Clinical and molecular characterization of parathyroid carcinoma in multiple endocrine neoplasia type 1.

Nineteen cases of parathyroid carcinoma in patients with multiple endocrine neoplasia type 1 have been reported in the literature, of which 11 carry an inactivating germline mutation in the MEN1 gene. Somatic genetic abnormalities in these parathyroid carcinomas have never been detected. In this paper, we aimed to describe the clinical and molecular characterization of a parathyroid carcinoma identified in a patient with MEN1. A 60-year-old man was diagnosed with primary hyperparathyroidism during the postoperative period of lung carcinoid surgery. Serum calcium and parathyroid hormone levels were 15.0 mg/dL (8.4-10.2) and 472 pg/mL (12-65), respectively. The patient underwent parathyroid surgery, and histological findings were consistent with parathyroid carcinoma. Analysis of the MEN1 gene by next-generation sequencing (NGS) identified a novel germline heterozygous nonsense pathogenic variant (c.978C>A; p.(Tyr326*)), predicted to encode a truncated protein. Genetic analysis of the parathyroid carcinoma revealed a c.307del, p.(Leu103Cysfs*16) frameshift truncating somatic MEN1 variant in the MEN1 gene, which is consistent with MEN1 tumor-suppressor role, confirming its involvement in parathyroid carcinoma etiology. Genetic analysis of CDC73, GCM2, TP53, RB1, AKT1, MTOR, PIK3CA and CCND1 genes in the parathyroid carcinoma DNA did not detect any somatic mutations. To our knowledge, this is the first report of a PC case presenting both germline (first-hit) and somatic (second-hit) inactivation of the MEN1 gene.

Mediastinal Thyroid Carcinoma and Graves' Disease: A Rare Presentation.

BACKGROUND: Mediastinal thyroid carcinoma is extremely rare, with few cases reported in the literature. Case Report. A 73-year-old man presented with weight loss for 6 months. Imaging by computed tomography (CT) documented a large mediastinal mass below the thyroid gland and pulmonary metastases. Neck ultrasound found two spongiform nodules in the right thyroid lobe, and fine-needle aspiration citology (FNAC) of these nodules revealed they are benign. Endobronchial ultrasound-guided needle biopsy of the mediastinal mass was compatible with papillary thyroid cancer. A few weeks later, the patient developed overt hyperthyroidism due to Graves' disease, which was treated with antithyroid drugs. 99mPertechnetate scintigraphy showed increased diffuse uptake in the thyroid parenchyma but the absence of uptake in the paratracheal mass and in the lung nodules. The patient was not considered eligible for surgical intervention or therapy with tyrosine kinase inhibitor due to tracheal and mediastinal vessel invasion and was treated with palliative radiotherapy. Two months later, restaging PET-FDG showed an intense uptake in the right lobe of the thyroid gland, lymph nodes, lungs, bone, muscle, myocardial, kidney, and adrenal gland. CONCLUSION: In this case, thyroid carcinoma presented as a mediastinal mass with concurrent hyperthyroidism due to Graves' disease. Although uncommon, the clinicians should be aware of these situations. Obtaining a prompt histological examination of an intrathoracic mass is crucial to ensure an early diagnosis and treatment.

A novel TRPM6 variant (c.3179T>A) causing familial hypomagnesemia with secondary hypocalcemia.

SUMMARY: Familial hypomagnesemia with secondary hypocalcemia (FHSH) is a rare autosomal recessive disorder (OMIM# 602014) characterized by profound hypomagnesemia associated with hypocalcemia. It is caused by mutations in the gene encoding transient receptor potential cation channel member 6 (TRPM6). It usually presents with neurological symptoms in the first months of life. We report a case of a neonate presenting with recurrent seizures and severe hypomagnesemia. The genetic testing revealed a novel variant in the TRPM6 gene. The patient has been treated with high-dose magnesium supplementation, remaining asymptomatic and without neurological sequelae until adulthood. Early diagnosis and treatment are important to prevent irreversible neurological damage. LEARNING POINTS: Loss-of-function mutations of TRPM6 are associated with FHSH. FHSH should be considered in any child with refractory hypocalcemic seizures, especially in cases with serum magnesium levels as low as 0.2 mM. Normocalcemia and relief of clinical symptoms can be assured by administration of high doses of magnesium. Untreated, the disorder may be fatal or may result in irreversible neurological damage.