Tellam Jane J, Abdulrasool Ghusoon, Ciin Louise C H
Royal Brisbane and Women's Hospital, Herston, Queensland, Australia.
University of Queensland, Herston, Queensland, Australia.
Endocrinol Diabetes Metab Case Rep. 2020 Jun 22;2020. doi: 10.1530/EDM-20-0004.
Distinguishing primary hyperparathyroidism (PHPT) from familial hypocalciuric hypercalcaemia (FHH) can be challenging. Currently, 24-h urinary calcium is used to differentiate between the two conditions in vitamin D replete patients, with urinary calcium creatinine clearance ratio (UCCR) <0.01 suggestive of FHH and >0.02 supportive of PHPT. A 26-year-old Caucasian gentleman presented with recurrent mild hypercalcaemia and inappropriately normal parathyroid hormone (PTH) following previous parathyroidectomy 3 years prior. He had symptoms of fatigue and light-headedness. He did not have any other symptoms of hypercalcaemia. His previous evaluation appeared to be consistent with PHPT as evidenced by hypercalcaemia with inappropriately normal PTH and UCCR of 0.0118 (borderline low using guidelines of >0.01 consistent with PHPT). He underwent parathyroidectomy and three parathyroid glands were removed. His calcium briefly normalised after surgery, but rose again to pre-surgery levels within 3 months. Subsequently, he presented to our centre and repeated investigations showed 24-h urinary calcium of 4.6 mmol/day and UCCR of 0.0081 which prompted assessment for FHH. His calcium-sensing receptor (CASR) gene was sequenced and a rare inactivating variant was detected. This variant was described once previously in the literature. His mother was also confirmed to have mild hypercalcaemia with hypocalciuria and, on further enquiry, had the same CASR variant. The CASR variant was classified as likely pathogenic and is consistent with the diagnosis of FHH. This case highlights the challenges in differentiating FHH from PHPT. Accurate diagnosis is vital to prevent unnecessary surgical intervention in the FHH population and is not always straightforward.
Distinguishing FHH from PHPT with co-existing vitamin D deficiency is difficult as this can mimic FHH. Therefore, ensure patients are vitamin D replete prior to performing 24-h urinary calcium collection. Individuals with borderline UCCR could have either FHH or PHPT. Consider performing CASR gene sequencing for UCCR between 0.01 and 0.02. Parathyroid imaging is not required for making the diagnosis of PHPT. It is performed when surgery is considered after confirming the diagnosis of PHPT.
区分原发性甲状旁腺功能亢进症（PHPT）和家族性低钙血症性高钙血症（FHH）可能具有挑战性。目前，对于维生素D充足的患者，24小时尿钙用于区分这两种情况，尿钙肌酐清除率（UCCR）<0.01提示FHH，>0.02支持PHPT。一名26岁的白人男性在3年前接受甲状旁腺切除术后出现复发性轻度高钙血症，甲状旁腺激素（PTH）水平异常正常。他有疲劳和头晕的症状。他没有任何其他高钙血症的症状。他之前的评估似乎与PHPT一致，高钙血症伴PTH异常正常以及UCCR为0.0118（根据>0.01与PHPT一致的指南，处于临界低值）可证明这一点。他接受了甲状旁腺切除术，切除了三个甲状旁腺。术后他的血钙短暂恢复正常，但在3个月内又回升至术前水平。随后，他来到我们中心，重复检查显示24小时尿钙为4.6 mmol/天，UCCR为0.0081，这促使对FHH进行评估。对他的钙敏感受体（CASR）基因进行了测序，检测到一种罕见的失活变异。这种变异此前在文献中仅被描述过一次。他的母亲也被证实有轻度高钙血症伴低钙尿症，进一步询问后，发现她有相同的CASR变异。该CASR变异被分类为可能致病，与FHH的诊断一致。这个病例凸显了区分FHH和PHPT的挑战。准确诊断对于防止对FHH患者进行不必要的手术干预至关重要，而且并不总是那么简单。
区分FHH和并存维生素D缺乏的PHPT很困难，因为这可能会模仿FHH。因此，在进行24小时尿钙收集之前，要确保患者维生素D充足。UCCR处于临界值的个体可能患有FHH或PHPT。对于UCCR在0.01至0.02之间的情况，考虑进行CASR基因测序。诊断PHPT不需要甲状旁腺成像。在确诊PHPT后考虑手术时才进行甲状旁腺成像。
