Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Prevention of Metabolic Disorders Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, P.O. Box: 19395-4763, No. 24, Parvaneh Street, Velenjak, Tehran, Iran.
BMC Endocr Disord. 2021 Nov 4;21(1):220. doi: 10.1186/s12902-021-00881-9.
Primary hyperparathyroidism (PHPT) and familial hypocalciuric hypercalcemia (FHH) are the most important differential diagnosis of parathyroid hormone (PTH)-dependent hypercalcemia. The clinical features of FHH and PHPT can overlap in some cases. Therefore, these two diseases must be differentiated to prevent unnecessary parathyroidectomy. Here, we present a case that was not entirely matched with any of the known differential diagnoses of hypercalcemia.
A 19-year-old girl with no history of any disease presented with persistent hypercalcemia without any specific musculoskeletal complaint. We found persistent hypercalcemia in her routine laboratory data from 3 years ago; while no data was available during the childhood period. Her dietary calcium intake was normal. She did not mention any history of renal stone, bone fracture as well as family history of hypercalcemia. Biochemical features showed normal values of serum creatinine, high normal serum calcium (range, 10.3-11.3 mg/dL; (normal range: 8.8-10.4)), and non-suppressed PTH levels (range, 37.2-58.1 pg/mL; (normal range: 10-65)). Serum 25 OH vitamin D level at the first visit was 16.1 ng/mL that treated by vitamin D supplementation. Since then, all 25 OH vitamin D levels were in the acceptable range. After correction of vitamin D deficiency during the follow-up period the calcium creatinine clearance ratio(s) (CCCR) were calculated in the range of 0.009 to 0.014 (means below 1%). The clinical and laboratory data indicate more FHH rather than PHPT. Genetic studies were negative for the common genes associated with FHH (CASR, GNA11, and AP2S1 genes) and multiple endocrine neoplasia type1 (MEN1). On the other hand, no evidence of autoimmunity was found in her to support an autoimmune FHH-like syndrome. Hence, the case did not match completely to any diagnosis of FHH and PHPT, so we decided to follow her.
We presented a patient with FHH phenotype whose common genetic tests were negative. Further research is needed to ascertain other causes leading to similar manifestations.
甲状旁腺功能亢进症（PHPT）和家族性低钙血症性高钙血症（FHH）是甲状旁腺激素（PTH）依赖性高钙血症的最重要鉴别诊断。在某些情况下，FHH 和 PHPT 的临床特征可能会重叠。因此，必须区分这两种疾病以防止不必要的甲状旁腺切除术。在这里，我们介绍了一个与任何已知的高钙血症鉴别诊断都不完全匹配的病例。
一名 19 岁女孩，无任何疾病史，持续高钙血症，无任何特定的肌肉骨骼症状。我们发现她 3 年前的常规实验室数据中存在持续性高钙血症；而在儿童时期没有数据。她的膳食钙摄入量正常。她没有提到任何肾结石、骨折以及高钙血症家族史。生化特征显示血清肌酐值正常，血钙值偏高（范围为 10.3-11.3mg/dL；（正常值范围为 8.8-10.4）），PTH 水平无抑制（范围为 37.2-58.1pg/mL；（正常值范围为 10-65））。第一次就诊时血清 25 羟维生素 D 水平为 16.1ng/mL，经维生素 D 补充治疗。此后，所有 25 羟维生素 D 水平均处于可接受范围。在随访期间纠正维生素 D 缺乏后，钙肌酐清除率比值（CCCR）计算值在 0.009 至 0.014 之间（均值低于 1%）。临床和实验室数据表明更符合 FHH，而非 PHPT。常见的与 FHH 相关的基因（CASR、GNA11 和 AP2S1 基因）和多发性内分泌肿瘤 1 型（MEN1）的基因研究均为阴性。另一方面，在她身上没有发现自身免疫的证据，无法支持自身免疫性 FHH 样综合征。因此，该病例与 FHH 和 PHPT 的任何诊断均不完全匹配，因此我们决定对其进行随访。
我们介绍了一位具有 FHH 表型的患者，其常见的基因检测均为阴性。需要进一步研究以确定导致类似表现的其他原因。
