种系PRKACA重复变异相关的原发性色素沉着性结节性肾上腺皮质病1例

doi:10.3969/j.issn.1674-8115.2025.11.015

上海交通大学学报（医学版） ›› 2025, Vol. 45 ›› Issue (11): 1552-1558.doi: 10.3969/j.issn.1674-8115.2025.11.015

• 病例报告 • 上一篇

种系PRKACA重复变异相关的原发性色素沉着性结节性肾上腺皮质病1例

周建华, 张宏利, 李晓华()

上海中医药大学附属第七人民医院内分泌代谢科，上海 200137

收稿日期:2025-08-19 接受日期:2025-10-11 出版日期:2025-11-28 发布日期:2025-12-03
通讯作者: 李晓华，女，主任医师，博士；电子信箱：z18702172007@163.com。
基金资助:
上海市浦东新区卫生健康委员会领先人才培养计划(PWR12021-06);上海市中管局“十四五”中医特色专科和中医急诊能力提升项目孵育项目（中医内分泌科）(ZYTSZK2-18);中央财政支持中医药传承创新发展示范试点项目(YC-2023-0201)

A case of primary pigmented nodular adrenocortical disease associated with germline PRKACA duplication variation

ZHOU Jianhua, ZHANG Hongli, LI Xiaohua()

Department of Endocrinology and Metabolism, the Seventh People′s Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 200137, China

Received:2025-08-19 Accepted:2025-10-11 Online:2025-11-28 Published:2025-12-03
Contact: LI Xiaohua, E-mail: z18702172007@163.com.
Supported by:
Shanghai Pudong New Area Health Commission Leading Talent Training Plan(PWR12021-06);Shanghai Central Administration Bureau′s“14th Five-Year Plan” Traditional Chinese Medicine Specialty and Traditional Chinese Medicine Emergency Capacity Improvement Project Incubation Project (Traditional Chinese Medicine Endocrinology Department)(ZYTSZK2-18);Central Fiscal Support for Demonstration Pilot Projects on the Inheritance and Innovative Development of Traditional Chinese Medicine(YC-2023-0201)

摘要/Abstract

摘要：

原发性色素沉着性结节性肾上腺皮质病（primary pigmented nodular adrenocortical disease，PPNAD）是一种罕见的非促肾上腺皮质激素（adrenocorticotropic hormone，ACTH）依赖性库欣综合征亚型，也是卡尼综合征（Carney complex，CNC）最常见的内分泌腺病变。该文报道1例成年起病的PPNAD和CNC患者。患者双眼周皮肤呈现斑点样色素沉着，无典型库欣综合征体貌特征，表现出糖尿病、高血压病、骨质疏松症症状。其血皮质醇水平昼夜节律消失，小剂量地塞米松与大剂量地塞米松抑制试验均未被抑制，24 h尿游离皮质醇升高，肾上腺增强CT显示双侧肾上腺增生，且增强后呈现均匀强化。通过基因检测，发现先证者19p13.2-p13.12区域存在约0.69Mbp的重复（拷贝数=3），该区域包含环磷腺苷依赖性蛋白激酶催化亚基α基因（protein kinase cAMP - dependent catalytic subunit α，PRKACA）；先证者女儿基因检测也呈现同样的基因组重复拷贝。该患者最终确诊为PPNAD和CNC，并接受腹腔镜右侧肾上腺全切除术。术中病理见肾上腺皮质增生及灰褐色结节；术后病理证实肾上腺皮质增生，胞质内见较多脂褐素。术后给予短期醋酸泼尼松片替代治疗，3个月后停药。目前患者病情平稳，进一步随访中。

关键词: 原发性色素沉着性结节性肾上腺皮质病, 非促肾上腺皮质激素依赖性库欣综合征, 基因组重复拷贝, PRKACA, 卡尼综合征

Abstract:

