Endocrine Abstracts

Background: Thyroid cancers are less common in children than in adults, with papillary thyroid carcinoma (PTC) being the most frequent type. Although papillary thyroid carcinoma (PTC) has been reported in adults with CDC73 mutations, there are no previous reports of this occurring in children.

Case: An asymptomatic 15-year-old male under regular monitoring for unilateral PUJ obstruction was found to have persistent hypercalcemia and primary hyperparathyroidism. Biochemistry showed: adjusted calcium of 3.08 mmol/l (2.15–2.74), PTH of 26.4 pmol/l (1.1–6.9), and an increased urine calcium: creatinine ratio of 1.13 mmol/ mmol Cr (<0.60). USS neck and Tc-99m sestamibi scan localized the parathyroid adenoma to the right neck. Familial hyperparathyroidism gene panel reported a heterozygous CDC73 likely pathogenic variant. A jaw radiograph was normal. Family genetics didn’t report this mutation in first-degree relatives. Normal calcium levels were achieved with cinacalcet. He underwent a right-sided neck exploration for parathyroid adenoma excision. Due to central neck lymphadenopathy and his genetic risk, a right hemithyroidectomy and central neck dissection was also performed. Histology confirmed a right parathyroid adenoma with metastatic PTC in the lymph nodes. The patient subsequently underwent completion of thyroidectomy, followed by radioiodine therapy. Postoperatively, he recovered well and is currently on levothyroxine and oral calcium supplements.

Discussion: Papillary thyroid carcinoma accounts for 90% of childhood thyroid cancers. Commonly associated gene mutations include RET, BRAF, RAS, and NTRK; less common gene mutations include DICER1, TP53, and PTEN. CDC73 mutations are usually autosomal dominant but can also arise de novo. CDC73-related disorders include HPT-JT syndrome, familial isolated hyperparathyroidism (FIHP), and parathyroid carcinoma. Presentation often occurs in late adolescence or early adulthood with a single parathyroid adenoma. This condition predisposes to tumours in various sites, including the jaw bones, kidneys, uterus, and ovaries. Our case offers a rare and valuable insight into the potential role of CDC73 mutations in paediatric thyroid cancer. Although there are no established national guidelines for the management of patients with CDC73 mutations, studies recommend offering genetic testing to parents and first-degree relatives and regular biochemical and radiological screening to the affected members.