PDF(Pubmed)
Abstract：
A total of 1 out of 10 patients with primary hyperparathyroidism (PHP) presents an underlying genetic form, such as multiple endocrine neoplasia types 1, 2A, etc., as well as hyperparathyroidism-jaw tumour syndrome (HJT). We aimed to summarise the recent data, thus raising more awareness regarding HJT, from the clinical perspective of PHP in association with the challenges and pitfalls of CDC73 genetic testing and parafibromin staining. This narrative review included a sample-focused analysis from the past decade according to a PubMed search. We identified 17 original human studies (≥4 patients per article). The mean age at disease onset was between 20.8 and 39.5 years, while the largest study found that 71% of patients had HJT recognised before the age of 30. Males and females seemed to be equally affected, in contrast with sporadic PHP. PHP represented the central manifestation of HJT, occurring as the first manifestation in up to 85% of HJT cases. A biochemistry panel found a mean serum calcium level above the level of 12 mg/dL in PHP. PTH was elevated in HJT as well, with average values of at least 236.6 pg/mL. The most frequent pathological type in PHP was a parathyroid adenoma, but the incidence of a parathyroid carcinoma was much higher than in non-HJT cases (15% of all parathyroid tumours), with the diagnosis being established between the age of 15 and 37.5. In some families up to 85% of carriers suffered from a parathyroid carcinoma thus indicating that certain CDC73 pathogenic variants may harbour a higher risk. An important issue in HJT was represented by the parafibromin profile in the parathyroid tumours since in HJT both parathyroid adenomas and carcinomas might display a deficient immunoreactivity. Another frequent manifestation in HJT was ossifying fibromas of the jaw (affecting 5.4% to 50% of patients; the largest study found a prevalence of 15.4%). HJT was associated with a wide variety of kidney lesion (mostly: kidney cysts, with a prevalence of up to 75%, and renal tumours involved in 19% of patients). The risk of uterine lesions seemed increased in HJT, especially with concern to leiomyomas, adenofibromas, and adenomyosis. The underlying pathogenic mechanisms and the involvement of CDC73 pathogenic variants and parafibromin expression are yet to be explored. Currently, the heterogeneous expression of parafibromin status and, the wide spectrum of CDC73 mutations including the variety of clinical presentations in HJT, make it difficult to predict the phenotype based on the genotype. The central role of HJT-PHP is, however, the main clinical element, while the elevated risk of parathyroid carcinoma requires a special awareness.
摘要：
10例原发性甲状旁腺功能亢进症（PHP）患者中有1例表现出潜在的遗传形式，如多发性内分泌瘤1型，2A型，等。,以及甲状旁腺功能亢进-颌骨肿瘤综合征（HJT）。我们旨在总结最近的数据，从而提高了对HJT的更多认识，从PHP的临床角度来看，与CDC73基因检测和纤维旁蛋白染色的挑战和陷阱相关。根据PubMed搜索，此叙述性审查包括过去十年的以样本为重点的分析。我们确定了17项原始人体研究（每篇文章≥4名患者）。发病时的平均年龄在20.8至39.5岁之间，而最大的研究发现，71％的患者在30岁之前就已识别HJT。男性和女性似乎同样受到影响，与零星的PHP相反。PHP代表了HJT的核心表现，在高达85%的HJT病例中首次出现。生物化学小组发现PHP中的平均血清钙水平高于12mg/dL。PTH在HJT也升高，平均值至少为236.6pg/mL。PHP中最常见的病理类型是甲状旁腺腺瘤，但甲状旁腺癌的发病率远高于非HJT病例（占所有甲状旁腺肿瘤的15％），诊断是在15岁至37.5岁之间建立的。在一些家庭中，高达85％的携带者患有甲状旁腺癌，因此表明某些CDC73致病性变体可能具有更高的风险。HJT中的一个重要问题是甲状旁腺肿瘤中的纤维旁蛋白谱，因为在HJT中，甲状旁腺腺瘤和癌都可能表现出免疫反应性不足。HJT的另一种常见表现是颌骨骨化性纤维瘤（影响5.4％至50％的患者；最大的研究发现患病率为15.4％）。HJT与多种肾脏病变有关（主要是：肾囊肿，患病率高达75%，和肾脏肿瘤涉及19％的患者）。HJT子宫病变的风险似乎增加，尤其是对平滑肌瘤的关注,腺纤维瘤,和子宫腺肌病。潜在的致病机制以及CDC73致病变体和纤维旁蛋白表达的参与尚待探索。目前,非纤蛋白的异质表达状态，广泛的CDC73突变，包括HJT的各种临床表现，这使得很难根据基因型来预测表型。HJT-PHP的核心角色是，然而,主要的临床因素，而甲状旁腺癌的风险升高需要特别的认识。
