Mogl Martina T, Goretzki Peter E
Chirurgische Klinik, Charité Campus Mitte/Campus Virchow-Klinikum, Berlin, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin und Humboldt-Universität zu Berlin, Charitéplatz 1, 10117, Berlin, Deutschland.
Chirurgie (Heidelb). 2023 Jul;94(7):586-594. doi: 10.1007/s00104-023-01897-8. Epub 2023 Jun 8.
Between 2% and 10% of patients with primary hyperparathyroidism (pHPT) are diagnosed with hereditary forms of primary hyperparathyroidism (hpHPT). They are more prevalent in younger patients before the age of 40 years, in patients with persistence or recurrence of pHPT and pHPT patients with multi-glandular disease (MGD). The various forms of hpHPT diseases can be classified into four syndromes, i.e., hpHPT associated with diseases of other organ systems, and four diseases that are confined to the parathyroid glands. Approximately 40% of patients with hpHPT suffer from multiple endocrine neoplasia type 1 (MEN-1) or show germline mutations of the MEN‑1 gene. Currently, germline mutations that lead to a specific diagnosis in patients with hpHPT have currently been described in 13 different genes, which enables a clear diagnosis of the disease; however, a clear genotype-phenotype correlation does not exist, even though the complete loss of a coded protein (e.g. due to frame-shift mutations in the calcium sensing receptor, CASR) often leads to more severe clinical consequences than merely a reduced function of the protein (e.g. due to point mutation). As the various hpHPT diseases require different treatment approaches, which do not correspond to that of sporadic pHPT, a clear definition of the specific form of hpHPT must always be strived for. Therefore, before surgery of a pHPT with clinical, imaging or biochemical suspicion of hpHPT, genetic proof or exclusion of hpHPT is necessary. The differentiated treatment approach for hpHTP can only be defined by taking the clinical and diagnostic results of all the abovenamed findings into account.
在原发性甲状旁腺功能亢进症(pHPT)患者中,2%至10%被诊断为遗传性原发性甲状旁腺功能亢进症(hpHPT)。它们在40岁以下的年轻患者、pHPT持续或复发的患者以及患有多腺体疾病(MGD)的pHPT患者中更为普遍。hpHPT疾病的各种形式可分为四种综合征,即与其他器官系统疾病相关的hpHPT,以及四种局限于甲状旁腺的疾病。大约40%的hpHPT患者患有1型多发性内分泌肿瘤(MEN-1)或显示MEN‑1基因的种系突变。目前,已在13个不同基因中描述了导致hpHPT患者明确诊断的种系突变,这使得能够对该疾病进行明确诊断;然而,即使编码蛋白的完全丧失(例如由于钙敏感受体CASR中的移码突变)通常比仅仅蛋白功能降低(例如由于点突变)导致更严重的临床后果,但不存在明确的基因型-表型相关性。由于各种hpHPT疾病需要不同的治疗方法,这与散发性pHPT的治疗方法不同,因此必须始终努力明确hpHPT的具体形式。因此,在对临床、影像学或生化检查怀疑为hpHPT的pHPT患者进行手术前,有必要进行hpHPT的基因证明或排除。只有综合考虑上述所有检查结果的临床和诊断结果,才能确定hpHPT的差异化治疗方法。