Primary pigmented nodular adrenocortical disease (PPNAD) is a rare subtype of adrenocorticotropic hormone (ACTH)-independent Cushing′s syndrome and the most common endocrine gland lesion in Carney complex (CNC). This article reported a case of PPNAD and CNC in an adult patient. The patient presented with speckled pigmentation around both eyes, lacked typical Cushingoid features, and exhibited symptoms of diabetes, hypertension, and osteoporosis. The circadian rhythm of blood cortisol levels disappeared, and neither the low-dose nor high-dose dexamethasone suppression tests were inhibited. The 24-hour urinary free cortisol was elevated. Enhanced adrenal computed tomography (CT) showed bilateral adrenal hyperplasia with uniform enhancement after contrast. Through genetic testing, an approximately 0.69Mbp duplication (copy number=3) was found in the 19p13.2-p13.12 region of the proband, which contained the protein kinase cAMP-dependent catalytic subunit α gene (PRKACA). The genetic test of the proband′s daughter also revealed the same genomic duplication. The patient was eventually diagnosed with PPNAD and CNC and underwent laparoscopic right adrenalectomy. Intraoperative pathology showed adrenal cortical hyperplasia and gray-brown nodules. Post-operative pathology confirmed adrenal cortical hyperplasia with abundant lipofuscin in the cytoplasm. The patient received short-term replacement therapy with prednisone acetate tablets, which was discontinued after 3 months. Currently, the patient′s condition is stable and further follow-up is in ongoing.

Key words: primary pigmented nodular adrenocortical disease (PPNAD), ACTH-independent Cushing′s syndrome, genomic duplication, protein kinase cAMP - dependent catalytic subunit α (PRKACA), Carney complex (CNC)

中图分类号:

R587

周建华, 张宏利, 李晓华. 种系PRKACA重复变异相关的原发性色素沉着性结节性肾上腺皮质病1例[J]. 上海交通大学学报（医学版）, 2025, 45(11): 1552-1558.

ZHOU Jianhua, ZHANG Hongli, LI Xiaohua. A case of primary pigmented nodular adrenocortical disease associated with germline PRKACA duplication variation[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2025, 45(11): 1552-1558.

图/表 4

表1 患者术前及术后皮质醇节律及24 h尿游离皮质醇水平

Tab 1 Patients′ preoperative and postoperative cortisol rhythm and 24-hour urinary free cortisol levels

Time	8:00ACTH/ (pg·mL^-1)	8:00Cortisol/ (μg·dL^-1)	16:00ACTH/(pg·mL^-1)	16:00Cortisol/(μg·dL^-1)	24:00ACTH/(pg·mL^-1)	24:00Cortisol/(μg·dL^-1)	24hUFC/ (μg·dL^-1)
preoperative	<1	23.53	<1	25.34	<1	22.40	403.60
LDDST	‒	15.88	‒	‒	‒	‒	‒
HDDST	‒	16.24	‒	‒	‒	‒	701.80
postoperative	<1	10.51	<1	8.08	<1	8.09	90.00
1-year postoperative	<1	6.95	<1	5.92	<1	5.19	‒

图1 肾上腺增强CTNote： A. Left adrenal CT with contrast enhancement, showing hyperplasia of the left adrenal gland with homogeneous enhancement (indicated by the red arrow). B. Right adrenal CT with contrast enhancement, showing hyperplasia of the right adrenal gland with homogeneous enhancement (indicated by the red arrow).

Fig 1 Contrast-enhanced CT of the adrenal glands

图2 患者右侧肾上腺病理组织Note： Adrenal cortex hyperplasia and gray-brown nodules were seen in the cytoplasm.

Fig 2 Pathological tissue of the patient's right adrenal gland

图3 患者肾上腺病理组织切片（苏木精-伊红染色，×100）

Fig 3 Adrenal pathological tissue section of the patient (H-E staining, ×100)

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种系PRKACA重复变异相关的原发性色素沉着性结节性肾上腺皮质病1例

A case of primary pigmented nodular adrenocortical disease associated with germline PRKACA duplication variation

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