasia (MEN) is a rare autosomal dominant disorder marked by benign or malignant tumors across one or more endocrine glands. MEN4, caused by germline CDKN1B mutations, overlaps phenotypically with MEN1, yet limited case numbers and the absence of standardized clinical guidance leave its clinical features insufficiently defined. This case report describes a 59-year-old woman with progressive facial changes, a pituitary mass, and whole-exome sequencing-confirmed CDKN1B pathogenic variants. The course highlights phenotypic diversity, including acromegaly, hyperparathyroidism, and additional malignancy.

LanguageEnglish

CategoryHealthcare

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Background/Objective

Case Report

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AACE Endocrinology and Diabetes 13 (2026) 502—506 Endocrinology and Diabetes [www.endocrinologydiabetes.org](www.endocrinologydiabetes.org) Case Report A Rare Case of Acromegaly and Prolactinoma in MEN4 Caused by a CDKN1B Mutation Liu Yuke, MD, Wang Hongxing, Tan Huiwen, MD, PhD *, Li Jianwei, MD, Yu Yerong, MD Department of Endocrinology and Metabolism, West China Hospital, Sichuan University, Chengdu, China | a r t i c l e i n f o | a b s t r a c t | | --- | --- | | Article history: | Background/Objective: Multiple endocrine neoplasia (MEN) comprises a group of rare autosomal | | Received 16 June 2025 | dominant genetic disorders characterized by the development of benign or malignant tumors in 2 | | Received in revised form | or more endocrine glands, most commonly including the thyroid, parathyroid, pituitary, adrenal | | 20 December 2025 | glands, and pancreatic neuroendocrine tissues. MEN4 is a recently recognized subtype that | | Accepted 13 January 2026 | phenotypically overlaps with MEN1 and is caused by germline mutations in the cyclin-dependent | | Available online 20 January 2026 | kinase inhibitor 1B (CDKN1B) gene. However, due to the limited number of reported cases and the | | | lack of standardized clinical guidelines, the clinical characteristics of MEN4 remain insufficiently understood.
Case report: A 59-year-old female presented to our department with progressive facial changes for over 8 years and a pituitary mass detected 6 months prior. Whole-exome sequencing identified | | Key words:
acromegaly CDKN1B | | | hyperparathyroidism
multiple endocrine neoplasia pituitary neuroendocrine tumors hyperprolactinemia | pathogenic mutations in the CDKN1B gene, confirming the diagnosis of MEN4.
Conclusion: We report a rare case of MEN4 presenting with acromegaly, hyperparathyroidism, and papillary thyroid cancer, caused by a CDKN1B mutation. This case highlights the phenotypic diversity of MEN4 and underscores the importance of genetic testing in patients with overlapping endocrine neoplasms. We also added a literature review to raise clinical awareness of MEN 4 and improve management.
© 2026 American Association of Clinical Endocrinology. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license ([http://creativecommons.org/licenses/by-nc-nd/4.0/](http://creativecommons.org/licenses/by-nc-nd/4.0/)). | Background Multiple endocrine neoplasia (MEN) is a rare autosomal dominant genetic endocrine disorder characterized by tumors in one or more endocrine glands.1 MEN can be classified into MEN1, MEN2A, MEN2B, and MEN4 based on the pathogenic gene mutation, affected endocrine glands and nonendocrine tissues, hormone secretions, and clinical manifestations. MEN1 is mainly characterized by the primary hyperparathyroidism, pancreatic neuroendocrine tumors, and pituitary adenoma. MEN2 patients Abbreviations: GH, growth hormone; MEN, multiple endocrine neoplasia; MIBI, methoxyisobutylisonitrile; MRI, magnetic resonance imaging; NET, neuroendocrine tumors; TSH, thyroid-stimulating hormone. * Address correspondence to Dr Tan Huiwen, Department of Endocrinology and Metabolism, West China Hospital, Sichuan University, Guoxue Road 37, Chengdu 610041, China. E-mail addresses: [liuyuke0809@163.com](liuyuke0809@163.com) (L. Yuke), [huiwent2016@scu.edu.cn](huiwent2016@scu.edu.cn) (T. Huiwen). usually present with medullary thyroid carcinoma, pheochromocytoma and primary hyperparathyroidism. And MEN2 is further divided into MEN2A and MEN2B. In MEN2B, the medullary thyroid carcinoma follows a more aggressive course, requiring earlier and more active intervention.1 In 2002, a newtype of MEN syndrome with the same phenotypic characteristics as MEN1 and MEN2 was discovered in rats and was named MENX. The study found that the syndrome is caused by the cyclin-dependent kinase inhibitor 1B (CDKN1B) gene mutation, which plays a role in regulating cell cycle progression.2 P

FAQs

What causes MEN4 in this report?

MEN4 is caused by germline mutations in the CDKN1B gene. Whole-exome sequencing in this patient confirmed pathogenic variants in CDKN1B.

What clinical conditions are reported in the 59-year-old patient?

The patient presented with progressive facial feature changes and a pituitary mass, with biochemical findings including elevated prolactin, growth hormone/IGF-1, and hypercalcemia. The report describes MEN4 presenting with acromegaly and hyperparathyroidism, along with papillary thyroid cancer.

Why is genetic testing emphasized for MEN4?

Because MEN4 has limited reported cases and substantial phenotypic diversity, genetic testing helps confirm diagnosis in patients with overlapping endocrine neoplasms and supports appropriate management.

Sep 23, 2026

Uploaded by McQueen