肾上腺库欣综合征:一名患有卡尼综合征的 10 岁男孩的诊断和治疗。

IF 2.6 3区 医学 Q3 ENDOCRINOLOGY & METABOLISM
Domenico Corica, Cecilia Lugarà, Jerome Bertherat, Eric Pasmant, Mariella Valenzise, Giorgia Pepe, Francesco Ferraù, Salvatore Cannavò, Tommaso Aversa, Malgorzata Gabriela Wasniewska
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引用次数: 0

摘要

简介与促肾上腺皮质激素无关的库欣综合征(CS)在儿童中非常罕见。原发性色素性结节性肾上腺皮质疾病(PPNAD)是导致库欣综合征的一种罕见病因,在大多数病例中,它是在卡尼综合征(CNC)的背景下发生的。CNC 是一种常染色体显性遗传综合征,通常是由于 PRKAR1A(蛋白激酶 A 的调节亚基 R1A)基因的致病变异所致。临床表现为皮肤色素斑、心脏、皮肤和乳腺肌瘤、黑素细胞分裂瘤、内分泌疾病和内分泌腺肿瘤(主要是肾上腺、垂体和甲状腺):一名 10 岁男孩因严重肥胖首次来到我们的门诊就诊。在头三个月的随访中,身高增长率正常,但对饮食行为指征的反应不佳,体重下降缓慢。后来,在最后一次评估的 10 个月后,有证据表明肥胖症明显恶化,出现了生长停滞、动脉高血压以及躯干和四肢根部出现红色皮纹。研究人员对导致肥胖和发育不良的内分泌原因进行了调查。皮质醇、促肾上腺皮质激素和皮质醇尿的昼夜节律提示存在促肾上腺皮质激素依赖性高皮质血症。排除了先天性原因。肾上腺超声波和计算机断层扫描初步显示左肾上腺内侧臂存在结节或增生。相反,磁共振成像显示肾上腺整体尺寸明显增大,双侧肾上腺呈微小结节状。考虑到 ACTH 依赖性皮质醇过多症与 PPNAD 之间的关联,对患者进行了遗传学调查,结果发现 PRKAR1A 基因存在致病变异。在为期两年的随访中,患者开始接受甲萘醌治疗,并且耐受良好。临床症状略有改善,皮质醇尿恢复并保持在正常范围内,但促肾上腺皮质激素抑制仍然存在:这是首次报道使用甲萘醌治疗 PPNAD 相关高皮质醇血症(CNC 儿童患者)两年的临床和生化效果。目前,还没有治疗 PPNAD 相关高皮质醇血症的成熟方案,尤其是在儿科领域,相关数据非常稀少。药物疗法可能有助于减少双侧肾上腺切除术的需要,至少在初期是这样。不过,还需要进一步的研究来澄清这方面的问题。在因 PPNAD 而导致 CS 的病例中,如果最初采用的是药物治疗,而临床、辅助治疗和生化治疗没有明显改善,则可能必须停用甲萘醌,转而采用其他方法,包括手术治疗。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Adrenal Cushing Syndrome: Diagnosis and Management in a 10-Year-Old Boy with Carney Complex.

Introduction: Adrenocorticotropic hormone (ACTH)-independent Cushing syndrome (CS) is very rare condition in children. Primary pigmented nodular adrenocortical disease (PPNAD) is a rare cause of CS, which in most cases occurs in the context of Carney complex (CNC). CNC is a rare autosomal-dominantly inherited genetic syndrome, usually due to pathogenic variants of the PRKAR1A (regulatory subunit R1A of the protein kinase A) gene located at 17q22-24. The clinical picture is characterized by spotty skin pigmentation, cardiac, cutaneous, and mammary myxomas, melanocytic schwannomas, endocrinopathies, and tumours of the endocrine glands (mostly adrenal, pituitary, and thyroid).

Case presentation: A 10-year-old boy first came to our outpatient clinic due to severe obesity. During the first 3 months of follow-up, the height growth rate was normal, but the response to dietary-behavioural indications was poor in terms of weight loss. Later, 10 months after the last evaluation, there was evidence of significant worsening of obesity, growth failure (growth velocity 0.7 cm/year), arterial hypertension, and the occurrence of violaceous striae at the trunk and root of the limbs. Endocrinological causes of obesity associated with growth failure were investigated. The circadian rhythm of cortisol, ACTH, and cortisoluria were suggestive of ACTH-independent hypercortisolaemia. Iatrogenic causes were ruled out. Adrenal ultrasound and computer tomography scan were performed, which initially indicated the presence of a nodule or hyperplasia of the medial arm of the left adrenal gland. Conversely, magnetic resonance imaging showed a significant increase in the global dimensions of the adrenals with a bilateral micronodular appearance. In light of the association between ACTH-independent hypercortisolism and bilateral micronodular adrenal hyperplasia, a genetic investigation was performed, which found a pathogenic variant of the PRKAR1A gene. The patient was begun on treatment with metyrapone which was well tolerated over a 2-year period. The clinical picture has slightly improved, cortisoluria returned and remains within normal limits, but ACTH suppression persists.

Conclusion: This is the first report on the clinical and biochemical effects of 2-year medical treatment with metyrapone of PPNAD-related hypercortisolaemia in a paediatric patient with CNC. Currently, there are no established protocols for the management of hypercortisolism in PPNAD and data are scarce, especially in the paediatric field. Medical therapies may play a role in reducing the need, at least initially, for patients to undergo bilateral adrenalectomy. However, further studies on larger case series are needed to clarify this aspect. In cases of CS due to PPNAD in which medical therapy was the initial approach, in the absence of clear clinical, auxological, and biochemical improvements, metyrapone may have to be discontinued in favour of another approach, including surgery.

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来源期刊
Hormone Research in Paediatrics
Hormone Research in Paediatrics ENDOCRINOLOGY & METABOLISM-PEDIATRICS
CiteScore
4.90
自引率
6.20%
发文量
88
审稿时长
4-8 weeks
期刊介绍: The mission of ''Hormone Research in Paediatrics'' is to improve the care of children with endocrine disorders by promoting basic and clinical knowledge. The journal facilitates the dissemination of information through original papers, mini reviews, clinical guidelines and papers on novel insights from clinical practice. Periodic editorials from outstanding paediatric endocrinologists address the main published novelties by critically reviewing the major strengths and weaknesses of the studies.
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