Successful use of cinacalcet to treat parathyroid-related hypercalcemia in two pediatric patients

Summary Two pediatric patients with different causes of hyperparathyroidism are reported. First patient is a 13-year-old male with severe hypercalcemia due to left upper parathyroid gland adenoma. After successful surgery, calcium and phosphate levels normalized, but parathormone levels remained elevated. Further studies revealed a second adenoma in the right gland. The second patient is a 13-year-old female with uncommon hypercalcemia symptoms. Presence of pathogenic calcium-sensing receptor gene (CASR) mutation was found, resulting in diagnosis of symptomatic familial hypocalciuric hypercalcemia. Cinacalcet, a calcium-sensing agent that increases the sensitivity of the CASR, was used in both patients with successful results. Learning points: Hyperparathyroidism is a rare condition in pediatric patients. If not treated, it can cause serious morbidity. Genetic tests searching for CASR or MEN1 gene mutations in pediatric patients with primary hyperparathyroidism should be performed. Cinacalcet has been effective for treating different causes of hyperparathyroidism in our two pediatric patients. Treatment has been well tolerated and no side effects have been detected.

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Think twice: a rare calcium sensing receptor mutation and a new diagnosis of familial hypocalciuric hypercalcaemia

Endocrinology Diabetes and Metabolism Case Reports ◽

10.1530/edm-20-0004 ◽

2020 ◽

Vol 2020 ◽

Author(s):

Jane J Tellam ◽

Ghusoon Abdulrasool ◽

Louise C H Ciin

Keyword(s):

Vitamin D ◽

Surgical Intervention ◽

Urinary Calcium ◽

List Type ◽

Calcium Sensing Receptor ◽

Clearance Ratio ◽

Calcium Sensing ◽

New Diagnosis ◽

Learning Points ◽

Parathyroid Imaging

Summary 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. Learning points: 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.

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Mutations of calcium-sensing receptor gene: two novel mutations and overview of impact on calcium homeostasis

Acta Endocrinologica ◽

10.1530/eje-11-0121 ◽

2011 ◽

Vol 165 (2) ◽

pp. 353-358 ◽

Cited By ~ 2

Author(s):

Elena Livadariu ◽

Renata S Auriemma ◽

Catherine Rydlewski ◽

Silvia Vandeva ◽

Etienne Hamoir ◽

...

Keyword(s):

Calcium Homeostasis ◽

Genetic Disorders ◽

Receptor Gene ◽

Correct Diagnosis ◽

Gene Mutations ◽

Calcium Excretion ◽

Coding Region ◽

Calcium Sensing Receptor ◽

Calcium Sensing ◽

Exon 4

ObjectiveGenetic disorders of calcium metabolism arise in a familial or sporadic setting. The calcium-sensing receptor (CASR) plays a key role in maintaining calcium homeostasis and study of theCASRgene can be clinically useful in determining etiology and appropriate therapeutic approaches. We report two cases of novelCASRgene mutations that illustrate the varying clinical presentations and discuss these in terms of the current understanding of CASR function.Patients and methodsA 16-year-old patient had mild hypercalcemia associated with low-normal urinary calcium excretion and normal-to-high parathyroid hormone (PTH) levels. Because of negative family history, familial hypocalciuric hypercalcemia was originally excluded. The second patient was a 54-year-old man with symptomatic hypocalcemia, hyperphosphatemia, low PTH, and mild hypercalciuria. Familial investigation revealed the same phenotype in the patient's sister. The coding region of theCASRgene was sequenced in both probands and their available first-degree relatives.ResultsThe first patient had a novel heterozygous inactivatingCASRmutation in exon 4, which predicted a p.A423K change; genetic analysis was negative in the parents. The second patient had a novel heterozygous activatingCASRmutation in exon 6, which predicted a p.E556K change; the affected sister of the proband was also positive.ConclusionsWe reported two novel heterozygous mutations of theCASRgene, an inactivating mutation in exon 4 and the first activating mutation reported to date in exon 6. These cases illustrate the importance of genetic testing ofCASRgene to aid correct diagnosis and to assist in clinical management.

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